Category Archives: Cardiovascular Disease

What causes heart disease part XLII (forty two)

9th December 2017

Stress/strain – again

It has been a long time since my last blog, but life can get in the way of other things. Three lectures to give, a deadline for my book and revalidations. The latter a complete pain that UK doctors have to go through every five years, which means gathering together evidence of all the things I have done, the learning I have learned, the hoops I have jumped through – and suchlike.

Then, my cousin dropped dead of a cerebral haemorrhage. At least he died doing something he enjoyed. He had just holed a putt on a golf course near Edinburgh, when his number came up in the great lottery of life. It reminds me that whatever we know, however much we learn, fate rules us all, and makes a mockery of our belief that we can control everything. ‘As flies to wanton boys are we to the gods.’

In this blog, I am going to return to stress, which I prefer to call strain.

Just after writing my last blog someone was kind enough to send me information about a study that had been done, showing that people who are under financial stress are thirteen times more likely to die of cardiovascular disease, and people in stressful jobs are six times as likely to have a heart attack. Not yet published research, but presented at a conference in South Africa. You may have read it1.

As those who have read my blog over the years will know, I have long argued that chronic negative stress is, from a population perspective, the single most important driver of cardiovascular disease. The mind/body connection is key to health, and thus, illness. This, I think I further emphasised by the point that mental illness is associated with the greatest impact on life expectancy.

‘Serious mental illnesses reduce life expectancy by 10 to 20 years, an analysis by Oxford University psychiatrists has shown – a loss of years that’s equivalent to or worse than that for heavy smoking….

The average reduction in life expectancy in people with bipolar disorder is between nine and 20 years, while it is 10 to 20 years for schizophrenia, between nine and 24 years for drug and alcohol abuse, and around seven to 11 years for recurrent depression.’2

Up to twenty years reduction in life expectancy.

Yes, when your mind goes wrong, your body follows, with disastrous consequences for physical health. Of course, there is overlap between mental illness, drug use, smoking and suchlike. However, you can strip all the other things out, and you are left with the ferocious power of the mind/body connection. The power to nurture, and the power to destroy.

I usually tell anyone, still listening after I have bored them on various other issues, that health is a combination of physical, psychological and social wellbeing. Three overlapping sets. The holy Trinity of wellbeing. You must get them all right, or nothing works. As Plato noted, a few years back, “the part can never be well unless the whole is well.”

Who are the shortest-lived peoples in the world? Are they the poor? Not necessarily, although poverty can be a clear driver of ill-health. The shortest-lived people in the world are people who live in the places of greatest social dislocation. Or, people who have had their societies stripped apart, with massive resultant stress. Australian aboriginals, NZ Maoris, North American aboriginals, the Inuit.

‘Indigenous Australians have the worst life expectancy rates of any indigenous population in the world, a United Nations report says. But it’s not news to Aboriginal health experts. They say it simply confirms what Australian health services have known for years.

Aboriginal Medical Services Alliance of the Northern Territory (AMSANT) chief executive officer John Paterson said the findings of the report, which examined the indigenous populations of 90 countries, were no surprise. The UN report – State of the World’s Indigenous Peoples – showed indigenous people in Australia and Nepal fared the worst, dying up to 20 years earlier than their non-indigenous counterparts. In Guatemala, the life expectancy gap is 13 years and in New Zealand it is 11.’3

I continue to find it absolutely amazing that mainstream medical thinking casually dismisses mental ‘stress’ as a cause of anything, other than mental health. The connection is always dismissed in the following way.

People who are depressed, anxious, suffering from PTSD and suchlike are more likely to drink and smoke and participate in other unhealthy lifestyles, and it is this that causes their higher rate of CVD and reduced life expectancy, and suchlike. There is a degree of truth to this, but some researchers have looked at this issue and found that the ‘unhealthy lifestyle’ issue explains very little.4

Underlying such an explanation, it has been noted that financial worries can increase your risk of heart disease by thirteen-fold (relative risk). Many of the arguments about CVD currently rage around diet, with people battling about HFLC vs LFHC, [high fat low carb vs low fat high carb].

In all the dietary studies I have seen, we are talking about increased, or reduced, risks in the order of 1.12, or 0.89. Which means a twelve per cent increased risk, or an eleven per cent reduced risk. These figures may just reach statistical significance, but they are so small as to be, to all intents and purposes, completely irrelevant.

On the other hand, a thirteen-fold increase in risk can be written another way. This is a 1,300% increase in risk. Compare this to anything to do with diet, or raised cholesterol, or blood pressure, or blood sugar or – any of the other mainstream risk factors. It is like comparing Mount Everest to a mole hill.

Yet, and yet, attempting to divert attention, and discussion, away from diet, or cholesterol, or sub-fractions of cholesterol, or suchlike seems an impossible task. People may say that they cannot see how stress can cause CVD. To which I say, every single step has been worked out, many times, by many different people.

Chronic stress → dysfunction of the hypothalamic pituitary adrenal axis (HPA-axis) → sympathetic overdrive + raised stress hormones → metabolic syndrome (raised BP, raised blood sugar, raised clotting factors, raised cortisol, raised all sorts of things) → endothelial damage + increased blood clotting → plaque formation and death from acute clot formation.

And if you want to close this loop further, stress also increases LDL levels, in some studies by over 60%5. So, when you see raised LDL, in association with increased CVD, it is not the LDL causing the CVD. It is stress, causing both.

 

1: https://www.medicalnewstoday.com/articles/320037.php

2: http://www.ox.ac.uk/news/2014-05-23-many-mental-illnesses-reduce-life-expectancy-more-heavy-smoking

3: http://www.sbs.com.au/nitv/article/2010/01/15/indigenous-life-expectancy-worst-world

4: http://www.euro.who.int/__data/assets/pdf_file/0005/98438/e81384.pdf

5: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370130/

What causes CVD part XL1 (Part forty-one)

12th November 2017

Another slight detour I am afraid. This is due to the recent publication of the ORBITA study. Reported in the British Medical Journal (BMJ), thus:

‘Percutaneous coronary intervention (PCI) is not significantly better than a placebo procedure in improving exercise capacity or symptoms even in patients with severe coronary stenosis, research has found.1

The ORBITA study, published in the Lancet, is the first double blind randomised controlled trial to directly compare stenting with placebo in patients with stable angina who are receiving high quality drug treatment.’ Compared to the sham-controlled group:

  • PCI did not significantly improve exercise time. The numerical incremental increase in average exercise time was 16 seconds (P=0.20).
  • PCI did not significantly improve measures on well-validated patient-centered angina questionnaires.
  • PCI did not significantly improve the Duke treadmill score or peak oxygen uptake.
  • PCI did significantly improve the dobutamine stress echo wall-motion index, indicating that stenting reduced ischemic burden.

In short, PCI did nothing at all. I can hear cardiologists across the US putting plans for new swimming pools on hold. 2

As many people know, the purpose of a stent is to open up obstructed coronary arteries, and then keep them open, using a metal framework ‘stent’, that sits within the artery. This procedure has been done on thousands, millions, of people. In an acute myocardial infarction (MI or heart attack to you) it provides benefits. However, in non-acute blockage it does nothing, apart from enrich interventional cardiologists.

Frankly, I was surprised that these researchers got ethical approval for this study. Carrying out a sham operation is a pretty major thing to do to a patient. I am further surprised they managed to get any volunteers, but they did. I very much take my hat off to these researchers. Bold, very bold, indeed. They must have been pretty damned certain they were going to see no benefit from stents.

Anyway, this study only proves what many people had suspected for some time. Stents, in the non-acute situation, do not work. Of course, this study has already been attacked and dismissed. Here is one review from SouthWestern medical centre, entitled ‘Stents do work: A closer look at the ORBITA study data.’:

ORBITA was small – too small, in fact, considered definitive evidence that cardiologists should change the role of stents in clinical practice.

I participate in a number of cardiology care guidelines committees and even wrote a piece about the ORBITA trial for the American College of Cardiology. In order for regulating bodies to change clinical practices, research studies must present data from a much larger pool, such as the 2007 COURAGE PCI study, which enlisted more than 2,000 participants. In general, larger trials present data that are more statistically significant and more appropriate to apply to specific patient segments.3

Too small? Wrong patient type, no doubt the wrong atmospheric pressure as well. Unlike the studies that were used when cardiologists first started doing stents, where the study size was precisely zero. In fact, if you read the entire article from the Southwestern medical centre, it is gibberish. But it will have the desired effect. The ORBITA study will have no impact stenting revenue. Like many other ideas in medicine, it is too seductive, and far too lucrative. The artery is blocked, it must be opened. End of.

Many years ago, Bernard Lown had precisely the same issue with Coronary Artery Bypass Grafting (CABG). Another massively lucrative intervention which rapidly became the operation – based on no evidence whatsoever. It was such an obviously brilliant idea that to question it was to defy ‘common sense.’ You have a blockage in an artery, bypass it with a graft.’

One thing that you find about good science is that it is usually very far removed from ‘pure common sense.’ It is counterintuitive. It is counterintuitive because it challenges established thinking a.k.a. prejudices. As Einstein had to say. ‘Common sense is nothing more than a deposit of prejudices laid down in the mind before age eighteen.’ He also said that ‘It is harder to crack prejudice than an atom.’

If you want a really good read, I recommend Bernard Lown [he is my hero]. He was the first to challenge the orthodoxy that CABG was an unquestioned good. For which he was of course, roundly attacked. His essay on this can be read here4. I include a particularly poignant section by Bernard Lown discussing CABG:

‘One might wonder why patients acquiesced to undergoing a painful and life-threatening procedure without the certainty of improving their life expectancy. I have long puzzled at such acquiescence. Surprisingly, patients not only agreed to the recommended intervention but commonly urged expediting it. Such conduct is compelled by ignorance as well as fear. Patients are readily overwhelmed by the mumbo-jumbo of medical jargon. Hearing something to the effect of “Your left anterior descending coronary artery is 75 percent occluded and the ejection fraction is 50 percent” is paralyzing. To the ordinary patient such findings threaten a heart attack or, worse, augur sudden cardiac death.

Cardiologists and cardiac surgeons frequently resort to frightening verbiage in summarizing angiographic findings. This no doubt compels unquestioning acceptance of the recommended procedure. Over the years I have heard several hundred expressions, such as: “You have a time bomb in your chest” and its variant “You are a walking time bomb.” Or, “This narrowed coronary is a widow maker.” And if patients wish to delay an intervention, a series of fear-mongering expressions hasten their resolve to proceed: “We must not lose any time by playing Hamlet.” Or, “You are living on borrowed time.” Or, “You are in luck — a slot is available on the operating schedule.” Maiming words can infantilize patients, so they regard doctors as parental figures to guide them to some safe harbour.’

The man is a genius and he can write far better than wot I can. I should hate him.

Some forty years later, or so, we find that CABG has been replaced by PCI/stenting. Exactly the same knuckle headed stupidity has driven stenting. The noise of sheep bleating ‘Narrow artery bad, open artery good,’ fills the air. My goodness, I think they’ve got it. Who could possibly argue with that? Kerching!

Those who have read my endless blog on the causes of on CVD will know I have long been highly sceptical of stenting as the answer to anything very much. Other than the removal of large sums of money from person A, to hospital B, and interventional cardiologist C.

Why does it not work? How can it possibly not work?

Because the heart is not simply a pump, arteries are not simply pipes, and humans are not inanimate objects whereby our function, or lack thereof, is purely dependant on some form of medical or surgical intervention. Thus endeth the lesson on stenting.

1: http://www.bmj.com/content/359/bmj.j5076

2: https://www.medscape.com/viewarticle/888115?pa=ItuYp8yggqEV0rOdozORa13VwlwcjMMn88tJMLYfucZ3N%2FNEihiaVx2Ypnp0WNqT8SIvl8zjYv73GUyW5rsbWA%3D%3D

3: http://www.utswmedicine.org/stories/articles/year-2017/stent-PCI-ORBITA.html

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

What causes heart disease part XL (part forty)

27th October 2017

As readers of this blog will know, for many years I have pursued the idea that ‘stress’ was the primary cause of cardiovascular disease. Actually, it is strain. Stress is the force applied, strain is the effect that stress produces. For the sake of simplicity, I will just use the word stress.

This journey started when I began to take an interest in the rate of heart disease death in Scotland and France. Being Scottish born and bred, (OK, my father was English, but I forgive him) I felt I knew a bit about the lifestyle of the average Scot, aye Jimmy.

I had also travelled to France many times, so I felt I knew a bit about the French as well. The other reason for looking at France and Scotland was that, in my formative years, Scotland had one of the highest rates of heart disease in the world, perhaps the highest. I am talking primarily about death from myocardial infarction here. On the other hand, the French rate was very low, perhaps the lowest in the world, and has since then got lower.

Why such a massive difference? The conventional explanation was that the Scots had such a terrible diet. The famed deep-fried Mars bar is oft quoted. ‘How can a country that deep fries a Mars bar expect anything less.’ As if everyone in Scotland does nothing but stuff their faces with deep-fried Mars bars, all day, every day.

I do not have the statistics to hand, but I would be very surprised to find that even fifty per cent of Scots have eaten even one. Indeed, if you have made the mistake of eating a deep-fried Mars bar, you will never (unless very drunk) eat another. However, the Scottish ‘unhealthy diet’ meme is so firmly embedded in most people’s brain that it cannot be removed.

Ironically, a Mars bar contains almost no fat at all, it is made almost entirely from sugar a.k.a. carbohydrate. If you wrap it in batter, and stick it in a deep fat fryer full of vegetable fats, you have, according to current thinking, just made it significantly healthier. More carbs wrapped round the outside, and now dripping with vegetable/polyunsaturated fat. Mmmmm … you can just feel your arteries unclogging.

In reality, as with most other well-known facts about heart disease, when I started to look closely, the only significant difference that I could find about the diets in France and Scotland, was that the Scots ate slightly less saturated fat. They also ate fewer vegetables.

On the other hand, the French smoked more, took a bit less exercise and, at the time, had an identical BMI and blood pressure to the Scots. Rates of diabetes were also identical, as were average total cholesterol levels.

In short, I could find no significant difference in ‘classic’ risk factors. If anything, they slightly favoured the Scots over the French. Yet, and yet, age-matched, the French suffered one fifth the rate of deaths from heart disease. If you open up a risk calculator designed for a UK population, and use it to calculate risk for the French, you still have to divide the answer you get, by four. [Which might suggest that risk calculators are not capturing the major causes of CVD].

This gave me to think that there may be something else going on. Other than diet.

What? There have been many papers written about the ‘French Paradox’. The paradox being that they eat masses of saturated fat (highest consumption in Europe, probably the world), they have average to high cholesterol levels and a vanishingly low rate of heart disease.

Scientifically the French paradox should really be called the ‘French refutation of the diet-heart hypothesis and the LDL hypothesis, and all other hypotheses about cardiovascular disease you can think of’. Instead, a range of protective factors have been proposed. Eating garlic, drinking red wine, lightly cooked vegetables, and suchlike. But if you chase them down, and I have, they explain nothing – at all. Primarily, because they are just not true a.k.a. unsupported by evidence.

So, what was going on? What was the key thing that caused the Scots to die of heart disease in great numbers? One obvious and outstanding difference between the Scots and French was not what they ate, but the way that they ate. Scots saw, and in many cases still see, eating very much as a refuelling exercise. On the other hand, mealtimes, and eating, is a massive part of French life. Time is taken, food is appreciated, families tend to eat together – and suchlike.

Could it be, I thought, that the way food is eaten is more important that what is eaten?

If you eat whilst you are relaxed and socialising with friends and family, will your body deal with food in a different way? The answer is, of course, yes. Just to put it in the most basic terms. If you are highly stressed, either physically or psychologically, your fight or flight system will be activated. The sympathetic nervous system will be directing blood from the digestive system, to muscles, acid production in the stomach will be down, the heart rate will be up – and suchlike.

At the same time the stress hormone: adrenaline (epinephrine), growth hormone, glucagon, and cortisol levels will be high and surging round your bloodstream. This will be activating catabolism – the breakdown of energy stores – sugar levels will be up, free fatty acids circulating, blood clotting systems activated, insulin levels down, and on and on. This is not, it should be added, the perfect metabolic situation in which to eat food.

If you look at most animals, after they have eaten they like to lie down, relax and fall asleep. This allows the food that has been eaten to be digested. Humans seem happy to leap to their feet and rush about after eating. I started thinking about the fast food culture of the US. They began the trend for fast eating, fast living, eating and driving. Rush, rush, busy, busy, work, work, bang, bang. They were first to suffer a high rate of heart disease.

I began to study the effect of stress on metabolism. I looked at a condition known as post-aggression metabolism. The state the body finds itself in after trauma such as a car crash or major operation. In such cases the stress hormones are sky high, blood sugar moves into the diabetic level, insulin cannot achieve anything as it is battling against a catabolic system on full throttle. Not a good time to be eating food.

Then I looked at less dramatic situations. My attention drifted onto Cushing’s disease. A condition where the stress hormone cortisol is over-produced by the adrenal glands. Usually because of a cortisol secreting tumour. Cushing’s disease represents a form of chronic ‘fight or flight’, constant stress.

I discovered that, in Cushing’s there is a spectrum of metabolic, and other physiological, abnormalities such as:

  • High blood sugar level
  • High insulin level
  • High clotting factors
  • High VLDL (triglycerides)
  • Low HDL
  • High blood pressure
  • Abdominal obesity.

I also noted that, Cushing’s increases the risk of CVD by, at least, 600%.

I then realised that Cushing’s syndrome and the metabolic syndrome shared exactly the same set of metabolic and physiological abnormalities. So I began to think. ‘This is beginning to look interesting.’ Actually, I was thinking this before the term metabolic syndrome existed. At the time is was called either Reaven’s syndrome, or syndrome X. The term “insulin resistance syndrome” is now popular.

Then I was pointed to the work of Per Bjorntorp, who had been looking at the Hypothalamic Pituitary Adrenal axis (HPA-axis). This is the central control system for the stress/flight of fight response. It links together the sympathetic and parasympathetic nervous system, with the actions of the stress hormones, the adrenal glands, thyroxine, glucagon, insulin etc. etc. A complex beast of a thing.

Bjorntorp established that chronic psychological stress (chronic strain) creates a dysfunction of the HPA-axis that can be monitored, most easily, by looking at twenty-four-hour cortisol secretion. A dysfunctional HPA-axis leads to a flattened and unresponsive (burnt-out) cortisol release during the day. This does not mean cortisol levels are high, or low, they just flat-line.

He studied various populations e.g. Sweden and Lithuania, and found that the Lithuanians (at the time) were far more likely to have a dysfunctional HPA-axis than the Swedes, and their rate of CVD was four times as high as that in Sweden. A study done only on men at the time. I then started to look at other conditions where the HPA-axis is damaged. Depression, schizophrenia – in fact almost all psychiatric illness – PTSD, survivors of childhood abuse. In all cases the same pattern emerged. HPA-axis dysfunction, greatly increased risk of metabolic syndrome/insulin resistance syndrome and greatly increased risk of CVD death.

I detoured round spinal cord injury. Most people are probably unaware that spinal cord injury is associated with a very much higher rate of CVD. People who suffer spinal cord injury also have a damaged HPA-axis. Some more than others. It depends on the level of the damage, and whether or not the autonomic nervous system is damaged. [The autonomic nervous system is the name given to the network of nerve fibres that make up the sympathetic and parasympathetic nervous system. It travels down the spine, but not in the spinal canal].

I then had a look at corticosteroids. These are the drugs used in many diseases as anti-inflammatory agents. They are used in diseases such as asthma and rheumatoid arthritis and Crohn’s disease and systemic lupus erythematosus (SLE), all ‘auto-immune’ diseases where the body attacks itself. Corticosteroids dampen down the ‘inflammatory’ response.

Corticosteroids are synthesized from cortisol, which is one of the body’s own steroid hormones. Which is why they are called corticosteroids (steroids manufactured in the cortex of the adrenal gland). They are fantastic drugs, and widely used. However, if you take corticosteroids for a long time you will end up with the metabolic syndrome, and a greatly increased risk of CVD, around a 400% increase.

The more I looked, the more it seemed very clear that the unconscious neuro-hormonal system was the key player in CVD, both heart attacks and strokes. It also seemed that cortisol was probably the lynch pin. It still does. Which is why my favourite graph on CVD comes from Lithuania. I have used it before, and I make no bones about using it again.

The rate of heart disease in Lithuania was gradually falling during the 1980s, until the year 1989. At which point the Berlin wall came down, the Soviet Union broke apart and the structure of society was torn apart. It was a very, very, stressful time.

What happened to the rate of heart disease in men, under 65.

Latvia and Estonia showed the same pattern, as did Russia three years later when Gorbachov was deposed by Yeltsin. In non-Soviet European countries, nothing happened. Heart disease rates continued their gentle fall.

I had been looking for evidence that abrupt social disruption leads to stress which leads to CVD. The problem is that, normally, gigantic social disruption = war. During war medical statistics tend to get overlooked, or other causes of sudden death distort the picture.

For the first time in history, a gigantic social upheaval occurred right in front of our eyes. It was not war, and the WHO was there, recording away, as part of the MONICA project. [Myocardial infarction and coronary deaths in the World Health Organization]. Cause, and effect? I believe so.

Which takes me back to Scotland. Glasgow was a very big city, then it shrank. It shrank because social engineers decided to move people from the tenements, which were considered crowded and unhealthy, to wonderful new towns, and high-rise flats. Such as these shown below.

As you can imagine people very much enjoyed living in these inhuman monoliths. A great sense of community and fun developed. So much so that they have now all been demolished.

Whilst this great forced location of people was taking place, the rate of CVD in and around Glasgow exploded. Yes, Scotland as a whole had a high(ish) rate, but greater Glasgow, whilst all this was going on, had by far the highest rate of all. Cause, and effect?

So, my thought experiment that started in Scotland, ended up back in Scotland. I then looked around the world for populations with extraordinarily high rates of CVD. I hypothesized that populations that had suffered enormous social stress would have high rates. So I looked at Australian aboriginals, Maoris, migrant populations, native Americans, and suchlike.

What did I see. Well, pretty much the same things everywhere. Social upheaval followed by high rate of CVD. At present Australian aboriginals have, I believe, the highest rate of CVD in the world. A population where lifestyle and culture has been shredded. If you use a CVD risk calculator on a young aboriginal woman, you have to multiply the predicted ten-year risk by thirty.

Exceptions, of course, exceptions. The Rosetta community of Pennsylvania US. An immigrant population that had moved from Rosetta Italy to Rosetta US – en masse. They became famous for a very, very, low rate of heart disease. What made them different? Here is a section from a Huffington Post article:

‘What made Rosetans die less from heart disease than identical towns elsewhere? Family ties. Another observation: they had traditional and cohesive family and community relationships. It turns out that Roseto was peopled by strongly knit Italian-American families who did everything right and lived right and consequently lived longer.

In short, Rosetans were nourished by people.

In all ways, this happy result was exactly the opposite expectation of well-proven health laws. The Rosetans broke the following long-life rules, and did so with a noticeable relish: and they lived to tell the tale. They smoked old-style Italian stogie cigars, malodorous and remarkably pungent little nips of a cigar guaranteed to give a nicotine fix of unbelievably strong potency. These were not filtered or adulterated in any way.

Both sexes drank wine with seeming abandon, a beverage which the 1963 era dietician would find almost prehistoric in health value. In fact, wine was consumed in preference to all-American soft drinks and even milk. Forget the cushy office job, Rosetan men worked in such toxic environs as the nearby slate quarries. Working there was notoriously dangerous, not merely hazardous, with “industrial accidents” and gruesome illnesses caused by inhaling gases, dusts and other niceties.

And forget the Mediterranean diets of olive oil, light salads and fat-free foods. No, Rosetans fried their sausages and meatballs in…..lard. They ate salami, hard and soft cheeses all brimming with cholesterol.2

The tenements of Glasgow were filthy and rat infested and crowded and had poor sanitation. But if you speak to those who lived in them, their memories were of close family ties, strong community support, fun, playing football in the street. Then they were shifted to the Brave New World of sterile social engineering. Isolation, loneliness, breakdown of community. Death.

You want to know one of the most important ways to avoid dying of CVD?

 

1: 1https://www.researchgate.net/publication/13659734_Increased_Psychosocial_Strain_in_Lithuanian_Versus_Swedish_Men

2; https://www.huffingtonpost.com/dr-rock-positano/the-mystery-of-the-roseta_b_73260.html

What causes heart disease part XXXVIII (part thirty-eight)

24th September 2017

‘The flow of rivers and streams in their boundaries . . . the circulation of the blood in our arteries and veins . . . the flight of the insect, the bird and the airplane; the movement of a ship in the water or of a fish in the depths . . . these are all, in major degree, varied expressions of the laws of fluid mechanics … Everywhere we find fluids and solids in reactive contact, usually in relative motion; and everywhere in this domain, the laws of fluid mechanics must control.

Application of the laws of fluid mechanics to the natural conditions in the circulatory system reveals a rational and demonstrable basis for the localization, inception, and progressive development of atherosclerosis.

Atherosclerosis does not occur at random locations. It does occur uniformly at specific sites of predilection that can be precisely defined, predicted, and produced by applying the principles of fluid mechanics. The areas of predilection for atherosclerosis are consistently found to be the segmental zones of diminished lateral pressure produced by the forces generated by the flowing blood.

Such segmental zones of diminished lateral pressure are characterized by tapering, curvature, bifurcation, branching, and external attachment. Serpentine flow in a relatively straight vessel also produces segmental zones of diminished lateral pressure.

Although these anatomic configurations occur in many variations of geometry, their common feature is a pattern of blood flow conducive to the production of localized areas of diminished lateral pressure. This is the initial stimulus.

Atherosclerosis may therefore be considered to be the biologic response of blood vessels to the effect of the laws of fluid mechanics, that is, the diminished lateral pressure generated by the flowing blood at sites of predilection determined by local hydraulic specifications in the circulatory system.’1

Not my words, and quite poetic I suppose. What does it mean. It means, if you accept what is written, is that atherosclerosis forms exactly where you would expect it to form – if the initial stimulus is ‘diminished lateral pressure’.

My last blog was primarily a looking at the primary stimulus for the initial formation of atherosclerotic plaques. I like to use the term biomechanical stress. I am not entirely certain if this means anything. But the general idea is that atherosclerotic plaques start at the points in blood vessels where there is the greatest ‘biomechanical stress.’

Several people who know far more about fluid dynamics questioned this. I think that they are all probably right in what they say, and the mathematics are well beyond my understanding. However, what I do know, and what are facts, are the following:

  • Atherosclerotic plaques inevitably occur where is there is tapering, curvature, bifurcation, branching and areas of external attachment.
  • Plaques never develop in veins, regardless of tapering, curvature and branding and suchlike.
  • Plaques never develop in the arteries and veins in your lungs – unless you develop pulmonary hypertension (raised blood pressure in the lungs) – though a caveat applies.
  • Plaques often appear on one side of an artery, and not the other (i.e., they do not encircle the artery).
  • If you take a vein from the leg, and use it as a coronary artery bypass graft, it will rapidly develop atherosclerotic plaques.

Therefore, whatever term you want to use, however, you wish to understand it, it is clear that in order to get a plaque to start, you need to apply some form of ‘stress’ to the blood vessel, and the blood pressure needs to be at a certain level – or else nothing will happen. This is true, no matter what the LDL level, or the blood sugar level, or whether you smoke, or [insert any one of eight thousand risk factors here].

Ergo, there must be some form of damage occurring at the point of high biomechanical stress, that triggers plaque development. Under biomechanical stress, the first part of the artery to suffer will be the endothelium – the layer of cells that lines the arteries. If endothelial cells are stressed, damaged, or dysfunctional, this is the trigger for plaques to start:

In view of the ever-increasing prevalence of ischaemic heart disease in the developed and developing world, it has become imperative to identify and investigate mechanisms of early, potentially reversible pre-atherosclerotic changes in the endothelium. To date, the most clearly defined and well-understood early precursor of atherosclerosis is Endothelial Dysfunction. In fact, Endothelial Dysfunction can be regarded as the primum movens of atherosclerotic disease.’2

I guess that primum movens is Latin for ‘the single most really important thing.’

In short, you damage the endothelium, and that releases the atherosclerotic dogs of war. What sort of things are known to increase endothelial stress/damage. Here is a list, off the top of my head, of a few factors that have been identified.

  • Smoking
  • Air pollution
  • Diabetes
  • Cocaine use
  • Dehydration
  • Infections/sepsis
  • Systemic Lupus Erythematosus (SLE)
  • Lead
  • Stress hormones
  • Avastin
  • Omeprazole
  • Cushing’s disease
  • Kawasaki’s disease.

I could go on, and on, but I think that is enough to be going on with. All of these factors have been demonstrated to cause significant damage to the endothelium – in different ways – and there is another thing that they all do. They all increase the risk of dying of CVD. Some of them enormously increase the risk. A young woman with SLE has an increased risk of dying of CHD of 5000% (relative risk increase).

When you are looking at a 5000% increase in risk you are, without the slightest shadow of a doubt, looking at a cause.

The only other increased risk I have ever seen to match this, or in fact beat this, is in young people with sickle cell anaemia where the increased risk of stroke is 33,000% (relative increase in risk). Yes, not many young people get strokes, but an increase of 33,000% is difficult to argue with.

Why do they get so many strokes? It is, in part, because the ‘sickle’ shaped red blood cells clump together more easily than normal shaped red blood cells. Once they clump together, they form clots, and these clots block arteries. Often in the brain – but also elsewhere. It is not as simple as this, but that will do for now.

There is another thing about sickle cells anaemia that I find of great interest. It is the only condition (at least the only condition I have come across), where atherosclerotic plaques can form in the lungs – at normal blood pressure.3

Why does this happen? Well sickle cells are not round and smooth. They are crescent shaped, and spiky at the ends, and stiffer than normal red blood cells, and they are more likely to cause mechanical damage to the endothelium.

‘A further mechanism of endothelial dysfunction is attributed to the rigidity of sickled erythrocytes (red blood cells) causing mechanical injury to the endothelial cells.’3

In addition:

‘The sickling process leads to vascular occlusion, tissue hypoxia and subsequent reperfusion injury, thus inducing inflammation and endothelial injury. This causes a blunted response to nitric oxide (NO) synthase inhibition.’3

Yes, our old friend Nitric Oxide again. Put simply, sickle cells crash into, and damage endothelial cells, which then stop producing as much NO. This endothelial dysfunction then leads on to atherosclerosis. All of this happens with no other risk factors present, and in arteries where atherosclerosis is normally never seen. Which means that we are looking very directly at cause, and effect. Physical damage to endothelial cells, no other factors required.

Now, I am aware that many people wonder why my series on what causes heart disease/cardiovascular has been so long and meandering. One major reason is that there is so much to try and find out, and explain. Also, and perhaps more critically, if you are going to try and understand cardiovascular disease fully, you must attempt to fit everything together, and that does take time.

For example, you must explain how: SLE, sickle cell anaemia, Kawasaki’s disease, omeprazole, diabetes, smoking and infections (to name but seven) can all cause CVD when, superficially, there is nothing to link them. Certainly none of the established, mainstream, risk factors.

There is no point in saying that, yes, they all cause heart disease, and that’s that, just add them to the list. There is a requirement to fit them within a single process, and it must make sense. It also has to be supported by the facts – as far as that is possible.

Equally, there is no point in saying CVD is ‘multifactorial’, which is the normal defence of the mainstream when pressed on why many people, with no risk factors for CVD, still get CVD. The word “multifactorial” explains nothing, it is just an escape route for those pressed to explain the many ‘paradoxes’ or refutations that keep on appearing.

If, for example, you cannot explain how sickle cell anaemia causes atherosclerotic plaque formation, in pulmonary arteries, this means you do not understand, or do not wish to understand, the underlying process. It fits nowhere within the accepted major risk factors, yet it increases the risk of stroke by 33,000%, and causes plaques to develop in the lungs. So, you cannot just ignore it, relatively rare though it may be.

So, where have we got to? Where we have got to, I believe is to demonstrate that the trigger factor for CVD is damage to the endothelium. If you don’t damage the endothelium nothing else happens. The damage happens at well recognised places where the biomechanical stress is at its greatest. Which means that, with no biomechanical stress, there can be no atherosclerotic plaques.

However, it takes more than just biomechanical stress. You also have to have, at least one, extra factor present to trigger endothelial dysfunction. Then … next episode.

References:

1: From Chapter 8 Coronary Heart Disease: The Dietary Sense and Nonsense: George V. Mann: 9781857560725: Amazon.com: Books

2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721957/

3: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780857/

What causes heart disease part XXXVII (Part thirty-seven)

16th September 2017

Beginning at the end.

Whilst there is significant controversy about how atherosclerotic plaques may start, and grow, the final event in cardiovascular disease is, in most cases, pretty much accepted – even by me. The formation of a blood clot. Yes, there are many caveats here, and also a number of different processes that can occur, but I am not covering them in this blog. I am using the simple ending. The obstructive blood clot.

If a blood clot forms in the coronary arteries – blood vessels supplying blood to the heart – it can fully block the artery, jam up blood flow, vastly reduce oxygen supply, and cause a myocardial infarction (MI). The clot usually forms on the surface of a pre-existing atherosclerotic plaque.

If a blood clot forms in the carotid arteries – main blood vessels supplying blood to the brain – it can then break off, travel up into the brain where it gets stuck, jams up blood flow, reduces oxygen supply, and cause a cerebral infarction (ischaemic stroke). Again, blood clots in the carotid arteries almost always form on the surface of atherosclerotic plaques formed earlier.

What this means is that reducing the formation of blood clots will, or definitely should, reduce the risk of heart attacks and strokes. And, of course, it does. Aspirin, for example, has anticoagulant action, and it lowers the risk of CVD, although not by a huge amount.

However, recently, a study was published in the New England Journal of Medicine which demonstrated that if you add rivaroxaban – an anticoagulant, primarily used to prevent strokes in patients with Atrial Fibrillation – to aspirin, this further reduces the risk of CVD1.

The trial was reported thus, in the Daily Mail on the 11th of September:

‘Phenomenal’ pill slashes the risk of death from heart disease by 22% and could save millions of lives, ‘ground-breaking’ trial finds.’

Oh yes, we do like a phenomenal pill, do we not. Mockery of such ridiculous hype aside, this was an impressive result. Far more impressive than any statin trial, it must be added – with no impact on LDL levels at all. Only one slight problem, it would be rather expensive to add rivaroxaban to everyone taking aspirin. Minimum cost, about £6Bn/years ($8Bn/year) in the UK alone.

Of course, there are other things that can reduce the risk of blood clotting. Omega 3 fatty acids, for example which reduce ability of platelets to stick together2 – an action almost identical to aspirin. Then there is Von Willibrand disease – a condition where people lack a key blood clotting element called the Von Willebrand factor. Patients with this condition have a 60% reduction in the risk CVD.

Those with haemophilia had – prior to the development of clotting factors to replace those that were missing –around 20% the risk of CVD of the surrounding population.

On the other hand, there are situations where the risk of blood clotting increases. Use of non-steroidal drugs e.g. brufen, naproxen, diclofenac etc. These increase the risk of clotting, and CVD. There are conditions, such as Hughes syndrome and Factor V Leiden where the risk of blood clotting goes up, and so does the risk of CVD and so on, and so forth.

In fact, I think it can be stated with complete confidence that any drug, condition, or anything else that reduces the risk of blood clotting, also reduces the risk of CVD, and vice-versa. Of course, if you reduce the risk of blood clotting, you can also increase the risk of serious bleeding. So, it is not all positive. All is balance. Yin and Yang, and suchlike. Even the relatively benign aspirin, in low doses, can lead to chronic blood loss, anaemia, and, in extreme cases, death.

What does this prove. Well it certainly proves that blood clotting and CVD are intimately related. So much so that the word ‘atherothrombosis’ is often used to describe the processes of CVD. ‘Athero-‘ = the atherosclerotic plaque growing then ‘-thrombosis’, the clot that forms top of the plaque that then kills you. That, at least, is the official Soviet party line.

However, I never liked the idea that we have two almost completely different processes going, that are linked together, but only at the final event. I wanted to explore the idea that a single process – blood clotting – could be responsible for plaque starting, growing and then ‘rupturing’ causing the whole spectrum of atherothrombosis. Blood clots, from start to finish.

This took me on a pretty amazing journey, a long and winding route indeed. I have come to believe that the system of blood coagulation must be, just about, the most complex physiological system in the body. It is beyond mind-boggling. Just when you think you have read about every factor involved, another one pops up. Indeed, I think I am forgetting facts about blood clotting faster than I can learn them. My brain is full.

However, the other day, I came across an expression that captured something about blood clotting that I have always struggled to put into words. It described the coagulation system as ‘idling’, as in sitting with the engine running. The blood coagulation system is never ‘off’ it is always turning over in the background, constantly producing small combination of substances that make up a full blood clot.

I suppose this is because, if you suffer a significant wound, or damage to a large blood vessel, the coagulation system cannot hang about. It must accelerate from zero to one hundred in the blink of an eye. Bang, go, stamp on the accelerator. At the same time, if it accelerates out of control, the clot will be too big, it will spread too rapidly, blocking blood vessels all over the place.

So, almost the moment you stamp on the accelerator, you are hammering on the brake. Accelerate, brake, accelerate, brake. Build up the clot, break down the clot. A fantastically dynamic system with feedback loop upon feedback loop. Too little clotting, you die. Too much clotting, you die. This is going on, all the time, in your body. A system constantly hunting, and hunting, to find equilibrium.

What is the greatest, the most powerful trigger, for a clot to form? It is a substance called Tissue Factor (TF). It is found almost everywhere in the body, but it is found in the highest concentrations within the walls of the larger arteries and veins. This, of course, makes perfect sense. If an artery, or vein, is damaged, the place you want a blood clot to form is exactly at that point. Bang, go.

Tissue factor is sometimes called extrinsic factor. It is called this because it does not float about (freely) in the bloodstream, it sits ‘externally/extrinsically’ to the blood. [In fact, platelets and white blood cells also contain TF, but it is inactive/not expressed unless other things are triggered first].

Other parts of the clotting system are often referred to as intrinsic factors that trigger the ‘intrinsic clotting system’. Factors you may have heard of, such as factor VIII, or factors IX and X and Xa etc. The intrinsic system tends to operate more slowly, and less powerfully, than the extrinsic (massive over-simplification warning).

Normally, the ‘intrinsic’ clotting factors, and the extrinsic system operate together to drive and amplify the clotting response once it is triggered. All of which means that, normally, you want to keep the blood well away from contact with TF, because the moment there is contact, all hell breaks loose and a blood clot will form, instantly, at that point.

The single most important barrier that keeps the blood separated from TF is the endothelium. Which means that an intact and healthy endothelium is the best protection against accidental blood clots forming. Yes, blood clots can form with no TF contact. A deep vein thrombosis (DVT) can develop in veins with intact endothelium. The process is different, the blood clot formed is also very different. It is mainly an intrinsic process.

Forgetting other types of blood clot that can form elsewhere in the body, the only way a clot will form in the larger arteries is due to endothelial damage. No endothelial damage, no clot. Once a blood clot has formed, then stabilised, what happens?

Well, normally the clot will not have been allowed to get too big, because all the feedback loops will kick into action to slow things down. So, most clots will not fully block an artery, nor even half block an artery. They also get shaved down in size quickly. Primarily through the action of Tissue Plasminogen Activator (TP(a)).

TP(a) is an enzyme floating about in the bloodstream that converts plasminogen into plasmin. Plasminogen is an inactive enzyme that is incorporated into all blood clots as they form. When TP(a) converts plasminogen to plasmin, it slices fibrin apart, chopping blood clots into small pieces. A process known as fibrinolysis. Two of the major components of a blood clot are platelets – small sticky cells that coordinate the clotting response – and fibrin – long sticky strands of protein that binds the clot together.

However, there will be always be a part of the clot that remains clamped to the artery wall. Because if all the clot was fully broken down/fibrinolysed, the bloodstream would be exposed to TF again, and the entire blood clotting process would simply kick off…. again.

Which means that once a clot has been formed, a part of it will always be left stuck to the artery wall. This then needs to be got rid of. How does this happen? Well, it is not like scratching your skin, whereby a clot (scab) forms, the endothelium re-grows underneath it, then the scab falls to the ground. If this were the process that happened in an artery, where do you think that clot would go? Down the artery, to get stuck where it narrows, to cause an infarction. Not a very good design feature, I would argue.

So, what happens is something far cleverer. A replacement endothelial layer is created from Endothelial Progenitor Cells (EPCs). These are synthesized in the bone marrow, and float about in the bloodstream. Chemicals released, when endothelium is damaged, attract EPCs to the area of damage/blood clot.

Once they arrive they stick to the surface of any remaining clot, then they grow into fully mature endothelial cells, forming a new endothelial layer. What this means is that any remaining blood clot now sits beneath the new endothelial layer, and within the artery wall itself. It cannot now break off and get stuck somewhere else in the body.

Even more clever is the fact that EPCs have the capability, to become something other than mature endothelial cells. They can travel down another road in the developmental pathway, to become monocytes. Monocytes, in turn, mature into macrophages.

Macrophages are white blood cells whose job it is to clear up all alien materials in the body. Dead cells, invading bacteria, any damaged tissue. They squirt nitric oxide out, oxidise dead and damaged material, such as anything found in a blood clot, then engulf it, before travelling off to the lymph glands. Here, the dead, damaged and alien materials are further broken down, before excretion from the body.

Thus, with EPCs, you have the entire repair and clearance system all in one package. Some of the EPCs that arrive on the scene, form the new endothelial layer. The rest turn into monocytes, then macrophages, which clear away the remnant blood clot.

This process of repair and clearance is what I call ‘healing’. Others choose to call it inflammation, and claim it is the underlying cause of CVD. Good for them. I suspect it may not be a fertile route to travel down.

The other thing to note here is that the substance which is most intimately bonded to the exposed endothelium, at least in humans, is lipoprotein (a) (LP(a). Lipoprotein (a) is Low Density Lipoprotein (LDL) with an extra protein attached to it. A protein called apolipoprotein A. This protein is fascinating, because it has an almost identical structure to plasminogen. Identical apart from a single amino acid.

However, this difference, though very slight, is critical, because it means that TP(a) cannot have any effect on apolipoprotein A. There can be no conversion to plasmin. Thus, any blood clot, or part of the blood clot, containing Lp(a) is extremely resistant to fibrinolysis. It cannot be broken apart, and so remains attached to the artery wall, and will be a major component of the remnant blood clot that is then drawn into the artery wall – and then broken down by macrophages.

This is where Linus Pauling, Mattias Rath, vitamin C, and guinea pigs come into play. I have discussed this area before, but I am going to discuss it again…. Soon.

Before fully signing off on this blog I shall leave you with another thought, which is this. Lp(a) is identical to LDL ‘bad cholesterol’ – apart from a single attached protein – apolipoprotein A. So, if you were closely studying the contents of an atherosclerotic plaque, it would be quite easy to think you were looking at LDL, when you were actually looking at Lp(a)?

Of course, what I have done here is to describe a process of clot formation, and repair, that is probably happening all the time. The next question is obvious. When, and how, can this process become ‘abnormal?’ When, and how, does it lead to CVD?

1: http://www.nejm.org/doi/full/10.1056/NEJMoa1709118#t=article

2: https://www.ncbi.nlm.nih.gov/pubmed/8925184?log$=activity

P.S. those interested in a great deal more complexity, this paper is a belter. http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2007.02515.x/full

Here is one section that explains a great deal in a few words. ‘Recent evidence suggests that ECs [endothelial cells] in regions of disturbed flow in arteries are primed for activation (they have increased levels of NF-κB in their cytoplasm) and that systemic imbalances (e.g. associated with sepsis or cardiac risk factors) may result in the translocation of NF-κB to the nucleus and increased expression of procoagulants such as tissue factor (TF) and adhesion molecules. TM, thrombomodulin; t-PA, tissue-type plasminogen activator; EPCR, endothelial protein C receptor; TFPI, tissue factor pathway inhibitor; VWF, von Willebrand factor.’ And there, I think you have it, in a nutshell. Although I realise that most people have never heard of any of those things.

What causes heart disease part XXXVI (part thirty-six)

5th September 2017

Wipe your mind clear of all previous ideas about CVD. About as easy as standing in the corner and not thinking about a tiger. In reality, once you have read about, and talked about, and researched, and thought about anything, patterns are created in your mind. Familiar landscapes develop, and well-worn pathways become the comfortable and easy routes to travel down.

Say what you like about Ancel Keys (and I had better not, for I would end up swearing a lot), he created the tightly patrolled mental box for everyone. Diet and cholesterol and cardiovascular disease. These are the great beacons that mark out, the map of the mind, where all thinking and discussion must take place. They illuminate all, and beyond them is darkness.

Now, blow out the beacons. Move out into darkness. We shall create a new landscape of thought. We have control of the vertical, and the horizontal, you are entering the Outer Limits. [I suspect some people may not get that reference]. We are breaking free of the box. In fact, there is no box, it no longer exists.

In the distance, there is a glimmer of light… it is our first fact. At least we hope it is a fact. We approach the glittering light and scrape way the grime that has been obscuring it for many years, to reveal…

Atherosclerotic plaques only develop in larger arteries.

Quite close to it, almost hidden away, lies another fact.

Atherosclerotic plaques never develop in veins.

There are two exceptions to the second fact – well, there are more, but these are the most obvious. First, if you take a vein, and use it to create a coronary artery bypass graft, it will develop atherosclerosis very rapidly. Secondly, if you create an arteriovenous fistula AV-fistula (fusing an artery and vein together) for dialysis patients, the venous section will develop atherosclerotic plaques.

Setting aside these exceptions, these two facts were as close to inarguable as I have been able to find. Inevitably, they lead to my first question. Why do plaques develop in arteries, and not in veins? Right now, I can see you doing what everyone does, searching for a simple answer, with thoughts such as:

  • There is less oxygen in veins, and oxygenation is damaging to arterial walls
  • The pressure is less in veins
  • The LDL level is lower in veins (it’s not, but I have heard a lot of people say this)
  • Arteries and veins have a different structure (they do not).

And so on, and so forth. Isn’t the search for a quick and simple answer fun…?

After exploring almost every avenue that I believed could possibly be involved in CVD, I found myself returning more and more often to the difference in blood pressure in veins and arteries as the place where the answers were most likely to be found.

However, I knew pressure, by itself, is not going to cause anything, unless you succeed in ‘bursting’ an artery, or ‘bursting’ the lining of the artery. I mean, this can be done. You can develop an aneurysm (thinned and ballooned area) in an artery, which can then rupture – usually with catastrophic consequences.

But before that, what can pressure do? Force things carried within the artery into the artery wall behind? No, that does not make sense. For that would mean everything carried in the bloodstream would simply be blasted into all artery walls, everywhere. The smallest molecules would go first, molecules such H20 to start with. Does this happen…. No, of course not. Our arteries, and the endothelial cells that line our arteries (and veins), are not leaky.

In short, differences in pressure cannot provide any sort of an explanation.

However, there is a law of fluid dynamics which says – words to the effect – if the pressure in a tube is higher, the velocity of the fluid flowing through a tube will also be higher. Which means that blood is travelling far faster in an artery than a vein. A veritable white-water maelstrom, compared to a meandering river as it approaches the sea.

Thus, it is easy to imagine that anything lining an artery is going to be exposed to far greater ‘forces’ than anything lining a vein. These forces, which I shall call biomechanical stresses, will be particularly intense in certain places. For example, where arteries branch (bifurcate) e.g. where the carotid arteries, that supply blood to the brain, branch off (bifurcate) from the aorta.

Another place of extreme biomechanical stress is within the coronary arteries. These arteries are exposed to a unique stress, in that they are compressed with great force when the heart contracts. Some have likened this to stomping on a hose every second. Indeed, blood cannot flow in coronary arteries during systole (ventricular contraction) because they are squeezed shut.

In general, if you look at where atherosclerotic plaques develop, you find that they most often occur at maximum biomechanical stress. Where carotid arteries (main arteries supplying blood to the brain) branch from the aorta, and also where other arteries branch from the aorta, and within the coronary arteries. It seems, therefore, that biomechanical stress is required for plaques to develop. This is not the same as high blood pressure, but it is closely associated with high blood pressure.

In truth, this idea is not in any way contentious. This is a highly jargon filled section from a paper called ‘Biomechanics of Atherosclerotic Coronary Plaque: Site, Stability and In Vivo Elasticity Modelling.’

Although the coronary and peripheral systems in their entirety are exposed to the same atherogenic cells and molecules in the plasma, atherosclerotic lesions form at specific regions of the arterial tree. Such lesions appear in the vicinity of branch points, the outer wall of bifurcations and the inner wall of curves. Pathologic studies, have shown that healed plaque ruptures are predominantly in the proximal portions of the left anterior descending (LAD), right coronary (RCA), left circumflex (LCx) and left main (LM) arteries. Investigations over the last decade have elucidated both fluid mechanical and most recently structural biomechanical factors that mediated the site of plaque formation.’1

Which is all fine and sensible. However, this very same paper states the following:

‘Plaque formation is now recognized as an inflammatory process triggered by high levels of serum LDL that enter the coronary wall, encounter oxygen reactive species, and become oxidized. The oxidization, in turn, stimulates the recruitment of monocytes that convert to macrophages to phagocytize oxidized LDLs. This forms a necrotic core with recruitment of smooth muscle cells from the media to seal over the fatty core.’

That is the official party line as to how CVD starts, and develops. But if you believe that, you immediately face a conundrum. How can you reconcile the hypothesis that raised LDL entering the artery wall initiates plaque development, with the observation that atherosclerotic lesions form at specific regions of the arterial tree? It is surely one, or the other, but it cannot be both. Sorry, but at this point I need to take you back into the landscape of raised LDL and CVD.

You may think, in fact you probably are already thinking: “Well, biomechanical stress damages the endothelial cells, allowing LDL to enter.” Now, that could be true. However, if that is true, then you have (if you believe in the cholesterol hypothesis), just made a move that will result in checkmate against you.

The argument goes like this:

If LDL can only leak into the artery wall at an area where the endothelial layer is damaged, and this is where plaques develop, this means it cannot leak through in areas where the endothelium is not damaged. Ergo, the first step in the development of plaques cannot be LDL ‘leaking’ into the artery wall past the endothelium, it is damage to the endothelium. Ergo, a raised LDL level is not the primary cause of CVD. Checkmate.

You don’t like that logic? If you prefer a few more facts, using a different approach.

If you think LDL is capable of, simply, transporting itself past the endothelium, then you need to define a mechanism. Is it simply osmotic pressure, with LDL travelling down a concentration gradient from the bloodstream into the artery wall? Is it actively transported through endothelial cells? Does it leak between the endothelial cells? These are the mechanisms that I have seen most commonly proposed – although they are often presented with so much surrounding jargon that it is almost impossible to work out what is being said.

In truth, I have spent years and years trying to establish if LDL can, or cannot, move into the arterial wall, past the healthy, undamaged, endothelium. If I had been organised enough, I could have gathered together ten thousand papers saying that it can, and another ten thousand saying that it cannot.

Having torn up twenty thousand papers, on the basis of complete uselessness, I began with, what may seem a simple question, a thought experiment if you like. Why would endothelial cells allow LDL to pass through them, to then allow LDL to be oxidised in the arterial wall behind? This process serves no physiological purpose, other than to kill you from cardiovascular disease!

The idea that endothelial cells simply cannot prevent this from happening is, frankly bonkers. Cells can quite easily control the passage of single atoms/ions through their cell membranes Indeed, this is one way that all cells function. To give one example, they can pump individual sodium ions out, and individual potassium ions in, to maintain an electrical action potential. They only lose the ability to control their own internal environment, within very tight parameters, when they die.

Therefore, the idea that an endothelial cell cannot prevent a relatively massive LDL molecule from entering the side facing the bloodstream, then passing straight though, then ejecting itself out the other side, is complete nonsense. Complete… nonsense.

Indeed, it has been well established that the only way LDL can enter a cell, is for that that cell to manufacture an LDL receptor, wave it about it the bloodstream to lock onto an LDL molecule, before dragging the receptor and the LDL back inside. Ergo, LDL does not get into an endothelial cell, unless the cell wants LDL to enter. It activates complex processes to allow this to happen.

The reason why some people have very high LDL levels is because they cannot manufacture enough LDL receptors, or the LDL receptors they manufacture are faulty. A lack of LDL receptors, or faulty receptors is, of course, the underlying problem in Familial Hypercholesterolaemia(FH). Proof, if proof were truly needed, that LDL cannot force its way into cells – no matter what the concentration in the bloodstream.

In short, even a superficial understanding of how cells control the passage of atoms and molecules, leads to the inescapable conclusion that LDL cannot possibly travel straight through an endothelial cell, without the activation of complex and highly controlled cellular process.

This problem has been duly noted by those who support the LDL/cholesterol hypothesis. So, the current thinking, although I have never seen it expressed clearly, is that there must be gaps between endothelial cells, wide enough for LDL to leak past.

Again, no. The fact is that, in a healthy artery wall, with healthy endothelium, there simply are no gaps between endothelial cells. Here, from a paper entitled. ‘Endothelial Cell Junctional Adhesion Molecules.’ [jargon alert].

‘Endothelial cells line the lumen of all blood vessels and play a critical role in maintaining the barrier function of the vasculature. Sealing of the vessel wall between adjacent endothelial cells is facilitated by interactions involving junctionally expressed transmembrane proteins, including tight junctional molecules, such as members of the junctional adhesion molecule family, components of adherence junctions, such as VE-Cadherin, and other molecules, such as platelet endothelial cell adhesion molecule.’2

At the risk of simply repeating what this paper says, there are no gaps between endothelial cells. Instead, there is a highly complex structure of proteins and other molecules between each endothelial cell ensuring that nothing gets past – unless the endothelial cells are instructed to let them past. This happens with white blood cells, they can open the junctions between endothelial cells, and move into the artery wall – then out again. Clever stuff.

Of course, if most things travelling in the bloodstream had to overcome complex barriers to get past the endothelium you would die, as your blood would simply circulate round and round, struggling to exchanging nutrients back and forth with the underlying tissue. Which kind of negates the point of having a circulatory system in the first place.

Nature, in the way that nature does, noted this potential problem, and came up with a solution. As blood vessels get smaller, and smaller, the endothelium develops holes – called fenestrations. These fenestrations allow almost everything present in the blood to flow freely in and out of the surrounding tissues/organs. Red blood cells would be one exception.

Why, you could ask, would endothelial cells have fenestrations in them to allow the free passage of molecules in and out, if things can freely pass in and out of non-fenestrated, tightly bound, endothelium?

At this point, I am overwhelmed with the need to make a quick summary:

1: It is impossible for LDL to pass straight through a living endothelial cell

2: Endothelial cells are tightly bound together, and will not allow anything to pass between them.

In addition, here are a couple of other facts to consider.

The first of which is that, in the brain, the endothelium never becomes fenestrated. There are no holes, even in capillaries (the smallest blood vessels in the body). Which means nothing can move into, or be removed from the brain, that the endothelial cells do not grant passage. This barrier function is usually referred to as the blood brain barrier (BBB):

‘Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation.’ 3

To put this another way, if LDL could pass the BBB, then the brain would not need to synthesize its own cholesterol, and the brain does synthesize cholesterol within specialised glial cells. Which is further confirmation that an intact, non-fenestrated endothelium, blocks the passage of LDL.

Now here is a final fact (a final fact in this blog at least) that I would like you to ponder. Which is that large blood vessels have their own blood vessels, known as vasa vasorum. Literally, ‘blood vessels of the blood vessels’. Vasa vasorum surround and penetrate large arteries, and veins, supplying them with the required nutrients.

They are, of course, fully fenestrated (full of holes). Thus LDL, or anything else, can simply leak out of the vasa vasorum and into the artery wall if it so wishes – yes, even down a concentration gradient, if you like to think of it in this way.

Which means that there is absolutely no need for LDL, or anything else, to be absorbed through the endothelium lining the arteries, as it can get in from ‘behind’, so to speak. Which takes me back to my first question here. Why would endothelial cells transport LDL past themselves, and into the artery wall behind – if LDL can perfectly easily get into the artery wall from the vasa vasorum? This truly would be an exercise in pointlessness.

I could go on, as I have only touched upon a small part of the complexity involved here. But I hope to have given you enough food for thought. Yes, you easily can make statements such as ‘Plaque formation is now recognized as an inflammatory process triggered by high levels of serum LDL that enter the coronary wall’. Certainly, if you say it fast enough, and do not think about it, such a statement can seem reasonable.

However, if you start looking at the actual process required for LDL to travel into the arterial wall, you begin to realise that it is (with a healthy and intact endothelium) simply not possible. Or, if it is possible, it should be happening everywhere, in all arteries and veins. Not at discrete points.

At which point, you begin to realise that the cholesterol hypothesis, whilst is sounds superficially reasonable, requires mechanisms of action that just do not exist.

LDL cannot enter the arterial wall, at least not from the lumen of the artery, unless the endothelium has been damaged in some way. If you damage the endothelium, all hell breaks loose – and then we have a completely different story on our hands. One where LDL may have a role in plaque formation, or it may not, but it most certainly cannot be the primary role.

This is a conclusion that I arrived at a long time ago. Not, initially, because I set out to debunk the hypothesis. I simply wanted to understand how a raised LDL could cause atherosclerosis. ‘Because it does’, has never ever been a reply that I am happy to accept. In fact, nowadays I would translate this particular ‘because it does’ into ‘because it must.’ It must, because if LDL cannot pass through, or past, a healthy endothelium, the cholesterol hypothesis is wrong. And it can’t, so it is.

Now I have got that out of the system, I shall move on to look at what happens when you damage the endothelium. For that, logically, must be the first step in plaque formation.

1: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722860/

2: http://atvb.ahajournals.org/content/36/10/2048

3: https://www.hindawi.com/journals/cholesterol/2012/292598/

What causes heart disease part XXXV (thirty five)

19 August 2017

Having spent many years smashing everything into pieces in an attempt to work out what is going on with cardiovascular disease, I am now going to attempt the amazing feat of bringing everything together in some sort of coherent structure. I have no idea how long this may take, so please bear with me while I first set the scene by making a couple of point that need to be made.

Point One:

Explanations exist; they have existed for all time; there is always a well-known solution to every human problem — neat, plausible, and wrong.’ H.L. Mencken.

Cardiovascular disease is best seen as a process. Attempts to find the key, single, cause has created the massive multifactorial monster we see before us today. Unfortunately, the trap of searching for a/the cause seems to be hard wired into our thinking. This approach has worked well for things such as infectious diseases and suchlike, but it does not work here. I have lost track of the number of times someone has come up with the new cause of CVD, then tried to crowbar all observations to fit. Or simply dismiss contradictory evidence.

  • It’s caused by infections
  • It’s all due to vitamin C deficiency
  • It’s all due to blood sugar
  • Its’ all due to inflammation etc. etc. etc. etc. etc.

It’s…….

In truth, I was as guilty of this as everyone else. I believed that ‘stress’ was the cause, and everything could be incorporated within this factor. This is not true. Stress/strain represents one factor that is capable of causing CVD – quite an important one – but it cannot explain everything.

Whilst there obviously are ‘causes’ of cardiovascular disease, they cannot be understood in isolation from process(es). What is going on, and why, and how can things that seem to cause cardiovascular disease be fitted into these processes.

It may seem intellectually unsatisfactory to move away from a simple, single, cause model. We all want the E=MC2 moment, or the untangling of the structure of DNA moment. Eureka! That was never going to happen here, or it would already have happened. If there truly were a single cause it would have been found by now – and it hasn’t.

Point Two:

The evidence base is flawed. In part because studying complex biological systems is, in itself, very difficult to do. The number of variables involved is mind-boggling, and the number possible interactions between those variables is mind boggling to the power one trillion. If you are looking for absolute certainty…. look elsewhere.

Just to give one example of how many potential factors there are. Here is part of a paper by researchers, who looked at geomagnetic disturbance and its impact on heart attacks and strokes (Russian paper):

‘It was shown statistically that during geomagnetic disturbances the frequency of myocardial infarction and brain stroke cases increased on the average by a factor of two in comparison with quiet geomagnetic conditions. These results are close to results obtained by (Stoupel, 1999), for patients suffering with acute cardiological pathology. Our recent study (with L.Parfeonova) revealed the relation between heart ventricular ectopic activity (VEA) and geomagnetic conditions in patients with CHD. On the average 1995 episodes of VEA having on one patient within 24 hours have been revealed in patients, whose records coincided with the periods of geomagnetic storms and 1440 VEA episodes for active conditions. Minimal quantity of VEA episodes was found for unsettled condition: 394. In a quiet geomagnetic condition VEA episodes appeared more often than in periods of unsettled conditions.’1

How many researchers have taken geomagnetic disturbances into account as a potential confounding factor in their research? I would suggest, none. Yet here is a factor that can (possibly) increase the risk of CVD events by 100%.

I chose this example, almost at random, to highlight the point that this stuff is complicated, and there any many, many, uncertainties involved. Can you control any study for all factors ever found to be associated (causally or otherwise) with CVD? No, you cannot.

Alternatively, you can do what many people do. Dismiss research that seems contradictory, or just daft. I can see many people automatically seeking to dismiss a Russian study about the effect of geomagnetic disturbance on CVD on the dual grounds that is a: Russian and b: bonkers. That would be unwise.

Of course, there is the other problem that much of medical research (especially in the highly lucrative area of CVD) has been funded by the pharmaceutical industry, resulting in the problem that most research findings are false:

‘There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias.2

This is a famous paper, one of the most cited and read in medical research history. It was written in 2005 and things have got worse, not better, since then.

Oh, but of course, peer review keeps everything on the straight and narrow:

‘The mistake, of course, it to have thought that peer review was more than a crude means of discovering the acceptability – not the validity – of a new finding. Editors and scientists alike insist on the pivotal importance of peer review. We portray peer review to the public as a quasi-sacred process that helps to make science our most objective truth teller. But we know that the system of peer review is biased, unjust, unaccountable, incomplete, easily fixed, often insulting, usually ignorant, occasionally foolish, and frequently wrong.’ Richard Horton, editor of the Lancet.

In this morass, where does one turn?

This is a question that has no definitive answer. Shall I just choose evidence that suits my argument, and dismiss all else? To an extent, the difficulty in disentangling evidence was my spur to write the book Doctoring Data. In it, I attempted to determine what is valid and what is not. How to spot the biases and errors. How to know what it true, from the other stuff?

Answer… it cannot be done. Not for certain. Whatever evidence I choose, it can be criticised – in one way or another. Did the study I am quoting control for geomagnetic disturbance or not? As a general rule, any study – and I mean any study – can be pulled apart and dismissed, if you so wish. Which could leave most of what I do as a smoking ruin.

However, most of the research I look at has one major advantage. There is not much, if any, financial interest, behind it. Other than suppressing it, I suppose.

Yes, of course, I bring certain biases to the discussion. I am almost entirely anti-statin. I am not a great believer in blood pressure lowering – at least not at current levels. I do not believe in the cholesterol hypothesis and I think that the anti-saturated fat dogma is completely bonkers and has no evidence to support it – at all. I believe that salt is good for and, in most people, protects against CVD.

I believe that a high carbohydrate low fat diet is utterly bonkers – especially in those with diabetes. And suchlike. In short, I believe that almost everything we are told is good for you, is bad for you, and vice-versa. With the exception of smoking (bad) and exercise (good).

Having got that out of my system. Let us begin….. in the next blog.

1: http://adsabs.harvard.edu/abs/2014cosp…40E1114G

2: http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0020124

What causes heart disease part XXXIII

29th July 2017

Viagra…. again

When I began this long and winding series on cardiovascular disease (CVD) I already knew a few things that I thought were critically important to the processes underlying CVD.

The first was that, in order to get atherosclerotic plaques started, you needed to damage the endothelium in some way [the endothelium being the layer of cells lining blood vessels]. The second was that blood clot formation was the next key event – thrombogenesis.

Therefore, if you could protect the endothelium and/or stop blood clots from forming, you would most likely see some significant benefits on the risk of CVD. Mainstream medicine is fully in agreement that drugs that reduce the risk of blood clotting will usually have some benefit on CVD risk. Drugs such as aspirin and Clopidogrel – and suchlike.

In addition, most of the acute management of strokes and heart attacks is focussed on getting rid of the blood clot causing the acute event. We have clot busters and stents and other interventions to remove, squash, blow apart and bypass the clot. I often describe interventional cardiologists as ‘blood clot managers’ – obviously not to their faces. They like to think it is all far more cleverer than that.

In short, the importance of blood clotting in CVD is beyond any dispute. Which is why CVD sometimes sits under the umbrella term of ‘atherothrombosis.’

However, the role of the endothelium garners far less attention. If it is ever mentioned, it is towards the end of the process of atherosclerotic plaque development, where it has been noted that in advanced plaques the endothelium is often completely missing. Or if not missing, significantly dysfunctional.

The reason for this, never openly stated, is that to promote the idea that atherosclerotic plaques start with endothelial dysfunction, completely undermines the cholesterol hypothesis. The current hypothesis is that low density lipoprotein (LDL) a.k.a. ‘bad cholesterol’ leaks past/through the endothelium, and into the arterial wall behind.

This in turn triggers the inflammatory processes that creates the plaque (I am paraphrasing madly here). Once the plaque has grown to sufficient size, the overlying endothelium is: weakened, damaged, dysfunctional – choose the word you like best, or add your own. This, in turn makes it more likely that a blood clot will form, as a dysfunctional endothelium no longer represent a powerful anti-coagulant surface, which in my mind I like to think of as a brand new ‘Teflon non-stick frying pan.’

However, if you believe that endothelial dysfunction is the first step, then an entirely different process opens. One that goes like this: The endothelium is damaged/dysfunctional, so a clot forms at that point. The clot is then drawn into the arterial wall and becomes the core of an atherosclerotic plaque which can then grow through repeated blood clots forming at the same point.

This, as I think I have explained many times, fits all the observed phenomena far better than the current cholesterol hypothesis. However, it does knock LDL off its perch as the key factor causing CVD. It can only have a bit part, amongst many other players, in this particular game.

Currently whilst all other conjectures on CVD are allowed to change shape, and swirl around in a massive multifactorial dance, one idea lies beyond challenge, which is that LDL is the conductor, the key player, the factor without which nothing else happens:

Three Rings for the Elven-kings under the sky,
Seven for the Dwarf-lords in their halls of stone,
Nine for Mortal Men doomed to die,
LDL for the Dark Lord on his dark throne
In the Land of Mordor where the Shadows lie.
LDL to rule them all, LDL to find them,
LDL to bring them all and in the darkness bind them
In the Land of Mordor where the Shadows lie.

 

Or something of the sort.

Currently, it is certainly true that the dark lord rules Mordor, and the ever-seeing eye seeks out all those who criticise the cholesterol hypothesis. Here, for example, is a recent missive from Mordor:

Statin Denial: An Internet-Driven Cult With Deadly Consequences (Editorial JAMA 25th July 2017)

‘We are losing the battle for the hearts and minds of our patients to websites developed by people with little or no scientific expertise, who often peddle ‘natural’ or ‘drug-free’ remedies for elevated cholesterol levels,” adds Steven Nissen. This “Internet-driven cult” denies statins’ benefits and whips up fears of side effects, then profits from the resulting confusion by peddling snake oil.’1

I think I need to shout ‘House’ at this point. Nissen has manage to get in the full set of insults. ‘Denier’, ‘cult’, ‘deadly’, ‘whips up’, ‘fears’, ‘profit from selling snake oil’. What’s missing. Mass murderers…child killers.

Would this be the same Steven Nissen who stated the following, when the new cholesterol guidelines came out in 2013:

“The science was never there for the LDL targets.’ He said. ‘Past committees made them up out of thin air.’ He added.”2 Make your mind up Steven. Either there should be LDL targets or not.

Where was I. Oh yes, just explaining that anyone who dares criticize the cholesterol hypothesis – which is basically interchangeable with statin worship – can find themselves under significant attack. As you can imagine, those working in mainstream research are going to make sure they never do such a silly thing. Grants have a nasty habit of drying up. Tenure can be whipped from under your feet at any time. Do not attract the interest of the ever-seeing eye, my precious.

However, facts have this nasty habit of coming along that cannot be fitted within the LDL hypothesis, and are completely supportive of the ‘endothelial damage/clotting’ hypothesis. A few blogs ago I wrote of a study demonstrating that men with diabetes, who used Viagra, or other PDE5 inhibitors e.g. Cialis, were far less likely to die from CVD.

We know that Viagra/sildenafil has, as a primary mode of action, increasing nitric oxide synthesis in endothelial cells. This is how it maintains erections in erectile dysfunction. It also reduces blood pressure, particularly reducing blood pressure in the lungs. Nitric oxide is also the most powerful anti-coagulant agent known to man. Furthermore, it protects the endothelium from damage, and stimulates the production of endothelial progenitor cells in the bone marrow.

What effect does it have on LDL? None.

What effect does it have on cardiovascular and overall mortality? Well, very recently I was sent this paper: ‘Association between treatment for erectile dysfunction and death or cardiovascular outcomes after myocardial infarction.’

This was a study on over forty-three thousand men over a six-year period, who had previously had a myocardial infarction (MI). Just over forty thousand did not have medication dispensed for erectile dysfunction (ED) (40,077), three thousand did (3,068). They were split into three groups: lowest number of ED scripts, medium and highest number.3

For the sake of brevity here I am just looking at the highest script group.

 

 

Well, well, well. Perhaps a couple of other well, wells for luck.

Yes, this study was observational. Yes, this means that other factors that may be at play. For example, those men requesting Viagra and other PDE5 inhibitors, may have been healthier than those who did not. But it is hard to believe they were over five times as healthy. The simple fact is that, when you see an effect as massive as this, it can generally be considered that you are looking at a causal relationship.

To put it another way, this is 81% relative risk reduction in overall mortality. Compare this with statins, in secondary prevention (using best figures possible), statins achieved a 15% relative risk reduction in overall mortality. But statins lower cholesterol levels…right? That is how they work…right? So, LDL does have an impact?

Well, it is of course true that statins lower the LDL level. However, they also do some other things as well. Now, in general I am not a great fan of animal studies. However, I am just presenting one study, done on atorvastatin, looking at the impact on many factors (including NO synthesis) that have nothing whatsoever to do with LDL lowering.

The study was called:

Atorvastatin enhanced nitric oxide release and reduced blood pressure, nitroxidative stress and RANTES levels in hypertensive rats with diabetes.’

A quick summary:

  • Atorvastatin had no effect on blood glucose or cholesterol levels
  • Blood pressure was reduced by 21% (in diabetic rats)
  • RANTES levels were reduced by 50% (RANTES is a ‘chemokine’ associated with endothelial damage)
  • Nitric Oxide (NO) was increased
  • ONOO (peroxynitrate) was decreased. (ONOO is a potent inhibitor of NO).

Summary: ‘These findings provide insights into mechanisms of restoration of endothelial function and vascular protection by atorvastatin in diabetes and hypertension.’ 4

When statins first emerged, they swept all before them. Included the discussion on what causes CVD. Cholesterol skeptics, such as, Professor Michael Oliver, were completely bowled over, and admitted they had been wrong, when statins were shown to lower CVD risk (the true magnitude of the benefits was massively over-hyped, but that is a discussion for another day).

Statins were designed to lower LDL/cholesterol and lower CVD risk and they did. End of argument.

Well, perhaps not quite.

If you decide to look more closely at the process of CVD, and more closely as the actions of statins, a different picture emerges. One which fully supports endothelial damage as the first step in plaque formation. Because statins do many more things than LDL lowering. It could be said that statins are simply the poor man’s Viagra (other PDE5 inhibitors are available).

 

1: http://www.latimes.com/science/sciencenow/la-sci-sn-statin-denial-20170724-story.html

2: http://www.nytimes.com/2013/11/13/health/new-guidelines-redefine-use-of-statins.html

3: https://www.ncbi.nlm.nih.gov/pubmed/14692706

4: https://www.ncbi.nlm.nih.gov/pubmed/25716966

What causes heart disease – part XXX

Inflammation – or not

Over the last few years there has been a significant shift, from many researchers, towards the idea that atherosclerosis is an inflammatory process, to a greater or lesser extent. Below is a quote from a cardiac surgeon. A man who admits he was wrong about cholesterol being the main underlying cause CVD, so I can applaud him for that. He goes on to say:

‘Simply stated, without inflammation being present in the body, there is no way that cholesterol would accumulate in the wall of the blood vessel and cause heart disease and strokes. Without inflammation, cholesterol would move freely throughout the body as nature intended. It is inflammation that causes cholesterol to become trapped.

Inflammation is not complicated — it is quite simply your body’s natural defence to a foreign invader such as a bacteria, toxin or virus. The cycle of inflammation is perfect in how it protects your body from these bacterial and viral invaders. However, if we chronically expose the body to injury by toxins or foods the human body was never designed to process, a condition occurs called chronic inflammation. Chronic inflammation is just as harmful as acute inflammation is beneficial.’1

And so on and so forth. More recently, a friend and fellow cholesterol sceptic, Aseem Malhotra, was lead author on an article in the British Journal of Sports Medicine entitled: ‘Saturated fat does not clog the arteries: coronary heart disease is a chronic inflammatory condition, the risk of which can be effectively reduced from healthy lifestyle interventions.’

A major statin study called JUPITER, was designed to look at lowering C-reactive protein with rosuvastatin, to see if this would lower the risk of CVD – in those with low or normal cholesterol levels. C-reactive protein (CRP) is a non-specific marker of inflammation. To quote the lead investigator:

The recent JUPITER trial demonstrated that potent statin therapy reduces by 50 % the risk of heart attack and stroke among men and women with low levels of low-density lipoprotein (LDL)-cholesterol who are at increased vascular risk due to elevated levels of C-reactive protein (CRP), a biomarker of low-grade systemic inflammation. In JUPITER, both absolute risk and the absolute risk reduction with statin therapy were related to the level of CRP, whereas no such relationship was observed for LDL-C.’2

I could find another ten thousand papers all stating that CVD is caused by inflammation. Case proven? Well, the case is certainly proven, beyond doubt, that atherosclerosis is strongly associated with inflammation in the arterial wall. To which my response would be… and so what exactly?

If you twist your ankle, and tear ligaments, you will also find a great deal of inflammation in the surrounding area. You would, however, be stretching reality to suggest inflammation is the underlying cause of ankle ligament damage. I suppose you could try.

In my simple little world, inflammation is a result of underlying damage. It is not, and cannot be the underlying cause. Inflammation is a manifestation of the body attempting to heal itself. In fact, whenever I see the word inflammation, I mentally replace it with the word ‘healing.’ For many years I have smiled enigmatically at the widely accepted advice following a badly sprained ankle. RICE (Rest, Ice, Compression, Elevation). These are all ways of reducing inflammation, sorry, healing.

Just looking at the ‘I’ in RICE. Ice:

Ice works by decreasing the blood flow to an area, thus temporarily diminishing the swelling and inflammation that accompanies most injuries —- (when the tissue re-warms … the inflammatory process resumes). But in the 1970s we knew very little about the healing process.   We did not understand that inflammation is actually a very important initiating event of the overall healing process.

When you are injured, the blood vessels to the area dilate. That causes the swelling and warmth you notice. The increase in blood flow brings with it very potent chemicals, proteins and cells.   Those chemicals and cells set off a cascade of reactions that we refer to as inflammation. More importantly, this is also what initiates the HEALING process.   Yes, inflammation is a necessary part of the healing process. The inflammation chemicals send a message to other cells to come to the injured area… they also wake up sleeping or dormant cells already residing in the area of the injury. Those cells in turn start to repair the ligament, muscle or skin at the site of injury.’3

Finally, conventional sports medicine catches up with Chinese traumatology. In Chinese medicine, we NEVER recommend ice for injuries. Simple physics will tell you that ice applications will constrict blood vessels which will reduce blood flow to the injury, meaning less waste products removed and less nutrition delivered therefore slower healing.’4

I say, reduce inflammation at your peril. You may reduce the swelling, and some of the bruising, and things will certainly look less ‘damaged’. But, again, so what. Two billion years of evolution have created some pretty effective healing processes, which we also call inflammation. Interfere with inflammation, and the results are predictable.

The most powerful anti-inflammatory agents known to man are corticosteroids, so called as they are all synthesized around the base compound, cortisol (a corticosteroid). Medically they are used in a number of auto-immune/inflammatory conditions, ranging from rheumatoid arthritis, ulcerative colitis, eczema, lupus, transplant organ rejection and suchlike [Asthma is a bit different].

In these conditions, there is a rationale for reducing inflammation. Here, we have the body ‘seeing’ various proteins as alien, and attacking them, through an ‘auto-immune’ response. Yes, there is inflammation. However, this is not the body trying to repair itself. This is the immune system causing damage, by attacking the body itself, with resulting inflammation. In short, do not confuse inflammation with inflammation.

However, if inflammation were the underlying cause of CVD, then corticosteroids should reduce the risk of CVD, as they are the most potent anti-inflammatories known to man. But they very much do not. A paper was published recently, called ‘Can machine-learning improve cardiovascular risk prediction using routine clinical data?’ A fascinating paper indeed. The purpose was, as follows:

‘Current approaches to predict cardiovascular risk fail to identify many people who would benefit from preventive treatment, while others receive unnecessary intervention. Machine-learning offers opportunity to improve accuracy by exploiting complex interactions between risk factors. We assessed whether machine-learning can improve cardiovascular risk prediction.’

I have not written about this paper before, although it identified LDL as completely irrelevant in predicting CVD risk, and the risks it did identify were almost completely different from those in the current risk calculators. In fact, the number one risk factor of cardiovascular risk was Chronic Obstructive Pulmonary Disease (COPD). I have never seen this on any risk calculator before, and I am trying to digest the implications.

However, getting back on track, the main point of interest here is looking at number three on the list of factors that can increase CVD risk:

Oral corticosteroid prescribed

At number eight:

Immunosuppressant prescribed

Immunosuppressants are also designed, effectively, to impair the inflammatory response. They are used in much the same sort of conditions as steroids. In fact, corticosteroids could also be termed immunosuppressants.

The highly damaging effect of corticosteroids, or other drugs designed to suppress the immune response, should not really come as any surprise. There is a medical condition called Cushing’s disease, in which too much cortisol is produced by the adrenal glands. The impact of Cushing’s disease on CVD is to increase the risk by, at least, 500%. 5

Other anti-inflammatory drugs have similar, if less spectacular effects, on CVD risk. The FDA recently increased the warning level on non-steroidal anti-inflammatory drugs (NSAIDs). Drugs such as ibuprofen, naproxen, diclofenac.

The FDA is strengthening an earlier warning about the cardiovascular safety of non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), both prescription and non-prescription, the agency said Thursday. After a comprehensive review of new safety information, the FDA is requiring updates to the labels of all prescription NSAIDs to reflect recent information on risk of heart attack and stroke. Over-the-counter non-aspirin NSAIDs already contain some safety information, but the labels on these drugs will also require an update, said the FDA in its announcement posted online.

The new labels for prescription NSAIDs should contain the following information, according to the FDA:

  • The risk of heart attack can occur within weeks of starting an NSAID, and that risk may increase with longer use.
  • The risk seems to be higher at higher doses.
  • It’s not clear if the risk of heart attack and stroke is the same for all NSAIDs.
  • The drugs can raise the risk of heart attack or stroke in both patients with a risk of heart disease and patients without.
  • Patients with heart disease or risk factors for it are at a greater risk of heart attack or stroke following the use of NSAIDs, because they have a higher risk at baseline.
  • There is also an increased risk of heart failure for patients using NSAIDs.6

Of course, it can be argued, and it has, that steroids and non-steroidal anti-inflammatory agents have other potentially damaging effects on the CVD. Whilst this is undoubtedly true (to an extent), you would still not expect agents that are, primarily, anti-inflammatory, to vastly increase the risk of CVD. If CVD is an inflammatory disease.

Personally, think that the science here has been done. Agents designed to reduced inflammation all greatly increase the risk of CVD – from moderately to spectacularly*. Thus, whilst it is true that you can find inflammation within arteries where atherosclerosis is developing, this DOES NOT mean that the inflammation is causing the problem.

What you are seeing is the body trying to heal damage, and then getting cause and effect twisted through one hundred and eighty degrees. ‘That’s looks abnormal, let’s get rid of it’. A pretty good summary of a great deal of medical research over the last few hundred years, I suppose.

 

1: https://www.sott.net/article/242516-Heart-surgeon-speaks-out-on-what-really-causes-heart-disease

2: https://www.ncbi.nlm.nih.gov/pubmed/23225175

3: http://www.howardluksmd.com/orthopedic-social-media/ice-ice/

4: http://www.drmirkin.com/fitness/why-ice-delays-recovery.html

5: https://www.ncbi.nlm.nih.gov/pubmed/8187313

6: https://www.medpagetoday.com/publichealthpolicy/fdageneral/52530

*aspirin is the exception. However, aspirin has strong anti-coagulant effects. It stops platelets sticking together. In this way, the anti-coagulant effects of aspirin, outweigh the damaging anti-inflammatory effect.

What causes heart disease part XXIX, part B.

Alcohol – an update

My last blog on alcohol caused somewhat of a stir, as I suspected it would. To those who did not read it, I recommended that, from a cardiovascular health point of view, those who do not drink alcohol should start. I recommended this because there is strong evidence that moderate alcohol consumption significantly reduces the risk of cardiovascular disease – and can also reduce overall mortality/increase life expectancy.

There were many objections, scientific and, in some ways, moral. Because of this, I felt the need to go over the area again, which is a bit unusual for me. I think there were three main objections that were raised:

1) People who do not drink are not drinking because they have illnesses that have stopped them drinking, therefore they are less healthy than moderate drinkers to begin with. Ergo, you are not comparing apples with apples.

2) None of the studies have been randomised controlled studies, they are purely observational.

3) If people who do not drink, are advised to start drinking, a proportion of them will end up drinking too much and will damage their health.

1) People who do not drink are not drinking because they have illnesses that have stopped them drinking, therefore they are less healthy than moderate drinkers.

This is probably the easiest objection to refute. The massive one million patient study in the BMJ, that I quoted in my previous blog, looked at this potential confouder1. By which I mean that the researchers took care to separate out those who had drunk previously, from those who had never drunk.

Whilst the BMJ study looked at all sorts of outcomes, I shall restrict myself to two here. The ones that are most important. Namely, fatal cardiovascular disease (CVD), and all-cause mortality.

Increased risk of fatal CVD vs. moderate drinking

  • Non-drinker = 1.32 (32% increased risk)
  • Former drinker = 1.44 (44% increased risk)

Increase risk of all-cause mortality vs. moderate drinking

  • Non-drinker = 1.24 (24% increased risk)
  • Former drinker = 1.38 (38% increased risk)

As you can see, there is some merit to the argument that former drinkers are less healthy than never drinkers. However, if you remove former drinkers from the equation, non-drinkers remain at a significantly increased risk of CVD, and overall mortality, compared to moderate drinkers.

2) None of the studies have been randomised controlled studies, they are purely observational.

I cannot really argue too powerfully against this objection, for it is true. No-one has, to the best of my knowledge, taken a large number of people and split them into two groups. One to drink alcohol, the other to abstain. Then, after ten years or so, find out which group did better. I should point that that whilst such a trial could be randomised, and controlled, there is no way it could be placebo controlled, or double blinded (double blinded means that neither the participant or the researcher would know if the participant was, or was not, drinking alcohol). Thus, no perfect trial could ever be done.

The reality is that, in medicine and medical research you just have to roll with what you have got. In recent years, I have seen a growth in a research fundamentalist belief, which is that the only way you can ever prove anything is through a randomised placebo controlled double blind study, with tens of thousands of people in each arm.

I find this somewhat strange, and more than slightly strange. The vast, vast, majority of things that are done in medicine, have no randomised controlled studies to support. Do you think penicillin was subjected to a controlled study before it was used? Um, no. Do you think hip replacements have ever been studied in a randomised controlled trial? Um, no. Do you think breast cancer screening has ever had a single randomised controlled study? Coronary artery bypass grafts, Um, no. Almost any surgical intervention you think of. Um, no. Vaccines. Um, no.

I could keep going on for a long, long, long time on the interventions that are widely accepted, which have far less evidence to support them, than the benefits of moderate alcohol consumption. I worked with the European Society of Cardiology (ESC) at one time, to develop their educational website. By our estimate, around 13% of cardiology interventions had any evidence at all to support them (let alone randomised controlled studies). This statistic may have improved, but I doubt it.

Much of practice was defined by ‘expert consensus’. Which I also call ‘Eminence Based Medicine’.

My view is that, to dismiss all evidence that does not fit into the ‘gold standard’ of placebo controlled randomised double blind study is easy – of course. But if you are going to do this, you would have to also dismiss all the evidence on smoking and lung cancer – for example.

Certain things will never, can never, be studied in randomised controlled studies. So, we must look at best possible evidence, and make decisions based on that. Otherwise what are we to do? We can chuck all antibiotics, and vaccines, into the dustbin for starters.

3) If people who do not drink, start drinking, a proportion of them will end up drinking too much and damaging their health.

This last point is clearly the most difficult to argue against. What if I do advise people to start drinking and a significant proportion become alcoholics. Will I not have done great harm? Well, of course, this is not impossible. However, I consider it highly unlikely, because non-drinkers are almost certainly a very different group of people from already drinkers. Probably highly health conscious and well controlled people.

To be frank, I suspect many non-drinkers do not drink for moral and religious reasons, and would not start drinking even if the evidence for benefit was utterly overwhelming. [Nor would I expect them to, some things are not up for discussion].

There is also the counterargument that if many were to benefit from moderate drinking, this would counterbalance the possible harm of a smaller number becoming alcoholics. The greater benefit for the greater number? Yes, I know, this is one definition of fascism, but hey…

I shall move to the example of sunbathing here. Yes, it is true that sun exposure can cause various skin cancers (probably not malignant melanoma). Doctors urge everyone to avoid the sun, almost at any cost. In doing so, we will prevent a certain amount of skin damage, and certain skin cancers. This is, of course, good.

However, as a study from Sweden demonstrated, the trade-off is that you are far more likely to die from CVD, and you will also reduce your life expectancy by about the same amount as if you smoke ‘Avoidance of sun exposure as a risk factor for major causes of death: a competing risk analysis of the Melanoma in Southern Sweden cohort.’

OBJECTIVE:

Women with active sunlight exposure habits experience a lower mortality rate than women who avoid sun exposure; however, they are at an increased risk of skin cancer. We aimed to explore the differences in main causes of death according to sun exposure.

METHODS:

We assessed the differences in sun exposure as a risk factor for all-cause mortality in a competing risk scenario for 29,518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 (aged 25-64 years at the start of the study). We obtained detailed information at baseline on sun exposure habits and potential confounders. The data were analysed using modern survival statistics.

RESULTS:

Women with active sun exposure habits were mainly at a lower risk of cardiovascular disease (CVD) and non-cancer/non-CVD death as compared to those who avoided sun exposure. As a result of their increased survival, the relative contribution of cancer death increased in these women. Non-smokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group, indicating that avoidance of sun exposure is a risk factor for death of a similar magnitude as smoking. Compared to the highest sun exposure group, life expectancy of avoiders of sun exposure was reduced by 0.6-2.1 years.

CONCLUSION:

The longer life expectancy amongst women with active sun exposure habits was related to a decrease in CVD and non-cancer/non-CVD mortality, causing the relative contribution of death due to cancer to increase.2

Why do medics write in such a convoluted way? Is there a course on ‘complete obfuscation of the reader’ that I missed somewhere along the line? Anyway, the point here is that sun exposure meant you very significantly avoid CVD death and live longer (good). But, if you die, you have more chance of dying of cancer (bad?). Of course, if you reduce death from CVD you will, by default, increase the risk of dying of cancer – well you have to die of something. Less of A means more of B.

As a cardiologist once said to me. ‘My job is to keep people alive for long enough for them to die of cancer.’ Sorry, but I do love black humour.

The general point here is that you must look at the greatest benefit to the greatest number. Could I tell a lot of people to avoid drinking alcohol because some people may, I repeat may, turn into alcoholics.

I shall leave you with a quote from an article ‘Ethanol and cardiovascular diseases: epidemiological, biochemical and clinical aspects.’

Conclusion: to drink or not to drink?

‘It is not easy to answer this Hamlet’s question, because alcohol consumption is like a razor-sharp double-edged sword. Current guidelines of the American Heart Association (AHA) state that moderate alcohol consumption is beneficial for cardiovascular health, but the AHA clearly states that non-drinkers should not begin drinking alcohol in middle age due to possible counter-balancing ill consequences of alcohol consumption. Before the definitive decision prospective randomized blinded trials would be important: engage a large pool of non-drinkers, half of whom would commence a moderate drinking regimen, whilst the other half remained abstainers.

The two groups would be followed for years in a search for eventual differences in cardiovascular disease and heart-related deaths. First possible data were available in 2008. King et al observed that of 7697 participants who had no history of cardiovascular disease and were non-drinkers at baseline 6.0% began moderate alcohol consumption and 0.4% began heavier drinking.

After 4 years, new moderate drinkers had a 38% lower chance of developing CVD than did their persistently nondrinking counterparts. Those who began drinking moderately experience a relatively prompt benefit of lower rate of CVD morbidity with no change in mortality rates after 4 years. The collected data make a strong case of the cardiac benefit of controlled drinking.’3

Thank you and cheers. Not that I expect I will have convinced anyone who objected to my last article.

 

1: http://www.bmj.com/content/356/bmj.j909

2: https://www.ncbi.nlm.nih.gov/pubmed/26992108

3: Ginter E, Simko V. ‘Ethanol and cardiovascular disease: epidemiological biochemical and clinical aspects.’ Bratisl Lek Listy 2008: 109(12) 590-4

What causes heart disease – part XXIX

Alcohol

Many moons ago when I wrote The Great Cholesterol Con I provided a very short section at the end on what people should do, to avoid heart disease. It went something like this:

1: Do not smoke cigarettes (to which I would now add  – or anything else).

2: Take exercise – that you enjoy. Don’t try to drive yourself into the ground. Walking outside is particularly good, especially on a sunny day.

3: If you don’t drink alcohol, start. If you do drink, drink regularly – don’t binge drink – and make sure that you enjoy what you drink. Drink with friends, drink sociably, don’t drink to get drunk.

4: If you hate your job, get another one – don’t feel trapped.

5: Make a new friend, join a club, find an area of life that you enjoy. Praise other people and try to compliment other people more often.

6: Look forward to something enjoyable every day, every month, and longer term.

Not a very long list I admit, and even at the time I was aware that there were other things that could be done. However, I was reluctant to write yet another ‘ten ways to stop heart disease completely – forever (money back if you die)’ type of book. My sister was critical of my ‘advice free’ book. ‘People want to be told what to do.’was her terse comment. She is good at terse.

My view was that advice should be accepted by the bucketful, but only given out by the thimbleful. People need, I replied with the utmost pomposity, to make their own decisions about what to do with their lives, and not keep looking for some fluffed up latter day prophet to guide them. Not giving direct advice has the added advantage that you won’t get sued, or lose your license to practice medicine. Or at least, it makes it far less likely.

However, in my long and winding series on what causes heart disease I have popped in a few bits of advice along the way. In this particular blog, I am returning to my Great Cholesterol Con advice on alcohol. Whilst writing that book I had noticed, and have continued to notice, that moderate alcohol consumption is associated with a lower risk of dying of cardiovascular disease (CVD). Also, that non-drinkers generally have the shortest life expectancy. In short, if you don’t drink, start drinking.

The rest of the medical profession absolutely hates this message. At heart, you see, most of them are secret puritans. The idea that doing something enjoyable, might also be good for you, is just too much to bear.

“Puritanism: The haunting fear that someone, somewhere, may be happy.” H.L. Mencken

Which means that the medical profession have done their best to attack any evidence that alcohol may be good for you. The most common argument used to dismiss the fact that non-drinkers have the shortest life expectancy, is that they have some underlying illness that stops them drinking. It is the underlying illness that then causes them to die, and not the fact that they do not drink.

There are ongoing debates about the role of combining different types of current non-drinkers in producing this apparent protective effect (of moderate drinking). Specifically, former or occasional drinkers might have reduced or ceased drinking because of ill health, making the aggregated non-drinking group artificially seem to have a higher risk of cardiovascular disease and mortality.’1

Or maybe not.

You may recognise the exact same argument used on cholesterol levels. In general, those with the lowest cholesterol levels also have the shortest lifespan. A phenomenon noted in almost all long-term studies. This, we are told, is absolutely and certainly NOT because a low cholesterol level is harmful. It is because an underlying illness lowers cholesterol levels and it is the underlying illness that kills people– not the low cholesterol levels themselves. Good try (no evidence).

The irony, of course, is that this would seem to be the perfect illustration of the fact that a low cholesterol level is caused by ill health, and not a sign of good health. Or to put this another way, if a low cholesterol level is caused by an underlying illness, that kills you, then a low cholesterol level can hardly be considered something to be striven for. Can it? (See under PSCK-9 inhibitors increasing overall mortality.)

At present our glorious cardiovascular experts are happy to inform us, in all seriousness, that a low cholesterol level can be both a sign of underlying illness, and a cause of good cardiovascular health.  Or, to put it another way, the cholesterol level can be both an effect of illness and a cause of illness. That’s the problem with logic. Misuse it, and it will come around and bite you on the bum.

Anyway, returning to alcohol. Is there any evidence that people who do not drink, do so because they are suffering from an underlying illness? No, there is not. Or, if there is I have never seen it. It is just a meme which, because it fits with firmly held underlying prejudices, has become accepted as a fact.

Actually, when it comes to prejudices, my own is that alcohol – as a chemical – is not protective against CVD. It is protective because in the various forms that humans drink it, it is relaxing, reduces stress/strain, and when it is drunk in company it is part of a lifestyle that is protective. In short, if you are looking for CVD protection, you would be best not to stir sixteen grams of pure alcohol into a beaker containing two hundred mls of water, then consume every morning before breakfast. [Two units].

Far better to uncork a bottle of red wine, (white wine, what is all that about?) thirty minutes before a nice home cooked meal. Then pour it lovingly into a glass, swirl it around a bit, then enjoy. If you can also do this outside, looking over a sapphire blue bay, with boats bobbing in a light breeze, so much the better. [This was never really an option whilst growing up in Scotland.]

In short, I do not believe drinking alcohol is a true ‘drug’ effect. The lifestyle around drinking has a major part to play. However, I may be wrong. Researchers have studied the effects of different types of drink on factors that I consider key for CVD. Endothelial function, and blood clotting factors. It seems that red wine, and beer are the most beneficial.

Here, from a paper entitled: ‘Acute effects of different alcoholic beverages on vascular endothelium, inflammatory markers and thrombosis fibrinolysis system.’

CONCLUSIONS:

‘Acute consumption of red wine or beer improves endothelial function and decreases vWF levels, suggesting that the type of beverage may differently affect endothelial function and thrombosis/fibrinolysis system in healthy adults.’2

vWF is von Willibrand Factor, something I have written about in the past. Research has demonstrated that people with low vWF levels are up to 60% less likely to die from CVD. vWF tends to make platelets sticky and more likely to cause blood clots. Alcohol consumption also considerably reduces fibrinogen levels, a key clotting factor, at all levels of drinking.

However, if you drink a great deal, the effects can reverse. You also get a sharp rebound in some clotting factors. Heavy drinking appears to increase tissue factor (THE key clotting factor), factor VII, and other pro-clotting factors such as plasminogen activator inhibitor 1 (PAI-1). 3

Clearly, therefore, there does seem to be a ‘therapeutic window’ for alcohol consumption. An amount of drinking where the benefits are greater than the potential harms. Actually, I hate writing the words ‘therapeutic window’ alongside ‘alcohol consumption’. To me, this turns the act of drinking alcohol into a dull and joyless disease prevention activity

Viewing alcohol as some form of drug completely misses the point that there is, I strongly believe, ‘happy’ drinking and ‘unhappy’ drinking. How you drink, is a least as important as how much. I make this point with great confidence despite having no evidence at all to support the statement.

However, if you want to treat drinking alcohol as something like taking a vitamin tablet, or a daily aspirin, then I suppose you can. And good luck with that. You would be like a relative of mine who had been persuaded that drinking red wine was particularly heart healthy. He drank one point five, standard, glasses of red wine every evening with his meal.  Not a drop more, not a drop less.

I have no idea if he enjoyed the red wine or not. He was not the sort of man to share that sort of information. He was more of a ‘life is to be endured, not enjoyed’, sort of a man. Still, with his meticulous wine drinking regimen, he remained alive for twenty-five years after a massive, nearly fatal heart attack. So, maybe he was right – and I am wrong.

Anyway, the main reason for writing this blog is that, just before I went on holiday, I noticed that there had been a massive study done on the effect of drinking alcohol on CVD, published in BMJ open. It had the snappy title:

‘Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records.’4

Ah, the poetry, the emotional power of it all. Why do researchers feel they must use such emotionally crippled language, the dreaded passive voice? Of course, I know the reason, they won’t get published if they dare use an active verb, or a personal pronoun. ‘I did this.’ Is not a phrase you will ever see in a research paper. More’s the pity. Language and emotion are closely linked, but attempting to use only the most stripped out passive language does not add scientific accuracy, it just makes it very, very, very, dull to read.

Back to the paper itself. It was, of course, observational. However, it was very big. They looked at 1,937, 360 people. And there were 114,859 cardiovascular events, of various sorts. From heart attacks, to strokes, to a first heart failure diagnosis. It also included something that I have not really come across before ‘unheralded coronary death.’ Which means, I presume, dropping dead of a heart attack without any prior diagnosis of heart disease, or any kind.

The results that I was most interested in were the following. The comparison between non-drinkers and moderate drinkers.

Non-drinking was associated with

  • 33% increased risk of unstable angina
  • 32% increased risk of myocardial infarction (heart attack)
  • 56% increased risk of unheralded coronary death
  • 24% increase risk of heart failure
  • 12% increased risk of ischaemic stroke
  • 22% increased risk of peripheral arterial disease
  • 32% increased risk of abdominal aortic aneurysm

Interestingly, these increased risks were very similar in heavy drinkers: Heavy drinking (exceeding guidelines) was associated with

  • 21% increased risk of unheralded coronary death
  • 22% increased risk of heart failure
  • 50% increased risk of cardiac arrest
  • 11% increased risk of transient ischaemic attack
  • 33% increased risk of ischaemic stroke (intracerebral
  • 37% increased risk of cerebral haemorrhage
  • 35% increased risk of peripheral arterial disease
  • 12% lower risk of myocardial infarction
  • 7% lower risk of stable angina

Which reinforces the fact that there is a level of drinking that is beneficial which lies somewhere between non-drinking and heavy drinking. It is called moderate, but it is very difficult to know what this means. I would guess between one and four units a day.

At what point does ‘heavy drinking’ start. Again, this is difficult to say, as researchers tend to clump anyone who drinks more than ‘moderately’ into the group of heavy drinking. This is a game that I call statistical clumping.

By which I mean, we have (for example) four groups. Non-drinkers, occasional drinkers (one or two drinks a week), moderate drinkers (one or two units a day), then heavy drinkers. ‘Heavy drinkers’ as a group, contains all those who drink more than two units a day. In effect, you are ‘clumping’ together those who drink more than two units a day with those who drink two bottles of gin a day. This kind of skews your figures and makes it impossible to know when beneficial drinking stops and damaging drinking starts. [The same game is played with obesity].

So, where are we? Adjusting left right and centre for all confounders, we are left with a simple fact. If you drink alcohol in moderation (with all the provisos attached to that statement), you will significantly reduce your risk of developing, and dying, or CVD.

So, I stand by my statement made in The Great Cholesterol Con. If you don’t drink alcohol, start. Did the authors of the study recommend that non-drinkers start dinking? Of course not. They would never dare. Here is as close as they got.

‘Similarly, while we found that moderate drinkers were less likely to initially present with several cardiovascular diseases than non-drinkers, it could be argued that it would be unwise to encourage individuals to take up drinking as a means of lowering their risk (although it must be noted that the findings from this study do not directly support this as we did not consider transitions from non-drinking to drinking).

This is because there are arguably safer and more effective ways of reducing cardiovascular risk, such as increasing physical activity and smoking cessation.’

Well, I would agree that stopping smoking and exercise would be more effective than starting drinking. However, the statement is still ridiculous. What of those who do not smoke, and who do take exercise. What of those who will not stop smoking and will never takes exercise. Should they still not drink alcohol, and thus fail to gain the obvious benefits?

The other statement is equally ridiculous…. ‘We did not consider transitions from non-drinking to drinking.’ So, we know that moderate drinking is beneficial. We know that not drinking increases risk. But we don’t know that if you start drinking, this will be beneficial.

I shall state this in a different way. ‘We did a placebo controlled study where we saw that those taking the drug gained benefit. However, we did not start giving those on the placebo the active drug, so we do not know if moving from taking placebo to the active drug would be beneficial.’ Using this logic, no clinical study ever done has ever proven anything. Sigh. Where is the God of logic when you need him – or indeed her.

In the end, I have this to say about alcohol. Moderate drinking (whatever that may be) is not harmful. It is probably beneficial. My own view is that alcohol consumption is tightly wrapped within healthy lifestyles to do with sociability friendship and suchlike, and that the amount of alcohol is only a part of the story. However, if you want to drink a couple of glasses of red wine in the evening – go for it.

1: http://dx.doi.org/10.1136/bmj.j909

2: https://www.ncbi.nlm.nih.gov/pubmed/18295937

3: https://www.ncbi.nlm.nih.gov/pubmed/9607117

4: http://www.bmj.com/content/356/bmj.j909

What causes heart disease part XVIII

Viagra

For those who have read my endless series of blogs on cardiovascular disease, you may know exactly where I am going at this point.

Some time ago, Pfizer were developing a drug to treat angina. It blocked an enzyme called phosphodiesterase type-5. [Although I believe that its exact mechanism of action was not known at first]. To put it another way, this drug was a phosphodiesterase type-5 inhibitor (PDE5i).

The moment Pfizer found out what enzyme this drug blocked, they tried to patent the pathway that blocked this enzyme. Pharmaceutical companies trying to patent biological pathways. Perhaps I should try to patent the Krebs cycle, and charge everyone on the planet for having such a thing. Kerchingggg!

‘The U.S. patent office appears to have granted Pfizer a patent covering any drug that blocks this enzyme, meaning that it can sue all of its potential competitors.’1

Luckily, this time they were rebuffed.

Anyhoo, back to the drug. During phase one clinical trials, where humans are given the drug for the first time to see what effects it may have, many of the volunteers were hanging on to their medication, rather than handing them back. This was very unusual. Almost unknown in fact.

When researchers went out to find out why this was happening it was discovered, not quite sure who admitted to this, that sildenafil/Viagra improved erectile function. Thus, Viagra, the first PDE5i, was born. The first drug that worked simply and effectively to improve erectile dysfunction (ED). As for treating angina… that piffling indication was rapidly shelved as the dollar signs appeared in the sky above Pfizer HQ. Sex, as they say, sells.

In truth, it is actually one of the best drugs ever. Not only does is treat ED, but it can also be used by mountaineers to prevent pulmonary oedema (fluid filling up in the lungs), which is one of the major symptoms of altitude sickness. It does this by reducing the blood pressure in the pulmonary vessels (blood vessels in the lungs).

To explain a little further. If you climb very high, and the oxygen level drops, the heart pumps blood harder and harder through the lungs to get as much oxygen as possible into the system. This can result in fluid leaking out of the vessels and into the lung tissue, so they fill up with fluid. At which point you effectively drown, so you die. Viagra stops this happening, by lowering the blood pressure in the lungs.

Unsurprisingly, Viagra is used to treat people who have pulmonary hypertension (high blood pressure in the blood vessels in the lungs) at sea level. It is sold under the name Ravatio, for this indication – but we know that it is just Viagra. In addition, Viagra can be used to treat Raynaud’s disease, where the small blood vessels supplying the fingers and toes constrict, leading to painful cold fingers.

So, here we have a drug that can treat angina, pulmonary hypertension, erectile dysfunction and Raynaud’s disease at the same time. Thus, you can have great sex at twenty thousand feet above sea level, not get chest pain, or breathless, and stay warm at the same time. What more could a man ask for?

How does it do all these things? The answer is that it increases Nitric Oxide (NO) synthesis in endothelial cells. When it does this in the penis, it stimulates erections. In the heart, it opens up coronary arteries. In the lungs, it dilates the blood vessels, in fingers and toes it opens up arteries. So, all of the many different effects, are all due to exactly the same process – increased NO synthesis. Viagra also lowers blood pressure – as you would expect.

At the risk of blowing my own trumpet, I talked about this in my book ‘Doctoring Data,’ under the heading ‘Viagra and the drugs of unintended consequences.’ I posed the question. ‘If we were to prescribe Viagra as an antihypertensive, which is entirely possible, and it were found to reduce the risk of heart disease and stroke, which effect do you think would be responsible for the benefit? The blood pressure lowering effect, or the anticoagulant effects? Or something else.

Since I wrote those words, someone has actually looked at the impact of PDE5is on cardiovascular disease. Researchers at Manchester University, in the UK, studied the use of Viagra in people with diabetes – who often have erectile dysfunction. Here is what they found:

‘Viagra could prevent heart attacks, according to research. Patients taking the male impotence drug were found to have a lower risk of having a heart attack or dying from heart failure than those not on the medication. The lead scientist told the Daily Express the findings are “incredibly exciting”.2

The research paper was published in ‘Heart’, a BMJ journal. Actually, this paper was published last year, but only seems to have hit the press in the last few days. I spotted it in the Times a few days ago.

Here are the main results (for those readers who like their statistics)

‘Results: Compared with non-users, men who are prescribed PDE5is (Viagra, Cialis and the likemy words) (n=1359) experienced lower percentage of deaths during follow-up (19.1% vs 23.8%) and lower risk of all-cause mortality (unadjusted HR=0.69 (95% CI: 0.64 to 0.79); p<0.001)). The reduction in risk of mortality (HR=0.54 (0.36 to 0.80); p=0.002) remained after adjusting for age, estimated glomerular filtration rate, smoking status, prior cerebrovascular accident (CVA) hypertension, prior myocardial infarction (MI), systolic blood pressure, use of statin, metformin, aspirin and β-blocker medication. PDE5i users had lower rates of incident MI (incidence rate ratio (0.62 (0.49 to 0.80), p<0.0001) with lower mortality (25.7% vs 40.1% deaths; age-adjusted HR=0.60 (0.54 to 0.69); p=0.001) compared with non-users within this subgroup.’3

For those who don’t like their statistics quite as much as me (shame on you). I shall attempt to simplify.

  • Over a seven year period, those men taking PDE5is (Viagra Cialis and the like) had a 4.7% reduction in overall mortality – compared to men who did not.
  • Those taking Viagra were 38% less likely to have a myocardial infarction
  • If you did have a myocardial infarction, those who were taking PDE5is had a 25.7% death rate. Those who were not taking PDE5is had a 40.1% death rate. So, if you were unfortunate to have a heart attack, you were 14.6% less likely (absolute risk reduction) to die if you were taking PDE5is.

Or, to shorten this even more

  • 4.7% reduction in overall mortality
  • 38% reduction in MI (relative risk reduction)
  • 14.6% reduction in death after an MI

Whilst the first figure of a 4.7% reduction in overall mortality may not sound terrible exciting, it knocks all antihypertensives and cholesterol lowering medication into a cocked hat. Even if you add them together and multiply by two – on their best day. Because 4.7% is an absolute risk reduction. [Absolute mortality reduction in the Heart Protection Study (HPS), the most positive statin trial, was 1.8% over five years]

The benefits of Viagra are even more startling when it comes to having a heart attack (MI). The current ‘gold standard’ treatment of choice is Primary Percutaneous Coronary Intervention (PCI), which basically means popping a stent into a blocked coronary artery to open it up again.

It has been estimated that PCI results in a 2% absolute reduction in mortality4. On the other hand, Viagra gives you, very nearly, a 15% reduction in overall mortality. Or, to put it another way, Viagra may be seven and a half times as effective as PCI.

But it does not end here. it was also found that men with heart failure were 36% less likely to die if they took a PDE5i.

‘In the other subgroups, there was an inverse association between PDE5i use and all-cause mortality. Those with a recorded history of congestive cardiac failure, TIA and PVD had 36%, 40% and 34% lower risk, respectively.’ [A TIA is a transient Ischaemic attack/small stroke. PVD is peripheral vessel disease.]

Congestive cardiac failure is usually shortened to heart failure. [This 36% is a relative risk reduction, and I could not work out what the absolute risk was from the paper. I am probably too thick].

The effect on heart failure is almost certainly because another benefit of increasing NO is that you increase ‘angiogenesis’, otherwise known as, ‘the creation of new blood vessels’. If a coronary artery does completely block, this often leads to heart failure, as not enough oxygen and other nutrients can get into the heart muscle downstream.

However, if collateral blood vessels develop, the blood will be directed around the blockage and back into the artery downstream, through these newly created blood vessels. Although collateral circulation is not as effective as a fully patent coronary artery, it will create a significant flow of oxygen and nutrients once more. Thus, heart failure will be greatly improved.

Louis Ignarro, who identified nitric oxide (NO) as the key chemical messenger that dilated blood vessels, and won the Nobel Prize for doing so, decided to start treating people who have end stage heart failure with l-arginine. He had been looking for a substance that would, naturally increase NO, and found l-arginine did the job best. He has had some amazing results. Perhaps he should start using Viagra instead.

This study, I must add, was not interventional, it was observational. However, it strongly supports the hypothesis that increasing NO synthesis is just about the most important thing you can do. If you want to avoid dying from CVD.

Do I think everyone should take Viagra? Well, if you have heart failure, diabetes and a high risk of CVD – probably. Will you get a doctor to prescribe it for you, for CVD prevention? Absolutely no chance. Will anyone ever fund a study on this? With the drugs now off patent – no chance.

Oh, the joys of modern medicine. Unless someone does a controlled randomised double blind study on a medication, doctors will not prescribe – are not allowed to prescribe. However, virtually the only people with the money to do such studies are pharmaceutical companies. If the patent life of a drug has expired, no money can be made. So, no trial will be done. So, drugs that are almost certainly beneficial wither on the vine.

Unusually, for me, I do not blame the pharmaceutical companies for this. They are not charities. They need to make money or they die. You cannot expect them to spend hundreds of millions on a clinical study, without any possible means of gaining a return on their investment. We live in a funny old world.

In the meantime, look to other things that can increase NO synthesis. L-arginine/L-citrulline does this. Potassium does this. Sunlight does this. Exercise does this. Meditation does this. Vitamin D does this, as does Vitamin C. What are you waiting for? Go for a walk in the sun and eat an orange – you will live forever.

 

1: https://www.forbes.com/2002/10/23/cx_mh_1023pfizer.html

2: http://www.independent.co.uk/life-style/health-and-families/health-news/viagra-could-lower-heart-attack-risk-and-risk-of-dying-from-heart-failure-a7082801.html

3: http://heart.bmj.com/content/early/2016/07/26/heartjnl-2015-309223.full

4: https://www.ncbi.nlm.nih.gov/pubmed/12517460?access_num=12517460&link_type=MED&dopt=Abstract

What causes heart disease part XXVI

[Hold the front page]

Last night I watched a you tube presentation which completely astonished me. It was given by Professor Salim Yusuf, who is as mainstream as mainstream can possibly be. Here, from Wikipedia:

‘Salim Yusuf (born November 26, 1952) is an Indian-born Canadian physician, the Marion W. Burke Chair in Cardiovascular Disease at McMaster University Medical School and currently the President of the World Heart Federation, a world-renowned cardiologist and epidemiologist. In 2001, he published a landmark study that proved the benefits of clopidogrel in acute coronary syndrome without ST elevation.

Here, from Forbes magazine in 2012:

‘McMaster University’s Salim Yusuf has tied for second place in the annual ranking of the “hottest” scientific researchers, according to Thomson Reuter’s Science Watch. Yusuf was a co-author of 13 of the most cited papers in 2011. Only one other researcher, genomic pioneer Eric Lander of the Broad Institute of MIT, had more highly-cited papers than Yusuf.’1

On February the 12th he gave a presentation at a cardiology conference in Davos, Switzerland which can be seen on YouTube. In this presentation, he makes the following points:

  1. Saturated fat does raise LDL, a bit, but has no effect on CVD – maybe slightly beneficial. Monounsaturated fats are slightly beneficial. Polyunsaturated fats are neutral.
  2. Carbohydrate intake is most closely associated with CVD
  3. Fruit and vegetable intake has little or no impact on CVD – nor does fish intake [He wonders where the five portions of fruit and vegetable intake recommendations actually came from]. Vegetables in particular have no benefit.
  4. Legumes – beans and suchlike – are beneficial.
  5. The recommendations on salt intake are completely wrong, and set far too low. For those who do not have high blood pressure, low salt intake increase mortality. On the other hand, high salt intake does no harm.
  6. He recommends higher potassium intake.
  7. He criticizes Ancel Keys and lauds Nina Teicholz [Author of big fat surprise].

Well, good for him. It seems to have taken him a long time to get there, but he did in the end. Of course, mainstream medicine will remain in shocked silence, so you will likely hear nothing of this in the mainstream media. But, hey, you get to see it here. Perhaps someone would like to send this presentation to the BHF and the AHA and ask them for a comment?

The YouTube presentation is here:

 

1: http://www.forbes.com/sites/larryhusten/2012/04/25/when-youre-hot-youre-hot-salim-yusuf-second-most-influential-scientist-in-2011/#6ac825575abe

What causes heart disease part XXV

Lead

I have been studying cardiovascular disease for well over thirty years now. I have come across a million different hypotheses about what causes it. There is almost no foodstuff, vitamin, infectious agent, chemical compound, atomic element or activity [lack of, or excess] that has not been proposed at some point.

Many of them can look very promising, and the underlying hypothesis is often elegant – very elegant indeed. But what you must do with any hypothesis is to hold it close to the unforgiving flame of mortality data, and see if it is tempered by the heat – or simply melts.

I resolved very early on in my long and winding study on cardiovascular disease that any hypothesis had to explain everything – not just some things. For example, as almost everyone in the entire world knows a raised cholesterol level is considered the most important cause of cardiovascular disease. But it is exceedingly easy to find facts that seem to completely contradict this.

Here, for example, is a little graph looking at only two countries. It compares the death rate from heart disease in Russia and Switzerland, in men under the age of sixty-five relation to the average cholesterol level in those two countries.

lead-post

in Russia, with an average cholesterol level of 5.1mmol/l (197mg/dl) had a death rate 834% higher than that in Switzerland, which had an average cholesterol level of 6.4mmol/l (248mg/dl). Yes, this graph is the right way around. Yes, these data come from the World Health Organisation, and can be found on the British Heart Foundation (BHF) website. These particular statistics are now very deeply buried, but can still be found here: https://www.bhf.org.uk/publications/statistics/european-cardiovascular-disease-statistics-2008

I sometimes wonder if anyone at the BHF actually looks at these data, but that is a question for another day. Of course, when presented with facts like this, the dismissals. and creation of ad-hoc hypotheses rapidly reach into the sky. The word ‘paradox’ will be used pretty heavily, that’s always a good, temporary, escape route. In reality these two figures represent a full-blown black swan. But, hey, facts are slippery things.

Anyway, in my quest to explain everything about heart disease, perhaps the hardest single thing to explain is the fact that the rate of cardiovascular disease (heart attacks and strokes) has been going down in pretty much every single Western country for decades. I would say ‘first world’ country, but my son (a geography graduate) informs me that this terminology is now virtually barred for being racist. I shall be considered an ancient, prejudiced reactionary for using such a term.

So, I will say, Western Europe, North American, Australia, Japan, New Zealand and suchlike.

Now, the decline in CVD did not start at the same time, in all these countries. At this point I will make myself a hostage to fortune and make some sweeping statements. The rate of CVD peaked first in the US, in the late 1950s and has been falling since. It peaked next in Finland in the 1960s. In most of the other countries CVD peaked in the 1970s, before falling. It is impossible to say that there was a uniform worldwide effect. [Today, some countries are on the way up the mortality curve e.g. China and India].

However, I will make the general statement that CVD has been falling in most ‘first world’ countries for decades. This started long before any effective medical interventions were available. In the US, in the 1950s, there were no effective blood pressure lowering agents, no stents, no CABG, no clot busters…. Nothing really.

Possibly the greatest single factor has been the reduction in smoking. At the end of the second world war virtually all men smoked. Nearly 90% in the UK in the 1950s. Since that time the number of smokers has fallen, and fallen.

In addition to this, during the 60s, 70s, 80s and onwards, medical interventions have also greatly improved. In-hospital survival from a heart attack or stroke has improved almost year on year. The figures are complex, but around 60% of those admitted to hospital with a heart attack used to die – it is now around 30%, maybe less.

Some of this is due to the fact that ‘strict bed rest’ following a heart attack, the key medical intervention for decades, was abandoned. A piece of medical mismanagement that killed millions and millions… and millions.

What else may have cause the fall? I think that in the UK, the clean air act has a significant effect. The Great Smog of London, in the early 1950s, killed tens of thousands in less than a week. Much of this was from respiratory complications, but also CVD. It is now more clearly established that air pollution, in general, increases the risk of CVD. Most Western countries have drastically reduced air pollution.

Now, I would like to consider something almost never mentioned. Lead. That is the element, not the verb. Or the noun, as in dog lead.

In the 1920s someone discovered that if you put lead in petrol/gasoline it had all sorts of benefits on engine performance and wear and tear – and so on. Unfortunately, lead also caused all sorts of problem for human performance, and wear and tear. It is a heavy metal and, like other heavy metals, a powerful human toxin.

Despite the fact that lead toxicity was known for decades, it took until the nineteen-sixties before countries starting banning it from fuel – and pipes in housing – and the like. Which reversed a long-term trend of lead building up inside human beings. It lasts for decades within bone – gradually leaking out.

With regards to lead and CVD, is there a link?

A researcher called Weisskopf looked at the amount of lead in bones, and the rate of CVD. He found that those with the most lead in their bones were 837% more likely to die from CVD (relative risk)1 than those with the least lead in their bones. Now, whilst that is a relative risk, it is of the magnitude where we can safely say we are looking straight at a direct cause of CVD.

How does lead cause CVD. Most likely through the following mechanisms

‘Lead causes endothelial dysfunction by binding and inhibiting endothelial nitric oxide synthase and decreasing nitric oxide production.’2

Yes, we are straight back to my old friends, endothelial dysfunction and decreased nitric oxide (NO) production. In the world of cardiovascular disease, if you know where to look, all roads lead to NO.

If lead does cause CVD, is there any evidence that removing lead from the body can reduce the risk of CVD? [‘Reversibility’ and ‘Experimental Evidence’, the two most powerful of Bradford Hill’s canons for causation]. Which brings me to TACT. A trial designed to look at the impact of chelation on CVD. A way of removing heavy metals from the body…

What I love about this trial is that it was set up primarily to prove that chelation was nonsense, to be laid alongside homeopathy, and suchlike – by mainstream researchers. To quote an article in Medscape:

‘The original TACT trial wrestled with enrolment, ultimately taking over a decade to yield results, in part because cardiologists were absolutely convinced that chelation was a load of horse hockey.’ 3

TACT stands for Trial to Assess Chelation Therapy. When I first heard about chelation, I too, dismissed it as horse hockey. However, it turns out that I done the thing that I always advise everyone else against doing. I placed it in the ‘impossible/horse hockey’ category without making the effort of trying to find out what it was really about.

As it turns out, I should have made more effort…

‘TACT found that patients randomized to a regimen involving up to 40 separate three-hour infusions of a chelation-therapy solution (disodium ethylenediaminetetraacetic acid [EDTA], ascorbic acid, magnesium chloride, potassium chloride, sodium bicarbonate, B vitamins, procainamide, and a small amount of standard heparin) experienced an 18% drop in the trial’s primary end point (all-cause death, reinfarction, stroke, revascularization, or hospitalization for angina) compared with patients randomized to a placebo infusion.’3

More extraordinary than this:

‘When we broke the composite down to look at our secondary end points, we found that we had about a 40% reduction in total mortality, a 40% reduction in recurrent MI, and about a 50% reduction in mortality [in patients with diabetes],”3

A 40% – 50% reduction in mortality. Well, well, well. Eat your heart out statins. In fact, eat your heart out every single pharmaceutical product ever tested. What has been the effect on mainstream thinking on CVD? As you would expect, absolutely nothing has changed in the slightest. Still TACT2 is now being set up – so we can all look forward to that being ignored in about seven to ten years’ time.

Anyway, in an attempt to bring some structure to this blog, I am going to return to the start. Why has the rate of CVD gone down in most first world countries over the last fifty years? One of the reasons, I believe, is that the level of heavy metal pollutants (in particular, lead) has been dropping since around the mid nineteen sixties.

I think it could be argued that the US was the first country to embrace the motor car. Thus lead toxicity would have hit the US before anywhere else. I am not going to argue this too strongly, but I place it before you, for your consideration.

I shall finish by saying that, if you want to look for reasons for the pattern on CVD over the last sixty years, or so, you really need to start looking outside the box. For there are more things in heaven and earth Horatio, than are dreamt of in your philosophy.

1: Weisskopf MG, Jain N, Nie H, et al. ‘A prospective study of bone lead concentration and death from all causes, cardiovascular diseases, and cancer in the Department of Veterans Affairs Normative Aging Study’. Circulation 2009;120(12):1056-64.

2: Natalia V. Solenkova et al: ‘Metal pollutants and cardiovascular disease: Mechanisms and consequences of exposure.‘ Am Heart J 2014;168:812-22

3: http://www.medscape.com/viewarticle/814643?pa=QYKVfN05tfWXqq6%2BfjZ30whyKyHVDGvMW4WYyHO8jprcrUBo6WRIR4VFzOaThtqB8SIvl8zjYv73GUyW5rsbWA%3D%3D

What causes heart disease part XXIV

In my long and winding road around cardiovascular disease I have often visited the same themes a few times. In part, this is because we are not dealing with Newtonian physics here. If billiard ball A strikes billiard ball B, at five metres per second, at an angle of 45 degrees, billiard ball B will move off at angle C at velocity D, assuming perfect elasticity. This will always happen, every single time.

On the other hand, with CVD, the complexity of human physiology and psychology, environmental factors, genetics the time of day, even sunspot activity – can have an effect – so some people have reported.

‘Space proton flux and the temporal distribution of cardiovascular deaths.

The influence of solar activity (SA) and geomagnetic activity (GMA) on human homeostasis has long been investigated. The aim of the present study was to analyse the relationship between monthly proton flux (> 90 MeV) and other SA and GMA parameters and between proton flux and temporal (monthly) distribution of total and cardiovascular-related deaths. The data from 180 months (1974-1989) of distribution in the Beilinson Campus of the Rabin Medical Centre, Israel, and of 108 months (1983-1991) from the Kaunas Medical Academy, were analysed and compared with SA, GMA and space proton flux (> 90 MeV). It was concluded: monthly levels of SA, GMA and radiowave propagation (Fof2) are significantly and adversely correlated with monthly space proton flux (> 90 MeV); medical-biological phenomena that increase during periods of low solar and/or geomagnetic activity may be stimulated by physical processes provoked by the concomitant increase in proton flux; the monthly number of deaths related (positively or negatively) to SA are significantly and adversely related to the space proton flux (> 90 MeV).’1

Oh yes, I do cast my net far and wide when looking at cardiovascular disease, as I feel I must. Quite what we are all supposed to do when the space proton flux is greater than 90MeV, I am not certain. Perhaps a tin foil hat would become appropriately protective headgear. By the way, this paper can be found in the National Institutes of Health on-line library – Pubmed. Referenced, peer-reviewed, and everything.

The point being? The point being that if you are looking for ‘billiard ball’ certainty, you are not going to find it here. If you were to do absolutely everything that I believe to be protective against cardiovascular disease, you will shift the odds in your favour, but you could still get struck down by a heart attack or stroke.

Anyway, with that proviso firmly in place, I shall move ahead, or maybe backwards. On the basis that some subjects need a second visit, I have decided to return to look at vitamin C again. First, because I have just been harangued by someone who believes that if you take high doses of vitamin C every day, you can reverse/cure heart disease completely and utterly. He also felt that I had completely ignored the work of G C Willis ‘The reversibility of atherosclerosis’, and also the research of Pauling and Rath on vitamin C.

It is true that I have not actually mentioned Willis before, but I have certainly written at length of Pauling and Rath. However, I realise that time passes, people forget things, and previous blogs settle to the bottom of the sediment layer. Therefore, it is not a bad idea to refresh things from time to time. I am also returning to vitamin C and the issues around it, because I have been getting a lot of correspondence about lipoprotein (a) (Lp(a)) recently. It seems this lipoprotein is gaining increasing attention. Of course, vitamin C and Lp(a) are tightly bound together.

Time, I think, for a quick refresher about this whole area. Particularly as it helps to confirm my central hypothesis that CVD is a disease of blood clotting, and you would struggle to explain the vitamin C/Lp(a) axis in any other way.

To begin. At some point in the distant past, our ancestors lost the ability to manufacture vitamin C. This happened, so I recently read, around sixty-one million years ago. Seems a long way back, but there you go. It has happened to some other animal groups, but not many. Quite why it occurred is unclear. You probably think you know, but I suspect you are wrong.

Interestingly, and as a bit of an aside, vitamin C is synthesized through a multi-step process, and the original molecule is glucose. Humans lack the last step in the process. Perhaps, because of this, glucose and vitamin C have some interesting interactions in the body. Mainly, it seems, that high levels of glucose prevent vitamin C from entering cells. Particularly immune cells, which need a lot of vitamin C to operate effectively. Make of that what you will.

Moving on, because humans cannot synthesize their own vitamin C, we must obtain it from within our diet. If we do not manage to eat enough, we will end up with scurvy. Scurvy presents with many different symptoms, but the one I am going to focus on in this blog is bleeding.

Bleeding occurs, because vitamin C is essential for collagen synthesis – a critical building block of supportive tissue throughout the body. Loss of collagen leads to break down of various structures in the body. For example, the walls of blood vessel walls which, start to break down and ‘crack.’

As blood vessel walls crack, they leak, and bleed. This leads to the best known symptom of scurvy, which is bleeding gums. This was well recognised several hundred years ago, mainly in sailors who had a highly-restricted diet during long voyages. In scurvy there is also bleeding in many other blood vessels, but you can’t easily see it. The usual cause of death in severe scurvy is internal bleeding.

On the positive side, after sixty-one million years, or so, evolution came up with a partial solution to the early stages of scurvy. Namely, the synthesis of a substance to block the cracks in the blood vessel walls, and control the bleeding. This substance is, or course, lipoprotein (a).

Lipoprotein (a) (Lp(a)) is synthesized in the liver, and it travels around in the bloodstream, looking for any cracks in blood vessels walls a.k.a. damaged endothelium. When a crack is spotted Lp(a) is attracted to the area and sticks very firmly, and cannot easily be removed. Of course, the rest of the blood clotting system also moves into action, so all hell breaks loose. Therefore Lp(a) becomes mixed up with platelets, red blood cells, fibrin, and almost everything else in the blood, including all the other lipoproteins.

However, Lp(a) has a very special trick up its sleeve. It mimics plasminogen.

After a blood clot forms, anywhere in the circulation, it has to be broken down, and removed – once the blood vessel underneath it has repaired. I liken this (not very accurately) to road works. If the road surface is damaged, the repair team comes in, sets up barriers and traffic lights and suchlike, then they repair the road. Then all the barriers, and traffic lights, and suchlike, must be removed.

Within a blood vessel, removal of barriers, and traffic lights, is a tricky exercise. Where does the blood clot go? Once a large blood clot has formed, over a ‘crack’ in the wall, it cannot stay there forever, restricting, or totally obstructing, blood flow. On the other hand, if the entire clot simply broke off, and travelled down the artery, it would get stuck as the artery narrowed – causing a complete blockage. Not a good idea.

Ergo, there is a need for a process that removes blood clots that have formed within blood vessels. It is called thrombolysis, or fibrinolysis. To ‘lyse’ means to break down.

The main player in thrombolysis is plasminogen. It becomes incorporated into (almost) all blood clots that form. It is activated by tissue plasminogen activator (t-PA). This turns plasminogen into plasmin, the ‘active’ enzyme that slices fibrin apart [fibrin is a long, and very strong, string of fibrinogen molecules that wraps round blood clots and binds them together].

t-PA can be manufactured and given to people who have heart attacks and strokes, to break apart the blood clots that are blocking the arteries in the brain, or the heart. You may have heard of t-PA referred to as a ‘clot-buster.’ Great stuff, but not so good if your stroke is due to a bleed in the brain, rather than a blood clot. In which case….

t-PA has been around for a while now and, with heart attacks at least, has mainly been superseded by angioplasty. Which is to open up the blocked artery, and stick a metal support (stent) into the artery. T-PA is still use in ischaemic strokes. That is, after you have had a brain scan to work out what sort of stroke you are having.

Sorry to appear to be going off in different directions here, but the systems of blood clotting are highly complex, and I think that explaining where Lp(a) fits in, is important.

Lp(a) is actually a lipoprotein, just like LDL. In fact, it is exactly like LDL, because it is basically LDL. It is the same size and shape, it contains triglyceride and cholesterol. However, it differs in one important aspect. Whilst LDL has a protein stuck to it called apolipoprotein B-100, Lp(a) has another protein stuck to it called apolipoprotein (a). Which is why it is called lipoprotein (a).

The fascinating thing about the protein, apolipoprotein (a), is that is has almost exactly the same chemical structure as plasminogen. So close, that you could hardly tell it apart. However, apolipoprotein (a) is completely unaffected by t-PA. It does not convert to plasmin, it is inert. So, when you want to break down a clot (fibrinolysis), the parts that have Lp(a) incorporated into it, cannot be broken down.

Which means that if you have a high Lp(a) level, you will develop bigger and more difficult to break down blood clots. Exactly what evolution had in mind for creatures that cannot manufacture vitamin C, and need to plug cracks in artery walls when the vitamin C level falls. However, not so good, if you want to stop atherosclerosis from developing.

Because these Lp(a) rich blood clots have to go somewhere, and the only place that they can go is to be absorbed into the artery wall itself, and then broken down. However, these clots are more difficult to break down, so, with repeated clots over the same area of artery wall, bigger and bigger plaques will grow.

That, anyway, is the theory.

What G.C. Willis did in 1957 was to study guinea pigs. Guinea pigs are another animal that does not synthesize vitamin C. He made them scorbutic (vitamin C deficient a.k.a. scurvy). Actually, he did not make them all scorbutic. He had a control group of twelve guinea pigs that he put on a vitamin C deficient diet, then injected them with vitamin C. None of these twelve guinea pigs developed any measurable atherosclerosis.

On the other hand, those guinea pigs on a scorbutic diet rapidly developed atherosclerosis. When I say rapidly, I mean within days. I think this point is worth repeating. If you make a guinea pig scorbutic, it will develop plaques, identical to those found in human arteries within days.

Willis then started feeding his guinea pigs vitamin C, and he found that the lipid filled plaques quite rapidly disappeared. He describes what he saw happening to the guinea after they were fed vitamin C.

‘The results of this investigation indicate that early lesions of atherosclerosis are quickly resorbed. The stages of this process are first a fading of lipid staining in the region of the internal elastic membrane with later a disappearance of all extracellular fat. Active phagocytosis of lipid by macrophage occurs, and when these macrophages finally disappear no evidence of the lesion remains.’ 2

I shall translate that passage for those with a non-science background.

What Willis found was that if you remove vitamin C from the guinea pig diet, they develop fat filled atherosclerotic plaques within days. If you then add vitamin C to the diet again, the plaques rapidly disappear (within days). The process of removal appears to be that the fat/lipid is ingested (phagocytosed) by white blood cells – known as macrophages.

However, if you let the plaques grow for too long, it is far more difficult to get rid of them.

‘More advanced lesions are considerably more resistant to reversal. Extensive lipid deposits clear in some parts of plaque but islands of intensely staining lipid persists in other parts. The macrophage response to such areas is only slight.’

It seems that if you don’t get rid of the plaque pretty much straight away, you don’t get rid of it at all. [Or maybe he didn’t wait long enough to see what happened over months, or years. Although my childhood memory of guinea pigs is that they tend to drop dead at the slightest excuse].

Of course, this was guinea pigs, not humans, so we must be careful not to extrapolate too far. However, previously, Willis had studied humans. Not many, only sixteen. Ten people with identified plaques were given vitamin C, six were not. In those ten treated with vitamin C, the plaques got bigger in three, stayed the same in one, and reduced in size in six. In those six not given vitamin C, three remained the same, and in three the plaques got bigger. Interesting, but hardly cast-iron proof of anything.

At this point there are a number of strands to gather together. We now know that humans cannot synthesize vitamin C, so we need to eat it. Without enough vitamin C, our blood vessels crack and bleed, and in severe cases we bleed to death.

In order to provide a degree of protection against vitamin C deficiency (scurvy), we produce lipoprotein (a) to fill up the cracks the blood vessels. However, unsurprisingly, a high level of lipoprotein (a) Lp(a) is associated with a higher rate of CVD.

‘In summary, elevated Lp(a) levels associate robustly and specifically with increased CVD risk. The association is continuous in shape without a threshold and does not depend on high levels of LDL or non-HDL cholesterol, or on the levels or presence of other cardiovascular risk factors.’ 3

This raises two inter-connected questions. Does vitamin C supplementation lower Lp(a) levels, and does it reduce the risk of CVD? It is of course entirely possible that vitamin C could reduce CVD risk by protecting blood vessels from ‘cracking’ without having any effect on Lp(a) levels.

Now you would think that this would have been an area of research interest to someone…. Anyone. However, the only people who seem to have looked at this area in any details are Linus Pauling (double Nobel prize winner, now dead) and Matthias Rath. A man whose reputation within the mainstream medical profession makes that of Andrew Wakefield look like mother Teresa. This from Wikipedia:

‘The Sunday Times (Johannesburg) has described Rath as an “international campaigner for the use of natural remedies” whose “theories on the treatment of cancer have been rejected by health authorities all over the world.”

On HIV/AIDS, Rath has disparaged the pharmaceutical industry and denounced antiretroviral medication as toxic and dangerous, while claiming that his vitamin pills could reverse the course of AIDS. As a result, Rath has been accused of “potentially endangering thousands of lives” in South Africa, a country with a massive AIDS epidemic where Rath was active in the mid-2000s. The head of Médecins Sans Frontières said “This guy is killing people by luring them with unrecognised treatment without any scientific evidence”; Rath attempted to sue him.

Rath’s claims and methods have been widely criticised by medical organisations, AIDS-activist groups, and the United Nations, among others Former South African President Thabo Mbeki and former Minister of Health Manto Tshabalala-Msimang have also been criticised by the medical and AIDS-activist community for their perceived support for Rath’s claims According to doctors with Médecins Sans Frontières, the Treatment Action Campaign (a South African AIDS-activist group) and a former Rath colleague, unauthorised clinical trials run by Rath and his associates, using vitamins as therapy for HIV, resulted in deaths of some participants. In 2008, the Cape High Court found the trials unlawful, banned Rath and his foundation from conducting unauthorised clinical trials and from advertising their products, and instructed the South African Health Department to fully investigate Rath’s vitamin trials.’

Matthias Rath even managed to fall out with Linus Pauling, before Pauling’s death, and law suits ensued. Rath has also successfully sued the BMJ, received £100,000 in damages. So, as you can see, not really a poster boy for mainstream medical research.

I include this information, as I think it is critical to the entire Vitamin C discussion. Because Matthias Rath is viewed as absolute scientific poison this has made the whole area of vitamin C supplementation a complete no-go area for any respectable scientist. If, as a doctor, you try to suggest that vitamin supplementation may be a possible treatment for, say, CVD, you might as well hand you licence over to the authorities at the same time – to save them the trouble of striking you off the medical register (almost a joke, but not quite).

So, essentially, we have a huge void here. The only research that I have ever seen (maybe I missed some) to establish if vitamin C supplementation does actually lower Lp(a) levels was done by Matthias Rath. And, according to him, it does. More so, in those with higher levels to start with. I am not referencing this research, but I would suggest you have a look around Rath and Pauling and vitamin C and Lp(a). See what you think. I think the research is robust.

With regard to the critical question, does vitamin C reduce the risk of CVD [with or without lowering Lp(a)]. I would say, case currently unproven. This does not mean that it does not (in fact I believe that it probably does). What I mean by ‘case currently unproven’ is that no-one has done a large scale interventional study using vitamin C to find out if it really reduces CVD.

The problem here is that such a study is almost certainly never going to be done. There is no way anyone can make money from doing such a study. Vitamin C cannot be patented, so if a company spend several hundred million ‘proving’ that vitamin C reduced CVD death, they would never get any money back.

You would have to find a Governmental organisation, tax payer funded, to do such a study. And with Matthias Rath around, that just ain’t going to happen. No-one would touch it.

However, there is one way to definitely reduce Lp(a) levels, and that is to take l-carnitine. Here, from a study called ‘L-carnitine reduces plasma lipoprotein(a) levels in patients with hyper Lp(a)’

‘L-carnitine, a natural compound stimulating fatty acid oxidation at the mitochondrial level, was tested in a double blind study in 36 subjects with Lp(a) levels ranging between 40-80 mg/dL, in most with concomitant LDL cholesterol and triglyceride elevations. L-carnitine (2 g/day) significantly reduced Lp(a) levels… the reduction being more dramatic in the subjects with the more marked elevations. In particular, in the L-carnitine group, 14 out of 18 subjects (77.8%) had a significant reduction of Lp(a) vs only 7 out of 18 (38.9%) in the placebo group. In a significant number of subjects the reduction of Lp(a) resulted in a return of this major cardiovascular risk parameter to the normal range.’ 4

Does this then result in a reduction in CVD risk? The answer is that I do not know, for sure. A meta-analysis of L-carnitine supplementation has been done. This consisted of five trials on three thousand people. L-carnitine supplementation did show some benefit – which did not reach statistical significance, but came very, very close.

For those of you who like a bit of statistics, here we go

‘The interaction test yielded no significant differences between the effects of the four daily oral maintenance dosages of L-carnitine (i.e., 2 g, 3 g, 4 g, and 6 g) on all-cause mortality (risk ratio [RR] = 0.77, 95% CI [0.57-1.03], P = 0.08)’5

CI [0.57 to 1.03] – close, but no cigar.

To put this into figures anyone can understand. In the intervention groups (those taking L-carnitine) there were 83 deaths. In the control group (those not taking L-carnitine) there were 106 deaths. Total study population was 3108, split in two groups: control and intervention. This gets as close to statistical significance as you can get (virtually). In fact, if this had been a statin trial, you would never have heard the end of it. ‘Ladies and gentlemen a 22% reduction in overall mortality with L-carnitine supplementation.’ [Oh, what fun statistics are].

So, what do we know?

  • A high level of Lp(a) is associated with a higher risk of CVD.
  • There is a probable causal mechanism linking Lp(a) to CVD death
  • Lp(a) is synthesized in animals that cannot make their own Vitamin C
  • A lack of vitamin C causes blood vessels to crack open – and potentially leads to atherosclerotic plaques development
  • Animal models have shown that a lack of vitamin C does lead to rapid atherosclerotic plaque development, and that replacement of vitamin C causes rapid regression of atherosclerosis
  • Some evidence from humans suggest that vitamin C supplementation causes regression of atherosclerotic plaques
  • Vitamin C supplementation does seem to lead to a reduction in Lp(a) levels
  • L-carnitine supplementation does lead to a reduction in Lp(a) levels
  • L-carnitine supplementation may reduce overall mortality.

What would I now recommend? If you have a high Lp(a) level take lots of vitamin C and l-carnitine and see if your Lp(a) level falls. If it does, keep taking lots of vitamin C and l-carnitine for the rest of your life. If it does not fall? Not sure.

As for the rest of us? Well I have no idea how much vitamin C anyone should take, or how much l-carnitine is required. There is literally no area of medicine that is less clear than our true vitamin requirements. You can find a thousand shouty people supporting high vitamin supplementation – any or all vitamins.

My view. I do not think the RDAs for vitamins are remotely accurate, or useful. They were established in times of absolute deficiency. The agreed Vitamin B12 levels, for example, were based on seven people, over sixty years ago, and remain unchanged to this day. All seven had pernicious anaemia (caused by vitamin B12 deficiency).

So, I do not believe in the RDAs at all. They are often, I believe, too low for optimal health. I can see no harm coming to people from taking lots of vitamin C or lots of l-carnitine. So, supplement away. You will probably reduce your risk of dying from CVD.

 

References
1: https://www.ncbi.nlm.nih.gov/pubmed/9140214

2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1823880/?page=3

3: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295201/

4: https://www.ncbi.nlm.nih.gov/pubmed/11213533

5: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223629/

What causes heart disease part XXIII

As 2016 draws to an end, I believe that a change is in the air. The dietary guidelines, or perhaps I should call them the ‘dietary misguidedlines’, are under a sustained attack. This, finally, may actually result in success. We will be able move on from believing that fat, or saturated fat, in the diet is responsible for cardiovascular disease or, indeed, any form of disease.

But where to then? The current dogma is that saturated fat in the diet raises cholesterol levels and this, in turn, leads to cardiovascular disease. However, as many of you may have spotted earlier this year, in the Minnesota Coronary Experiment (MCE), substituting saturated fat with polyunsaturated fat was effective at lowering cholesterol levels. However, it had absolutely no effect on deaths for heart disease, and greatly increased the overall risk of death.

The summary of this trial was, as follows:

  • It involved 9423 women and men aged 20-97
  • A cholesterol lowering diet was used, replacing saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine).
  • The low saturated fat group had a significant reduction in serum cholesterol compared with controls.
  • There was no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts.
  • For every 0.78mmol/l reduction in serum cholesterol [Around a 20% reduction], there was a 22% higher risk of death [This is about a 30% reduction in cholesterol level]

Big deal, you might think. This is just one trial, so what difference does it make. However, this was no ordinary trial. It was absolutely pivotal for four main reasons:

  • It was the largest controlled trials of its kind ever done. That is, substituting saturated with polyunsaturated fats.
  • It was done by Ancel Keys (who started the entire diet-heart hypothesis in the first place)
  • It was finished, before the main clinical nutritional guidelines were developed
  • It was not published at the time, for reasons that have never been explained, by anyone.

As the authors of the re-analysis note.

Whatever the explanation for key MCE data not being published, there is growing recognition that incomplete publication of negative or inconclusive results can contribute to skewed research priorities and public health initiatives. Recovery of unpublished data can alter the balance of evidence and, in some instances, can lead to reversal of established policy or clinical practice positions.” 1

Which is a polite way of saying that a bunch of liars hid the results. Almost certainly because the results contradicted their self-promoted message that saturated fats are unhealthy. It is clear that these researchers, in particular Ancel Keys, did this quite deliberately, and then continued to promote their own dietary dogma.

I think it is almost impossible to overestimate the long-term impact of the non-publication of this trial.

  • For want of a nail the shoe was lost.
  • For want of a shoe the horse was lost.
  • For want of a horse the rider was lost.
  • For want of a rider the message was lost.
  • For want of a message the battle was lost.
  • For want of a battle the kingdom was lost.
  • And all for the want of a horseshoe nail.

Here is my updated version

  • For want of the MCE trial evidence the McGovern hearings were lost
  • For want of the hearings the guidelines were lost
  • For want of the guidelines the message was lost
  • For want of the message battle was lost
  • For want of the battle saturated fat was lost
  • All for the want of the MCE trial data.

The McGovern hearings which set the entire direction of nutritional thinking, and guidelines, took place in 1977. The MCE trial ran from 1968 to 1973. Had the data from this study been made available, the dietary guidelines in the US, the UK and the rest of the world (In their current form, demonising saturated fat) simply could not have been written.

If those guidelines had not been written, then the entire world of cardiovascular research would almost certainly have gone off in a different direction. The role of LDL in causing CVD would have been consigned to the dustbin history. Goldstein and Brown wouldn’t have done their research on Familial Hypercholesterolaemia, statins would never have been developed, and we not have been forced to endure fifty years of the damaging, destructive diet-heart/cholesterol hypothesis.

The fact that the diet-heart/cholesterol hypothesis is complete nonsense, has been clear as day to many people for many years. In 1977 George Mann, a co-director of the Framingham Study, writing in the New England Journal of Medicine called it ‘the greatest scam in the history of medicine.’ In my view, anyone with a moderately functioning brain, can easily see that it is nonsense.

So, if not fat and cholesterol, what does cause cardiovascular disease, and more importantly, what can be done to prevent it, or at least delay it? At last (some of you are thinking) I will state what I believe to be one of the most important things you can do to reduce the risk.

Returning to the central process of cardiovascular disease (CVD), for a moment. If you are going to reduce the risk of cardiovascular disease, you must do, at least, one of three things:

  • Protect the endothelium (lining of blood vessels) from harm
  • Reduce the risk of blood clots forming – especially over areas of endothelial damage
  • Reduce the size and tenacity (difficulty of being broken down) of the blood clots that develop

If you can do all three, you will reduce your risk of dying of a heart attack, or stroke, to virtually zero.

What protects the endothelium?

There are many things that that can do this, but the number one agent that protects the endothelium is nitric oxide (NO). Thus, anything that stimulates NO synthesis will be protective against CVD. Which brings us to sunshine and vitamin D.

  • Sunlight on the skin directly stimulates NO synthesis, which has been shown to reduce blood pressure, improve arterial elasticity, and a whole host of other beneficial things for your cardiovascular system, not least a reduction in blood clot formation.
  • Sunlight on the skin also creates vitamin D, which has significant impact on NO synthesis in endothelial cells, alongside many other actions. It also prevents cancer, so you get a double benefit.

Therefore, my first direct piece of direct advice for those who want to prevent heart disease, is to sunbathe. In the winter when the sun is not shining take vitamin D supplementation. Alternatively, go on holiday to somewhere sunny. Or get a UVB sunbed, and use it.

My only note of warning here is to say, don’t burn, it is painful and you don’t need to.

By the way, don’t worry about skin cancer. Sun exposure protects against all forms of cancer to a far greater degree than it may cause any specific cancer. To give you reassurance on this point, here is a Medscape article, quoting from a long-term Swedish study on sun exposure:

‘Nonsmokers who stayed out of the sun had a life expectancy similar to smokers who soaked up the most rays, according to researchers who studied nearly 30,000 Swedish women over 20 years.

This indicates that avoiding the sun “is a risk factor for death of a similar magnitude as smoking,” write the authors of the article, published March 21 in the Journal of Internal Medicine. Compared with those with the highest sun exposure, life expectancy for those who avoided sun dropped by 0.6 to 2.1 years.

Pelle Lindqvist, MD, of Karolinska University Hospital in Huddinge, Sweden, and colleagues found that women who seek out the sun were generally at lower risk for cardiovascular disease (CVD) and noncancer/non-CVD diseases such as diabetes, multiple sclerosis, and pulmonary diseases, than those who avoided sun exposure.

And one of the strengths of the study was that results were dose-specific — sunshine benefits went up with amount of exposure. The researchers acknowledge that longer life expectancy for sunbathers seems paradoxical to the common thinking that sun exposure increases risk for skin cancer.

“We did find an increased risk of…skin cancer. However, the skin cancers that occurred in those exposing themselves to the sun had better prognosis,” Dr Lindqvist said.”2

In short, avoiding the sun is a bad for you as smoking. In my opinion ordering people to avoid the sun, is possibly the single most dangerous and damaging piece of health prevention advice there has ever been. The sun has been up there, shining down, for over four billion years. Only very recently have we hidden from it. If you believe in evolution, you must also believe that sunshine provides significant health benefits. It cannot be otherwise.

Happy, sunny, CVD risk reduced, 2017

I have just added a little poem that was just sent as a comment on my blog. Thanks for the laugh.

Ancel Benjamin Keys
Researched dietary disease.
When the facts turned out contrarian,
He simply up and buried ’em. [Martin Back]

1: http://www.bmj.com/content/353/bmj.i1246
2: http://www.medscape.com/viewarticle/860805

The diet heart hypothesis suffers another attack – hoorah!

[Go Canada go]

I was writing another blog, on another matter, when someone sent me an email containing a petition signed by over two hundred Canadian doctors. You can read more about it here https://www.facebook.com/photo.php?fbid=10103115611237481&set=a.10103115599810381.1073741857.58002911&type=3&theater

It begins

Re: Canada’s Food Guide Consultation

From: Group of concerned Canadian Physicians and Allied Health Care providers

For the past 35+ years, Canadians have been urged to follow the Canadian Dietary Guidelines. During this time, there has been a sharp increase in nutrition-related diseases, particularly obesity and diabetes.

We are especially concerned with the dramatic increase in the rates of childhood obesity and diabetes. In 1980, 15% of Canadian school-aged children were overweight or obese. Remarkably, this number more than doubled to 31% in 2011; 12% of children met the criteria for obesity in the same reporting period. This has resulted in a population with a high burden of disease, causing both individual suffering, and resulting in health care systems which are approaching their financial breaking points. The guidelines have not been based on the best and most current science, and significant change is needed.

From the Report of the Standing Senate Committee on Social Affairs on Obesity in Canada, “Canada’s dated food guide is no longer effective in providing nutritional guidance to Canadians. Fruit juice, for instance, is presented as a healthy item when it is little more than a soft drink without the bubbles”

They have put together a list of things that they believe should happen

Points for Change

The Canadian Dietary Guidelines should:

  1. Clearly communicate to the public and health-care professionals that the low-fat diet is no longer supported, and can worsen heart-disease risk factors
  2. Be created without influence from the food industry
  3. Eliminate caps on saturated fats
  4. Be nutritionally sufficient, and those nutrients should come from real foods, not from artificially fortified refined grains
  5. Promote low-carb diets as at least one safe and effective intervention for people struggling with obesity, diabetes, and heart disease
  6. Offer a true range of diets that respond to the diverse nutritional needs of our population
  7. De-emphasize the role of aerobic exercise in controlling weight
  8. Recognize the controversy on salt and cease the blanket “lower is better” recommendation
  9. Stop using any language suggesting that sustainable weight control can simply be managed by creating a caloric deficit
  10. Cease its advice to replace saturated fats with polyunsaturated vegetable oils to prevent cardiovascular disease
  11. Stop steering people away from nutritious whole foods, such as whole-fat dairy and regular red meat
  12. Include a cap on added sugar, in accordance with the updated WHO guidelines, ideally no greater than 5% of total calories
  13. Be based on a complete, comprehensive review of the most rigorous (randomized, controlled clinical trial) data available; on subjects for which this more rigorous data is not available, the Guidelines should remain silent.

Oh, happy days. My sense of what is now happening is that the momentum against the very stupid and damaging nutritional guidelines that have dominated the Western World for the last forty years is reaching breaking point. This group even managed to throw ‘restricting salt intake’ into the dustbin. Oh, happy days.

If this carries on, I will have nothing left to blog about soon. Suits me.

High cholesterol low heart disease – The Sami

(Of course, it is a paradox…. Paradox number 112, or thereabouts)

As a nod to a regular contributor to this blog, who lives not far from the area, I thought I should write about the Sami. When I was younger we would probably have called the Sami ‘Eskimos’ – because anyone who lived north of the Arctic circle and dressed in fur was, clearly, an Eskimo. This term is now, I believe, a dread insult. A bit like calling a Scotsman an Englishman, or an Austrian a German. Or, I believe, a Canadian an American. Wars have been fought over less.

The Sami, unlike the Inuit, who reside mainly in North America, live in the North of Scandinavia: Northern Sweden, Norway and Finland and suchlike. In what used to be called Lapland. However, we now call the Lapps, the Sami (please keep up), so do they live in Samiland?

What I know about the Sami is that they obviously enjoy the cold, eating reindeer and smoking. They must do other things too, but I am not entirely sure what. This makes them very similar to the Inuit, who also enjoy: the cold, eating seals, caribou, and smoking. Neither the Sami, nor the Inuit, have the least interest in eating vegetables. I suppose there may be the occasional frozen carrot – or suchlike – from Iceland (that is a UK based joke).

Apart from not eating vegetables, smoking, and eating lots of fat, the Inuit and the Sami have one other thing in common. You can probably guess what it is. Yes, they both – those that live a traditional lifestyle anyway – have a very low rate of death from heart disease.

This came to my attention during an e-mail discussion I was having about whether the human brain required any glucose – at all. Those taking part were the usual suspects, Richard Feinman, Gary Fettke, Nina Teicholz, Jimmy Moore, Jason Fung, Tim Noakes etc. [Yes, good bit of name dropping there].

The consensus was that the human brain could use Ketone bodies for much of its energy requirement. However, there was an absolute need for about forty grams of glucose per day. The final statement on this matter, the one everyone seemed to agree on anyway, was as follows:

1)     The brain requires no dietary glucose. It has a requisite use of 40 grams/day, but these grams can easily be provided from glycerol, and normal ingestion of not particularly high amounts of protein in a high fat, zero carbohydrate diet.

2)     But this is a time dependent situation. Short term fasting will not be a problem for most otherwise healthy people. However, more prolonged starvation will eventually kill you as the brain will pirate 40 grams of glucose/day from protein and lipid, until you have neither fat stores, nor adequate diaphragm or heart muscle left to survive.

Don’t worry, there were about a thousand papers quoted in creating these statements, so the science seems robust. This discussion started because I had an interest in how hunter gatherers, who ate no carbohydrates, kept their brains going. What was the mechanism by which the Massai, Inuit and Sami, power their brains with glucose, if they don’t eat any carbohydrates?

Well, it seems that you can get a certain amount of glucose from fat. Fat is made up of triglycerides, and each triglyceride contains three fatty acids and one glycerol molecule. Two glycerol molecules stuck together (by the liver) makes one glucose molecule.

In short, pure fat does contain some glucose, which can be used to power the brain. However – assuming you are eating no carbs – the brain requires more glucose than can be provided by the glycerol held in triglycerides. Thus, you still need to convert some dietary protein into glucose. If you are not eating any food at all, the body will need to break down muscle to get at the protein required to synthesize glucose.

To cut a very long story short, the end point of the discussion was an agreement that you do not actually need to eat any carbohydrates to remain heathy. The body, and the brain, can get all the glucose it requires from glycerol and dietary protein.

The reason why I was interested in this issue was that ‘the absolute need for carbohydrates’ is a ‘fact’ that is thrown at me from time to time by ‘experts.’ I have always known they were wrong, because there are people e.g. the Massai, who never eat any carbohydrates, and remain far healthier than any expert I have ever cast my eyes upon. However, I wanted to be sure of the facts.

Anyway, time to return to the Sami. For, during this lively discussion, someone posted up two papers on the Sami that I had not seen before. Both papers noted that the Sami, despite having very high cholesterol levels, a high level of smoking, a high fat diet and almost zero carbohydrate intake – and suchlike – had a very low rate of cardiovascular disease.

This was particularly interesting for a couple of reasons. Firstly, most of the Sami live in Finland, and the Finns – at one time – had the highest rate of heart disease in the world. Not only that, but the Sami live in an area of Finland, North Karelia, which had the highest rate of heart disease in Finland. The worst of the worst.

In addition, the Sami had considerably worse ‘traditional’ risk factors for heart disease than the surrounding population. Higher cholesterol and LDL, high fat diet, far more smoking etc.

‘The finding of high cholesterol and high prevalence of smoking the Sami area are compared with the reference rate, and high cholesterol in the Samis and Finns in the north, conforms with similar observations. in studies performed previously. As the classic risk factors indicate a high risk of CHD in the north, other factors, possibly the antioxidants, are important in the low CHD mortality there.’1

[Antioxidants and their impact on CHD were studied in the Heart Protection Study (HPS), and found to have no effect on CHD whatsoever. Whilst this study was done by Rory Collins, and has many issues, the data on the lack of impact of antioxidants on CHD appear robust].

Other researchers have also tried to establish why the Sami have such a low rate of CHD/IHD. As noted in the paper ‘‘Low mortality from ischaemic heart disease in the Sami district of Finland’:

An exceptionally low mortality from IHD was found here in the Sami district of Finland and an exceptionally high mortality in a neighbouring Finnish area, a 2-3-fold contrast or even wider, depending on age and time. No difference in IHD of this magnitude between areas located so close to each other has previously been described in the literature.’2

Of course, they looked for the reasons.

‘Reasons for the rarity of IHD in the Sami district of Finland

Our current knowledge of cardiovascular risk factors cannot explain the low mortality from IHD in the Sami district of Finland. Serum cholesterol is, in fact, relatively high in the far north of Finland, and it is higher in the Sami than the Finns, the same being true of the prevalence of smoking, while the low blood pressure frequently found in the far north and among the Sami would be insufficient to cause any substantial reduction in the risk of IHD. Similar differences in serum cholesterol, blood pressure and smoking have also been found between Norwegian Sami and Norwegians of Finnish ancestry. Serum high density lipoprotein cholesterol (HDL)is usually similar in both ethnic groups, although a Finnish study found even lower HDL-total cholesterol ratios in the Sami, which would indicate an elevated risk of IHD… The high serum cholesterol in the Sami can be attributed to their fatty diet.’

In short, the Sami live in area of Finland that had the highest rate of heart disease in the world. Their risk factors were worse than the surrounding population (LDL 4.45mol/l on average), yet their heart disease rate remained very low. It was postulated that this was due to a high intake of antioxidants, but the impact of antioxidants on heart disease has been subjected to large double blind placebo controlled trial, and antioxidants were found to have no impact on heart disease.

At this point you may cry, enough of finding populations that eat a high fat diet, have high LDL levels and low rates of heart disease. It is like shooting fish in a barrel. Not that the experts pay the slightest attention to such contradictory facts. They merely label such findings a ‘paradox’ and move on. But I thought it was interesting. Another nice shiny nail in the cholesterol hypothesis. ‘You call it a paradox, I call it a contradiction… let’s call the whole things off.’

Next, my series on what truly does cause heart disease continues.

1: ‘High serum alpha-tocopherol, albumin, selenium and cholesterol, and low mortality from coronary heart disease in northern Finland’: P. V. LUOMA, S. NAYHA, K. SIKKILA & J. HASSI. Journal of lnternal Medicine 1995; 237: 49-54

2: Simo Nayha: ‘Low mortality from ischaemic heart disease in the Sami district of Finland.’ Soc. Sci. Med. Vol. 44 No. 1, pp. 123-131, 1997

P.S. I am feeling much better, thanks for those who were concerned over my welfare.

Saturated fat and heart disease

The greatest scam in the history of medicine’ George Mann

I have been a bit quiet of late, mainly because I got a cough that ended up as a nasty chest infection, that also caused my brain to turn to mush for about three weeks. Maybe it was the antibiotics. Anyway proof, as far as I am concerned, that the mind and body are closely connected.

Yes, another little detour from my series, trying to explain what causes cardiovascular disease. But I thought I need to look, once again, at the hypothesis that saturated fat consumption is a cause – perhaps the cause of cardiovascular disease?

To be honest, I have studied saturated fat consumption many, many… many, many, times. The one thing that has always stood out, most starkly, is the complete lack of any real evidence to support the idea that it causes cardiovascular disease.

On the other hand, evidence contradicting it arrives on an almost daily basis. The following study was sent to me a few days ago, although it is now almost ten months since it was first published. The researchers looked at nearly thirty-six thousand people over twelve years. It was done in the Netherlands. The main conclusions were that that:

‘Total saturated fat intake was associated with a lower IHD (Ischaemic Heart Disease) risk (HR per 5% of energy 0.83). Substituting SFAs with animal protein, cis-monounsaturated fats, polyunsaturated fats or carbohydrates was significantly associated with higher IHD risks (HR 1.27 – 1.37).’1

One thing scientific researchers have learned over the years is that you can never say anything in a straightforward way. I think the game is that, if anyone can easily understand your findings, you lose. A game played to its illogical conclusion by French Philosophers. Something I remarked to my son, who was trying to quote Derrida at me. Here would be one snappy Derrida quote:

“Every sign, linguistic or nonlinguistic, spoken or written (in the usual sense of this opposition), as a small or large unity, can be cited, put between quotation marks; thereby it can break with every given context, and engender infinitely new contexts in an absolutely nonsaturable fashion. This does not suppose that the mark is valid outside its context, but on the contrary that there are only contexts without any center of absolute anchoring. This citationality, duplication, or duplicity, this iterability of the mark is not an accident or anomaly, but is that (normal/abnormal) without which a mark could no longer even have a so-called “normal” functioning. What would a mark be that one could not cite? And whose origin could not be lost on the way?”

Yes, indeed. Couldn’t agree more.

As with Derrida, so with scientific papers. What these researchers should have said is the following. ‘The more saturated fat you eat, the lower your risk of dying of cardiovascular disease, and vice-versa.’ A thirteen per cent reduction in death for every five per cent increase in energy obtained from saturated fat consumption. Why do they run away from making such easy to understand statements? I think Derrida could probably tell us. If we could ever understand anything he ever wrote, or said.

However, I am not going to bombard you with endless facts contradicting the saturated fat hypothesis, I am going to get a little more philosophical here. To ask, what is it about some scientific ideas/hypotheses that they become so quickly entrenched – without the need for the tedious requirement of any actual facts.

My thoughts were drawn to this issue by something seemingly unconnected. Which is a legal hearing the UK concerning shaken baby syndrome. Most experts in paediatrics are absolutely convinced that there is such a thing. It is quoted in textbooks as an undisputed fact. Many parents, and other adults, have been convicted, and sent to jail, for shaking their babies so hard that it caused the ‘triad’ of shaken baby syndrome: subdural hematoma, retinal bleeding, and brain swelling

On the other hand, we have Dr Waney Squier, a paediatrician who used to provide expert opinion on child abuse cases in the UK. She was struck off by the General Medical Council (GMC) for, well the exact judgement is, as per Derrida, impossible to understand.

The GMC judgement has certainly been criticized:

‘Michael Mansfield, Clive Stafford Smith and others argue that the General Medical Council is behaving like a “21st-century inquisition” in the case of Dr Waney Squier (Shaken baby syndrome doctor struck off, 22 March).’

The GMC responded thus:

‘Far from wishing to suppress different views, we recognise that scientific advance is achieved by challenging as well as developing existing theories, and importantly in this context we are absolutely clear that neither the GMC nor the courts are the place where such scientific disputes can be resolved. To be clear, it is possible that a doctor who ultimately was proved to have the correct theory could present their evidence in such a way as to mislead, just as it is possible for a doctor advocating a theory ultimately proved to be flawed to present their case in context and with integrity.’

Niall Dickson

Chief executive, General Medical Council

The only possible response to Niall Dickson’s remark is ‘bollocks.’ You can present the correct theory in a way to mislead, and you can present a flawed hypothesis with integrity? George Orwell would surely nod in approval of such perfect doublethink. You are right, but we don’t like the way you present being right. We would rather listen to someone talk absolute nonsense using the correct professional manner. Can I have my knighthood now, please?

Leaving the machinations of the GMC aside, the main issue is simple. Dr Waney Squier does not believe that shaken baby syndrome exists. Of course she knows that the triad of subdural haematoma, retinal bleeding and brain swelling exists. But she believes there could be other explanations. Including, perish the very thought, an accidental fall.

Because she does not believe in shaken baby syndrome, she has presented evidence in court which has tended to undermine the prosecution case against parents and carers, accused of shaking a baby and causing severe brain damage. Much to the annoyance of the police and they then, for it was indeed them, reported Dr Squier to the GMC.

Now, I know what most of you are thinking. Surely ‘shaken baby syndrome’ exists. This must have been proven. Well, it has not. If you think about it, how could it be proven? How do you think a study on shaken baby syndrome could ever be done? Get five hundred children, shake them forcefully and see what happens to their brains. I suspect you might find gaining ethical approval for a such a study might be tricky.

Despite this, and the fact that shaken baby syndrome represents an ‘unproven hypothesis’ almost all experts around the world are convinced that shaken baby syndrome exists. Dr Squier, who seems a well-rounded and sensible lady, has made the terrible mistake of questioning that this dogma. There could be, shock horror, other possible causes.

The police objected, judges objected, her peers objected, and she has been struck off. No longer able to practice medicine anywhere in the world. She has become a medical pariah.

The good news is that her case in going in front of an actual court of law in the UK. I strongly suspect (maybe I just hope) that her ‘conviction’ will be overturned. She does have the support of a number of other paediatricians around the world. However, in the meantime, other doctors, who do not believe in shaken baby syndrome, will not dare go to court to testify in support of those accused of shaking babies. Such is the power of the Spanish Inquisition.

Shaken baby syndrome: saturated fat consumption.

On the fact of it shaken baby syndrome and saturated fat consumption have very little in common. However, from another perspective the parallels are clear. Both are seductively simple ideas that appeal to common sense. That most deadly of all senses.

Most people can clearly see how a small, vulnerable, baby will suffer significant brain injury if it is shaken too hard. Close your eyes and you can virtually see it happening. If you can bear having that image in your head for any length of time.

Most parents, I think, can almost see themselves doing it, or having done it – when their child will ‘just not dammed well stop crying.’ In short, shaken baby syndrome can easily be visualised, and it triggers a kind of visceral horror. We can easily see how a feckless parent may lack the self-control required to stop themselves doing it. ‘Shut up, shut up, shut up….’

And that, dear reader, is as scientific as shaken baby syndrome gets. A hypothesis based on visceral fear, prejudice, and knee-jerk judgement. This makes it almost perfectly resistant to any contradictory evidence. Try to argue against it, and you will meet anger and bluster and the idee fixe.

I was once told a story which goes as follows. It concerns a psychiatrist trying to convince a patient that he is not dead. A battle that that had gone on for many years, eventually the psychiatrist comes up with a brilliant idea….

Psychiatrist:       ‘Do dead people bleed?’

Patient:                                   ‘No, I guess not.’

Psychiatrist:       (Takes pin from lapel and pricks the patient’s thumb, and a drop of blood appears). ‘Aha, do you see that?’

Patient:                 (Looks at thumb) ‘What do you know, I guess dead people do bleed then.’

 

The ‘saturated fat causing heart disease hypothesis’ comes from a very similar place called – well, it’s obvious isn’t it, just common sense. Heart disease is basically a build of fat in the arteries, isn’t it.? Where can that possibly come from? Fat in the diet. Especially the thick, sticky, gooey stuff that you get on a pork chop, or suchlike. That’s got to be it hasn’t it? The thick horrible squidgy gooey fat that you eat, ends up as thick horrible squidgy gooey fat in your arteries. Serves you right for eating fat, and MacDonald’s, and suchlike.

There rests the entire scientific argument against saturated fat. As such it is difficult to argue against. Facts simply bounce off. As demonstrated very clearly to me in a more recent publication. A very major review was published a few weeks ago on the Journal of Food and Nutrition Research called ‘Food consumption and the actual statistics of cardiovascular diseases: an epidemiological comparison of 42 European countries.’ 2

‘The aim of this ecological study was to identify the main nutritional factors related to the prevalence of cardiovascular diseases (CVDs) in Europe, based on a comparison of international statistics.

What did they find? Well, they found lots of things, but the key things they found were the following:

We found exceptionally strong relationships between some of the examined factors, the highest being a correlation between raised cholesterol in men and the combined consumption of animal fat and animal protein (r=0.92, p<0.001). The most significant dietary correlate of low CVD risk was high total fat and animal protein consumption.’

Now that paragraph really needs a however in it. Just after p<0.001 and the ‘The.’ Yes, they found that animal fat (mainly saturated fat) and animal protein did indeed raise cholesterol. However, animal fat and animal protein consumption showed the most powerful correlation with low risk of cardiovascular disease.

Which food items showed the highest correlation with increased CVD risk? Have a guess.

‘The major correlate of high CVD risk was the proportion of energy from carbohydrates and alcohol, or from potato and cereal carbohydrates.’

The conclusion of the authors:

‘Our results do not support the association between CVDs and saturated fat, which is still contained in official dietary guidelines. Instead, they agree with data accumulated from recent studies that link CVD risk with the high glycaemic index/load of carbohydrate-based diets. In the absence of any scientific evidence connecting saturated fat with CVDs, these findings show that current dietary recommendations regarding CVDs should be seriously reconsidered.’

When the British Heart Foundation was presented with the findings from this study they found a Dr Mike Knapton to make the following statement:

“Other studies, however, show diets high in saturated fat are linked to raised cholesterol levels, which is a risk factor for heart disease. So, for you and me, we should consider our diet as a whole to reduce our overall risk, such as a traditional Mediterranean style diet, which is a style of eating associated with a lower rate of coronary heart disease. The key is a balanced diet over all, rather than considering individual foods. There are many factors which cause heart disease and stroke and no single food or nutrient is solely responsible for this. We will continue to recommend switching saturated fat for unsaturated fat.”

As you can see, when presented with evidence, the BHF refuses to consider it, and turns to gibberish. Dr Mike Knapton argues that this study should be ignored, because other studies have shown that saturated fat raised cholesterol levels, and this is a risk factor for heart disease.

‘Hellooo Dr Knapton. This study also showed that saturated fat increased blood cholesterol levels. However, what it also showed is that this reduced the risk of heart disease. Did you even read that bit, or do you simply dismiss papers contradicting the diet-heart hypothesis on the basis they must be wrong – so what it the point of actually reading them?’

On many occasions I, and others, have tried to engage the BHF in debate. However, you can’t. They just provide ‘statements’. The statements never change, the evidence they use never revealed. However big a study, however contradictory it is, it will be met with statement such as Other studies, however, show diets high in saturated fat are linked to raised cholesterol levels, which is a risk factor for heart disease.

Made up scientific hypothesis are, I find, very difficult to dislodge with evidence.

1: ‘The association between dietary saturated fatty acids and ischemic heart disease depends on the type and source of fatty acid in the European Prospective Investigation into Cancer andNutrition–Netherlands cohort’ Jaike Praagman, Joline WJ Beulens, Marjan Alssema, Peter L Zock, Anne J Wanders, Ivonne Sluijs, and Yvonne T van der Schouw. Am J Clin Nutr doi: 10.3945/ajcn.115.122671

2: http://www.foodandnutritionresearch.net/index.php/fnr/article/view/31694

Buy this new book

Fat and Cholesterol Don’t Cause Heart Attacks

There is a group of doctors, scientists and researchers called the International Network of Cholesterol Skeptics (THINCS) www.thincs.org. I am a member, and recently a number of us have contributed chapters to a new book called Fat and Cholesterol Don’t Cause Heart Attacks And Statins are Not the Solution.

This was written in honour of the founder of THINCS, Uffe Ravnskov, a Swedish doctor and researcher who has been arguing against the current die-heart/cholesterol hypothesis for many years. He has written several books, many, many, research papers, and had the dubious honour of having one of his book burned, live, on television. [Finland 1992, the book was The Cholesterol Myths]. He has also been ruthlessly attacked, both professionally and personally. Yet he has never given up.

Ravnskov, like all of us in THINCS, started looking at heart disease, or cardiovascular disease (CVD) and recognised that the widely accepted views were simply wrong. Something recognised by many people over the years, including Professor George Mann (who helped to start up and run the Framingham study).

‘Saturated fat and cholesterol in the diet are not the cause of coronary heart disease. That myth is the greatest scientific deception of this century, perhaps of any century.’

George Mann, like many others was silenced. Kilmer McCully, who discovered the role of homocysteine in CVD, and suggested that it could be more important that cholesterol was also attacked. Funding for his research disappeared, leading to the loss of his laboratory. His hospital director told him to leave and ‘never come back’. His Harvard affiliation and tenure were terminated.

Another contributor to this book, Professor Michel De Logeril, set up and ran the seminal Lyon Heart Health Study. Possibly the seminal work on the ‘Mediterranean Diet.’ Yet he is a trenchant critic of the diet-heart hypothesis, and believes that statins do more harm than good. He is, again, attacked ruthlessly.

Yes, there is a pattern here. Dare to criticise the current dogma that saturated fat in the diet raises cholesterol, which then goes on to cause CVD, and your chances of progression in the research world are, precisely, zero. Your chances of getting anything published are, pretty close to zero. You will be attacked both personally and professionally. You will be accused of killing thousands of people by putting them of taking statins – and suchlike.

However, those in THINCS have never given up in their efforts to get the ‘truth out there’ and never will. This book is a further way to help inform the public about the true facts. There are chapters on competing hypotheses as to the cause(s) of CVD, there are chapters outlining the flaws in the current ideas. Some chapters are technical, others not.

Everything is held together by Paul Rosch, a brilliant researcher, writer and editor, clinical professor of Medicine and Psychiatry and New York Medical College, Chairman of the Board of the American Institute of Stress, and a great, deep thinker, on many subjects. Would that there were more like him.

thincs-coverart-frontcover-sm

You can get a copy direct from the Publishers here…

Or if you prefer to support Amazon, it’s on Amazon UK here and Amazon USA here


Amazon.co.uk
Amazon.com