Review of statins needed

7th September 2019

In the UK, it has been decided that high intensity statins can now be sold over the counter to people – no prescription required. The European Society of Cardiology has decreed that there is no normal level for cholesterol, the lower the better. It goes on, and on.

However, there are some glimmers of light, occasionally. Aseem Malhotra, and I, wrote a letter to Sir Norman Lamb MP. Chairman of the Science and Technology Select Committee – at his request – asking for a review of statins, and safety issues.

It was reported in the few news outlets that had any space left after Brexit. You can see the video on Sky with Aseem, here


(or here is the link to YouTube… https://www.youtube.com/watch?v=RxCO9iiJYDw)

The letter is below.

Sir Normal Lamb MP

Chairman, Science and Technology Select Committee
29/08/2019

Dear Norman,

Re: The need for an independent reappraisal of the effects of statins

Statins are the most widely prescribed class of drugs in the UK.[1] They were designed to lower the blood cholesterol (LDL) level and therefore prevent cardiovascular disease.

Publications based on clinical trials have reported reductions in cardiovascular disease in people at high and low risk, and also a very low rate of side effects (drug-related adverse events).

It has been widely claimed that statins have therefore been responsible for the considerable reduction in the cardiovascular disease seen over the past 30 years both in the UK  and the rest of the Western World,[2] but there is evidence that refutes this claim. An ecological study using national databases of dispensed medicines and mortality rates, published in 2015, concluded: ‘Among the Western European countries studied, the large increase in statin utilisation between 2000 and 2012 was not associated with CHD mortality, nor with its rate of change over the years.[3] In the UK, despite far greater statin prescribing, the rate of cardiovascular disease has been rising for the past four years.[4]

In the absence of an analysis of the clinical trial data carried out by an independent group with full access to the raw data in the form of “clinical study reports”, there is good reason to believe that the benefits of statins have been ‘overhyped’ especially in those at low risk of cardiovascular disease, and the potential harms downplayed, unpublished, or uncollected.

Positive spin on the benefits of statins

It is well recognised that ‘positive spin’ is used to ‘hype’ the results from clinical trials. This should not happen but is widespread. According to one review: ‘Clinical researchers are obligated to present results objectively and accurately to ensure readers are not misled. In studies in which primary end points are not statistically significant, placing a spin, defined as the manipulation of language to potentially mislead readers from the likely truth of the results, can distract the reader and lead to misinterpretation and misapplication of the findings.’[5]

The authors continued: ‘This study suggests that in reports of cardiovascular RCTs with statistically nonsignificant primary outcomes, investigators often manipulate the language of the report to detract from the neutral primary outcomes. To best apply evidence to patient care, consumers of cardiovascular research should be aware that peer review does not always preclude the use of misleading language in scientific articles.’ [5]

As one example of such positive spin in relation to statins, the lead author of the JUPITER trial, Paul Ridker, writing in a commentary in the journal Circulation, summarised apparently statistically significant benefits between statin and placebo:

 The JUPITER trial was stopped early at the recommendation of its Independent Data and Safety Monitoring Board after a median follow-up of 1.9 years (maximum follow-up 5 years) because of a 44% reduction in the trial primary end point of all vascular events (P<0.00001), a 54% reduction in myocardial infarction (P=0.0002), a 48% reduction in stroke (P=0.002), a 46% reduction in need for arterial revascularization (P<0.001), and a 20% reduction in all cause mortality (P=0.02).’ [6]

Picking up on these figures, another well-known cardiologist wrote in equally positive terms: ‘Data from the 2008 JUPITER Trial suggest a 54 percent heart attack risk reduction and a 48 percent stroke risk reduction in people at risk for heart disease who used statins as preventive medicine. I don’t think anyone doubts statins save lives.’[7]

In fact in the JUPITER trial there was no statistically significant difference in deaths from cardiovascular disease among those taking rosuvastatin compared with placebo. There were 12 deaths from stroke and myocardial infarction in both groups among those receiving placebo, exactly the same number as in the rosuvastatin arm.[8] So the results of this clinical trial do not support claims that statins save lives from cardiovascular disease. This dissonance between the actual results of statin trials and the way they are reported is widespread.[9]

Other studies, looking at whether statins increase in life expectancy have found that, in high risk patients, they may extend life by approximately four days, after five years of treatment.[10] Doubts have also been raised about the claims of benefit in otherwise healthy people aged over 75, in whom statins are now being actively promoted.[11]

An overview of systematic reviews that examined the benefits of statins using only data from patients at low risk of cardiovascular disease found that those taking statins had fewer events than those not taking statins. However, when the results were stratified by the patients’ baseline risk, there was no statistically significant benefit for the majority of outcomes.[12] In conclusion, the absolute benefits in people at low risk are relatively small. If the 2016 guidelines are implemented in full, large numbers of otherwise healthy people will be offered statins, it has been estimated that 400 will need to take statins for five years to prevent one person from suffering a cardiovascular event.[13]

This information is not routinely given to patients, or indeed doctors who prescribe statins, and both doctors and patients therefore tend to have false expectations of the benefits of statins. Clinical guidelines call for shared decision making, including informing patients of the actual likelihood of benefits and risks, but this rarely occurs. There are also obvious questions in relation to value-for-money and the efficient use of finite healthcare budgets.

Side effects/adverse effects underplayed

There has been a heated debate about the adverse effects of statins. On one side, it is claimed that the rate of adverse effects is extremely low, affecting fewer than one in a thousand people.[14] Other studies have suggested adverse events are common, with up to 45% of people reporting problems.[15]

Attempts to resolve this important controversy have been hampered by the fact that  the data on adverse effects reported in the clinical trials are not available for scrutiny by independent researchers. The data from the major trials of statins are held by the Cholesterol Treatment Triallists Collaboration (CTT) in Oxford and they have agreed amongst themselves not to allow access by anyone else.[16] Many groups, have called for access to these data, but so far, this has not been granted.[17]

It is not even clear whether the CTT themselves have all the adverse effect data, since the relevant Cochrane Review Group does not seem to have had access to them. According to Professor Harriet Rosenberg of the Health and Society Program at York University: “It’s not clear if the AE (adverse events) data was withheld from the Cochrane reviewers (by CTT) or were not collected in the original trials.”[18]

When asked the lead author of the Cochrane review, Dr Shah Ebrahim, the CTT did not have the data. “Full disclosure of all the adverse events by type and allocation from the RCTs is now really needed, as the CTT does not seem to have these data.”[18]

Release of the data would undoubtedly help answer the question on how and whether the trials collected data on the most common side effects of muscle pain, weakness or cramps.

Summary

Rather than mass prescription based on incomplete and selective information, patients and the public deserve an objective account so that individuals can make their own informed decisions.

We believe there is now an urgent need for a full independent parliamentary investigation into statins:

  • a class of drug prescribed to millions in the UK and tens of millions across the world.
  • which, based on the publications available, have had their benefits subjected to significant positive spin, especially among people at low risk of cardiovascular disease, and their potential adverse effects downplayed
  • where independence would mean review of the complete trial data by experts with no ties to industry and who have not previously undertaken or meta-analysed clinical trials of statins.

Among the signatories to this letter, there are a range of views: some of us are deeply sceptical of the benefits of statins, others are neutral or agnostic. But all are strongly of the view that such confusion, doubt and lack of transparency about the effects of a class of drug that is so widely prescribed is truly shocking and must be a matter of major public concern.

Yours Sincerely,

Dr Aseem Malhotra, NHS Consultant Cardiologist and Visiting Professor of Evidence Based Medicine, Bahiana School of Medicine and Public Health, Salvador, Brazil.

Dr John Abramson, Lecturer, Department of Healthcare Policy, Harvard Medical School

Dr JS Bamrah CBE, Chairman, British Association of Physicians of Indian Origin.

Dr Kailash Chand OBE, Honorary Vice President of the British Medical Association  (signing in a personal capacity)

Professor Luis Correia, Cardiologist, Director of the Centre of Evidence Based Medicine, Bahiana School of Medicine and Public Health, Salvador Brazil. Editor in Chief, The Journal of Evidence Based Healthcare

Dr Michel De-Lorgeril, Cardiologist, TIMC-IMAG, School of Medicine, University of Grenoble-Alpes, Grenoble, France.

Dr David Diamond, Cardiovascular Research Scientist, Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA

Dr Jason Fung, Nephrologist and Chief of the Department of Medicine, The Scarborough Hospital, Toronto, Canada and Editor in Chief of the Journal of Insulin Resistance.

Dr Fiona Godlee, Editor in Chief, The BMJ

Dr Malcolm Kendrick, General Practitioner

Dr Campbell Murdoch, General Practitioner, NHS England Sustainable Improvement Team, Clinical Adviser

Professor Rita Redberg, Cardiologist, University of California, San-Francisco.

Professor Sherif Sultan, President, International Vascular Society

Sir Richard Thompson, Past President, The Royal College of Physicians

Professor Shahriar Zehtabchi, Editor in Chief, TheNNT.com, and Professor and Vice Chairman for Scientific Affairs Research, SUNY Downstate Health Science University, Brooklyn, New York

1: https://www.bhf.org.uk/informationsupport/treatments/statins

2: https://www.sciencedirect.com/science/article/pii/S1933287415004493

3: https://bmjopen.bmj.com/content/6/3/e010500

4: https://www.bhf.org.uk/what-we-do/news-from-the-bhf/news-archive/2019/may/heart-and-circulatory-disease-deaths-in-under-75s-see-first-sustained-rise-in-50-years

5: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2732330

6: https://www.ahajournals.org/doi/full/10.1161/CIRCOUTCOMES.109.868299

7: https://utswmed.org/medblog/statins-debate/

8: https://www.nejm.org/doi/full/10.1056/NEJMoa0807646

9:https://www.researchgate.net/publication/272189007_How_statistical_deception_created_the_appearance_that_statins_are_safe_and_effective_in_primary_and_secondary_prevention_of_cardiovascular_disease

10:  https://bmjopen.bmj.com/content/5/9/e007118

  1. Armitage J, Baigent C, Barnes E, Betteridge DJ, Blackwell L, Blazing M, et al. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. The Lancet. 2019;393(10170):407-15.
  2. Byrne P, Cullinan J, Smith A, Smith SM. Statins for the primary prevention of cardiovascular disease: an overview of systematic reviews. BMJ Open. 2019; 9(4):[e023085 p.]. Available from: https://bmjopen.bmj.com/content/bmjopen/9/4/e023085.full.pdf.
  3. Byrne P, Cullinan J, Gillespie P, Perera R, Smith SM. Statins for primary prevention of cardiovascular disease: modelling guidelines and patient preferences based on an Irish cohort. Br J Gen Pract. 2019. Available from: https://doi.org/10.3399/bjgp19X702701.

14: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31357-5/fulltext

15: https://www.lipid.org/nla/usage-survey

16: https://www.ctsu.ox.ac.uk/research/ctt

17: https://www.bmj.com/campaign/statins-open-data

18: http://healthinsightuk.org/2015/02/19/keep-statin-supremo-away-from-the-missing-side-effect-data/

 

Will this have any impact, on anything. We must keep bashing away, until the nonsense about cholesterol – has gone.

What causes heart disease part 64 – Not changing your mind

22 August 2019

‘A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it.’ Max Plank.

Perhaps the greatest challenge facing anyone who has a new idea is the sheer difficulty of getting anyone to change their mind. About anything. This difficulty is compounded if a committee, or any group of people, has to change their minds. Not only do they have to change their mind, they must make a public admission that they were wrong.

Many years ago, I was in contact with a geologist Thomas Gold. Yes, don’t worry, you have never heard of him. Neither had I. It was simply an honour that having read some of my ramblings he chose to reach out for a few on-line chats. Sadly, he is now dead.

He was a maverick. In the nineteen fifties he had been repeatedly thrown out of the American Geological Society for being a vigorous promoter of the tectonic plate hypothesis. Namely, that the Earth’s surface is make up of vast plates that glide about above the mantle. Not so much gliding as grinding very slowly.

Of course, this is now universally accepted as being true. Not so sixty years ago, when anyone mentioning tectonic plates was considered a dangerous fool, who understood nothing about geology, or science. Oh yes, indeed.

However, Thomas Gold did not stop with tectonic plates, he also promoted the abiotic theory of oil generation. I think he also came up with the idea of neutron stars as well. Anyway, getting back to abiotic oil generation, he did not believe that oil was created when trees – or other organic matter – died, rotted, went underground and was, gradually converted to oil.

He believed that oil was generated spontaneously within the Earth’s core. To quote:

‘Gold’s theory of oil formation, which he expounded in a book entitled The Deep Hot Biosphere, is that hydrogen and carbon, under high temperatures and pressures found in the mantle during the formation of the Earth, form hydrocarbon molecules which have gradually leaked up to the surface through cracks in rocks. The organic materials which are found in petroleum deposits are easily explained by the metabolism of bacteria which have been found in extreme environments similar to Earth’s mantle. These hyperthermophiles, or bacteria which thrive in extreme environments, have been found in hydrothermal vents, at the bottom of volcanoes, and in places where scientists formerly believed life was not possible. Gold argues that the mantle contains vast numbers of these bacteria.

The abiogenic origin of petroleum deposits would explain some phenomena that are not currently understood, such as why petroleum deposits almost always contain biologically inert helium. Based on his theory, Gold persuaded the Swedish State Power Board to drill for oil in a rock that had been fractured by an ancient meteorite. It was a good test of his theory because the rock was not sedimentary and would not contain remains of plant or marine life. The drilling was successful, although not enough oil was found to make the field commercially viable. The abiotic theory, if true, could affect estimates of how much oil remains in the Earth’s crust.’ 1

There you go. You have never heard of this before – ever. I think I can pretty much guarantee this. Neither had I. But I loved it. It was utterly and completely different to everything I had been told. Is it right, or is it wrong? No idea. I ain’t no geologist. Worth exploring as an idea though, surely.

What I do know, from speaking to Thomas is that almost all of his peers instantly rejected his ideas out of hand. Why? Because it didn’t fit with the knowledge they had been brought up with. Custom is king …

For many years it was taught that bacteria could not live in the human stomach. It was too hostile, too acidic. So, when it was proposed that a bacterium (H. Pylori), living in the stomach, could be an important cause of stomach ulcers, the idea was pretty much dismissed out of hand.

Warren and Marshall eventually proved that the scientific consensus on this matter was utter nonsense. This despite being attacked viciously from all sides. They eventually won the Nobel prize for their work where they were specifically praised for battling on in the face of implacable hostility. It is clear that had Warren not been a cussed swine, they could easily have given up, worn down by the opposition.

Had Max Plank not decided to publish some wild and whacky papers in his journal ‘Physics’, from a patent clerk, it is perfectly possible we may never have heard of a certain Albert Einstein.

When people ask me why do you think people cling onto the cholesterol hypothesis with such tenacity, is this vast conspiracy driven by the pharmaceutical industry? I expect most of them think I will say yes. I mean, obviously, there is a vast conspiracy going on to protect profits from cholesterol lowering.

However, the main reason why people cling to ideas is the natural human response – which is to reject new ideas out of hand.

“The mind likes a strange idea as little as the body likes a strange protein and resists it with similar energy. It would not perhaps be too fanciful to say that a new idea is the most quickly acting antigen known to science.”  Wilfred Trotter

Ooh, I do like Wilfred Trotter. Here is another one of his:

‘The truly scientific mind is altogether unafraid of the new, and while having no mercy for ideas which have served their turn or shown their uselessness, it will not grudge to any unfamiliar conception its moment of full and friendly attention, hoping to expand rather than to minimize what small core of usefulness it may happen to contain.’

What has this to do with heart disease, you could ask? The answer is: almost everything.

1: https://enviroliteracy.org/energy/fossil-fuels/abiotic-theory/

A second look at vaccination – answers that cannot be questioned

29th July 2019

 ‘No man can be forced to be healthful, whether he will or not. In a free society, individuals must judge for themselves what information they choose to heed and what they ignore.’ John Locke. ‘A letter concerning Toleration’

Here, I am going have another look at vaccination, before scurrying away from the subject for a bit, and getting back to the safe ground of cardiovascular disease. Much to the relief of some of the regular readers of this blog, no doubt.

I have to say that I thought long and hard about blogging on vaccination. It is the most brutal area for discussion that I have ever seen, and a reputation shredder. If you even dare to hint that there may just be the slightest issue with any vaccine, people come down upon you like a ton of bricks.

I also know that by daring to write on this subject, there will inevitably be people moving behind the scenes to have my blog taken down. I cannot imagine WordPress management going to the wire to protect my right to free speech. A little flick of a switch, and I will be gone from the airwaves.

However, as we move towards a world where it seems that all Governments around the world are going to pass laws mandating vaccination for everyone, and people are fined, or lose their jobs, for speaking out, or refusing to be vaccinated, then I feel that some attempt to discuss the area is essential.

Because, once something becomes mandatory, and any research into possible harms moves strictly off limits, we really need to be absolutely one hundred per-cent certain that there is no possibility that we may be doing harm. Or, that we are reducing any potential harm to the lowest level possible.

Can vaccines do harm?

‘Prof Martin Gore, 67, one of the UK’s leading cancer scientists, has died, the Royal Marsden NHS foundation trust has said. His death was following a yellow fever vaccination.’ 1

A tragedy for a brilliant medical researcher and his family. It was brought to my attention by my wife, who knew him quite well.

However, even here, we can see any criticism of vaccines being toned down and deflected. The words ‘caused by’ were carefully avoided. It was reported that he died following a yellow fever vaccination – which could mean he was vaccinated, then got hit by a bus. In fact, if you read a little more deeply, it becomes inarguable that the yellow fever vaccine was the direct cause of his death.

Yes, such an event is rare, but such events do occur. People can die following vaccinations, as a direct cause of that vaccination, although the information can be very difficult to find. In Germany, the Paul-Erlich Institute [PEI] is the organisation responsible for the reporting of vaccine security/safety.

‘Between 1978 and 1993 approximately 13,500 cases of undesired effects resulting from medications for vaccinations was reported to the Paul Erlich Institute (PEI) which is the institute which is responsible for vaccine security; the majority was reported by the pharmaceutical industry. In 40% of cases the complications were severe, 10% pertained to fatalities on account of the effects.’ 2

Yes, the numbers are relatively small – although by no means vanishingly small. In a fifteen-year period that is 1,350 deaths. If the Germans are preventing tens of thousands of deaths a year through vaccination, then a thousand severe complications and a hundred deaths or so, per year, may be a price worth paying? Discuss.

Primum non nocere

My own view is that you should never compel people to undergo a medical procedure that could result in severe damage – or death. But my philosophy is very much on the radical libertarian end of the spectrum. Others feel that personal liberties should be restricted for the overall good of society. A central philosophical divide, I suppose.

One of the other interesting facts from the Paul-Erlich Institute is that ‘severe cases’ of vaccine damage, that occur, that must be reported, include:

  • Encephalopathia: Encephalopathia is frequently overlooked as it does not always entail severe symptoms. However, there can later be developmental retardation. Encephalopathia can also trigger cri encéphalique
  • Seizures
  • Epilepsy
  • Autism
  • Sleeping sickness 2

These are not my words; these are the words of the PEI.

This list obviously raises the issue of potential brain damage following vaccination. Something that was seen with Pandemrix, used to protect against Swine Flu (HIN1).

‘An increased risk of narcolepsy was found following vaccination with Pandemrix, a monovalent 2009 HIN1 influenza vaccine that was used in several European countries during the HIN1 influenza pandemic. Narcolepsy is a chronic neurological caused by the brain’s inability to regulate the sleep-wake cycles normally. This risk was initially found in Finland, and then some other European countries also detected an association. Most recently, scientists at the United Kingdom’s Health Protection Agency (HPA) have found evidence of an association between Pandemrix and narcolepsy in children in England. The findings are consistent with studies from Finland and other countries.’ 2

[A finding not seen in any safety testing carried out prior to the launch of Pandemrix]

Thus, not only can vaccines cause severe reactions up to, and including, death. They can also lead to neurological damage such as narcolepsy. Is this all specifically to do with the vaccine itself, or the preservative it is carried in, or something else? Who knows?

Yet, and yet, despite the apparently indisputable evidence that vaccines can, and do, cause neurological damage we can find articles such as this below. Chosen pretty much at random, but it sums up the current mainstream thinking.

The “urban myth” of the association between neurological disorders and vaccinations

‘In modern society, a potentially serious adverse event attributed to a vaccination is likely to be snapped up by the media, particularly newspapers and television, as it appeals to the emotions of the public. The widespread news of the alleged adverse events of vaccination has helped to create the “urban myth” that vaccines cause serious neurological disorders and has boosted antivaccination associations. This speculation is linked to the fact that the true causes of many neurological diseases are largely unknown. The relationship between vaccinations and the onset of serious neuropsychiatric diseases is certainly one of coincidence rather than causality. This claim results from controlled studies that have excluded the association between vaccines and severe neurological diseases, therefore it can be said, with little risk of error, that the association between modern vaccinations and serious neurological disorders is a true “urban myth”. 3

What is being stated here, very forcefully indeed, is that there is no causal relationship between vaccination and neurological damage. It is simply a myth. I find the two bodies of evidence here impossible to reconcile.

Just to give two examples, the Paul Erlich Institute records encephalopathia, seizures, epilepsy, deaths and suchlike, following vaccination. The Pandemrix vaccine, in turn, has been proven to cause narcolepsy. Even the manufacturers, GSK, admitted that it did.

‘The 2009 H1N1 influenza pandemic left a troubling legacy in Europe: More than 1300 people who received a vaccine to prevent the flu developed narcolepsy, an incurable, debilitating condition that causes overpowering daytime sleepiness, sometimes accompanied by a sudden muscle weakness in response to strong emotions such as laughter or anger. The manufacturer, GlaxoSmithKline (GSK), has acknowledged the link, and some patients and their families have already been awarded compensation. But how the vaccine might have triggered the condition has been unclear.4

This is… I am not sure what it is. The evidence clearly says one thing, yet we are told we must believe that this evidence is simply an ‘urban myth.’ I feel as though I have been transported to Wonderland, or some scary totalitarian state, where the truth cannot be spoken.

Even when it comes to the most contentious area of all, vaccines and autism, it appears to have been accepted – at least in one case in the US – that vaccination lead to autism, with a girl called Hannah Polling.

‘Officials at the US Department of Health and Human Services investigating Hannah’s medical history said that vaccine had ‘significantly aggravated an underlying mitochondrial disorder, which predisposed her to deficits in energy metabolism’, causing damage ‘with features of autism spectrum disorder’. 2

The final part of the statement was very difficult to understand. ‘The officials said that the vaccine didn’t cause her autism, but ‘resulted’ in it.’ The vaccine resulted in her autism. Or, her autism resulted in her vaccination?

I have tried that statement a few different ways around, and I have no idea what that means. A lead to B, but A did not cause B. Because B resulted in A…

“Then you should say what you mean,” the March Hare went on.

I do, “ Alice hastily replied; “at least I mean what I say, that’s the same thing, you know.”

“Not the same thing a bit!” said the Hatter. “Why, you might just as well say that “I see what I eat” is the same thing as “I eat what I see!”  Alice in Wonderland.

However, the Polling case does raise a further potentially important issue. Namely, that it seems possible that some people have underlying ‘mitochondrial dysfunction,’ and that vaccination may aggravate this problem, with potentially serious consequences.

Narcolepsy, for example, is believed by some researchers to be a problem with energy production in the mitochondria. Others feel that ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) could be the result of a mitochondrial dysfunction triggered by various viral infections and, therefore, possibly vaccination?

All of which means that the possibility exists that vaccination could trigger, or exacerbate, significant mitochondrial dysfunction in susceptible individuals. This may or may not be true, but it must surely be an area for research?

To my mind it would be extremely important to establish if mitochondrial dysfunction represents a ‘risk’ for vaccination. We could then identify, using some genetic/epigenetic test, those individuals who are more likely to be damaged by vaccination. At which point we could look at ways to prevent the risk of damage – however small that risk may – be in a susceptible population.

For example, it could be possible to space out the vaccines, or only give separate vaccinations to these individuals. Maybe we could avoid vaccinating against relatively mild conditions e.g. chicken pox, or rubella (in boys) in these individuals. To me, these things seem eminently sensible areas for study.

However, it seems that we are trapped within a paradigm where it is impossible to suggest that any vaccine, for any disease, may be associated with/cause any degree of harm. In such an environment, objective scientific research becomes impossible. ‘As vaccine can harm no-one, we cannot try to find out who may be harmed. Thank you, comrade.’

As you can probably tell, I find this all very worrying and deeply, deeply, disturbing. If science has any purpose it is to seek the truth – however much that upsets the current status quo. When I see, what I believe to be important and valid questioning being crushed, I find it almost physically painful.

If that questioning results in the finding that vaccines truly do not cause any adverse effects, then that is fine. I would be more than happy with that outcome, although it currently seems inarguable that vaccines do cause adverse effects. However, as I see it, we currently have a situation whereby:

  • Pharmaceutical companies do their own safety testing on vaccines (somewhat like Boeing did on the 737 Max 8). The regulatory authorities have been, effectively, side-lined.
  • Many safety studies have only lasted days, with little or no research on any long-term effects. In fact, as far as I can establish, there has been no long-term safety research [see under Pandemrix]
  • Some vaccines have been proven to cause neurological damage
  • The preservatives and adjuvants in vaccines have not been studied for safety
  • There has never been a randomised controlled clinical study on the efficacy of any vaccine – beyond looking for a raised level of antibodies
  • Some/many people can suffer from the diseases they have been vaccinated against – and this is not monitored in any way.

Any of these things should be a very large red flag.

Looking specifically at efficacy, on that list, it is usually stated that vaccines are rigorously tested for efficacy. Here is what the University of Oxford has to say in its site ‘Vaccine Knowledge Project.’

‘Phase III trials gather statistically significant data on the vaccine’s safety and efficacy (how well it works). This means looking at whether the vaccine generates a level of immunity that would prevent disease, and provides evidence that the vaccine can actually reduce the number of cases.5

However, this does not actually test whether a vaccine really does reduce the number of cases of a disease. As I wrote in the previous blog, even in population with a 98% vaccination rate against measles, a school population still suffered a measles outbreak, and many of those previously vaccinated suffered from measles.

Which means that the statement from the Vaccine Knowledge Project…. and provides evidence that the vaccine can actually reduce the number of cases’ needs to be read very carefully. It could be taken to mean ‘provides all the evidence needed.’ Which is what it has been crafted to imply. However, it actually means ‘provides evidence regarding a ‘surrogate end-point’ which suggests that vaccines may reduce the number of cases.

If you want to know if a vaccine really works, vaccinate a hundred thousand people against a disease. Do not vaccinate another hundred thousand people (matched and randomised) – and then see what happens. Then you will know how well your vaccine works.

This is a requirement of all other forms of medical intervention (with provisos), but it is not a requirement for vaccines. A true efficacy study does not simply look at a ‘surrogate’ marker. It needs to study hard endpoints e.g. how many people are truly protected against the disease. Also, what the rate of adverse events may be.

Of course, there are those who think that such a trial would be ridiculous and unethical. Here, I quote from a website KevinMD:

‘….as some have actually demanded, we must have a randomized controlled trial (RCT), the gold standard of clinical research. RCTs use random assignment of subjects to one group or the other, in this case vaccine or a placebo (fake vaccine), and ensure both the subjects and evaluation team be blinded to who got what.

Think about this for a minute. They are demanding parents agree to subject their child to a trial in which they have a 50/50 chance of getting a fake vaccine. All this to satisfy the concerns of vaccine deniers.

It would be incredibly unethical to do such a study, and no institutional review board (aka human studies committee) would ever approve such a thing. For such trials, there must be reasonable uncertainty about which group is getting the better treatment, and in this case, there is none. The bottom line is any vaccine skeptic who demands proof like this is being massively disingenuous. It’s akin to demanding a randomized controlled trial of parachutes.’ 6

What is being said here is that there is no uncertainty that vaccines work, so there is no need for a randomised controlled trial. The counter argument to this is simply to turn the argument inside out. Without an RCT, how do you know that vaccines work? Where is your evidence? Or does ‘just knowing that it works’, count?

Medicine is littered with examples of interventions that were considered so inarguably beneficial that no trials were ever done. Strict bed rest following an MI, the radical mastectomy, x-ray screening for lung cancer, PCI in the non-acute setting.

Bernard Lown was a man who dared challenge the ‘unquestionable’ benefits of coronary artery bypass surgery. He had a long and arduous battle to publish his evidence that CABG may cause more harm than benefit. His blog on this, ‘A Maverick’s Lonely Path in Cardiology (Essay 28)’, is well worth a read. As he concludes:

‘A new treatment, whether involving drugs or procedures, is improper without indubitable supporting evidence of benefit. The patients’ well-being must not be compromised by imagined good when countervailing interests are at the same time being served. Our forty-year struggle essentially concerned medicine’s first and inviolate principle, primum non nocere. “First do no harm” is the litmus test sanctioning the privilege to practice medicine.’ 7

Bernard Lown is one hundred per cent correct, and I find it difficult to conceive that anyone who has the slightest understanding of science could write the words ‘The bottom line is any vaccine skeptic who demands proof like this [an RCT] is being massively disingenuous.’

Disingenuous… Personally, I demand proof like this for all medical interventions, wherever possible, and so should everyone else. The reason why, is because evidence from controlled clinical trials (with all their inherent flaws) is the only tool that we possess to properly assess benefit vs. harm. Without such evidence we are simply hoping and praying that benefits truly outweigh any downsides.

For example, with the Pandemrix vaccine. Had an RCT been done, it is possible, even probable, that the adverse impact on Narcolepsy would have been picked up. Therefore, it would not have been used, therefore many thousands of people would not have been harmed – above and beyond narcolepsy. Some of the key issues around Pandemrix were discussed in the BMJ article ‘Pandermix vaccine: why was the public not told of early warning signs?’

‘Eight years after the pandemic influenza outbreak, a lawsuit alleging that GlaxoSmithKline’s Pandemrix vaccine caused narcolepsy has unearthed internal reports suggesting problems with the vaccine’s safety.

‘…the raw numbers of adverse events were not small. Although it is often said that perhaps only up to 10% of adverse events are reported to national reporting systems, by late November, GSK had received 1138 serious adverse event reports for Pandemrix—a rate of 76 per million doses administered. By mid-December, there had been 3280 serious adverse event reports (68/million doses). The last report seen by the BMJ, dated 31 March 2010, shows 5069 serious adverse events for Pandemrix (72/million doses).8

As the article goes on to say:

“What is the purpose of pharmacovigilance if nobody is acting on the information? This information took eight years to come to light through academic work and litigation. Is this acceptable? If the information at our disposal is partial, that is the direct consequence of secrecy, which should not surround any public health intervention.”

Pandemrix and Arepanrix were designed for a pandemic and were removed from global markets after the pandemic. Whatever adverse events they may have caused, they are vaccines of the past. But the events of 2009-10 raise fundamental questions about the transparency of information. When do public health officials have a duty to warn the public over possible harms of vaccines detected through pharmacovigilance? How much detail should the public be provided with, who should provide it, and should the provision of such information be proactive or passive?’

All good questions.

Had Pandemrix not caused narcolepsy in large numbers, litigation against GSK would not have taken place – in Ireland. Had this not happened, data about the high rate of other adverse effect would never have seen the light of day. It seems that the European Medicines Agency had little interest in the matter.

‘What EMA knew—or could have known—about the comparative safety of GSK’s pandemic vaccines is hard to discern. It told The BMJ that “EMA does not perform comparative benefit and risk evaluations between products approved in the EU, or between EU products and products approved or used outside the EU.”

So, if monitoring product safety is not of interest to them, what exactly do the EMA do? Central here, however, is the fact that we had a vaccine causing a high number of serious adverse events and no-one did, or said, anything. Had there not been a lawsuit, we would still have been unaware of any problems. At least that is my understanding of what happened here.

Does anyone care? Well, in many countries you cannot even sue the manufacturer if a vaccine damages you – as also mentioned in the BMJ article.

‘Another element, adopted by countries such as Canada, the US, UK, France, and Germany, was to provide vaccine manufacturers indemnity from liability for wrongdoing, thereby reducing the risk of a lawsuit stemming from vaccine related injury.’ Quite extraordinary. In my view, beyond extraordinary.

A manufacturer makes a product that you believe may have damaged or killed a loved one, and you cannot do anything about it. Or, those who made the product cannot be sued. In banking they have a phrase for this. They call it moral hazard.

‘lack of incentive to guard against risk where one is protected from its consequences, e.g. by insurance.’ In this case no insurance is required. Governments have given pharmaceutical companies a free pass. Depending on your belief in the inherent ethical standards of pharmaceutical companies you may – or may not – find this reassuring.

Personally, I find it extremely worrying that people, and the entire medical profession, appear willing to accept that all vaccines, for all conditions, are entirely effective and have no adverse effects…. Even when it has been demonstrated, beyond doubt, that they do.

Anyway, I feel I should probably stop here. Others have gone much further than me, others have been braver. But there should be nothing ‘brave’ about asking legitimate scientific questions. As Richard Feynman said. ‘I would rather have questions that can’t be answered than answers that can’t be questioned.’

 

1: https://www.theguardian.com/uk-news/2019/jan/11/top-cancer-scientist-prof-martin-gore-dies-after-rare-reaction-to-yellow-fever-vaccination

2: Doctoring Data pp 228 – 9 ISBN 978-1-907797-46-0

3: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718347/

4: https://www.sciencemag.org/news/2015/07/why-pandemic-flu-shot-caused-narcolepsy

5: http://vk.ovg.ox.ac.uk/vk/vaccine-development

6: https://www.kevinmd.com/blog/2018/11/why-demanding-a-randomized-controlled-trial-for-vaccines-is-disingenuous.html

7: https://bernardlown.wordpress.com/2012/03/10/mavericks-lonely-path-in-cardiology/

8: https://www.bmj.com/content/362/bmj.k3948

My feelings about the vaccine debate

9th July 2019

As readers of this blog will know, my primary area of interest is cardiovascular disease, which a big and complex subject, where anyone questioning the ‘conventional’ ideas gets ruthlessly attacked. However, in comparison to the area of vaccination, the battles in cardiovascular disease pale into insignificance. Mere squabbles in the nursery.

I am a member of an on-line doctors’ community in the UK called Doctors Net. Not open to the public. Whenever any story about vaccination emerges, the vitriol, anger and naked rage is quite scary to observe.

Whenever the issue of MMR raises its head on Doctors Net, doctors have stated that Andrew Wakefield should be thrown in jail, and never allowed to earn any money ever again, that he is a crook and a criminal – and those are the nicer comments.

It is clear that, in the medical profession, there is an unquestioned faith in vaccination. That is, all vaccinations, for all diseases, everywhere – for everyone. Anyone who dares to hint that, ahem, there could be some negative issues associated with vaccination is subjected to withering contempt. ‘You will be responsible for killing millions of children.’ You don’t understand science.’ And suchlike.

When it comes to the science, it does amuse me that vaccination began before anyone understood any of the science – of anything to do with microbes and the immune system. It all began, so it is recorded, with the observation that milkmaids were much less likely to get smallpox.

This led to the idea that you should deliberately infect people with a bit of cowpox, to prevent them getting smallpox. Bold.

‘The terms vaccine and vaccination are derived from Variolae vaccinae (smallpox of the cow), the term devised by Jenner to denote cowpox. He used it in 1796 in the long title of his Inquiry into the Variolae vaccinae known as the Cow Pox, in which he described the protective effect of cowpox against smallpox.’ [from the website that cannot be named… Wikipedia actually]

This was suggested at a time when all doctors thought infections were spread by Miasma. Basically, a nasty smell. No-one had the faintest idea that there were bacteria, or viruses. Somewhat ironically, vaccination – giving a small amount of a substance to cure/prevent a nasty disease – became the underlying principle of homeopathy – which most doctors now angrily dismiss as ‘woo woo medicine.’

Clearly, vaccination did not start as science. It basically started as a hunch, based on no comprehension of the science at all. Of course, that doesn’t make it wrong, but you can hardly suggest it was founded on a thorough understanding of the human immune system. Edward Jenner did not know that such a thing existed, and nor did anyone else. It was just a good guess.

The science of vaccination then became, what I call, backwards rationalisation. ‘It works, now let us work out how the hell it actually works.’ Again, nothing wrong with this. The best science often starts with observation, not a hypothesis. Graphene is a recent example. Two scientists larking about in the lab with Sellotape and pencils.

Just in case you are wondering. Yes, I do believe that vaccination works. Or, to be more accurate I believe that some vaccination works. Most vaccination, all vaccinations?

However, I do speak as one who has had seven hepatitis B inoculations and, once, just about managed to provide a blood test to show that I had made enough antibodies – to allow me to work as a doctor. A friend, who worked as a surgeon, had twenty-two hep B inoculations, and never managed to raise an antibody. He did explain to me how he continued to work as a surgeon, but I have forgotten how he managed.

Which means that I have personal – and slightly painful – experience that vaccination is not equally effective for everyone. Why not? Does anyone care about such things? It seems not. Just close your eyes and vaccinate away. No-one can question anything. Such as, why do inoculations produce antibodies in some people, and not others? Kind of interesting you would think – but no. Question not, the mighty vaccination.

This is strange, because it has been clearly established that vaccination does not work in many people:

‘An outbreak of measles occurred in a high school with a documented vaccination level of 98 per cent. Nineteen (70 per cent) of the cases were students who had histories of measles vaccination at 12 months of age or older and are therefore considered vaccine failures. Persons who were unimmunized or immunized at less than 12 months of age had substantially higher attack rates compared to those immunized on or after 12 months of age.

Vaccine failures among apparently adequately vaccinated individuals were sources of infection for at least 48 per cent of the cases in the outbreak. There was no evidence to suggest that waning immunity was a contributing factor among the vaccine failures. Close contact with cases of measles in the high school, source or provider of vaccine, sharing common activities or classes with cases, and verification of the vaccination history were not significant risk factors in the outbreak.

The outbreak subsided spontaneously after four generations of illness in the school and demonstrates that when measles is introduced in a highly vaccinated population, vaccine failures may play some role in transmission but that such transmission is not usually sustained.’1  

We are told that if you reach a measles vaccination rate of 95%, in a population, you cannot get an outbreak. Seems that is wrong. You can get an outbreak in a 98% vaccinated population. Wouldn’t it be nice to know why?

It does seem weird that measles is the chosen battleground for the vaccine furies. I am not entirely sure why. You would think the highly vocal pro-vaccinators would point to smallpox, or polio – or suchlike. Although, to be frank, I look at smallpox and wonder. I wonder how the hell we managed to eradicate this disease so quickly and simply. The entire world successfully vaccinated in a few years – with a perfect 100% record. No vaccine failures, all populations in the entire world vaccinated? Quite some feat.

An alternative explanation is that some diseases naturally come and go. Measles, for example, was an absolute killer three hundred years ago. Captain Cook introduced it to South Seas islands. The mortality rate was enormously high in native populations that had never been exposed to it before. Gradually the death rate attenuated. In most of the Western World measles was becoming a ‘relatively’ benign disease by the time vaccination came along.

If we look back in history, the black death wiped out half the population of Europe. What was it? It was almost certainly not the plague, although many people claim that it was. From the descriptions of those who died from it, it seems it was possibly a form of Ebola (haemorrhagic fever).

‘The Black Death of the 1300s was probably not the modern disease known as bubonic plague, according to a team of anthropologists studying these 14th century epidemics. “The symptoms of the Black Death included high fevers, fetid breath, coughing, vomiting of blood and foul body odor,” says Rebecca Ferrell, graduate student in anthropology. “Other symptoms were red bruising or hemorrhaging of skin and swollen lymph nodes. Many of these symptoms do appear in bubonic plague, but they can appear in many other diseases as well.”

Modern bubonic plague typically needs to reach a high frequency in the rat population before it spills over into the human community via the flea vector. Historically, epidemics of bubonic plague have been associated with enormous die-offs of rats. “There are no reports of dead rats in the streets in the 1300s of the sort common in more recent epidemics when we know bubonic plague was the causative agent,” says Wood.’ 2

Of course, we cannot be sure what the Black Death was. We do know that it came, it killed, it went. It also appeared to leave a legacy of people with CCR5 Delta32 mutations. People with this mutation cannot, it seems, be infected by the Ebola virus (or, indeed HIV). Ebola and HIV both gain entry to cells using the CCR5 protein, and if it is missing, the virus cannot get in. [Yes, you can cure HIV by giving bone marrow transplant from a donor with the CCR5 Delta 32 mutation – little known fact].

Why would we have this mutation far more commonly in areas of Europe than, in say, Africa – where the Black Death did not occur? Unless it provided a survival advantage at some point, against a virus that was (or was very like), Ebola.

Looking back at smallpox, did vaccination get rid of it? Or did vaccination simply apply the final push to see off a weakened opponent?

The plague itself – where has it gone?

Yes, I do look at the official history of vaccination with a jaundiced eye. The greatest successes… Well, it seems inarguable that vaccination has created enormous health benefits. Polio and smallpox – gone. But has this been entirely due to vaccination – possibly? I am yet to be convinced.

In truth, I find the entire area of vaccination quite fascinating. But the problem, the great problem, is that even by writing this blog I will have said several things that cannot be said.

  • Vaccination does not always work – burn the unbeliever.
  • Vaccination may not have been entirely responsible for ridding the world of smallpox – burn the unbeliever.
  • Measles is not the killer disease that it once was – burn the unbeliever.
  • You can have measles vaccination and still get measles – burn the unbeliever.

To me, these are just facts, and to state them is simply part of valid scientific questioning. For some reason, I am not entirely sure why, to question any ‘fact’ about vaccination is to be flung into the outer darkness. People get very, very, angry. They close their minds and they get polarised. Parts of this blog will almost certainly be taken out of context and used to attack me.

I don’t really know how to open the debate out into something sensible. Something scientific, something questioning and positive. Screeching at people that they simply don’t understand ‘science’ is not a good approach. In addition, yelling that they are ‘killing thousands of children’ is not a way to conduct a debate.

I feel that I do understand ‘science’, whatever that means exactly. Or at least I understand the scientific method. Which primarily consists of questioning everything – and feeling free do to so. One thing I do know is that anyone who states that the science is settled, and inarguable, and all the experts agree, and must therefore be right – clearly does not understand anything about science. At all.

1: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1646939/

2: https://www.sciencedaily.com/releases/2002/04/020415073417.htm

Writer’s block

June 4th 2019

Several people have asked after my welfare as I have not updated this blog for some time. The answer is that I am okay. Thanks for your concern. There have been a few things going on, one of which I will be able to speak about – at some point in the future – that have been taking up inordinate amounts of my time.

I am also writing, but for some reason, every time I sit down to write a new blog my mind goes completely blank. A very difficult thing to explain. It is as if a million thoughts all gather and just mangle each other up. Things seem very clear when I am walking about, but the moment I try to get started – glomp.

I am not sure if this is what is called writer’s block. It cannot really be, because I am writing other things – such as another book. However, it is very frustrating. I did fear maybe that I have run out of things to say – but in truth each day sees a newspaper headline, or a medical research paper, that has me itching for the keyboard. How can there be so much nonsense written in the world?

So, instead I am writing this rambling nonsense, that is of very little interest to anyone I suspect, but it may get me started again. Re-set my brain into super-blog mode – if there is such a thing.

Because I still believe there is a need for voices to question the misleading rubbish   being churned out by people who claim to be scientists. Especially medical scientists, such as my great friends in Oxford who can write the most outrageous gibberish and get it published.

I have always liked to believe that science is a self-correcting system. Researchers can head of in the wrong direction for many years, decades even, but in the end the scientific truth will always catch up with them, tap them on the shoulder and make it very clear they are just being silly.

The days when there were special devices for blowing smoke up the rectum have faded from memory:

When an “apparently dead from drowning” person was pulled from the Thames [river running through London], it was thought that two things needed to happen to successfully resuscitate them: warming of the body and stimulation. Tobacco was becoming popular in Europe thanks to its exportation from the Americas, and a well known stimulant thanks to the alkaloid nicotine. The nearly dead drowning victim can’t smoke themselves, and certainly can’t swallow anything. And since hypodermic needles weren’t to be fully-invented for another hundred years, the only logical way to administer tobacco was rectally. Plus, the warm smoke would warm the individual from the inside. Win-Win. Thus, the tobacco smoke enema was born, and devices placed all along the Thames river.’ 1

From here came the mocking expression ‘Blowing smoke up your arse.’ Yes, doctors have always been keen on such activities. The first Chinese Emperor was advised by his doctors to inhale vaporised mercury – which was a magical substance so incredibly healthy that everyone should be ingesting it.

Inevitably he went mad through mercury poisoning, and started running around the forests naked before being overthrown and murdered. Still he did leave a nice tomb with terracotta soldiers and even, so it is said, an underground lake of mercury – to keep him healthy in the afterlife.

My how we laugh now at such silly ideas. But medicine has continuously felt the need to do something, anything, for the patient – even if they have not the faintest idea what will happen. Good, or bad. Bernard Shaw wrote about this over a hundred years ago in Doctors Dilemmas.

‘When your child is ill or your wife dying,” when you are confronted by “the spectacle of a fellow creature in pain or peril, what you want is comfort, reassurance, something to clutch at, were it but a straw. This the doctor brings you. You have a wildly urgent feeling that something must be done; and the doctor does something. Sometimes what he does kills the patient.”

Leeches, other forms of bloodletting, trepanning, full frontal lobotomies, removal of the toxic colon, the radical mastectomy, strict bed rest following a heart attack – all these things and many more. The ‘sometimes’ that kill the patient.

These things have all gone – mostly. Evidence, science, got rid of them. Stupidity cannot run forever. At least this was once true. Today, I am not so sure. The need to do something, anything, still runs deep in the psyche of all doctors. The concept of ‘sorry, I can’t really do anything about that’ has never been front of mind.

My personal motto is ‘Don’t just do something, stand there.’ I call it masterful inactivity; others may call it laziness.

Anyway, to return to the main issue here, which is that medical science may now be incapable of self-correction. Erroneous ideas will be compounded, built on, and can never be overturned. Because of a thing called non-reproducibility.

In most areas of science, there is nothing to stop a researcher going back over old research and trying to replicate it. The correct term is reproducibility. In every branch of science there is currently an acknowledged crisis with reproducibility.

‘Reproducibility is a hot topic in science at the moment, but is there a crisis? Nature asked 1,576 scientists this question as part of an online survey. Most agree that there is a crisis and over 70% said they’d tried and failed to reproduce another group’s experiments.’ 2

This is not good, but in medical research this issue is magnified many times. Because there is another in-built problem. You cannot reproduce research that has been positive. Take clinical trials into statins. You start with middle aged men, split them into two groups, give one a statin and one a placebo. At the end of your five-year trial, you claim that statins had a benefit – stopped heart attacks and strokes and suchlike.

Once this claim has been made, in this group, it becomes unethical/impossible to replicate this study, in this group – ever again. The ethics committee would tell you that statins have been proven to have a benefit, you cannot withhold a drug with a ‘proven’ benefit from patients. Therefore, you cannot have a placebo arm in your trial. Therefore, you cannot attempt to replicate the findings. Ever.

Thus, if a trial was flawed/biased/corrupt or simply done badly. That’s it. You are going to have to believe the results, and you can never, ever, have another go. Ergo, medicine cannot self-correct through non-reproducibility. Stupidity can now last for ever. In fact, it is built in.

We face a rather dismal eternity of blowing smoke up our arses.

1: https://naturespoisons.com/2014/07/29/the-exciting-history-of-blowing-smoke-up-ones-arse-tobacco-smoke-enema/

2: https://www.nature.com/articles/d41586-019-00067-3

Diet and heart disease – again!

April 25th 2019

Thank you to those of you enquiring after my health. I have had a horrible cough and cold and proper ‘man flu’ for the last couple of weeks, now settling. Before that, skiing, before that lecturing. But enough about me.

Over the last few weeks I have watched a flurry of activity from all directions, as the attacks on red meat and saturated fat intensify. Walter Willett must be writing up a new research paper every five minutes, such is the wealth of material he has cascaded down upon a grateful world in recent weeks (I suspect others may be doing much of the heavy lifting on his behalf).

It also seems that the Lancet has given up any pretence of being an objective seeker of the truth. Instead, the Lancet appears to have become a mouthpiece for the vegan movement. Here is what the Lancet has to say about their new EAT-Lancet project.

‘Food systems have the potential to nurture human health and support environmental sustainability; however, they are currently threatening both. Providing a growing global population with healthy diets from sustainable food systems is an immediate challenge. Although global food production of calories has kept pace with population growth, more than 820 million people have insufficient food and many more consume low-quality diets that cause micronutrient deficiencies and contribute to a substantial rise in the incidence of diet-related obesity and diet-related non-communicable diseases, including coronary heart disease, stroke, and diabetes. Unhealthy diets pose a greater risk to morbidity and mortality than does unsafe sex, and alcohol, drug, and tobacco use combined. Because much of the world’s population is inadequately nourished and many environmental systems and processes are pushed beyond safe boundaries by food production, a global transformation of the food system is urgently needed.’1

Many out there probably agree with much of this statement, especially the parts about environmental sustainability and insufficient food to feed many people. However, even if you do, you have to ask what an investigative medical journal is doing in this space. There is no longer even an attempt to be mildly objective. The Lancet has simply taken sides. Which is the exact opposite of what any scientific journal should ever, ever, do. You may notice that Professor Walter Willett was the lead author of the article quoted above

Here is one statement that I would like to further highlight. Unhealthy diets pose a greater risk to morbidity and mortality than does unsafe sex, and alcohol, drug, and tobacco use combined.’

At this point I completely part company with Walter Willett. For it is the most complete and absolute nonsense. For a start, how did he calculate the figures? For example, sexually transmitted disease – and death. How many people die of this? How many people suffer, and by how much? Do we have any idea?

Well, we know that many children die from congenital syphilis. How many around the world? I checked the WHO publications on this, and there are only estimates to be had. HIV? Gonorrhoea? Hundreds of millions that are infected, and affected, but how many millions? How many deaths? Unknown really.

We can perhaps be a little clearer on the other things such as cigarette smoking. Just looking at one country, the US:

‘Cigarette smoking is responsible for more than 480,000 deaths per year in the United States, including more than 41,000 deaths resulting from secondhand smoke exposure. This is about one in five deaths annually, or 1,300 deaths every day.’ 2

The US population is around three hundred million. The population of the world around seven billion. If 480,000 deaths a year occur in the US, this would equate to eleven million deaths a year around the world.

Alcohol?

Around the world, about 1 in 5 adults were estimated to drink heavily in any given 30-day period. The burden of ill health for alcohol was less than for tobacco, but still substantial: 85.0 million DALYs [Disability adjusted life years]. Alcohol-related illness was estimated to cause 33.0 deaths per 100,000 people worldwide.3

Thirty-three deaths per 100,000 people worldwide is two point three million deaths each year from alcohol, worldwide. As for ‘illegal’ drug deaths.

‘Globally, UNODC estimates that there were 190,900 (range: 115,900 to 230,100) drug-related deaths in 2015, or 39.6 (range: 24.0 to 47.7) deaths per million people aged 15-64 years. This is based on the reporting of drug-related deaths by 86 countries.’4

This figure seems low, based on the CDC review of drugs deaths in the US

‘70,237 drug overdose deaths occurred in the United States in 2017. The age-adjusted rate of overdose deaths increased significantly by 9.6% from 2016 (19.8 per 100,000) to 2017 (21.7 per 100,000). Opioids—mainly synthetic opioids (other than methadone)—are currently the main driver of drug overdose deaths. Opioids were involved in 47,600 overdose deaths in 2017 (67.8% of all drug overdose deaths).’ 5

70,237 in the US would extrapolate up to 1.623 million deaths a year worldwide. Maybe other countries don’t hand out opiods like sweeties to everyone. Although, in the UK, we are certainly following suit.

So, we have some figures to go on. Somewhere in the fifteen to twenty million per year killed by unsafe sex, alcohol, drug and tobacco use each year. Who knows what the morbidity might be?

This is a gigantic figure, and we are supposed to believe that unhealthy diets are worse than this? I would challenge Walter Willett to find a single randomised controlled clinical study demonstrating that any dietary substance has significantly increased the risk of death in anyone, ever.

By unhealthy, of course, what the authors mean is animal fats/saturated fat, red meat, bacon, sausages and suchlike. Essentially, anything that is not vegan.

What of saturated fat? The last time it was possible to get an accurate assessment of saturated fat and deaths from CHD in individual countries was in 2008. After that, the figures mysteriously disappeared. Luckily Zoe Harcombe kept a copy and sent it to me.6

From these figures, I present you with a graph. Sorry, it is a bit complicated. So, please take a little time to study it, because it has two axes. The percentage of energy from saturated fat in the diet is the top axis, going from 0% up to 18%. As you can see from this, saturated fat intake is highest in France at 15.5%, and lowest in Georgia at 5.7%. Second lowest Azerbaijan, then Ukraine, then Russia.

The other axis looks at deaths from CHD. With the highest being Russia, then Georgia, then Azerbaijan, then the Ukraine.

The fact that stands out is that the countries with the lowest saturated fat intake had, on average, six times the rate of death from CHD, in comparison to the four countries with the highest saturated fat intake. I like to wave this graph at people who tell me that saturated fat in the diet is the single most important risk factor for CVD. I also like teasing vegans with it. Although they rarely respond well to teasing – as you may imagine.

I would also like to enquire of Walter Willett what he makes of data like this? I presume he would just ignore it, or point to the vegetarians of La Loma California, or suchlike. But, as any scientists know, you cannot just pick and choose populations you like and ignore those that you don’t. Nor would I dream of saying that, from this graph, we can prove that saturated fat intake protects against CVD. However tempting that may be.

But I know that this is what the EAT-Lancet are likely to do, along with all other researchers who simply ignore things they don’t like. In fact, the games played to prove that saturated fat is bad for you, twist the fabric of logic well beyond breaking point.

Which takes to me to favourite paper of all time. ‘Teleoanalysis: combining data from different types of study.’ Published in the BMJ more than fifteen years ago. 7

The paper makes this statement:

‘A meta-analysis of randomised trials suggested that a low dietary fat intake had little effect on the risk of ischaemic heart disease.’ Good, I like that. It seems astonishingly accurate. Randomised trials on dietary fat have had no effect. Which is the point where this paper should really have fallen silent.

But no, the authors decided that we should ignore these pesky studies a.k.a. evidence. Instead we should use teleolanalysis. I shall now quote directly, and heavily from the papers itself.

‘Once a causal link has been established between a risk factor and a disease it is often difficult, and sometimes impossible, to determine directly the dose-response relation. For example, although we know that saturated fat intake increases the risk of ischaemic heart disease, the exact size of the effect cannot be established experimentally because long term trials of major dietary changes are impractical. One way to overcome the problem is to produce a summary estimate of the size of the relation by combining data from different types of study using an underused method that we call teleoanalysis. This summary estimate can be used to determine the extent to which the disease can be prevented and thus the most effective means of prevention. We describe the basis of teleoanalysis, suggest a simple one-step approach, and validate the results with a worked example.

What is teleoanalysis?

Teleoanalysis can be defined as the synthesis of different categories of evidence to obtain a quantitative general summary of (a) the relation between a cause of a disease and the risk of the disease and (b) the extent to which the disease can be prevented. Teleoanalysis is different from meta-analysis because it relies on combining data from different classes of evidence rather than one type of study.

In contrast to meta-analysis, which increases the precision of summary estimates of an effect within a category of study, teleoanalysis combines different categories of study to quantify the relation between a causative factor and the risk of disease. This is helpful in determining medical practice and public health policy. Put simply, meta-analysis is the analysis of many studies that have already been done; teleoanalysis provides the answer to questions that would be obtained from studies that have not been done and often, for ethical and financial reasons, could never be done.

In so doing we can prove that saturated fat causes heart disease. ‘I say, Bravo. Bravo, sir. You are truly a genius.’

It is upon such foundations as this that the EAT-Lancet authors can say – in all seriousness – Unhealthy diets pose a greater risk to morbidity and mortality than does unsafe sex, and alcohol, drug, and tobacco use combined.’

Keep saying it and people will end up believing you. Even if you have not a scrap of evidence to support it. A phenomenon first noted by Lewis Carroll in his magical poem the Hunting of the Snark…

“Just the place for a Snark!” the Bellman cried,

   As he landed his crew with care;

Supporting each man on the top of the tide

   By a finger entwined in his hair.

 

“Just the place for a Snark! I have said it twice:

   That alone should encourage the crew.

Just the place for a Snark! I have said it thrice:

   What I tell you three times is true.”

Unfortunately for the EAT-Lancet crew, repeating nonsense as many times as you like cannot magically transform it from nonsense to truth. The biggest recent study on the impact of diet and heart health was the PURE study. Which was reported thus, last year:

‘Findings from this large, epidemiological cohort study involving 135,335 individuals aged 35 to 70 years from 18 low-, middle- and high-income countries (across North America, Europe, South America, the Middle East, South Asia, China, South East Asia and Africa) suggest that high carbohydrate intake increases total mortality, while high fat intake is associated with a lower risk of total mortality and has no association with the risk of myocardial infarction or cardiovascular disease-related mortality.

Furthermore, a higher saturated fat intake appeared to be associated with a 21% lower risk of stroke. Why might these results be in such contrast with current dietary advice? “The conclusion that low fat intake is protective is based on a few very old studies with questionable methodology,” explains Professor Salim Yusuf (McMaster University, Hamilton, Ontario, Canada), senior investigator for the PURE study. “The problem is that poorly designed studies performed 25–30 years ago were accepted and championed by various health organisations when, in fact, there are several recent studies using better methods, which show that a higher fat intake has a neutral effect,” he continues, citing the example of the Women’s Health Initiative trial conducted by the National Institutes of Health in 49,000 women that showed no benefit of a low-fat diet on heart disease, stroke or cardiovascular disease.’ 8

Anyway, I know that facts are pretty much useless against the diet-heart behemoth. It eats facts, turns them through one hundred and eighty degrees and spits them out again. I just felt the need to let people know that IT IS ALL COMPLETE AND UTTER RUBBISH. Gasp. Thud. I feel my man flu returning.

Refs:

1: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31788-4/fulltext

2: ‘https://www.cdc.gov/tobacco/data_statistics/fact_sheets/fast_facts/index.htm

3: https://www.nhs.uk/news/medical-practice/tobacco-alcohol-and-illegal-drugs-are-global-health-threat/

4: http://www.unodc.org/wdr2017/field/Booklet_2_HEALTH.pdf

5: https://www.cdc.gov/drugoverdose/data/statedeaths.html

6: European cardiovascular disease statistics 2008 edition. Steven Allendar et al: Health Economics Research Centre, Dept of Public Health, University of Oxford.

7: https://www.bmj.com/content/327/7415/616

8: https://www.escardio.org/Congresses-&-Events/ESC-Congress/Congress-resources/Congress-news/the-pure-study-understanding-the-relationship-between-nutrition-and-heart-disease

What causes heart disease – Part 63

17th March 2019

[Is stress the most important cause of cardiovascular disease?]

Forgetting for a moment attacks by various people, and newspapers, that shalI remain nameless [Mail on Sunday UK], I thought I would return to the more interesting topic of what actually does cause cardiovascular disease and. As I have done several times before, I am looking at stress/strain.

I know that, deep down, most people feel that stress can lead to illness. ‘Oh, I was terribly stressed, then I went down with the flu.’ Or ‘He has been under a lot of stress and had a heart attack.’ If we go back over a hundred years William Osler, a famous physician, described a man suffering from angina as ” … robust, the vigorous in mind and body, the keen and ambitious man, the indicator of whose engines are always at ‘full speed ahead’ “.

The idea that hard driving Type A personalities were more likely to die of heart attacks gained great popularity at one time. But you don’t hear so much about this anymore. It is all diet, and cholesterol, and blood pressure and diabetes and tablet after tablet. Measure this, monitor that, lower this and that.

I believe that the side-lining of stress to be a monumental mistake. Because it remains true that stress is the single most important cause of heart disease, and I intend to try and explain exactly how this can be. Once more into the breach dear friend.

I shall start this little journey by explaining that stress is the wrong word to use. In fact, the use of the word stress has often been more of a barrier than an aid understanding. This is because, when we talk about stress, we really mean strain.

Stress or strain

It was Hans Seyle who coined the term ‘stress’ to cover the concept of negative psychological events leading to diseases, specifically heart disease. Of course, this is a terrible oversimplification, but it will do for now. Seyle later admitted that, had English been his first language (he was born in Slovakia) he would have used the term strain, not stress.

This is because stress is the external force placed on an object, or a human being. Strain is the resulting deformation or damage that can occur. Therefore, it is the resultant strain that is the driver of ill health.

For example, being told you are a useless idiot by one or another parent would be considered a significant external negative ‘stressor.’ The resultant anxiety and upset then represents the strain. However, the two things do not necessarily match up very well.

If you are highly resilient, or perhaps deaf, being told you are a useless idiot may have absolutely no effect on you whatsoever. You will continue to whistle a happy tune, whilst skipping along the pavement.

If, on the other hand, you are a rather more sensitive soul, or perhaps being told you are a useless idiot is a daily occurrence, then the resultant strain/deformation may be quite severe. In this case, the same external stressor can result in completely different levels of internal strain – depending on the resilience of the individual.

To give another example, some people enjoy giving public talks, they look forward to it. Others would rather chew their own arm off rather than stand up and talk in public. Once again, we have the same external stressor, resulting in completely different levels of internal strain.

The death of a close relative, such as a husband, is a major negative stressor which, for most people would cause a significant burden of strain. However, if the husband was an abusive bully, who regularly beat his wife, the death may be a blessed relief and the levels of strain will be reduced greatly. Then again, the conflicting feelings of guilt, relief, happiness and grief can lead to immense strain.

In short, there is no point in saying that an individual is under a great deal of stress. That may or may not be true, but it is very difficult to define, or measure. What matters is their response to negative stressors – real or perceived. The internal strain.

Of course, this does not mean that you can discount external stressors. These can be very important on both an individual, and a population wide basis. So, before looking at strain in more detail, I am going to review external ‘population-wide stress(ors)’.

Population-wide stressors

Whilst this is a fascinating area, the terminology used is more than a little variable, and confusing. One of the problems is that the terminology swirls around, and people write about the same thing using different words or use the same words to describe different things. A bit like using IHD, CHD, CAD and CVD to describe much the same thing, I suppose.

To keep this simple, and stripping terminology down things down to basics, the concept I am trying to capture, and the word that I am going to use, here to describe the factor that can affect entire populations is ‘psychosocial stress’. By which I mean an environment where there is breakdown of community and support structures, often poverty, with physical threats and suchlike. A place where you would not really want to walk down the road unaccompanied.

This can be a zip code in the US, known as postcode in the UK. It can be a bigger physical area than that, such as a county, a town, or whole community – which could be split across different parts of a country. Such as native Americans living in areas that are called reservations.

On the largest scale it is fully possible for many countries to suffer from major psychosocial stress at the same time. This happened very dramatically after the breakup of the Soviet Union, which started in some countries earlier than others e.g. Poland. But the main event was the fall of the Berlin wall, and the collapse of communism across most of Eastern Europe. It was studied quite closely by a number of researchers. Here is one paper:

‘The mortality crisis in transition economies. Social disruption, acute psychosocial stress, and excessive alcohol consumption raise mortality rates during transition to a market economy.’ 1

As the paper states:

‘Acute psychosocial stress was one of the main drivers of the sharp mortality increase experienced by the former communist countries of Europe. In central Europe, the post-communist mortality crisis was quickly solved, while in much of the former USSR, life expectancy at birth did not return to 1989 levels until 2013.’

The splintering of the Soviet Union is something to be, generally, celebrated. However, it caused a massive surge in premature deaths, mainly from cardiovascular disease (CVD).

Below is a graph which tracks at CVD deaths in men under 65s in four former Soviet countries: Russia, Kazakhstan, Ukraine and Belarus. The graph starts in the year 1980 and goes on to 2015 2.

CVD was similar in all four countries and was pretty steady, perhaps gently falling. Then, Berlin wall fell in 1989, with major disruption hitting Russia by 1991 when Gorbachev was ousted by Yeltsin. At which point CVD took off in all country.

It may be easier to see a clear pattern if we look at a single country in the Soviet Union, Lithuania. This is a graph that I have used several times before. Figures are from Euro Heart Statistics.

In Lithuania CVD was gently dropping until 1989 then – Bam! Virtually a doubling of the rate in a five-year period. Then it dropped straight back down again.

If you want a comparator country in Europe, here is the UK during the same time period. A steady uninterrupted fall (completley undisturbed by the launch of statins in 1987) Every other country in Western Europe, the USA, Canada, Australia etc. show the same pattern as the UK – a steady fall.

Getting back to the Soviet Union, it is it interesting that the main increase in those who died was seen in men, mainly middle aged men. To quote from the social disruption paper again:

‘Looking back, it could have been expected that the European mortality crisis would primarily have affected children, pregnant women, the elderly, and the disabled. Yet, as shown.. men were much more affected than women in every transition country. The fastest relative upswing in mortality was recorded for 20−39 year olds, who experienced a marked rise in violent deaths, while the fastest absolute rise occurred among 40−59 year olds, who were mainly affected by a rise in cardiovascular deaths.’

It seems inarguable that extreme psychosocial stress, as experienced in ex-Soviet Union countries after 1989, drove a massive spike in CVD deaths, which is only now beginning to settle down in many of the countries.

As an important aside, you may notice that, in Russia, the rate of CVD rose quickly from 1990 until about 1995, then dropped. Then it jumped up again in 1998. You may ask, what happened in 1998? Well, this was the year of the collapse of the Ruble – known as the Ruble crisis. It resulted in massive financial chaos, and levels of poverty exploded.

‘Mobs trying to get their savings were barred from entering the banks, executives flew to London to get suitcases full of dollars and coup plans were discussed in the newspapers. The value of the stock market dropped to 10 percent of its value of the previous year, the value of Ruble tumbled by 75 percent, and 18 of Russia’s 20 major banks effectively collapsed under massive debts. Foreign investors, some of them calling Russia “Indonesia with nukes,” fled the country.

Some have said the damage to the economy was greater than that unleashed by Hitler’s armies in World War II. By the time of the 1998 Ruble crash ran its course the poverty level had increased from 2 percent of the population in the Soviet era to 40 percent.’  3

Moving away from the Soviet Union to the population that has undergone the single greatest and most extreme form of social breakdown and disruption, social stress and dislocation known. This is the Australian aboriginals. A group of people that has been subjected to an immense burden of negative stressors.

Here are a few bullet points from a study carried out by the Australian Government:

  • Stress is a significant factor of the lives of Aboriginal young people.
  • High levels of self-harming intent and behaviour. Feelings connected to loss of hope – high levels of anxiety and depression
  • Rapid social change in Aboriginal communities.
  • Interpersonal violence, accidents and poisoning, stress, alcohol and norms of violence as in male to male fighting.
  • Domestic violence and child abuse, as well as sexual assault, are further stressors and sources of mental ill health.
  • These behavioural outcomes reflect the impact of historical factors, colonisation and disadvantage.

What impact has this had, specifically on cardiovascular disease rates? A research study was done, called the Perth Aboriginal Atherosclerosis Risk Study (PAARS) population. The investigators looked at CHD (coronary heart disease), not CVD (cardiovascular disease) – which would also include strokes. Sorry for jumping about in the terminology, but everyone does. Indeed, it is hard to find two studies that use the same terminology, or end points.

Sticking to CHD, which basically means deaths from heart attacks, researchers found that the CHD rate in Austrailian Aboriginals was 14.9 per 1000/year versus 2.4 for the general population. This is 1,490 per 100,000 per year [this is metric most commonly used] and represents the highest rate I have ever seen in any population, in any country, at any time – ever. Although Belarus came pretty close at one point.

What also stands out is that the rate of heart attacks in Aborignal Australians was six fold higher than the surrounding population. However, if we separate the figures from men and woman, we can see something even more astonishing.

For Aboriginal men the rate of CHD was 15.0 versus 3.8 per 1000 per year. A four hundred per cent increase on men in the surrounding population. For aboriginal women the CHD was almost exactly the same as for the men, 15.0 per 1000 per year – which is highly unusual in itself – as men normally have a much higher rate than women.

The astonishing fact is that Australian Aboriginal women had a rate of CHD that was ten times the rate of the surrounding female population. Or, to put it another way. One thousand per cent higher. 4

A similar picture, though less extreme, can be seen in Native Americans. As outlined in this 2005 paper. ‘Stress, Trauma, and Coronary Heart Disease Among Native Americans.5

‘This study quantified exposure to trauma among American Indians, adding to the existing evidence that this population experiences a disproportional amount of trauma. We were intrigued by the statement “It may be that high rates of trauma exposure contribute to the increasing prevalence of cardiovascular disease among American Indian men and women, the leading cause of death among this population” and wanted to lend support to this assertion. Indeed, American Indians now have the highest rates of cardiovascular disease in the United States.

In a study similar to the AI-SUPERPFP study (American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project (AI-SUPERPFP) Team). Koss et al. documented adverse childhood exposures among 7 Native American tribes and compared these exposures to levels observed in the Adverse Childhood Experiences (ACE) Study conducted by Kaiser Permanente and the Centers for Disease Control and Prevention in a health maintenance organization population. Compared with participants in the ACE study, not only did the American Indians have a significantly higher rate of exposure to any trauma (86% vs 52%), but they also had a more than 5-fold risk of having been exposed to 4 or more categories of adverse childhood experiences (33% vs 6.2%).’

Wherever you look, you can see that populations that have been exposed to significant social dislocation, and major psychosocial stressors, have extremely high rate of coronary heart disease/cardiovascular disease.

This can be supported if we look at the twenty countries in the world that have the highest rates of CVD – both men and women. Figures from WHO 2017 6.  Ex-soviet countries in bold

  • Turkmenistan
  • Ukraine
  • Kyrgyzstan
  • Belarus
  • Uzbekistan
  • Moldova
  • Yemen
  • Azerbaijan
  • Russia
  • Tajikistan
  • Afghanistan
  • Syria
  • Pakistan
  • Mongolia
  • Lithuania
  • Georgia
  • Sudan
  • Egypt
  • Iraq
  • Lebanon

I feel that some of these figures may not be entirely accurate. Such as the CVD rate in Syria, or Iraq in the last few years. As for the rest. I would not like to comment on the social and political situations in all of these countries in too much detail. However, we are not looking at peaceful and mature democracies here. Mainly dictatorships and countries riven by internal conflict.

Winding this back to the US, there is a pattern of CHD showing that certain counties suffer much higher rates than others. Figures taken from the CDC. On this graph darker means a higher rate of heart disease, lighter means less heart disease. These are deaths per 100,000 per year. You may discern a pattern.

The UK shows precisely the same sort of picture with inner cities and more deprived areas, having much higer rates than affluent suburbs.

Wherever and however you look it becomes apparent that higher levels of psychosocial stress are strongly associated with CVD/CHD. In some cases, very strongly indeed.

But how can psychosocial stress and factors such as childhood trauma, as seen in the Australian Aboriginals, or Native Americans, lead to a build up of atherosclerotic plaques in the arteries,the main cause of CVD?

Or to put it another way, how does a negative external stressor, lead to the internal physiological strain, that causes CVD? For that we need to turn to Sapolski, Bjortorp and Marmot. Which comes next!

 

1: https://wol.iza.org/uploads/articles/298/pdfs/mortality-crisis-in-transition-economies.pdf

2: https://www.bhf.org.uk/informationsupport/publications/statistics/european-cardiovascular-disease-statistics-2017

3: http://factsanddetails.com/russia/Economics_Business_Agriculture/sub9_7b/entry-5170.html

4: https://www.ncbi.nlm.nih.gov/pubmed/20427550

Cholesterol Games

3rd March 2019

Mahatma Gandhi. ‘First they ignore you, then they laugh at you, then they fight you, then you win.’

A few days ago, the health editor of the Daily Mail wrote to me [and Zoe Harcombe and Aseem Malhotra]. I was informed that the Mail on Sunday was gong to attack us for daring to question the cholesterol hypothesis and the benefits of statins.

Below is the e-mail I received.

From: Barney Calman
Sent: 28 February 2019 16:53
To: malcolmken
Subject: MOS/Right to reply

Dear Dr Kendrick – The Mail on Sunday plans to publish an article this weekend on growing concerns about claims you and a number of other individuals have publicly made about statins, the role of cholesterol in heart disease, and the allegations that researchers into the drugs are financially conflicted due to payments made to the organisations they work for, and so the evidence they provide about the effectiveness of these medications, and their side effects, are in some way untrustworthy.

Over the past 30 years, more than 200,000 patients have been put through the most rigorous forms of clinical trials to produce definitive proof the tablets lower heart attack risk by up to 50 per cent, and a stroke by 30 per cent, and reduce the risk of death – from any cause.

In January, the editors-in-chief of all 30 major heart health medical journals – each a leading cardiologist – signed a joint open letter, warning: ‘Lives are at stake [due to the] wanton spread of medical misinformation. It is high time that this stopped.’

A 2016 analysis from the London School of Hygiene and Tropical Medicine, which tracks outbreaks and public health concerns, found fake news about statins may have prompted 200,000 patients in Britain alone to quit the drug over a single six-month period following an article you wrote for the BMJ which claimed, incorrectly, that 20 per cent of statins patients quit the drug because of side effects.

They estimate that up for 2,000 heart attack and strokes could be a result of this. We would like to offer you the opportunity to respond to this and the following:

*In your latest book, A Statin Nation, you state: ‘People are being conned. The way to avoid heart disease… has nothing to do with lowering cholesterol.’ This is despite clinical trial evidence to the contrary, and despite no evidence that there is a con, which would imply that those who claim that lowering cholesterol can help lower the risk of heart disease know this is untrue and are deliberately misleading the public.

*It has been alleged that the potential consequences of claims you have made about statins and cholesterol, far outweigh that of the infamous MMR vaccine scandal with one researcher saying: ‘In terms of death and disability that could have been prevented, this could be far worse.’

*In our article, one leading cardiologist states that the facts you and others often cite about cholesterol and statins sound convincing but that in reality ‘they contain a grain of truth, mixed with speculation and opinion, which makes is very difficult for the public to know who to trust.’

*You often quote observational studies as proof of your claims about statins and cholesterol in articles and in media appearances which contradict findings of authoritative clinical trials, which you do not mention. This is misleading.

*In a recent blog you wrote: ‘Professor Sir Rory Collins and Professor Colin Baigent made a pact with the dev… sorry … they made a pact with the pharmaceutical industry to take hold of all the data on statins. They will not let anyone else see the data they hold. Including all the data on side-effects. It is kept completely secret.’ Also: ‘A fact that needs to be emphasised is that the CTT will not let anyone else see the data they hold. Including all the data on adverse events [side-effects] and serious adverse events.’ It is a version of similar claims you have made numerous times over the years. However, the CTT have stated numerous times that they did not originally request the data on all adverse events so did not have it. They also point out that the said data must be requested from the individual research organisation which carries out the trials, and is not in their gift to provide. They say you know this, as they have told you this, so to repeat the claim amounts to a lie.

*Your stance on statins and the link between cholesterol and heart disease amounts to misinformation.

*There is no evidence you work in NHS practice, or as a GP in private practice.

If you wish for any comments to be included in our article please send them to us by midday this Friday.

Many thanks,

_________________
Barney Calman
Health & Lifestyle Content Director
Mail on Sunday

 

I wondered whether or not I should bother to reply, as I knew that the article would already have been written, and very little was going to be altered – no matter what I wrote. Indeed, I thought long and hard about responding to the allegation that there is no evidence you work in NHS practice, or as a GP in private practice.

This would have been a complete lie, so I wondered about letting them print it, then suing their backsides off afterwards. Then I thought I will spend the next ten years having people write that I am not a doctor at all – on the basis of a lie printed in the Daily Mail. So, I disavowed them of printing this direct lie. Maybe I should just have let them get on with it.

They were also going to write this…

A 2016 analysis from the London School of Hygiene and Tropical Medicine, which tracks outbreaks and public health concerns, found fake news about statins may have prompted 200,000 patients in Britain alone to quit the drug over a single six-month period following an article you wrote for the BMJ which claimed, incorrectly, that 20 per cent of statins patients quit the drug because of side effects.

Frankly, I wish I had written that paper, but I did not. It was written by Aseem Malhotra. This, I trust, gives you some idea of the high level of fact checking going on at the Daily Mail. In the end I did write back to the Daily Mail, and this is what I said. Amazingly, there were very few swear words.

Dear Barney Calman,

Thank you for your e-mail. This is all very familiar ground to me. I am not entirely sure how you would like me to respond to each of your points.

First, I do work for the NHS as a GP, and if anyone wishes to claim that I do not – then that would be direct libel. I am employed by two NHS trusts East Cheshire and CCICP (Central Cheshire Integrated Care Partnership). Feel free to check with either trust, or look me up on the GMC website. But if anyone states that I am not employed in the NHS then I will most certainly sue. And I will win, so I would recommend caution on this point.

As for other specific points.

*You often quote observational studies as proof of your claims about statins and cholesterol in articles and in media appearances which contradict findings of authoritative clinical trials, which you do not mention. This is misleading.

Do I not mention that the studies I quote are observational, or that I do not mention the findings of authoritative clinical trials? Which of these is a problem, and why?

I would add that the proof of the link between smoking and lung cancer was based on observational studies. Does this mean that smoking does not cause lung cancer? Or is that not their argument. Whilst observational studies are not generally considered as robust as randomised clinical trials, they have value. Equally, most epidemiologists would agree that, whilst observational studies (demonstrating association) cannot prove causality (unless the hazard ratios are very high) a lack of association does disprove causation. So, it can be fully valid to rely on observational studies where there is no association, or the observation is in direct contradiction to the hypothesis.

*It has been alleged that the potential consequences of claims you have made about statins and cholesterol, far outweigh that of the infamous MMR vaccine scandal with one researcher saying: ‘In terms of death and disability that could have been prevented, this could be far worse.’

If I am wrong, then this statement could, perhaps be true, although it does represent a form of reprehensible bullying – accusing someone of causing many thousands of deaths. This is an accusation that Rory Collins has repeatedly made. He attacked the BMJ for publishing an article suggesting statins may have a high incidence of adverse effects. You may wish to see the e-mail exchange between Rory Collins and Fiona Godlee on this site https://journals.bmj.com/sites/default/files/BMJ/statins/SP13_Emails_between_Rory_Collins_and_Fiona_Godlee.pdf

I would also like to point you to a study published in the BMJ open Kristensen ML, et al. BMJ Open 2015;5:e007118. doi:10.1136/bmjopen-2014-007118

The main findings of this study – not refuted by anyone were…

6 studies for primary prevention and 5 for secondary prevention with a follow-up between 2.0 and 6.1 years were identified. Death was postponed between −5 and 19 days in primary prevention trials and between −10 and 27 days in secondary prevention trials. The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively.

What this study found was that if you took a statin for five years, the increase in life expectancy would be (on average) 3.5 days. That is around 0.75 days per year of statin treatment. That is the important outcome. The figures quoted by Collins and Baigent and the Oxford CTT group are relative risk reductions, and these figures are entirely meaningless unless you know the absolute risk. Equally, to state lives can be saved is meaningless. No-one’s life can be saved. The best we can achieve is to increase life expectancy. That is what matters. I covered much of this in my book Doctoring Data, which I would recommend you read, as it outlines the ways that data are presented to look as beneficial as possible.

*In our article, one leading cardiologist states that the facts you and others often cite about cholesterol and statins sound convincing but that in reality ‘they contain a grain of truth, mixed with speculation and opinion, which makes is very difficult for the public to know who to trust.’

I cannot answer this, what does a grain of truth mean? What is a grain of truth mixed with speculation and opinion? Specific and concrete examples would be required before I could provide any meaningful answer.

*In your latest book, A Statin Nation, you state: ‘People are being conned. The way to avoid heart disease… has nothing to do with lowering cholesterol.’ This is despite clinical trial evidence to the contrary, and despite no evidence that there is a con, which would imply that those who claim that lowering cholesterol can help lower the risk of heart disease know this is untrue, and are deliberately misleading the public.

Yes, I believe that people are being conned, and I believe the public are being deliberately misled. That is why I called my first book The Great Cholesterol Con. I would point out that there has been one major placebo controlled double blind statin study done. ALLHAT-LLT, which was funded by the National Institutes of Health in the US. The conclusions of the study, published in 2002, were that:

CONCLUSIONS:

Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C.  https://www.ncbi.nlm.nih.gov/pubmed/12479764

All of the industry funded studies were positive. This is either a remarkable coincidence – or something else. A con perhaps?

In a recent blog you wrote: ‘Professor Sir Rory Collins and Professor Colin Baigent made a pact with the dev… sorry … they made a pact with the pharmaceutical industry to take hold of all the data on statins. They will not let anyone else see the data they hold. Including all the data on side-effects. It is kept completely secret.’ Also: ‘A fact that needs to be emphasised is that the CTT will not let anyone else see the data they hold. Including all the data on adverse events [side-effects] and serious adverse events.’ It is a version of similar claims you have made numerous times over the years. However, the CTT have stated numerous times that they did not originally request the data on all adverse events so did not have it. They also point out that the said data must be requested from the individual research organisation which carries out the trials, and is not in their gift to provide. They say you know this, as they have told you this, so to repeat the claim amounts to a lie.

You could perhaps ask them to point you to any letter or any other form of communication that the CTT have had with me. I will let you know the answer, they have never communicated directly with me, at any time. So, for them to say that they have told me anything is, to be fully accurate, a lie. They claim do not hold the data, yet they have managed to publish major papers on statin adverse effects? For instance, this one. Interpretation of the evidence for the efficacy and safety of statin therapy. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31357-5/fulltext

Which contains sections such as these

‘The only serious adverse events that have been shown to be caused by long-term statin therapy—i.e., adverse effects of the statin—are myopathy (defined as muscle pain or weakness combined with large increases in blood concentrations of creatine kinase), new-onset diabetes mellitus, and, probably, haemorrhagic stroke. Typically, treatment of 10 000 patients for 5 years with an effective regimen (eg, atorvastatin 40 mg daily) would cause about 5 cases of myopathy (one of which might progress, if the statin therapy is not stopped, to the more severe condition of rhabdomyolysis), 50–100 new cases of diabetes, and 5–10 haemorrhagic strokes. However, any adverse impact of these side-effects on major vascular events has already been taken into account in the estimates of the absolute benefits. Statin therapy may cause symptomatic adverse events (eg, muscle pain or weakness) in up to about 50–100 patients (ie, 0·5–1·0% absolute harm) per 10 000 treated for 5 years.’

So, they have written a paper outlining all the issues of adverse effects and serious adverse effects – and yet they do not have the data. So, how did they manage that?

*Your stance on statins and the link between cholesterol and heart disease amounts to misinformation.

Perhaps you would like to read this paper (which I co-authored) ‘LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature.’ https://www.tandfonline.com/doi/pdf/10.1080/17512433.2018.1519391?needAccess=true  Which was THE most downloaded paper published by Taylor and Francis in the last year.

Or this paper ‘Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review.’ Published in the BMJ open in 2016

‘High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

Which was the most read paper in the journal for five months in a row.

All I see from your e-mail are ad-hominem attacks on me. I see no facts at all.  I hope that I have given you sufficient information

Yours Truly

Dr.Malcolm Kendrick

 

I followed up with a section of the battle that Prof Sir Rory Collins had with Fiona Godlee over the publication of the Aseem Malhotra paper where Rory Collins demanded an apology and a retraction of the paper. The BMJ took this so seriously they held an independent review.

I wrote a second e-mail to Barney Calman

I would also point you to this paragraph

A 2016 analysis from the London School of Hygiene and Tropical Medicine, which tracks outbreaks and public health concerns, found fake news about statins may have prompted 200,000 patients in Britain alone to quit the drug over a single six-month period following an article you wrote for the BMJ which claimed, incorrectly, that 20 per cent of statins patients quit the drug because of side effects.

I did not write that article. I suggest you check your facts a little more closely before putting any article out there.

Listen, we all know where this attack is coming from. The CTT and Professor Rory Collins and Baigent et al. They attacked Aseem Malhotra and Professor Abramson, then the BMJ, for publishing articles by Aseem and Abramson suggesting statins caused adverse effects in around 20% of people. Collins attacks were severe, and the BMJ was require to hold an investigation, in which Collins attacks on these papers were judged to be unfounded. The entire review can be seen here. https://www.bmj.com/content/bmj/349/bmj.g5176.full.pdf

I would strongly suggest that you read it in full. It is, in a restrained manner, damning of Rory Collins and the CTT.

Here are a couple of sections from that report

All-cause mortality —A recent editorial by Vinay Prasad in Annals of Internal Medicine illustrates a fundamental problem that has consistently concerned the panel. Prasad compared two meta-analyses of statins in primary prevention that differed in their statistical conclusions by less than half a percentage point and yet reached opposite conclusions—namely that that “statins reduce . . . total mortality” or conversely that “data. .. showed no reduction in mortality associated with treatment with statins.” Unfortunately, patients and clinicians have to make decisions in the grey area between these two diametrically opposed conclusions. The panel supports Prasad’s contention that “The Cholesterol Treatment Trialists’ study has a robust set of de-identified individual-patient data, which can improve our understanding, and those data should be made widely available.

The conclusions of the BMJ report, which are carefully written are worth considering

The panel was unanimous in its decision that the two articles do not meet any of the criteria for retraction. The error did not compromise the principal arguments being made in either of the articles. These arguments involve interpretations of available evidence and were deemed to be within the range of reasonable opinion among those who are debating the appropriate use of statins. In making this assessment, the panel is not expressing an opinion about the merits of these arguments, as that work was beyond the scope of the panel.

The panel did have one final comment. It became clear to the panel that the fact that the trial data upon which this controversy is based are held by the investigators and not available for independent assessment by others may contribute to some of the uncertainty about risks and benefits. Different investigators may come to different conclusions with the same data. In fact, a particularly germane example occurred recently in which two experienced Cochrane groups were charged with evaluating a particular intervention and, despite being given the same instructions, data, and resources, did not arrive at identical results or conclusions. The panel strongly believes that the current debates on the appropriate use of statins would be elevated and usefully informed by making available the individual patient level data that underpin the relevant studies

Yours truly

Dr Malcolm Kendrick

P.S. employed to work in the NHS as a doctor – which is a fact.

 

In other words, the attacks on Aseem Malhotra were completely unfounded, as were the attacks on the BMJ. The whole issue of all-cause mortality is complex and there is a need for debate. Rory Collins and his team hold the robust set of de-identified data and those data should be made widely available. That would be the data they claim not to have?

How can it possibly be allowed that one group of researchers hold all the data from the statin trial (not, apparently the adverse effects data – although they have written detailed papers on this issue) and refuse to share it with anyone else?

Anyway, this is probably enough for now. I just wanted to give you some idea of the attacks and battles that are gong on and to shine a little light on what happens. The Mail on Sunday have published a very long article attacking ‘statin deniers’ with pictures of me Zoe and Aseem at the front. I think I look quite dashing. Not as dashing as Aseem who is a very handsome swine, and also young, and intelligent – and brave. Yes, I hate him.

Nor am I as attractive as Zoe Harcombe. But hey, at least I got my picture in the national press. I wasn’t very keen on the bit where they called me self-pitying. But I was quite pleased that they included some of the stuff that I sent.

Until next time, best wishes from the mass-murdering, statin denying, self-pitying Dr Kendrick.

Adherence to statins saves lives

17th February 2019

[Adherence to placebo saves lives]

To an extent I am cursing myself for doing what I am about to do. I have been dragged, yet again, into reviewing a paper that has made headlines round the world which proved, yes proved, that adherence to statins saves lives. I am doing this review because a lot of people have asked for my opinion on the paper.

I do feel like saying. ‘Look, I wrote the book Doctoring Data so that you could read papers like this and work out why they are complete nonsense for yourselves’. Clearly, not enough people have read my book, and I would therefore heartily encourage another million or so people to do so. [Conflict of Interest statement – I will get lots of money if this happens, which I think of as “win, win”].

The paper, in this case was called ‘Association of statin adherence with mortality in patients with atherosclerotic cardiovascular disease.’ It was published in the New England Journal of Medicine (NEJM) a couple of days ago.

The main finding was:

‘Using a national sample of Veterans Affairs patients with ASCVD (atherosclerotic cardiovascular disease), we found that a low adherence to statin therapy was associated with a greater risk of dying. Women, minorities, younger adults, and older adults were less likely to adhere to statins. Our findings underscore the importance of finding methods to improve adherence.’ 1

First thing to say is that this was an observational study. So, it cannot be used to prove causality, especially as the improvement in outcomes that they observed was an increased mortality risk of 1.3 (HR) in those who were least adherent – compared to those who were most adherent.

As many people know… sorry I shall rephrase that… as many geeks like myself know, if the hazard ratio is less than two, in an observational study, the best thing to do with said paper is to crumple it up and throw it in the bin. Because it is almost certainly meaningless. To quote Sir Richard Doll and Richard Peto, two of the fathers of medical research and epidemiology:

“when relative risk lies between 1 and 2 … problems of interpretation may become acute, and it may be extremely difficult to disentangle the various contributions of biased information, confounding of two or more factors, and cause and effect.”2

Observational studies with relative risks between one and two, are the type of studies which find that drinking five cups of coffee protect against CVD – or would that be increase the risk of dying of CVD.  Or maybe it is tea, not coffee? [I apologise for mixing up odds ratios, hazard ratios and relative risk. For ease of understanding, think of them as the same thing].

For example, I was looking at this paper:

‘Tea and coffee consumption and cardiovascular morbidity and mortality’.

Where they found that drinking between three and six cups of coffee reduced CV mortality by 45%:

 ‘A U-shaped association between tea and CHD mortality was observed, with an HR of 0.55 for 3.1 to 6.0 cups per day.’3

That is a far better result than adhering to statins. After all it is a 45% reduction vs. 30% reduction. My advice therefore would be to stop the statins and have nice cup of tea instead. Life would be so much better, and you would live longer as well. Sorry, but I don’t know what sort of tea. English breakfast, Earl Grey, Darjeeling… So many questions. So many stupid studies to read. So much crumpling. So many bins to empty.

Leaving behind the nonsenses they are – the observational studies with a minute difference in hazard ratio – let us move on to the major confounder of this latest crumple, bin, paper. Which is that people who adhere to medications do far better than those who do not – even if that medication is a placebo.

This was first noted, with regard to cholesterol lowering medications, nearly forty years ago in another paper, coincidentally published in the NEJM. It was called:

Influence of adherence to treatment and response of cholesterol on mortality in the coronary drug project.

I have copied the abstract in full. In part because it is written in something akin to understandable English. Most unusual in any medical journal. In this study the researchers were looking at drugs used to lower cholesterol levels, prior to the invasion of the statins.

‘The Coronary Drug Project was carried out to evaluate the efficacy and safety of several lipid-influencing drugs in the long-term treatment of coronary heart disease.  Good adherers to clofibrate, i.e., patients who took 80 per cent or more of the protocol prescription during the five-year follow-up period, had a substantially lower five-year mortality than did poor adherers to clofibrate (15.0 vs. 24.6 per cent; P = 0.00011).

However, similar findings were noted in the placebo group, i.e., 15.1 per cent mortality for good adherers and 28.3 per cent for poor adherers (P = 4.7×10-16). These findings and various other analyses of mortality in the clofibrate and placebo groups of the project show the serious difficulty, if not impossibility, of evaluating treatment efficacy in subgroups determined by patient responses (e.g., adherence or cholesterol change) to the treatment protocol after randomization.’ 4

I think it is worth highlighting the main findings again.

Those who adhered to taking clofibrate               =          15% mortality

Those who had poor adherence to clofibrate     =          24.6% mortality

Those who adhered to taking placebo                 =          15.1% mortality

Those who had poor adherence to placebo        =          28.3% mortality

From this is can be established that it was worse for you to not take placebo regularly than it was to not take clofibrate regularly.

If we move forward in time, others have looked at adherence to taking statins. The first thing they noted was people who take their medication regularly are different in many, many, ways to those who have poor adherence.

The paper is called: ‘Statin adherence and risk of accidents, a cautionary tale.’ Published in the American Heart Association journal Circulation.

As they say in the introduction:

‘Bias in studies of preventive medications can occur when healthier patients are more likely to initiate and adhere to therapy than less healthy patients. We sought evidence of this bias by examining associations between statin exposure and various outcomes that should not be causally affected by statin exposure, such as workplace and motor vehicle accidents.’

As they conclude:

‘Our study contributes compelling evidence that patients who adhere to statins are systematically more health seeking than comparable patients who do not remain adherent. Caution is warranted when interpreting analyses that attribute surprising protective effects to preventive medications.’ 5

This takes us back to Hill and Peto:

“when relative risk lies between 1 and 2 … problems of interpretation may become acute, and it may be extremely difficult to disentangle the various contributions of biased information, confounding of two or more factors, and cause and effect”

In the case of this latest ‘nonsense’ paper on statins, it is not actually difficult to disentangle the various contributions of biased information.

We already know that people who take tablets regularly, and placebo regularly, are more health seeking than those who do not. We already know that if you take a placebo regularly, this almost halves your (absolute) mortality rate. These are both enormous confounders in the latest NEJM study.

In fact, the confounder effect unearthed in previous studies is far larger than the effect they found. Which, if you are going to be ruthlessly logical, would suggest you would be far better off regularly taking a placebo than regularly taking a statin. If you choose to do so, you could entitle their paper “Proof that statins have no beneficial effect”.

You sure as hell cannot use such data to suggest that adhering to statins is beneficial. Yet, the authors of this study have done so. I give their paper a mark of D-Fail, please try again.

Or else, I would say, please inform yourselves of the previous research done in this area before writing a paper. This will avoid wasting everyone’s precious time.

1: https://jamanetwork.com/journals/jamacardiology/article-abstract/2724695?fbclid=IwAR20HUGfxI9Cq8KVAgW0GY8Mu0MmK5goqGkqmErIb-hl5QZbcy_zahgNEvc

2: Richard Doll & Richard Peto, The Causes of Cancer 1219 (Oxford Univ. Press 1981).

3: https://www.ncbi.nlm.nih.gov/pubmed/20562351

4: https://www.ncbi.nlm.nih.gov/pubmed/6999345

5: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744446/

Response to the Lancet paper

3rd February 2019

A number of people have asked for my views on the Lancet Paper ‘Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomized controlled trials.’

It was reported in various major newspapers.

The Times reported the study thus: “Everyone over the age of 75 should be considered for cholesterol-lowering statins, experts have urged, after an analysis found up to 8,000 lives a year could be saved.”1  

The Telegraph had this to say. “Researchers said up to 8,000 deaths a year could be prevented if GPs simply prescribed drugs costing pennies a day.”

This comes hot on the heels of a concerted effort to silence statin critics around the world by a coalition of ‘experts. I suspect the coordinated timing is more than a coincidence.

‘The editors of more than two dozen cardiology-related scientific journals around the world published an editorial Monday to “sound the alarm that human lives are at stake” because of medical misinformation.

These physicians describe regularly encountering patients hesitant to take potentially lifesaving medications or adhere to other prescribed treatments because of something they read online. Or heard from friends. Or saw on television.

“There is a flood of bad information on the internet and social media that is hurting human beings,” said Dr. Joseph Hill, the architect of the essay and editor-in-chief of the American Heart Association journal Circulation. “It’s not just an annoyance, this actually puts people in harm’s way.”

The primary example illustrated in the editorial is the use of statins, a cholesterol-lowering medicine that can reduce heart attack and stroke risk in certain people. But doctors say too many of their patients shun taking statins because of bad information they picked up – often from politicians, celebrities and others who lack medical expertise.’2

Essentially, they feel that certain issues, such as prescribing statins, are so vitally important that critics should be silenced. Perhaps all these editors should try reading this:

‘Congress shall make no law respecting an establishment of religion or prohibiting the free exercise thereof; or abridging the freedom of speech, or of the press; or the right of the people peaceably to assemble, and to petition the Government for a redress of grievances.

Yes, the US founding fathers knew the first thing tyrannies always wish to do is remove freedom of speech. From that, all else follows. If they don’t get that message, they should all be forced to read 1984 by George Orwell.

“Freedom is the freedom to say that two plus two make four. If that is granted, all else follows.”

Getting back to the Lancet paper. What do I think of it? The first thing to note is ‘who done it.’ Well, of course, it was the Cholesterol Treatment Triallists Collaboration (CTT) from Oxford. Run by Professor Sir Rory Collins and Professor Colin Baigent. They do almost all these meta-analyses on statins, because they hold all the data. So, no-one else can really do them.

The CTT is in this hallowed position because they made a pact with the dev… sorry … they made a pact with the pharmaceutical industry to take hold of all the data on statins from all the pharmaceutical companies that manufacture statins and collate the data.

The CTT are very closely associated with the Oxford Clinical Trials Service Unit (CTSU) which is run by, and has employed, most of those in the CTT. Collins and Baigent etc. The CTSU is a clinical trials unit which, last time I looked, had obtained nearly £300 million in funding from the pharmaceutical industry for running clinical trials on various cholesterol lowering medications.

A fact that needs to be emphasised is that the CTT will not let anyone else see the data they hold. Including all the data on adverse events [side-effects] and serious adverse events. It is kept completely secret. I have the e-mail exchange between an Australian journalist and Professor Colin Baigent where the journalist attempts to find out if it is true that the CTT will not let anyone else see the safety data.

It starts quite well and the tone is amiable. Eventually Professor Colin Baigent clams up and refuses to answer any further questions. I have promised said journalist to keep this exchange under wraps, but almost every day I am tempted to publish it. It is toe-squirming.

Anyway, my point here is that the CTT is a horribly conflicted organisation, and has been paid, directly, or indirectly, a great deal of money by the pharmaceutical industry. Here are the conflicts of interest of those involved in writing the Lancet paper:

Conflicts of interest of statement from the Lancet paper: Commercial organisations in bold.

RO’C, EB, IF, CW, and JS have nothing to disclose. JF reports personal fees from Amgen, Bayer, Pfizer, Boehringer Ingelheim, Sanofi, and AstraZeneca, outside the submitted work; and non-financial support from Amgen, Bayer, and Pfizer, outside the submitted work. BM reports grants from the Medical Research Council, British Heart Foundation, and the National Institute for Health Research Oxford Biomedical Research Centre during the conduct of the study, and grants from Merck outside the submitted work. CR report grants from the Medical Research Council and British Heart Foundation during the conduct of the study; and grants from Merck, outside the submitted work. JE reports grants from the Medical Research Council and the British Heart Foundation during the conduct of the study, and a grant from Boehringer Ingelheim outside the submitted work. LB reports grants from the Medical Research Council and the British Heart Foundation during the conduct of the study. MK is an employee of a company that has received study grants and consulting fees from manufacturers of PCSK9 inhibitors and treatments for lipid disorders, outside the submitted work. AT reports personal fees from Amgen and Sanofi, outside the submitted work. PR reports a research grant from AstraZeneca during the conduct of the study; and research grants from Novartis, Pfizer, and Kowa, outside the submitted work. CP reports a grant from Merck, outside the submitted work; and personal fees from Merck, Pfizer, Sanofi, Amgen, and Daiichi-Sankyo, outside the submitted work. EL reports grants from AstraZeneca, Bayer, Boehringer Ingelheim, Amgen, and Merck, outside the submitted work; and personal fees from Bayer, Amgen, Novartis, and Sanofi, outside the submitted work. WK reports grants and non-financial support from Roche, Beckmann, Singulex, and Abbott, outside the submitted work; and personal fees from AstraZeneca, Novartis, Pfizer, The Medicines Company, GlaxoSmithKline, Dalcor, Sanofi, Berlin-Chemie, Kowa, and Amgen, outside the submitted work. AG reports personal fees from Aegerion Pharmaceuticals, Arisaph Pharmaceuticals, DuPont, Esperion Therapeutics, Kowa, Merck, Roche, Vatera Capital, ISIS Pharmaceuticals, Weill Cornell Medicine, and Amgen, outside the submitted work. SY reports a grant from AstraZeneca, outside the submitted work. RC reports support from the Nuffield Department of Population Health, during the conduct of the study; grants from the British Heart Foundation, Cancer Research UK, Medical Research Council, Merck, National Institute for Health Research, and the Wellcome Trust, outside the submitted work; personal fees from the British Heart Foundation and UK Biobank, outside the submitted work; other support from Pfizer to the Nuffield Department of Population Health (prize for independent research); and a patent for a statin-related myopathy genetic test licensed to University of Oxford from Boston Heart Diagnostics (RC has waived any personal reward). CB reports grants from the Medical Research Council and British Heart Foundation, during the conduct of the study; and grants from Pfizer, Merck, Novartis, and Boehringer Ingelheim, outside the submitted work. AK reports grants from Abbott and Mylan, outside the submitted work; and personal fees from Abbott, Amgen, AstraZeneca, Mylan, and Pfizer, outside the submitted work. LB reports grants from UK Medical Research Council and the British Heart Foundation during the conduct of the study.

As to the study itself. I wrote this as a ‘rapid response’ to an article Colin Baigent wrote in the BMJ about the study. It may be published, it may not be.

I would like to ask Colin Baigent one question on this study – at this time.  He claims that the Lancet study was a meta-analysis of twenty-eight RCTs. The study was called. ‘Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials.’

However, in the Appendix to the Lancet paper it is made clear that five of the studies are a comparison of high dose vs. low dose statins. PROVE-IT, A to Z, TNT, IDEAL and SEARCH. They cannot be used to test the hypothesis that statins are beneficial in the over 75s vs. placebo, as they were not done to answer this question.

Also, in nine of the RCTs used in the meta-analysis there were 0% participants over the age of 75 at the start of the study. These were 4S, WOSCOPS, CARE, Post CABG, AFCAPS/TexCaps, ALERT, LIPID, ASPEN and MEGA.

Which means that five of the studies could not address the question of statins vs placebo in the over 75s, and nine of the studies had no participants over the age of 75, which leaves fourteen studies that would be relevant to the issue of prescribing statins in the over 75s.

My question is, why did you call this study ‘Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials.

Yes, they claimed to have done a meta-analysis of twenty-eight studies, yet they could only use data from fourteen to make their claims. The largest of which was the Heart Protection Study (HPS), carried out by, guess who, Rory Collins from the CTSU and CTT.

As for the actual data, it is the usual obfuscation, skirting as close to the direct lie as possible without crossing that line. I am just going to look at one issue. The main claim was that “statin therapy or a more intensive statin regimen produced a 21% (RR 0·79, 95% CI 0·77–0·81) proportional reduction in major vascular events per 1·0 mmol/L reduction in LDL cholesterol.”

A 21% reduction in major vascular events. That sounds terribly impressive. However, if you have read my book Doctoring Data you will know that what is most important here is not what is said, it is what is not said.

Do you see any mention of overall mortality here? No, you don’t. Which means that it did not change. Also, you may note this wording ‘reduction in major vascular events.’ What is a major vascular event? Well, it is mainly a non-fatal heart attack or a non-fatal stroke. There are other CV events, but they are much less common.

Note again, no mention of fatal CV events. If there had been a reduction here, it would have been trumpeted from the rooftops. Which means that we have no reduction in mortality and no reduction in fatal CV events. Of course, it is worth preventing non-fatal heart attacks and strokes, as these can be extremely damaging and harmful things.

However, there is something worth mentioning here that I have not really covered before. There are heart attacks and heart attacks, and strokes and strokes. A heart attack (MI) can be a crushing near-death event, leaving the heart severely weakened and liable to trigger into a fatal heart arrythmia at any time. The patient can be left a cardiac cripple.

Alternatively, a heart attack can be diagnosed by a marginal rise in cardiac enzymes with no symptoms at all, and no residual problems. Yet, both of these events, so completely different in their impact, will be listed as a non-fatal heart attack, with precisely the same weighting.

Equally, a stroke can leave the person virtually paralysed down one side, incontinent, unable to speak, eat, or move. Or, it can be a half hour strange sensation with slight facial weakness that fully resolves. Again, both these events will be listed with precisely the same weighting.

That is a problem in itself, in that these trials list events of completely different severity as being equivalent. It also leads into another problem, who is going to make the diagnosis of a mild heart attack or stroke – and on what grounds?

It will most likely be a doctor, and that doctor will have prior knowledge of whether or not the patient was on a statin – or placebo. Yes, I know, clinical trials are supposed to be double-blinded, which means that neither the participant, nor the investigator, should know who is taking the drug, or the placebo.

However, in reality, they both know full well.

I was at a meeting a while back where one of the investigators for the PCKS-9 drug Repatha was talking about the study. At one point he mentioned that a trial participant had told him that he knew he was not taking the cholesterol lowering agent. When questioned how he knew this, the participant said – because my cholesterol level is the same as it always was.

He still wanted to continue on the trial, because he thought we was doing a ‘good’ thing and helping to move medicine forward – and suchlike. I feel it may be considered churlish to point out that the only thing he was helping to move forward was the profit margins for Amgen.

The reality is that when you have a medication that has a significant effect, e.g. lowering cholesterol by 40%, this is a very difficult to thing to hide from the patient, or the doctor. They can see the figures on a computer screen in front of them. And when you are on a clinical trial, and you enter hospital, the doctors have to be told you are in a clinical trial, and what it is.

So, these double blinded studies on statins are not effectively, or even remotely, double-blinded. Which means that bias in clinical decision making is now an option. Was it a heart attack, or not? Well, they are on a statin – so probably not. Or, they are taking a placebo, so it probably is. Bias, the very thing you are trying to remove has crept straight back in the side door.

Another issue with an event is that there are many different sorts of clinical event. Death would be one – obviously. Breaking your leg another. Kidney failure would also count as one, as would a severe rash, or emergency admission to a hospital for almost any reason.

So, when a study states, as this one does ‘reduction in major vascular events.’ My mind, as it is now trained to do, thinks to itself: “ What about other events, what happened to them? Were they also reduced, did they say the same, or did they go up?”

Because if you reduce major vascular events, but other serious events go up, then you have achieved exactly and precisely nothing. This is a variation on pushing people off cliffs to stop them dying of heart attacks.

Results: ‘Pushing one hundred people prevented all trial participants from suffering a fatal heart attack. We therefore recommend pushing everyone off a cliff to reduce the incidence of heart attacks in the general population.’ A.N. Idiot et al.

Statins reduce major vascular events. [A major non-fatal vascular event could also be called as Serious Adverse Event (SAE)]. But do they reduce all serious adverse events (SEAs). If not, you are simply replacing a major vascular event with something equally nasty.

Which leads on to the next question, do we know from the statin trials if statins do reduce SAEs in total? The answer is that we do not know this, for sure, because the CTT has these data, and refuses to let anyone else see them. However, some data has not been censored by big brother. The Cochrane collaboration (before they started the sad slide to bias and corruption) looked at this issue – way back in 2003.

They got as much data as they could from the five major primary prevention statin trials at the time. Here was their conclusion on Serious Adverse Events:

‘In the two trials where serious adverse events are reported, the 1.8% absolute reduction in myocardial infarction and stroke should be reflected by a similar absolute reduction in total serious adverse events; myocardial infarction and stroke are, by definition, serious adverse events. However, this is not the case; serious adverse events are similar in the statin group, 44.2%, and the control group, 43.9%.

This is consistent with the possibility that unrecognized serious adverse events are increased by statin therapy and that the magnitude of the increase is similar to the magnitude of the reduction in cardiovascular serious adverse events in these populations. This hypothesis needs to be tested by analysis of total serious adverse event data in both past and future statin trials. Serious adverse event data is available to trial authors, drug companies and drug regulators. The other measure of overall impact, total mortality, is available in all five trials and is not reduced by statin therapy.’ 3

What does this mean in reality? Well, gathering it all together. Statins (in the over 75s) do not reduce mortality. They do not prevent fatal Mis and strokes. Whilst they reduce serious cardiac events, previously published results demonstrate they do not reduce total serious adverse events.

Which means that they are, wait for it, absolutely and completely useless.

Two plus two does equal four. Always bear that fact in mind.

1: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31942-1/fulltext

2: https://www.heart.org/en/news/2019/01/28/medical-experts-sound-the-alarm-on-medical-misinformation

3: https://www.ti.ubc.ca/pages/letter48.htm

 

What causes heart disease part 62

19th January 2019

I suppose it is gratifying to see things I write very strongly supported a few days later. After telling everyone that a high cholesterol level is not a risk for stroke, out comes a study almost straight away, demonstrating that a low cholesterol level increases mortality in patients who have already had a stroke.

This was in a population – and I would highlight this fact – in a population who have high grade carotid artery stenosis. Which mean a high degree of atherosclerosis on the carotid arteries (supplying blood to the brain). The paper is called:

‘Lower cholesterol tied to increased mortality in ischaemic stroke patients with carotid artery stenosis.

Takeaway

In patients with acute, first-ever ischaemic stroke with high-grade internal carotid artery (ICA) stenosis and post-stroke functional dependence, lower total cholesterol level was associated with increased risk for 5-year mortality.

Why this matters:

Recent treatment guidelines of hyperlipidaemia suggest more aggressive treatment for reducing risk for atherosclerotic cardiovascular diseases and ischaemic stroke.

However, these findings suggest a careful consideration of aggressive treatment of hyperlipidaemia in patients with acute, first-ever ischaemic stroke with high-grade ICA stenosis and post-stroke functional dependence.

Study design:

Study prospectively evaluated 196 patients with acute ischaemic stroke with high-grade ICA stenosis and modified Rankin Scale score ≥3.

Patients were divided into 2 groups based on total cholesterol level at admission: ≥200 or <200 mg/dL.

Patients were followed-up for 5 years after initial assessment.

Key results:

After adjusting for established clinical predictors of adverse outcomes, lower total cholesterol level (aHR, 1.88; 95% CI, 1.09-3.23; P=.023) was a significant risk factor for 5-year all-cause mortality.

The prevalence of diabetes mellitus (P=.013) was significantly higher and that of atrial fibrillation (P=.011) was significantly lower in patients with high vs low total cholesterol level.

Patients with lower cholesterol level had significantly lower value of haemoglobin (P=.001), whereas glycohaemoglobin was significantly higher in patients with higher total cholesterol level (P=.001).

Funding: None.

Four most annoying words in the English language. ‘I told you so.’

Of course, this study will be dismissed out of hand. “We should still be prescribing statins to people who have had ischaemic strokes” we will be told. “Studies like this are purely observational” we will be told. “A high cholesterol level still needs to be lowered” we will be told. Nothing to see here, please move along!

I do become increasingly weary of finding evidence that directly and absolutely contradicts the cholesterol hypothesis. It never makes the slightest difference – to anything. Hopefully a few people are out there listening, whose minds are not made of reinforced concrete.

1: https://www.univadis.co.uk/viewarticle/lower-cholesterol-tied-to-increased-mortality-in-ischaemic-stroke-patients-with-carotid-artery-stenosis-651463

Lung YJ, Weng WC, Wu CL, Huang WY. Association Between Total Cholesterol and 5 year Mortality in Patients with Carotid Artery Stenosis and Poststroke Functional D ependence. J Stroke Cerebrovasc Dis. 2019 Jan 11 [Epub ahead of print]. doi: 10.1016/j.jstrokecerebrovasdis.2018.12.030. PMID: 30642665

What causes heart disease part 61 – strokes

15th January 2019

In this never-ending story on heart disease, I have tended to use the terms “heart disease” and “cardiovascular disease” almost interchangeably. Well, everyone else does it, so why not me? However, in this blog I shall be splitting cardiovascular disease into its two main components, heart attacks and strokes, and concentrating mainly on strokes.

The first thing to say is that there are three main causes of strokes.

  • Atrial Fibrillation (ischaemic)
  • A burst blood vessel in the brain (haemorrhagic)
  • A blood clot (ischaemic)

[There are also cryptogenic strokes (no known cause), strokes due to a hole in the heart, strokes due to antiphospholipid syndrome, strokes due to sickle cell disease etc. etc.)

Atrial Fibrillation (AF) is a condition where the upper chambers of the heart (atria) do not contract and relax smoothly every second or so. Primarily because there is a disruption in the electrical conduction system, causing the atria to spasm and twitch in a highly irregular fashion.

When this happens, blood clots can form in the left atrium then break off and head up into the brain and get stuck. Causing a stroke. They can also travel elsewhere in the body causing a blockage to an artery in the kidneys, the leg, the arm and suchlike. If they form in the right atrium, they will end up stuck in the lungs.

These clots are usually quite small, about the size of a large grain of rice, but this is still big enough to do quite considerable damage. The treatment for AF is either to try and reverse the fibrillation or, if this does not work, to give anticoagulants such as warfarin to stop the clots forming.

A haemorrhagic stroke is when a blood vessel in the brain bursts. Blood is then forced into the brain and causes a lot of damage – leading to a stroke. Haemorrhagic strokes are usually quite severe, as you can imagine. The treatment is to NOT give an anti-coagulant of any sort. Haemorrhagic strokes are often/usually caused by a thinning of the artery wall, causing a ballooned area (aneurysm), which then bursts.

An interesting question, and I have seen different views on this is whether a small blood clot travels to the brain where it gets stuck, but does not completely block the artery, so it does not cause a stroke, but it creates an area of damage – which is then repaired – that leaves a weakness in the artery that balloons out – an aneurysm.

Anyway, the most common cause of a stroke is that large atherosclerotic plaques form in the main arteries that supply blood to the brain (carotid arteries). These plaques usually form around the base of the neck. A blood clot then forms on top of the plaque, then breaks off and travels to the brain, where it gets stuck – as with atrial fibrillation – causing a stroke. The effect is the same as with AF, but the underlying causing is completely different.

According to the American Stroke Association 87% of strokes are ischaemic.

Which means that the vast majority of strokes are caused by atherosclerotic plaques in the neck. Just as the vast majority of heart attacks are caused by atherosclerotic plaques in the coronary arteries. Therefore, you would expect that the risk factors for stroke would be exactly the same as the risk factors for heart attacks, as the underlying process is the same.

Well, many of the standard risk factors are the same. Smoking, diabetes, high blood pressure and suchlike. However, a raised LDL most certainly is not. There is a research study called the Simon Broome registry, started in the UK, that tracks the health outcomes of people diagnosed with familial hypercholesterolaemia (FH).

It is a fascinating resource which, if you decide to interpret their data through a different prism, virtually rules out the raised LDL in familial hypercholesterolaemia as a cause of CVD. One of the earlier papers in the BMJ, on the findings of the Simon Broome registry, found that:

‘Familial hypercholesterolaemia is associated with a substantial excess mortality from coronary heart disease in young adults but may not be associated with a substantial excess mortality in older patients.1

For ‘may not be’, replace, ‘is not’. In fact, what the Simon Broome registry has found repeatedly is that, after the age of, about fifty, FH does not increase the risk of coronary heart. Thus LDL is a risk factor before the age of fifty, and not after? Which means that it cannot be a risk factor at all [the thing that kills young people with FH before the age of fifty is clotting factor abnormalities – not raised LDL]

Which is something covered in the magnificent and insightful paper: ‘Inborn coagulation factors are more important cardiovascular risk factors than high LDL-cholesterol in familial hypercholesterolemia.2 Yes, as you may have guessed, I was a co-author.

However, if we move away from heart disease, to strokes. FH has never been found to be a risk factor for stroke – at any age. Here, for example is a study done in Norway, and published in the Journal Stroke. It was called ‘Risk of ischaemic stroke and total cerebrovascular disease in familial hypercholesterolaemia.’

A total of 46 cases (19 women and 27 men) of cerebrovascular disease were observed in the cohort of people with FH, with no increased risk of cerebrovascular disease compared with the general population (standardized incidence ratio, 1.0; 95% CI, 0.8–1.4). Total number of ischemic strokes in the cohort of people with FH was 26 (9 women and 17 men), with no increased risk compared with the general population (standardized incidence ratio, 1.0; 95% CI, 0.7–1.5).3

In 2010 the Lancet published a major study looking at risk factor for stroke in the non-FH population3. They used the term population attributable risk factors (PAF), which ‘weights’ the factors, depending on how prevalent they are (i.e., how many people have got the various risk factors). Their list of PARs for stroke was as follows:

  • 51.8% – Hypertension (self-reported history of hypertension or blood pressure >160/90mmHg)
  • 18.9% – Smoking status
  • 26.5% – Waist-to-hip ratio
  • 18.8% – Diet risk score
  • 28.5% – Regular physical activity
  • 5% – Diabetes mellitus
  • 3.8% – Alcohol intake
  • 4.6% – Psychosocial stress
  • 5.2% – Depression
  • 6.7% – Cardiac causes (atrial fibrillation, previous MI, rheumatic valve disease, prosthetic heart valve)
  • 24.9% – Ratio of ApoB to ApoA (reflecting cholesterol levels)

You will see that LDL is not in that list. The ratio of ApoB to ApoA is. However, this is primarily the ratio of VLDL (triglycerides) to HDL (‘good’ cholesterol), which is an accurate reflection of ‘insulin resistance’ and bears no relationship to LDL. As I always say to people who ask me for advice on reviewing clinical research…’the most important thing to focus on is not what is there, it is what is not there.’

Any study on CVD will be examining LDL levels very closely. If a relationship were found it would be shouted from the rooftops. The fact that you hear nothing about LDL in this paper means that there was no correlation – at all.

You can, if you wish, try to find some evidence that the risk of stroke is increased by a raised LDL level. I must warn you that you will look for a long time, because there is no evidence, anywhere – at all. It has interested me for many years that this issue is simply swept under the carpet.

Now, write out one hundred times:

  • Raised LDL is not a risk factor for stroke
  • Raised LDL is not a risk factor for stroke
  • Raised LDL is not a risk factor for stroke….

Then, ask yourself the question. How can a raised LDL be a risk factor for heart disease and not stroke – as the two conditions are, essentially, the same condition? Atherosclerotic plaques in medium sized arteries with the critical/final event being the formation of a blood clot – on top of the plaque.

Then, ask yourself another question. If a raised LDL is not a risk factor for stroke, how can lowering the LDL level provide any benefit? The correct answer is that… it cannot. Yet statins do provide benefit in stroke (Usual proviso here. Not by a great amount in absolute terms, but the benefit does appear to exist).

‘A meta-analysis of randomized trials of statins in combination with other preventive strategies, involving 165,792 individuals, showed that each 1-mmol/l (39 mg/dl) decrease in LDL-cholesterol equates to a reduction in relative risk for stroke of 21.1 (95% CI: 6.3-33.5; p = 0.009)’ 4

Just to repeat the main point here. A raised LDL is not, and has never been, a risk factor for stroke. Yet it is claimed that lowering the LDL level reduces the risk of stroke? In reality, the evidence from the statin trials prove, beyond any doubt, that any benefit achieved by statins cannot be through lowering the LDL level.

The logic stripped down is, as follows:

  • A raised level of factor A does not cause disease B
  • Thus lowering factor A cannot reduce the risk of disease B
  • Thus, you cannot claim that lowering factor A can have any possible effect on disease B

However, every single cardiovascular expert seems delighted to inform us, in all seriousness, that lowering factor A does, indeed, reduce the risk of disease B. Despite this breaking the very fabric of logic in two.

“Alice laughed: “There’s no use trying,” she said; “one can’t believe impossible things.”

I daresay you haven’t had much practice,” said the Queen. “When I was younger, I always did it for half an hour a day. Why, sometimes I’ve believed as many as six impossible things before breakfast.” Alice in Wonderland.

1: https://www.bmj.com/content/303/6807/893

2: https://www.ncbi.nlm.nih.gov/pubmed/30396495

3: https://www.ahajournals.org/doi/10.1161/STROKEAHA.118.023456

4: https://www.ncbi.nlm.nih.gov/pubmed/19814666

What causes heart disease part 60 – prediction

2 January 2019

It is difficult to make predictions, particularly about the future.’ Old Danish proverb

The hallmark of a great scientific hypothesis is prediction. Einstein’s theory of special relativity predicted that gravitational fields could be demonstrated to bend light – and he was proven right during observations made during a total eclipse of the sun.

Unfortunately, things are rarely as black and white as that. Even if you understand almost all of the factors at play, it can be extremely difficult to predict certain events, particularly the timing. Earthquakes, hurricanes, which flu virus will be active next year? There are so many variables interacting with each other that things get very complex. When will San Francisco suffer the next major earthquake? According to the best predictions – about twenty years ago.

Chaos theory can also play its part. A very small change in one part of a system can trigger massive downstream effects. A butterfly flaps its wings in Africa, and two weeks later a hurricane devastates Florida.

So, what of predicting your future risk of cardiovascular disease? How good are the current models? Are they of any use at all?

In the US, the calculator that is most widely used was put together by the American Heart Association and American College of Cardiology.(AHA/ACC). It is called the ‘cvriskcalculator’ It can be found on-line here http://www.cvriskcalculator.com/ It asks you to provide data on ten different parameters:

  • Age
  • Sex
  • Race
  • Total cholesterol
  • HDL (good) cholesterol
  • Systolic blood pressure
  • Diastolic blood pressure
  • Treated for blood pressure: yes or no
  • Diabetes: yes or no
  • Smoker: yes or no

After you input your data, an algorithm kicks into action to work out your cardiovascular future. If it calculates that your risk of suffering a CV event is greater than 7.5%, within the next ten years, you will be recommended to start on a statin. This, you will have to take for the rest of your life.

One word of warning, all men by age of fifty-five – even men with no other risk factors at all – will have a risk greater than 7.5%. At least they will, using ‘cvrisk’. Because age is by far the most powerful risk factor of all – at least it is on ‘cvrisk’.

In the UK, a more complex risk factor calculator has been developed. In truth, it is only more complex in that it has an additional ten risk factors to consider. It is called Qrisk3. It uses twenty different factors to calculate risk https://qrisk.org/three/:   They are, in no particular order:

  • Age
  • Sex
  • Smoking
  • Diabetes
  • Total cholesterol/HDL ratio
  • Raised blood pressure
  • Variation in two blood pressure readings
  • BMI
  • Chronic kidney disease
  • Rheumatoid arthritis
  • Systemic Lupus Erythematosus (SLE)
  • History of migraines
  • Severe mental illness
  • On atypical antipsychotic medication
  • Using steroid tablets
  • Atrial fibrillation
  • Diagnosis of erectile dysfunction
  • Angina, or heart attack in first degree relative under the age of 60
  • Ethnicity
  • Postcode

How good are they at predicting a future event? A study was carried out in the US to analyse, in retrospect, how accurate the cvriskcalculator had been. They looked at the historical risk scores of several thousand people, then tracked forward in time to see what actually happened.

In the study they looked at CVD over five years, not ten, so all figures should be doubled to establish the ten-year risk that is used in most calculators:

‘A widely recommended risk calculator for predicting a person’s chance of experiencing a cardiovascular disease event — such as heart attack, ischemic stroke or dying from coronary artery disease — has been found to substantially overestimate the actual five-year risk in adults overall and across all sociodemographic subgroups. The study by Kaiser Permanente was published today in the Journal of the American College of Cardiology.

The actual incidence of atherosclerotic cardiovascular disease events over five years was substantially lower than the predicted risk in each category of the ACC/AHA Pooled Cohort equation:

For predicted risk less than 2.5 percent, actual incidence was 0.2 percent

For predicted risk between 2.5 and 3.74 percent, actual incidence was 0.65 percent

For predicted risk between 3.75 and 4.99 percent, actual incidence was 0.9 percent

For predicted risk equal to or greater than 5 percent, actual incidence was 1.85 percent

“From a relative standpoint, the overestimation is approximately five- to six-fold,” explained Dr. Go1

What this means is that you carefully input your parameters into a risk calculator, which took many years of painstaking work to develop, using data carefully gathered by experts from the world of cardiology, and it overestimates your risk by five to six-fold. (I.e., 400 – 500% exaggeration!)

Excellent. Just for starters, this means that millions upon millions of people have been told to take a statin based on a calculation that is so wildly inaccurate as to be virtually meaningless. How so, Dr Go?

On a similar note, a group of researchers in the UK decided to look at data gathered on 378,256 patients from UK general practices. They wanted to establish which factors were most important in predicting future risk. The paper was called ‘Can machine-learning improve cardiovascular risk prediction using routine clinical data?’ 2

If the ACC/AHA and Qrisk3 calculators truly are looking at the most important variables, then we should see all the same factors appearing in this UK study. Below, just to remind you, are the ten factors used in the ACC/AHA calculator:

  • Age
  • Sex
  • Race
  • Total cholesterol
  • HDL (good) cholesterol
  • Systolic blood pressure
  • Diastolic blood pressure
  • Treated for blood pressure: yes or no
  • Diabetes: yes or no
  • Smoker: yes or no

Here is what the UK researchers found to be the top ten risk factors for CVD, in order, with number one being highest risk and number ten lowest risk:

  1. Chronic Obstructive Pulmonary Disease (usually a result of smoking)
  2. Oral corticosteroid prescribed
  3. Age
  4. Severe mental illness
  5. Ethnicity South Asian
  6. Immunosuppressant prescribed
  7. Socio-economic-status quintile 3
  8. Socio-economic status quintile 4
  9. Chronic Kidney Disease
  10. Socio-economic status quintile 2

Compare and contrast, as they say. Do these lists look remotely the same? As you can see, there are only two factors on the ACC/AHA list that were replicated by the UK researchers. One of them is age – which you can do nothing about, and the other is ethnicity – which you can do nothing about. As for the rest. Where have they gone?

What of cholesterol, and sex, and blood pressure, and smoking, and diabetes. Well, out of a total of forty-eight factors analysed, here is where they ranked in importance. In this analysis factors could either be ranked protective, or causal:

Smoking                                  = 18

Sex/female                              = 19 (protective)

Total cholesterol                    = 25

HDL cholesterol                      = 28 (protective)

Systolic blood pressure          = 29

Diabetes                                  = 31

LDL ‘bad’ cholesterol              = 46

Yes, LDL ranked 46th out of 48 factors, well, well, who’d a thunk. The only things that scored lower than LDL were FEV1 and AST/ALT ratio. Factors that, unless you are medically trained, you will never have heard of. The first one, FEV1 stands for forced expiratory volume (from your lungs), measured over one second. The other is the ratio of two liver enzymes.

At present, it is true to say that the established risk factors, and the risk calculators, are almost completely useless. Not only that, they get more useless if you try to use them across different countries. If I took Qrisk3, or ‘cvrisk’ to France, whatever risk it calculated, I would then have to divide whatever figure I got, by four.

This is because, for exactly the same set of risk factors, someone in France will have one quarter the rate of CVD as a man in the US, or UK. Which means that the ‘cvrisk’ would actually overestimate risk by twenty-fold in France. Five times too high a calculated risk in the US, multiplied by four times too high a calculated risk in France. 5 x 4 = 20.

So, what should you measure? What can help you to predict your risk of CVD? Coronary calcium score (CAC)? That is, looking at the amount of calcium in your arteries. This is probably the most accurate way to establish your burden of atherosclerosis.

However, a high(er) CAC score does not mean that you are at risk of CVD, it means you have already got CVD, it is already there. The CAC score is just telling you how far along the CVD path you have traveled. So, it is not really predictive, it is more of a historical record.

What you really want is to stop the calcium forming in your arteries in the first place. Or then again, do you? A ‘calcified’ plaque is not, necessarily, a dangerous plaque. A dangerous plaque has an almost liquid core, which is in danger of rupturing. A dangerous plaque is often called a vulnerable plaque, and they don’t show up well, if at all, on a CAC scan.

If you have lots of vulnerable plaque what should you do?

Take a statin. Statins accelerate calcification.

Take warfarin. Warfarin accelerates calcification

Both reduce the risk of dying of CVD – if only by a small amount (at least small with statins). So, you could both increase calcification and reduce your risk of a CV event – simultaneously. What then to make of your CAC score? If you find it is zero, great. If you find it is four hundred?

Logically, a high score only tells you that you have CVD, and already having CVD means you are at higher risk of dying of a CV event. Which comes as no great surprise. What you really need to be able to do is to accurately predict what your CAC score would be – before you did it. And if you could do that, you really would have a scientific hypothesis worthy of the name.

The LDL hypothesis for example. If you could find you someone with an extremely high LDL level, say four to five times average, and a CAC score of zero – at the age of seventy-two then you would remove it as a factor for prediction.

So, here you go – I have blogged about this before – from a paper called: ‘A 72-Year-Old Patient with Longstanding, Untreated Familial Hypercholesterolemia but no Coronary Artery Calcification: A Case Report.’

The subject has a longstanding history of hypercholesterolemia. He was initially diagnosed while in his first or second year as a college student after presenting with corneal arcus and LDL-C levels above 300 mg/dL [7.7mmol/l] 3

He reports that pharmacologic therapy with statins was largely ineffective at reducing his LDL-C levels, with the majority of lab results reporting results above 300 mg/dL and a single lowest value of 260 mg/dL while on combination atorvastatin and niacin. In addition to FH-directed therapy, our subject reports occasionally using baby aspirin (81 mg) and over-the-counter Vitamin D supplements and multivitamins.

In the early 1990s, our patient underwent electron beam computed tomography (EBCT) imaging for CAC following a series of elevated lipid panels. Presence of CAC (coronary artery calcification) was assessed in the left main, left anterior descending, left circumflex, and right coronary arteries and scored using the Agatston score.

His initial score was 0.0, implying a greater than 95% chance of absence of coronary artery disease. Because of this surprising finding, he subsequently undertook four additional EBCT tests from 2006 to 2014 resulting in Agatston scores of 1.6, 2.1, 0.0, and 0.0, suggesting a nearly complete absence of any coronary artery calcification. In February of 2018, he underwent multi-slice CT which revealed a complete absence of coronary artery calcification.

Prediction, prediction. The risk factor calculators cannot do it. LDL levels don’t do it. I cannot do it with perfect accuracy either. I cannot say to anyone that you will not die of CVD. I cannot say to anyone that you will die of CVD. I can only help you to change the odds.

If you are an elderly, depressed, diabetic South Asian man with Chronic Obstructive Pulmonary Disease, taking steroids, with chronic kidney disease, living in a small council house in the UK then your odds of dying of CVD in the next year are pretty damned high. What should such a person do? Write a will, I would think.

Not many of us are at such high risk. Few of us are in such a bleak situation. What can the average person do to shift those odds in your favour? If you have read this blog from start to finish, I would imagine that you already know. If not, I am going to tell you next time. I am going to tell you how to change the odds, but I am unable to tell you how to get them to zero.

1: https://www.eurekalert.org/pub_releases/2016-05/kp-crt042916.php

2: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174944

3: https://www.cureus.com/articles/11752-a-72-year-old-patient-with-longstanding-untreated-familial-hypercholesterolemia-but-no-coronary-artery-calcification-a-case-report

Wikipedia a parable for our times

18th December 2019

As readers of this blog know I was obliterated from Wikipedia recently. Many have expressed support and told me not to get down about it. To be perfectly frank, the only time I knew I was on Wikipedia was when someone told me I was going to be removed. So it hasn’t caused great psychological trauma.

In fact my feelings about this are probably best expressed on a Roman tombstone. It has been translated in different ways, but my favourite version is the following:

I was not
I was
I am not
I care not

However, in the greater scheme of things, whilst my removal from Wiki is completely irrelevant, in another way it is hugely important. As Saladin said of Jerusalem, whilst he was battling with the Christians during the crusades. ‘What is Jerusalem? Jerusalem is nothing; Jerusalem is everything.’

My removal from Wikipedia is nothing. My removal from Wikipedia is everything. Not because it is me, but because of what it represents. Not to beat about the bush, there is a war going on out there between scientific enlightenment, and the forces of darkness.

You think that is too dramatic? Well, this is what Richard Horton – editor of the Lancet for many years – has to say about the current state of medical science.

‘The case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue…science has taken a turn towards darkness.’ Richard Horton

Science has taken a turn towards darkness? Of course science cannot really turn anywhere. It is not an entity. Science is simply made up of people. The scientific method itself is simply an attempt to discover what is factually true, by removing human bias. It is, like everything humans do, imperfect. Bias is always there.

What Horton means is that the methods used to pursue science have increasingly moved from the pure Olympian ideal, a disinterested quest for truth, to something else. Distortion, manipulation and bias. In some cases downright lies. I hesitate to use the term ‘fake news’, but that is what it is. What it is becoming.

As John Ioannidis had to say in his seminal paper ‘Why most published research findings are false’

‘Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. It is more likely for a research claim to be false than true.’1

I think, in truth, this very much depends on the area of science you are looking at. Someone examining the food intake of the fruit bat is probably working away free from any pressure to make their findings fit with pre-existing ideas. Whilst they could be wrong, they will not been working to any agenda.

Some areas are highly contentious, where truth becomes the first casualty. For example, global warming, where you can see dreadful science being done on all sides, as people desperately try to prove their point. I watch on, in scientific despair. I have no idea what to believe, or who to believe, anymore.

Moving back to medical scientific research, which is more my area. Much of what is going on here is a complete disaster, but nutritional science is particularly awful. A complete mess. I have virtually given up reading any paper in this area as they just annoy me so much. I simply look at the authors involved, and I know what the paper is going to say. This does save time.

Ioannidis has turned his attention to nutritional science, in some detail. To quote from The American Council on Science and Health:

Dr. Ioannidis bluntly states that nutrition epidemiology is in need of “radical reform.” In a paragraph that perfectly captures the absurdity of the field, he writes:

“…eating 12 hazelnuts daily (1 oz) would prolong life by 12 years (ie,1 year per hazelnut), drinking 3 cups of coffee daily would achieve a similar gain of 12 extra years, and eating a single mandarin orange daily (80 g) would add 5 years of life. Conversely, consuming 1 egg daily would reduce life expectancy by 6 years, and eating 2 slices of bacon (30 g) daily would shorten life by a decade, an effect worse than smoking. Could these results possibly be true?”

The answer to his rhetorical question is obviously no. So, how did this garbage get published?

How did this garbage get published? How does the garbage get published? On the other hand how did a major study on replacing saturated fat with polyunsaturated fat (The Minnesota Coronary Experiment) NOT get published?

Because it found that polyunsaturated fat did lower cholesterol levels, but the more it lowered the cholesterol level, the greater the risk of death! That is in the results, and you can read that for yourself – this was the conclusion:

Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid. 2

The results of this study were, eventually found in the garage of the son of one of the lead investigators. It was recovered and published forty years later in the British Medical Journal. Long after one of the lead investigators, Ancel Keys, had died. Yes, indeed.

I wrote the book “Doctoring Data” to try and shine some light on the methods used to distort and manipulate data. I try, as best as I can, to follow the scientific method. That includes discussion and debate, to test ones ideas in the furnace of sustained attacks.

However, if you try to do this, the forces of darkness come after you, and they come hard. Especially if ever dare to suggest that animal fats, saturated fats, are not in the least harmful. At which point you waken the vegan beast, and this beast is not the least interested in science, or the scientific method, or discussion or debate.

It has one aim, and that is to silence anyone, anywhere, who dares to question the vegan philosophy. Aided and abetted by the Seventh Day Adventist church. Below is a short list, non-exhaustive list, of those who have suffered their wrath:

Prof Tim Noakes – South Africa
Dr Maryanne Demasi – Australia
Dr Gary Fettke – Australia
Professor John Yudkin – UK
Dr Aseem Malhotra – UK
Dr Uffe Ravnskov – Sweden
Dr Andreas Eenfeldt – Sweden
Dr Zoe Harcombe – UK
Dr Robert Atkins – US
Nina Teicholz – US
Gary Taubes – US
Dr. Anna Dahlqvist – Sweden

Several of these doctors have been dragged in front of the medical authorities, usually by dieticians, who claim that patients are being damaged. So far, they have all won their cases – often after prolonged and expensive legal hearings. Luckily, the courts recognise logic when they see it.

Uffe Ravnskov has his book, the Cholesterol Myths, questioning the cholesterol hypothesis burned, live on air. All of the brave souls on this list have been accused of ‘killing thousands’ at one time or another. Maryanne Demasi lost her job with the Australian Broadcasting Company.

Now, it seems, the attacks have moved into a different area, such as a determined effort to remove everyone from Wikipedia. When the vegans find someone they don’t like, they work tirelessly to extinguish them from the record. They call them kooks and quacks – but they never ever reveal who they truly are. They exist in the shadows.

They got rid of me from Wikipedia; they are currently attacking Aseem Malhotra, Uffe Ravnskov, Jimmy Moore, and the entire THINCS network. (The International Network of Cholesterol Sceptics). There are even worse things going on, that I cannot speak about yet.

Yes, this is science today. At least it is one part of science – which is not science, and it has definitely turned to the darkness. You can be accused of being a kook and a quack by someone who hides behind anonymity and never dares to show their face. In truth, I know who it is. Someone found out for me. Yes MCE, it is you.

You want a debate, come out into the open, and reveal yourself, your motives and your arguments to the world. Then we can do science. Until then please expect me to hold you in the contempt that you deserve.

1: https://www.ncbi.nlm.nih.gov/pubmed/16060722/

2: https://www.bmj.com/content/353/bmj.i1246

 

 

Dr Malcolm Kendrick – deletion from Wikipedia

I thought I should tell you that I am about to be deleted from Wikipedia. Someone sent me a message to this effect. It seems that someone from Manchester entitled User:Skeptic from Britain has decided that I am a quack and my presence should be removed from the historical record.

I have no idea who this person is, perhaps it is possible to find out? It seems a bit harsh as I recently contributed money to Wikipedia to keep it going. Was this a terrible mistake?

To be frank, I am not entirely bothered if I no longer appear on Wikipedia, but I am increasingly pissed off that self-styled anonymous ‘experts’ can do this sort of thing without making it explicit why they are doing it, what their motives are, and if they have any disclosure of interest.

Perhaps user Skeptic from Britain would like to reveal himself and provide some information as to why he is so interested in trying to wipe me out? Perhaps one or two of you here could join in the discussion and see what emerges.

His reasons for trying to get rid of me are the following

Malcolm Kendrick is a fringe figure who agues(sic) against the lipid hypothesis. He denies that blood cholesterol levels are responsible for heart disease and in opposition to the medical community advocates a high-fat high-cholesterol diet as healthy. Problem is there is a lack of reliable sources that discuss his ideas. His book The Great Cholesterol Con was not reviewed in any science journals. Kendrick is involved with the International Network of Cholesterol Skeptics, I suggest deleting his article and redirecting his name to that. Skeptic from Britain (talk) 20:29, 2 December 2018 (UTC)

Come out, come out, whoever you are.

What causes heart disease – part 59

27th November 2018

A number of people have written to me asking how to read all the articles I have written on cardiovascular disease. I understand it is not exactly easy to do this. So, here I am going to attempt a short summary of everything I have written up to now.

Thrombogenic theory vs. LDL/cholesterol hypothesis

Since the mid-nineteenth century there have been two main, and almost entirely conflicting, hypotheses as to what causes cardiovascular disease. At present it may seem as if there is only one, the cholesterol or LDL hypothesis. Namely that a raised low-density lipoprotein is the underlying/primary/necessary cause.

I am not running through all the reasons why this hypothesis is wrong here. I will confine myself to one simple point. For the LDL hypothesis to be correct, it requires that LDL can travel past the lining of the artery, the endothelial cells, and into the artery wall behind. This is considered the starting point for atherosclerotic plaques to form.

The problem with this hypothesis is that LDL cannot get into any cell, let alone an endothelial cell, unless that cell wants it to. We know this, for certain, because the only way for LDL to enter any cell, is if the cell manufactures an LDL receptor – which locks onto, and then pulls the LDL molecule inside. There is no other passageway. This is an inarguable fact.

If LDL cannot enter a cell, unless allowed to do so, then it cannot pass through a cell, unless a cell wants it to. It most certainly cannot exit the other side of a cell, unless granted passage.

Others have argued that, oh well, the LDL simply slips through the gaps between endothelial cells and that is how it gets into the artery wall. Again, this is impossible. There are no gaps between endothelial cells. Endothelial cells are tightly bound to each other by strong protein bridges, known as ‘tight junctions.’

These tight junctions can prevent the passage of single ions – charged atoms – which makes it impossible for an LDL molecule to slip through, as it is many thousands of times bigger than an ion. This, too, is an inarguable fact.  Ergo, the initiation of an atherosclerotic plaque (the underlying problem in cardiovascular disease) cannot be triggered by LDL leaking into an undamaged artery wall.

Which means that, if you want to get LDL (or anything else) into the artery wall, you first must damage the endothelium/lining of the artery. This has been accepted by the mainstream medical world, although you wouldn’t really know it, because they don’t exactly shout it from the rooftops.

Here, however, is a quote from the National Heart Lung and Blood Institute in the US. An organisation which is as mainstream as it gets:

Research suggests that coronary heart disease (CHD) starts when certain factors damage the inner layers of the coronary arteries. These factors include:

  • Smoking
  • High levels of certain fats and cholesterol in the blood
  • High blood pressure
  • High levels of sugar in the blood due to insulin resistance or diabetes
  • Blood vessel inflammation
  • Plaque might begin to build up where the arteries are damaged

It has taken them a long time to admit that damage must come first, but it is inescapable when you think about it. For once, I am completely in agreement with the mainstream on this, the initial step.

However, it is what happens next, where we rapidly diverge in our thinking. The mainstream believes that, after damage has occurred, it is LDL, and only LDL, leaking into the artery wall that triggers a whole series of downstream reactions that lead to plaques forming.

However, once you have damaged the endothelium there is no longer a barrier to stop anything getting into the artery wall. So, why pick on LDL? You also have proteins, red blood cells, platelets and Lp(a) and VLDL. Indeed, anything in the bloodstream now has free entry.

It particularly makes no sense to pick on LDL, as there is already plenty of LDL in the artery wall to start with. It gets there via the vasa vasorum (blood vessels of the blood vessels) which supply the largest blood vessels with all the nutrients they need, and through which LDL can freely flow into, and out of, the artery wall.

Which begs a further question. Why should the LDL that gets into the artery wall, from the blood flowing through the artery, cause a problem, when the LDL that is already there – does nothing? The more you look at it, the more ridiculous the LDL hypothesis becomes.

A counter hypothesis is as follows.

If you damage the endothelium, the first thing that happens is that a blood clot forms at that point. This has been known for a long time. I was sent an article a while ago, written as far back as 1959. The findings stand today:

‘…any intimal injury can very easily precipitate a local process of coagulation, platelet agglutination and fibrin deposition.’1 [a.k.a. a blood clot]

You may wonder where the word ‘intima’ just appeared from. The endothelium, and the thin layer underneath the endothelial cells is sometimes called the ‘intima.’ Sometimes it is called the endothelial layer, some people call it the epithelium, or the epithelial layer. What you never get, in medicine, is people calling it the same thing… the same damned thing. Thank God these people don’t make aeroplanes, is all I can say.

Anyway, damage the endothelium, and a blood clot will form. This is the main mechanism the body uses to stop itself from bleeding to death. Damage the artery/endothelium → underlying artery wall exposed → blood clot forms → life continues.

What then happens? Well, most of the blood clot is shaved down in size by plasmin, an enzyme designed to break up (lyse) blood clots. Then a new layer of endothelium grows over the top of the remaining blood clot, and in this way, the clot becomes incorporated into the artery wall. Although I have added in a few extra bits, this is, essentially, the thrombogenic theory, first suggested by Karl von Rokitansky in 1852.

He proposed this because he noted that atherosclerotic plaques looked very much like blood clots, in various stages of repair. He further observed they contained red blood cells, fibrin and platelets, which are the main constituents of a blood clot. His ideas were then rubbished by Rudolf Virchow, who could not see how a blood clot could end up underneath the endothelium, and Rokitansky’s theory (almost) died a death.

However, from time to time, other researchers also noted that plaques do look awfully like blood clots. For example, a researcher called Elspeth Smith – who taught me at Aberdeen University. She had this to say

‘…in apparently healthy human subjects there appears to be a significant amount of fibrin deposited within arteries, and this should give pause for thought about the possible relationship between clotting and atherosclerosis.’ 2

As her paper went on to say:

‘In 1852 Rokitansky discussed the “atheromatous process” and asked, “In what consists the nature of the disease?” He suggests “The deposit is an endogenous product derived from the blood, and for the most part from the fibrin of the arterial blood”. One hundred years later Duguid demonstrated fibrin within, and fibrin encrustation on fibrous plaques, and small fibrin deposits on the intima of apparently normal arteries. These observations have been amply confirmed but, regrettably, the emphasis on cholesterol and lipoproteins was so overwhelming that it was another 40 years before Duguid’s observations had a significant influence on epidemiological or intervention studies.

Finally, for now, Dr Smith stated this in another paper:

‘After many years of neglect, the role of thrombosis in myocardial infarction is being reassessed. It is increasingly clear that all aspects of the haemostatic system are involved: not only in the acute occlusive event, but also in all stages of atherosclerotic plaque development from the initiation of atherogenesis to the expansion and growth of large plaques.’3

What she is saying here is that every step of CVD is due to various aspects of blood clotting. You damage the artery wall, a blood clot forms, it is then incorporated into the artery wall. A plaque starts, then grows. This description of how CVD starts and develops, is the process that I believe to be correct. With a couple of provisos.

The main proviso is that endothelial damage is going on all the time, in everyone’s arteries, to a greater or lesser extent. Therefore, we are not looking at an abnormality, or a disease, or a ‘diseased’ process.

The formation of blood clots following endothelial damage is also a healthy, normal, process. If it did not happen, then we would all bleed to death. As can happen in haemophilia, where blood clots do not form properly, due to a lack of clotting factors.

The next normal healthy process is that any blood clots that form must be incorporated into the artery wall. That is, after having been stabilised and shaved down. If clots simply broke off and travelled down the artery, they would get stuck when the artery narrows and cause strokes and heart attacks – and bowel infarctions and suchlike.

In short, the only way to repair any blood clot that forms on the lining of an artery wall, is to shave it down, then cover it over with a new layer of endothelial cells. Incorporating it into the artery wall.

At which point, repair systems swing into action. The main repair agents are white blood cells called macrophages. These break down and digest any remnant blood clot, before heading off to the nearest lymph gland where they too are broken down, with their contents, and removed from the body.

This ‘repair’ process leads to, what is referred to as ‘inflammation’ in the artery wall. Once again, however, this is not a disease process, it is all quite healthy and normal.

Problems only start to occur when the rate of damage, and resultant blood clot formation, outstrips the ability of the repair systems to clear up the mess.

Thus:

damage > repair = atherosclerosis/CVD

repair > damage = no atherosclerosis and/or reversal of plaques.

What factors can lead to the situation where damage outstrips repair? First, we need to look at those factors that increase the rate of damage. There are many, many, things that can do this. Here is a list. It is non-exhaustive, it is in no particular order, but it may give you some idea of the number of things that can cause CVD, by accelerating endothelial damage:

  • Smoking
  • Systemic Lupus Erythematosus
  • Use of oral steroids
  • Cushing’s disease
  • Kawasaki’s disease
  • Rheumatoid arthritis
  • High blood pressure
  • Omeprazole
  • Avastin
  • Thalidomide
  • Air pollution
  • Lead (the heavy metal)
  • Mercury
  • High blood sugar
  • Erythema nodosum
  • Rheumatoid arthritis
  • Low albumin
  • Acute physical stress
  • Acute mental stress
  • Chronic negative mental stress
  • Chronic Kidney Disease
  • Dehydration
  • Sickle cell disease
  • Malaria
  • Diabetes/high blood sugar level
  • Bacterial infections
  • Viral infections
  • Vitamin C deficiency
  • Vitamin B deficiency
  • High homocysteine level
  • Chronic kidney disease
  • Acute renal failure
  • Cocaine
  • Angiotensin II
  • Activation of the renin aldosterone angiotensin system (RAAS) etc.

Blimey, yes, that list was just off the top of my head, I could get you another fifty without much effort. And no, I did not just make it up. I have studied every single one of those factors, and many more, in exhaustive detail. The extent of how many factors there are, should not really come as a surprise to anyone, but it usually does.

After all, the bloodstream carries almost everything around the body, and the endothelium faces the bloodstream, it is the first point of contact. If damaging things are being carried about in the blood, the lining of the artery is going to be directly exposed to enemy attack.

Moving on, we need to look at factors that make the blood more likely to clot and/or make blood clots that are more difficult to shift. Again, in no particular order here and non-exhaustive:

  • Raised fibrinogen levels
  • High lipoprotein (a)
  • Antiphospholipid syndrome (Hughes’ syndrome)
  • Factor V Leiden
  • Raised plasminogen activator inhibitor 1 (PAI-1)
  • Raised blood sugar levels
  • High VLDL (triglycerides)
  • Dehydration
  • Stress hormones/cortisol
  • Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Acute physical stress
  • Acute mental stress.

For good health, you want to maintain a balance between the blood being too ready to clot, and the blood not clotting when you need it to. If you turn down the blood clotting system, bleeding to death can be a problem. This can happen if you have haemophilia, or if you take warfarin – or any of the other drugs used to stop blood clots forming in Atrial Fibrillation. Aspirin can also lead to chronic blood loss, and anaemia.

Looking at it from the other angle. You do not want your blood to clot too rapidly, or else equally nasty problems can occur. Antiphospholipid syndrome (APS), is a condition where the blood is highly ready to clot (hyper-coagulable). It greatly increases the risk of CVD:

Patients with APS are at increased risk for accelerated atherosclerosis, myocardial infarction, stroke, and valvular heart disease. Vascular endothelial cell dysfunction mediated by antiphospholipid antibodies and subsequent complement system activation play a cardinal role in APS pathogenesis.’4

Just to look more closely at one other factor on the list, which is fibrinogen. This is a short strand of protein that is made in the liver. It floats about in the blood doing nothing very much. However, if a clot starts to form, or the clotting system is activated, fibrinogen ends up being stuck end-to-end to form a long thin, sticky protein strand called fibrin. This is a bit like the strands that make up a spider’s web.

Fibrin wraps around everything else in a blood clot and binds it all very tightly, creating a very tough plug. You would guess that if you have excess fibrinogen in the blood, more fibrin will form, creating bigger and more difficult to shift blood clots.  I was first alerted to the dangers of having a high fibrinogen level by the Scottish Heart Health study.

‘This large population study confirms that plasma fibrinogen is not only a risk factor for coronary heart disease and stroke, but it is also raised with family history of premature heart disease and with personal history of hypertension, diabetes, and intermittent claudication.’ 5

To my surprise, a raised fibrinogen was found to be the most potent risk factor in the Scottish Heart Health Study, ranking above smoking. Because I don’t want to make this blog too long, I will simply say that all the other things in the list above both increase the tendency of the blood to clot and increase the risk of CVD.

Finally, we can look at factors that impair the repair systems. There are two basic parts to the repair systems.

  • Formation of a new layer of endothelium, to cover the blood clot
  • Clearing away of the debris left by the blood clot within the artery wall

What sort of things stop new endothelial cells being created?

  • Avastin
  • Age – which reduces endothelial progenitor cells (EPC) synthesis
  • Thalidomide
  • CKD – reduces EPC synthesis
  • Diabetes
  • Omeprazole
  • Activation of the renin-angiotensin aldosterone system (RAAS)
  • And drug that lowers nitric oxide synthesis
  • Lack of exercise.

What sort of things damage the clearance and repair within the artery wall?

  • Steroids
  • Age
  • Immunosuppressants
  • Chronic negative psychological stress
  • Certain anti-inflammatory drugs
  • Many/most anti-cancer drugs.

Knowing this, it seems counter intuitive that there has been a great deal of interest lately in using anti-inflammatory drugs to reduce the risk of CVD. My response to the idea that inflammation may cause CVD has always been that, the most potent anti-inflammatory agent known to man is cortisone/cortisol. This is one of the stress hormones, and it vastly increases the risk of CVD. As do immunosuppressants – which are also used to dampen down the inflammatory response.

On the other hand, inflammation is not always a healthy thing. There are many chronic inflammatory conditions such as: rheumatoid arthritis, Crohn’s disease, asthma, Sjogren’s disease and suchlike where the bodies immune system goes wrong and starts to see proteins within the body as ‘alien’ and attacks them. This can cause terrible damage.

The way to best treat (if not cure) these conditions is to use immunosuppressant drugs. Cortisol/cortisone – and the many pharmaceutical variants that have been synthesized from cortisol – is still widely used. Hydrocortisone cream, for example, is widely used in eczema.

Immunosuppressants are also commonly used in transplant patients, to stop the organ from being attacked by the host immune system. This is a good thing to achieve, but longer-term problems with CVD are now widely recognised.

‘With current early transplant patient and allograft survivals nearly optimized, long-term medical complications have become a significant focus for potential improvement in patient outcomes. Cardiovascular disease and associated risk factors have been shown in renal transplant patients to be related to the pharmacologic immunosuppression employed.6

‘Taking high doses of steroids (glucocorticoids) seems to increase the risk of heart disease including heart attack, heart failure, and stroke, according to new research. Steroids fight inflammation and are often prescribed for conditions including asthma, inflammatory bowel disease, and inflammatory arthritis. Prednisone and hydrocortisone are two examples of steroids.

Yet well-known adverse effects of these potent anti-inflammatory medications can increase the risk of developing high blood pressure, diabetes, and obesity — risk factors for heart disease.’7

The question I suppose is, can CVD possibly be a form of autoimmune condition? It seems highly unlikely. Although the inflammatory system can go wrong in all sorts of way. You may have heard of Keloid scars. These happen when you damage the skin, and the resulting healing response can create a very large ‘hypertrophic’ and unsightly scar.

Perhaps if you damaged the lining of an artery, and this triggered the equivalent of a ‘keloid’ scar in the artery wall, then if you could dampen down this reaction, an atherosclerotic plaque would then be much smaller. In which case, an inflammatory could be of benefit.

However, as of today, the more potent the anti-inflammatory drug, the greater the increase in CVD. Which suggests that if you interfere with the healing response to arterial injury, you are going to make thing worse – not better.

In truth, the real reason why inflammation is being seen as a possible cause of CVD is because inflammatory markers can be raised in CVD. To my mind this just demonstrates that in people with CVD, lots of damage is occurring, therefore there is more repair going on, so the inflammatory markers are raised.

However, the mainstream has decided to look at this from the opposite side. They see a lot inflammation going on and have decreed that the inflammation is causing the CVD – rather than the other way around. Frankly, I think this is bonkers. But there you go.

Anyway, where has all this got us to. I shall try to achieve a quick summary.

The LDL hypothesis is nonsense, it is wrong, and it does not remotely fit with any other factors known to cause CVD.

The thrombogenic theory, on the other hand, fits with almost everything known about CVD. It states that there are three, interrelated, processes that increase the risk of CVD:

  • Increased rate of damage to the endothelial layer
  • Formation of a bigger or more difficult to remove blood clot at that point
  • Impaired repair/removal of remnant blood clot.

Any factor that does one of these three things can increase the risk of CVD. Although, in most cases, a few factors probably need to work in unison to overcome the body’s ability to heal itself. Which means that people who have only one or two risk factors, are probably not going to be at any greatly increased risk. You need to have three or four, maybe more, and then things really get going.

There are a few things that I have mentioned that will greatly increase the risk of CVD with no need for anything else to be present. They are:

  • Steroids/Cushing’s disease
  • Chronic Kidney Disease
  • Sickle cell disease
  • Antiphospholipid syndrome
  • Immunosuppressants
  • Avastin
  • Diabetes
  • Systemic Lupus Erythematosus
  • Kawasaki’s disease.

All of which means that – in most cases – CVD has no single, specific, cause. It should, instead, be seen as a process whereby damage exceeds repair, causing plaques to start developing, and grow – with a final, fatal, blood clot causing the terminal event. The next blog will be a review of the things that you can do to reduce your risk of CVD.

1: Astrup T, et al: ‘Thromboplastic and Fibrinolytic Activity of the Human Aorta.‘ Circulation Research, Volume VII, November 1959.

2: https://www.sciencedirect.com/sdfe/pdf/download/eid/1-s2.0-0049384894900493/first-page-pdf

3; https://www.sciencedirect.com/sdfe/pdf/download/eid/1-s2.0-0049384894900493/first-page-pdf

4: http://www.onlinejacc.org/content/accj/69/18/2317.full.pdf

5: https://heart.bmj.com/content/heartjnl/69/4/338.full.pdf

6: https://www.ncbi.nlm.nih.gov/pubmed/12034401

7: https://www.webmd.com/asthma/news/20041115/steroids-linked-to-higher-heart-disease-risk

What causes heart disease part 58 – blood pressure

1st November 2018

A raised blood pressure, as a clinical sign, has always rather perturbed me. At medical school we were always taught – and this has not changed as far as I know – that an underlying cause for high blood pressure will not be found in ninety per cent of patients.

Ninety per cent… In truth, I think it is more than this. I have come across a patient with an absolute, clearly defined cause for their high blood pressure about five times, in total, and I must have seen ten thousand people with high blood pressure. I must admit I am guessing at both figures and may be exaggerating for dramatic effect.

Whatever the exact figures, it is very rare to find a clear, specific cause. The medical profession solved this problem by calling high blood pressure, with no identified cause, “essential hypertension”. The exact definition of essential hypertension is ‘raised blood pressure of no known cause.’ I must admit that essential hypertension certainly sounds more professional than announcing, ‘oh my God, your blood pressure is high, and we do not have the faintest idea why.’ But it means the same thing.

Doctors have never been good at admitting they haven’t a clue about something. Which is why we have a few other impressive sounding conditions that also mean – we haven’t a clue.

Idiopathic pulmonary fibrosis – progressive damage of the lungs – and we don’t know why

Cryptogenic stroke – a stroke caused by something – but we don’t know what

Essential hypertension – high blood pressure – we haven’t a clue why its high.

Can you turn something into a disease, simply by giving it a fancy Latin title? It appears that you can. Does it help you to understand what you are looking at? No, it most certainly does not.

So, why does the blood pressure rise in some people, and not in others. It is an interesting question. You would think that, by now, someone would have an answer, but they don’t. Or at least no answer that explains anything much.

Excess salt consumption has been blamed by some. However, even if you take the more dramatic figures, we are talking no more than 5mmHg. Indeed, the effect of reducing salt intake on people without high blood pressure is about 1mmHg, at most

‘Almost all individual studies of participants with normal blood pressure (BP) show no significant effect of sodium reduction on BP.’ 1

Which would mean that the effect of raising salt intake would be almost zero. So, if it is not salt, what is it? A magic hypertension fairy that visits you at night? Could be, seems as likely as anything else.

When you have a problem that is difficult to solve, I always like to turn it inside out, and see what it looks like from the opposite direction. Presently, we are told that essential hypertension increases the risk of cardiovascular disease.

Looking at this from the other direction, could it be that cardiovascular disease causes high blood pressure. Well, this would still explain why the two things are clearly associated, although the causal pathway may not be a → b. It could well be b → a.

I must admit that I like this idea better, because it makes some sense. If we think of cardiovascular disease as the development of atherosclerotic plaques, leading to thickening and narrowing of the arteries then we can see CVD is going to reduce blood flow to vital organs, such as the brain, the kidneys, the liver, the heart itself.

These organs would then protest, leading to the heart pumping harder to increase the blood flow and keep the oxygen supply up. The only way to increase blood flow through a narrower pipe, is to increase the pressure. Which is what then happens.

Over time, as the heart is forced to pump harder, and harder, the muscle in the left ventricle will get bigger and bigger, causing hypertrophy. Hypertrophy means ‘enlargement.’ So, in people with long term, raised blood pressure, we would expect to see left ventricular hypertrophy (LVH). Which is exactly what we do see.

LVH is often considered to be a cause of essential hypertension. I would argue that LVH is a result of CVD. This is not exactly a new argument, but it does make sense.

Two models strongly support the idea that CVD causes high blood pressure. The first is a rare condition called renal artery stenosis. This is where an artery to one of the kidneys narrows, or starts life narrowed. This causes the kidney to protest at a lack of blood supply and increase the production of renin.

Renin converts angiotensinogen, a protein made in the liver that floats about in the blood, into angiotensin I. Then angiotensin converting enzyme (ACE) turns angiotensin I into angiotensin II. And angiotensin II is a very powerful vasoconstrictor (narrows blood vessels), this raises the blood pressure.

Angiotensin II also stimulates the release of aldosterone, a hormone produced in the kidneys. Aldosterone increases the reabsorption of sodium and water into the blood from the kidneys, simultaneously driving the excretion of potassium (to maintain electrolyte balance). This increases the volume of fluid in the body, which also increases blood pressure.

This whole system is called the Renin angiotensin aldosterone system (RAAS), sometimes shortened to RAS. Activate at your peril. Angiotensin II is, amongst other things, a potent nitric oxide (NO) antagonist. Which, as you might expect, can do very nasty things to endothelial cells and the glycocalyx (glycoprotein layer that protects artery walls).

If you discover that the patient with very high blood pressure has got renal artery stenosis, the artery can be opened, and the blood pressure will – in most cases – rapidly return to normal. Which proves that narrow arteries can, indeed, lead to high blood pressure.

The other model is the situation whereby a number of blood clots build up in the lungs, a condition known as chronic thromboembolic pulmonary hypertension. It is not nice. The arteries are effectively narrowed by blood clots – in order to keep the blood flow up, the heart must pump harder. In this case the right side of the heart because it is this side that pushes the blood through the lungs.

So, you usually end up with Right Ventricular Hypertrophy (RVH). Eventually the heart cannot pump any harder and starts to fail, leading to Right Ventricular Heart Failure (RVF). Shortly after this, you die.

There is an operation that can be done to remove all the blood clots from the lungs. It has a very high mortality rate. Basically, you open up the lungs and pull out a great big complicated blood clot, that looks a bit like a miniature tree. If the operation is not fatal (pulmonary endarterectomy), the blood pressure drops, the LVF improves rapidly, and the outcomes are excellent.

This is another example which demonstrates that a rise in blood pressure is caused by narrowed blood vessels. Again, if you open the blood vessels the pressure drops, the stress on the heart falls, and rapid improvement can take place.

So, if CVD causes high blood pressure, is there any point in trying to lower the blood pressure with drugs. After all, you are doing nothing for the underlying disease.

Well, you would be taking pressure off the heart, so you might be improving left ventricular hypertrophy, and/or left ventricular failure. But, of course, you also lowering the blood flow to important organs, which is not so good. Indeed, it is well recognised that, in the elderly, you can increase the risk of falls by lowering the blood pressure – which can lead to fractured hips, and suchlike.

Also, if you lower the blood pressure too much the kidneys start to struggle, another major problem in the elderly. In fact, I often tell nurses working with me in Intermediate Care that dealing with the elderly can turn into a battle between the heart and the kidneys. Get one under control and the other one goes off.

Then, if you lower the blood pressure you are in danger of triggering the RAAS system into action as the body tries to bring the pressure back up again, and the RAAS system can be quite damaging to the blood vessel themselves. You will definitely disrupt the control of blood electrolytes such as sodium and potassium as aldosterone kicks into action.

I am forever battling to keep sodium levels up and potassium levels down, or vice versa, depending on which anti-hypertensive are being used. All of these are reasons why I do not bother to treat high blood with drugs, until it is far higher than the current medical guidelines would recommend.

What I do recommend to patients is:

  • Increase potassium consumption
  • Go on a high fat, low carb diet
  • Use relaxation techniques: mindfulness, yoga, whatever floats your boat
  • Take exercise
  • Get out in the sun – this stimulates NO synthesis
  • Try L-arginine and L-citrulline – as above
  • Increase magnesium consumption

This will often, if not always, do the trick.

If you must take medication, I was a very strong supporter of ACE-inhibitors, in that they blocked angiotensin II, and increased NO synthesis. Both good things. However, some research has come out recently, suggesting they may increase the risk of lung cancer. Not by a great deal, but there you go. Best to take nothing at all, if you possibly can.

1: https://www.cochrane.org/CD004022/HTN_effect-low-salt-diet-blood-pressure-and-some-hormones-and-lipids-people-normal-and-elevated-blood

What causes heart disease – part 57

11th October 2018

Blood pressure

I have tended to avoid talking about blood pressure, because I am not entirely sure what I think about it as a cause of CVD. However, since more people now take blood pressure lowering medication than any other type of medication in the world, including statins, it wold be remiss of me not to at least mention it.

Another problem is that, whilst blood pressure may seem a very simple subject. Either it is high, or it is not, nothing could be further from the truth. It is immensely complicated, and fragments rapidly into thousands of different strands, looping and whirling in front of you.

For example, let us take an apparently simple question, what is a high blood pressure? Well, with almost every passing year, this changes. The experts and the guideline writers get together on a regular basis and decide that well, hey ho, we thought 140/90 was high, turns out we are wrong. It is 130/85 – or whatever. By the way, the definition of a ‘normal’ blood pressure always goes down – never up. On current trends we should hit 0/0mmHg by the year 2067. What happens after that is hard to say.

I suppose a question that may seem reasonable to ask is the following; is average normal. Not, not even slightly. In a similar fashion to blood cholesterol levels, average and normal do not even remotely match up. Last time I looked eighty-five per cent of the population in almost all Western countries had high cholesterol levels. I would suspect another eighty-five per cent have high blood pressure.

In fact, if you wish to stretch logic to its very boundaries it is possible to propose that 99.9% of the population has a high blood pressure level. How can this make any sort of sense, you may ask? Well, in a moment of ennui I opened the American College of Cardiology/American Heart Association (ACC/AHA) risk calculator. You can find it here. http://www.cvriskcalculator.com/

I put in all my risk factors, kept them all the same, apart from my blood pressure which I started moving up and down, as you do when there is nothing good on the TV. What I found was that, as I reduced my blood pressure on the calculator, my CV risk went down, and down, until I got to a systolic (upper figure) of 90mmHg. You cannot make your blood pressure go any lower than this on the calculator.

The reason why you cannot get your blood pressure below 90mmHg is that if you go below this figure, you will be diagnosed with hypotension. Hypo = low. So, we have the weird situation whereby at 90mmHg your blood pressure is perfect. Above this, your risk of CVD goes up, below this the pressure is dangerously low and should be raised.

Therefore, at exactly 90mmHg your blood pressure is ‘normal’. At any other pressure it is abnormal – in that it increases the risk of death. Which is the definition of any ‘abnormal’ clinical test. It must be said that this constitutes a pretty narrow range. A doctor should be trying to keep your systolic blood pressure between 90mmHg and 90mmHg. And good luck with that. A very delicate titration indeed.

Clearly this is nuts, and it is not based on any clinical data whatsoever. There has never been a study whereby the systolic blood pressure has been lowered to 90mmHg. Nor will there ever be one done. This, I can guarantee. The mortality rate would be catastrophic.

So, how is this figure arrived at?

It comes from a mathematical smoothing technique whereby you get all the points on a graph, then draw the ‘best fit’ line through them all. I include an example here, which is where someone (Zoe Harcombe actually) looked at the cholesterol levels and rate of death from CVD in every country in the world (these are the dots). As you can see everything is rather scattered. [Data taken from the World Health Organisation].

However, there is a trend here, and that trend can be worked out. In this case, you feed in all the data points and a formula works out the underlying association between cholesterol and CVD death. As you can see in this case, as cholesterol goes up – CVD deaths go down. If you half close your eyes (which gets rid of the outlying points) the association between the dots and the line seems clearer.

(Or maybe that is just me).

What does this prove? Well, it proves nothing very much, for certain. What it almost certainly disproves, however, is an association between raised cholesterol and CVD.

When it comes to blood pressure it cannot be denied that. as the blood pressure rises, the risk of CVD also rises. However, the association is non-linear. By this I mean that, if your blood pressure goes from 100mgHg to 110mmHg, the risk of CVD does rise (but not by a statistically significant amount]. It only rises very, very slightly.

From 110mmHg to 120mmHg another very slight rise

From 120mmHg to 130mmHg another very slight rise

It is only when you get to about 160mmHg that the risk suddenly starts to go up sharply. From then on, things become rapidly worse. So, if your systolic blood pressure is above 160mmHg you should probably do something about it. However, what is the risk for a systolic blood pressure below this? Here we must rely on mathematics.

A paper that I have mentioned a few times, because I think it is a belter is from the European Heart Journal – from the year 2000 (believe me nothing of significance has happened since then). It is entitled ‘There is non-linear relationship between mortality and blood pressure.’

It is worth quoting the first two paragraphs in full. Sorry, for those not of a scientific bent:

‘Stamler stated that the relationship of systolic blood pressure (SBP) to risk of death is continuous, graded, and strong, and there is no evidence of a threshold…’ The formulation of this ‘lower is better’ principle, in terms of the linear logistic model (often referred to simply as the linear model) is the paradigm for the relationship of all cardiovascular risks to blood pressure and form the foundation for the guidelines for hypertension [and still does].

But it is often forgotten that when a study reports a linear (or any other) relationship between two variables it is not the data itself, but the model used to interpret the data, that is yielding the relationship. Almost universally, studies that report a linear relationship of risk to blood pressure do so via the linear models, such as the Cox model, or the linear logistic model.

Formally that model can be applied to any bivariate data and, independently of the data will always show that there is a linear relationship between the two variables. Before one can have confidence that the stated linearity correctly reflects the behaviour of the data, and is not just an artefact of the model, it is necessary to carefully examine the data in relation to the proposed model. At a minimum, it must be demonstrated that the model actually ‘fits’ the data and that it does not ‘smooth away’ important features of the data.1

To paraphrase, your carefully constructed mathematical model may well be bollocks. In fact, it most probably is.

The statisticians who wrote this paper went back to the Framingham study – from whence all guidelines on blood pressure have since flowed, in all countries, everywhere – and found that the data ‘statistically rejected the model.’ They made the following statement ‘the paradigm MUST be false.’

I hate to say it, but the first person to recognise that the linear model ‘in terms of the relationship of overall and coronary heart disease death to blood pressure was unjustified.,’ was Ancel Keys. I am not sure what to make of that, as Keys is my number one medical historical villain. Still, he wasn’t stupid.

Anyway, the response to the European Heart Journal paper was…. Complete silence. Nothing. No counter arguments were proposed, nothing. “First they ignore you, then they laugh at you, then they fight you, then you win.” Gandhi. In this case we never got beyond ‘first they ignore you.’ Oh well, such is life.

None of this means that blood pressure has no role to play in CVD – or vice-versa – I just wanted to make it clear that that the whole area has become such a mess that it is very difficult to see through the forest of bias. What is a fact here? Frankly, sometimes, I have no real idea.

So, where does this leave us regarding blood pressure and CVD? It leaves us with only a few certainties. First, and most important, the only blood vessels in the body that normally develop atherosclerosis are the larger arteries. These blood vessels have a high blood pressure in them. Let us say around 120/70mmHg.

[120mmHg is equivalent to a column of water about three metres high. The units used to measure blood pressure are mmHg i.e., millimetres of mercury. Mercury was used to measure blood pressure, because it is many times denser than water. To measure blood pressure using a water sphygmomanometer would need a device more than three metres tall.]

On the other hand, the larger arteries in the lungs (pulmonary arteries) have an average blood pressure of around 20/6mmHg. In normal circumstances they never develop atherosclerosis. The veins have a blood pressure of about 6mmHg. It does not go up and down, because the pressure in the veins is unaffected by the pumping of the heart. The veins never develop atherosclerosis.

This makes it clear that the blood pressure, and turbulent blood flow, needs to reach a certain level before atherosclerosis can start. I sometimes liken this to a river flowing down a mountainside, with rushing and roaring and white water foaming and raging. That would be an artery. When the river reaches the plain below, the speed of water flow drops, the river widens and meanders. That would be a vein.

I think it is pretty clear that the lining of an artery is put under far more biomechanical stress than the lining of a vein – or a pulmonary artery. Which is why atherosclerotic plaques develop in [systemic] arteries, and nowhere else.

This idea is further supported by the fact that it is perfectly possible to get atherosclerotic plaques to develop pulmonary arteries, and veins. But only if you significantly raise the blood pressure. There is a condition known as pulmonary arterial hypertension (high blood pressure in lungs). There are many causes of this, and I am not going through them all here.

Let’s just say that people who suffer from pulmonary hypertension can, and do, develop atherosclerosis in the lungs. It should be pointed out that the pressure still gets nowhere near that in the rest of the body, perhaps 50/20mmHg, or suchlike. However, the blood vessels in the lungs were never designed to cope with high(er) blood pressure, and so damage will occur at a lower level.

When it comes to veins, if you take a vein from the leg, and use it as a coronary artery bypass graft (CABG), it will very rapidly develop atherosclerosis. Both of which prove that there is nothing inherently different about arteries and veins that normally protects veins and pulmonary arteries. It is all due to pressure.

Low pressure – no atherosclerosis

High pressure – atherosclerosis

So, surely the lower you get the blood pressure the better? Maybe, maybe not. There are many, many, other issues to be taken into account here – some of which I will discuss in the next blog.

1: Port S, et al: ‘There is a non-linear relationship between mortality and blood pressure.’ Eur Heart J, Vol 21, issue 20 October 2000

What causes heart disease part 56 – a new paper

23rd September 2018

As you may know I am a member of an organisation known as The International Network of Cholesterol Sceptics (THINCS). When I say this, people always laugh. I suppose it is better than people shouting and screaming and slapping you repeatedly. The man who set it up was Uffe Ravnskov – our glorious leader.

He has done far better than me. His first book The Cholesterol Myths, was burnt, live on air, in a television studio in Finland. I am very jealous. Having your critics become so enraged, that the only thing they can think to do is burn your book, is a very great ‘sceptic’ honour. Although one must be slightly fearful that the mob doesn’t stop at burning your books.

Uffe has written many books and papers in this area, and from time to time I have been honoured to help him. Most recently we have battered away, trying to get a paper published on blood clotting factors in Familial Hypercholesterolaemia. Many rejections, and many years later. Hoorah.

The paper is called ‘Inborn coagulation factors are more important cardiovascular risk factors than high LDL-cholesterol in familial hypercholesterolemia.’ And you can see it here https://www.sciencedirect.com/science/article/pii/S0306987718304729.

We can provide fifty days free access to this paper, before the pay wall comes down. To make it free access forever would cost us thousands, and since none of us gets paid a bean for any of this work, this would be far too costly for a bunch of (in this area) independent researchers.

You need to be a major university, or a pharmaceutical company to make your papers free access. Although such are the costs that even these organisations are baulking. As Richard Smith– who edited the BMJ for many years –  said ‘The function of medical journals used to be to make research freely available to all. It is now to keep it hidden.’ Or words to that effect.

Anyway, a quick summary of this paper would be that it is not the raised LDL that causes an increased risk of CVD in familial hypercholesterolaemia (FH) – such as the risk may be, in some individuals. It is the fact that FH is also genetically linked to inborn areas of blood clotting abnormalities.

Which means that some of those with FH also have raised factor VIII and fibrinogen levels (there are also issues with the LDL receptor itself, which plays an important role in blood clotting – not covered in this paper). Our contention is that it is these factors that are important, not the LDL level. The data, as we analysed it, supports this contention.

Here is the abstract:

‘High low-density-lipoprotein cholesterol (LDL-C) is routinely described as the main cause of cardiovascular disease (CVD) in familial hypercholesterolemia (FH). However, numerous observations are in conflict with Bradford Hill’s criteria for causality: a) degree of atherosclerosis is not associated with LDL-C; b) on average the life span of people with FH is about the same as for other people; c) LDL-C of people with FH without CVD is almost as high as in FH patients of the same age with CVD; and d) questionable benefit or none at all have been achieved in the controlled, randomized cholesterol-lowering trials that have included FH individuals only. Obviously, those individuals with FH who suffer from CVD may have inherited other and more important risk factors of CVD than high LDL-C. In accordance, several studies of FH individuals have shown that various coagulation factors may cause CVD. Equally, some non-FH members of an FH kindred with early CVD, have been found to suffer from early CVD as well. The cholesterol-lowering trials have only been successful by using apheresis, a technique that also removes many coagulation factors, or in an animal experiment by using probucol, which has anticoagulant effects as well. We conclude that systematic studies of all kinds of risk factors among FH individuals are urgently required, because today millions of people with FH are treated with statins, the benefit of which in FH is unproven, and which have many serious side effects. We predict that treatment of FH individuals with elevated coagulation factors with anticoagulative drugs is more effective than statin treatment alone.’

Of course, this paper also supports my hypothesis that increased tendency to blood clotting (hypercoagulability) is one of the key processes in both accelerated atherosclerotic plaque formation, and the development of the final, fatal, blood clot.

Peter Gøtzsche – a scandal

19th September 2018

As many of you now know, Peter Gøtzsche was recently expelled from the Cochrane Collaboration. I was going to write a blog on it, but Maryanne Demasi has already written an excellent blog which covers most of what I was going to say. I would recommend that everyone reads it.1

I would simply add that, when an organisation that I had a lot of time for, the organisation now known as Cochrane, which used to be the Cochrane Collaboration, loses its way, one wonders if the lamps truly are turning out across the world. Perhaps never to be turned on again.

President Dwight Eisenhower made this warning to the world in 1961:

On Jan. 17, 1961, President Dwight Eisenhower gave the nation a dire warning about what he described as a threat to democratic government. He called it the military-industrial complex, a formidable union of defense contractors and the armed forces.

Eisenhower, a retired five-star Army general, the man who led the allies on D-Day, made the remarks in his farewell speech from the White House.

As NPR’s Tom Bowman tells Morning Edition co-host Renee Montagne, Eisenhower used the speech to warn about “the immense military establishment” that had joined with “a large arms industry.”

Here’s an excerpt:

“In the councils of government, we must guard against the acquisition of unwarranted influence, whether sought or unsought, by the military-industrial complex. The potential for the disastrous rise of misplaced power exists, and will persist.” 2

Had Eisenhower been alive today, I am certain that he would have recognised another player had joined the party. The ‘pharmaceutical/medical device industry complex.’ His warning about ‘the potential for the disastrous rise of misplaced power exists, and will persist,’ is equally valid today.

In fact, it is not a ‘potential.’ It has happened.

‘The lamps are going out all over Europe, we shall not see them lit again in our life-time.’ Edward Gray.

1: https://blogs.bmj.com/bmjebmspotlight/2018/09/16/cochrane-a-sinking-ship/

2: https://www.npr.org/2011/01/17/132942244/ikes-warning-of-military-expansion-50-years-later?t=1537279215799