Tag Archives: statins

Another point of view

As someone who considers myself to be a scientist, I thought I should present another view to you on statins. This piece (a transcript of a talk) can be seen on Medscacpe¹.

Please read on, and see what you think of his arguments:

I am Dr. Frank Veith, Professor of Surgery at New York University Medical Center and the Cleveland Clinic. Today I am going to talk about what I call the “statin witch hunt” and why, despite it, we should give more patients statin drugs.

The question of whether to give statins to more healthy patients is one of considerable interest to the public and considerable debate in both the medical community and the lay press. In November, the American College of Cardiology (ACC) and the American Heart Association (AHA) released their long-awaited new guidelines on the treatment of blood cholesterol to reduce the risk for adult atherosclerosis. T

This guideline, among other recommendations, guided physicians to expand the number of patients being treated with statin drugs. The guideline was greeted with many objections in both the medical community and the lay press. Most notable was a November 14 New York Times op-ed by 2 respected experts, Drs. John Abramson and Rita Redberg, titled “Don’t Give More Patients Statins.”

Other New York Times articles about Drs. Paul Ridker and Nancy Cook, and another by Gina Kolata, expressed similar reservations about the ACC/AHA guideline recommendation to broaden statin administration. All three of these New York Times articles were part of what I call the “statin witch hunt” which has generated much confusion among the public.

The op-ed by Drs. Abramson and Redberg makes the case that the recent ACC/AHA cholesterol guideline is incorrect to advocate the expansion of statin usage to more patients because such expansion “will benefit the pharmaceutical industry more than anyone else.” They state that the guideline’s authors were not “free of conflict of interest.” In addition, they claim that “18% or more” of statin recipients “experience side effects” and that the increase in statin administration will largely be in “healthy people” who do not benefit and who would be better served by an improved diet and lifestyle.

Although the latter is true for everyone, Drs. Abramson and Redberg convey the wrong message. Statins are the miracle drug of our era. They have proven repeatedly and dramatically to lower the disabling and common consequences of arteriosclerosis — most prominently heart attacks, strokes, and deaths in patients at risk. Statins avoid these vascular catastrophes not only by lowering bad blood lipids but also by a number of other beneficial effects that stabilize arterial plaques.

They have minimal side effects, most of which are benign. In several controlled studies, the patients who did not receive statins had an incidence of side effects equal to those who received them. Serious side effects are rare and manageable. Moreover, healthy patients are only healthy until they get sick. Many individuals over the age of 40 take a daily aspirin.

Statins are far more effective than aspirin in preventing the heart attacks and strokes that often occur unexpectedly in previously “healthy people.” Clearly it would be worthwhile for such healthy people to take a daily statin pill with few side effects, if it would lower their risk for such vascular catastrophes and premature death.

In contrast to what is implied in the Abramson-Redberg article, these drugs are an easy way for people to live longer and better, and statins cannot be replaced with a healthy lifestyle and diet — although combining the latter with statins is a good thing.

Lastly, with respect to the comments about the pharmaceutical industry benefiting from statin prescriptions, and the guideline authors’ conflicts of interest, both are less important than patient benefit, which has been demonstrated dramatically and consistently in many excellent and well-controlled statin trials. Moreover, most statins are now generic, so the cost for obtaining these miraculous drugs need not be prohibitive, and the guideline’s authors are experts who are eminently qualified to write them.

The statin witch hunt is a bad thing, and more patients should be on statin medication. I am Dr. Frank Veith, and that is my opinion.

1: http://www.medscape.com/viewarticle/822145?nlid=51963_1985&src=wnl_edit_medn_card&spon=2

(You will need to subscribe to Medscape to see the talk, and transcript. It is fairly straightforward to gain access. The site is www.medscape.com It is one of the biggest medical websites.)

I though you should know if Frank Veith has any conflicts of interest. He works at the Cleveland Clinic, so he probably doesn’t, as most of the medical experts who work there state that they give all of their income from working with the pharmaceutical industry to charity. Steven Nissen, a man of whom you may have heard me speak on a regular basis, is the chairman of Cardiovascular medicine at the Cleveland Clinic.

Here, for example, is Steven Nissens conflict of interest statement

Dr Steven Nissen
Medical Director
Cleveland Clinic Cardiovascular Coordinating Center

Dr. Nissen has received grant/research support from AstraZeneca Pharmaceuticals, Atherogenics; Eli Lilly and Co., Lipid Sciences, Pfizer Labs, Sankyo Pharma, sanofi-aventis, and Takeda Pharmaceuticals North America with all reimbursement directed to the Cleveland Clinic Cardiovascular Coordinating Center; and has been a consultant for Abbott Laboratories, AstraZeneca Pharmaceuticals, Atherogenics, Bayer Corp., Eli Lilly and Co., Forbes Medi-tech, GlaxoSmithKline Pharmaceuticals, Haptogard, Hoffman-LaRoche, Isis Pharmaceuticals, Kemia, KOS Pharmaceuticals, Kowa Optimed, Lipid Sciences, Merck/Schering Plough, Novartis Pharmaceuticals Corp., Novo-Nordisk, Pfizer Labs, Protevia, Roche Pharmaceuticals, Sankyo Pharma, sanofi-aventis, Takeda Pharmaceuticals North America, Vasogenix, Vascular Biogenics, Viron Therapeutics, and Wyeth Pharmaceuticals, all fees are paid directly to charity with no reimbursement paid to Dr. Nissen; and has served on the speakers’ bureaus of AstraZeneca Pharmaceuticals and Pfizer Labs, all fees are paid directly to charity with no reimbursement paid to Dr. Nissen.

Cleveland Clinic physicians and scientists may collaborate with the pharmaceutical or medical device industries to help develop medical breakthroughs or provide medical education about recent trends. The collaborations are reviewed as part of the Cleveland Clinic’s procedures. The Cleveland Clinic publicly discloses payments to its physicians and scientists for speaking and consulting of $5,000 or more per year, and any equity, royalties, and fiduciary relationships in companies with which they collaborate. The Cleveland Clinic requires its doctors to approve the public disclosures of their scientific collaborations with industry. As of 3/21/2014 the review process regarding Dr. Veith’s disclosure had not been completed. Patients should feel free to contact their doctor about any of the relationships and how the relationships are overseen by the Cleveland Clinic. To learn more about the Cleveland Clinic’s policies on collaborations with industry and innovation management, go to our Integrity in Innovation page.

Although now dead, the Cholesterolosaurus will march on

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A meta-analysis including 530,525 people, partly funded by the British Heart Foundation, and published in the Annals of Internal Medicine has just come to this conclusion:

Conclusion: Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats¹.

Or to put it another way, there is no evidence that saturated fat consumption has anything, whatsoever, to do with causing heart disease, or strokes. Once again I get to say ‘I told you so.’ Ah, the four most satisfying words in the English language. That is, when arranged in that particular order.

So, eat butter, drink milk, and throw away the horrible sugar-loaded low fat yoghurt. Go to France and enjoy the highest saturated fat diet in Europe and you, too, can enjoy the French rate of heart disease. Yes, of course, the lowest in Europe.

But now what happens? You see, the entire edifice of the cholesterol hypothesis is held together by two links in a chain. Link one is that saturated fat consumption raises cholesterol levels. Link two is that raised cholesterol levels then cause heart disease.

Various ‘experts’ have simplified this to the very simple equation:

A (saturated fat in the diet) > B (high cholesterol levels) > C (heart disease)

This is the cholesterol hypothesis, or the lipid hypothesis, and it has driven medical thinking for the last sixty years.

I have had it painstakingly explained to me, by very clever people, exactly how saturated fat raises cholesterol levels. Indeed, you will find ‘evidence’ for this almost universally accepted fact in literally thousands of clinical studies. Here is what Wikipedia has to say on the matter

‘There are strong, consistent, and graded relationships between saturated fat intake, blood cholesterol levels, and the mass occurrence of cardiovascular disease. The relationships are accepted as causal².’

Okay, let us accept that eating saturated fat does raise cholesterol levels. However, if consumption of saturated fat does not increase the rate of heart disease then….. Then raised cholesterol levels can have nothing whatsoever to do with causing heart disease. Just keep chasing the implications of that statement around in your head for a while.

So what happens now? We now have a cholesterol/lipid hypothesis that just had its head blown off. Yet, it still continues to wander about, unaware that it is actually dead.

As everyone knows you can chop the head off a chicken and it can wander about for years. I was also informed, when I was an open-mouthed child, that you could shoot a dinosaur through the head and it would continue to blunder about for some time, the rest of its body blissfully unaware that it was actually dead.

Well, the cholesterol hypothesis has just been shot dead, but I suspect it will continue to rampage about, stomping on puny humans for many years, before it finally keels over and admits that it is dead.

But I say, farewell Cholsterolosaurus. You are now a deceased hypothesis. Gone to meet your maker. You just don’t know it yet. Because the people that believe in you do not understand logic.

1: http://annals.org/article.aspx?articleid=1846638
2: http://en.wikipedia.org/wiki/Saturated_fat

A sorry little patient tale

162 Replies

Working as a GP in England becomes increasingly difficult as the drive to put more and more people on statins gathers pace. Virtually every day I see a patient taking statins who is suffering a clear adverse effect.

I know that this is a very biased sample, because patients in the area know that I am ‘the doctor who writes stuff about statins.’ So there is a degree of self-selection going on here. People who think they may be having adverse effects choose to see me.

However, there is another degree of self-selection going on here. When I see that a patient is on statins, I tend to be on high alert for any mention of statin related adverse effects. Whilst most other doctors happily dismiss such things as: tiredness, memory loss, joint pains, muscle pains depression, irritability, impotence, stomach pains, skin rashes and the like as ‘nothing to do with statins.’ I tend to think the statin may be the cause.

I then usually say. Stop the statin for a couple of months and see what happens to your, tiredness, memory loss, joint pains etc etc. Very often these symptoms go away. Then what? Then the practice statin prescribing statistics start to look quite bad. The senior partner (who is pretty sympathetic to my cause), has had words. The practice is losing money. I have had to ‘exempt’ more and more patients from the cardiovascular disease indicators.

The prescribing lead from the local Clinical Commissioning Group has also had words. It is clear that my non-prescribing of statins is very much frowned upon. Although nothing concrete has yet happened, the pressure to conform cranks up. At times I wonder why I bother. Should I just focus my anti-statin efforts at a more global level? Writing articles, lecturing, speaking to journalists, writing books, and the like. .What difference can I make with a few patients in the practice?

Yesterday, however, I saw a lady who had been admitted to hospital with severe abdominal pains. So severe that she had scans, tests, and was very nearly taken down to surgery for an exploratory operation. Did she have galls stones, appendicitis, cancer? Nothing could be found.

She was discharged with strong painkillers, and follow-up appointments were arranged. She came to see me between Christmas and the New Year to get more painkillers to tide her over. I suggested that the statin may be causing her stomach pain, and that she should stop them, which she did.

Guess what. Of course, the stomach pains have gone. She also reported that she’d had three episodes of Transient Global Amnesia whilst taking statins. This is where your memory goes, you wonder about as if in a fugue, and can remember nothing of what went on. She had not reported these episodes to anyone, but since being made aware that stains can cause them, she now knows what happened.

Since stopping the statins she also reports that her energy levels are back to normal, and that she feels human again. Her life, her quality of life, has returned.

After thanking me for helping her, she then asked. ‘What do you think I should do, doctor. Should I go back on them again, the other doctors say that I should, but I don’t want to.’

A farewell to statins – part two

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And so it begins:

‘ …..a Pfizer rep confirmed to me that they were now telling all GP’s that statins do have side-effects and shouldn’t be prescribed anymore but to prescribe the new post-statin drugs…………. how two-faced can you get!!!!’

This was in an e-mail from a friend and supporter of mine, who has close contacts with the pharmaceutical industry.

Well, if you are going to challenge the dominant position of statins, the first thing that you have to do is to attack them. What is the best line of attack? Go after their greatest weakness, which is that they cause serious adverse effects, and damage the quality of life of many people. Something I have been saying for a long, long, time.

For years the experts have informed us that this is utter rubbish, statins are wonder-drugs, and adverse effect free. All of a sudden, now that the pharmaceutical industry is about to launch new cholesterol lowering agents, we are suddenly going to find that, why, after all, statins do cause a whole range of nasty adverse effects.

If you want to see exactly how this is going to be done, watch this discussion on Medscape. The Medscape site needs a password, however you can get one fairly simply. In this ‘educational’ discussion we see three professors talking about the new cholesterol lowering agents that are soon to arrive. The dreaded PCSK9-inhibitors.

The names of these three professors are Prof Christie Ballantyne, Prof Stephen Nicholls and – yes, you guessed it – Prof Steven Nissen. Is there a new cardiovascular drug in development that he does not get involved with?

The first part of the discussion focusses entirely on the terrible problem of people being statin intolerant; people being unable to take high doses of statins, and the high burden of adverse-effects from statins.

A slide is shown from the PRIMO observational study showing that 15% of people taking atorvastatin have significant adverse effects, and 20% of those taking simvastatin suffer significant adverse effects. These, of course, are the two statins with by far the greatest market share. My, what a coincidence.

The discussion then opens out into the worrying problems with statins causing both diabetes and cognitive dysfunction (something vehemently denied for many, many years). Ballantyne was particularly eloquent on these issues.

The entire tone is one more of sorrow than anger. ‘Statins….great drugs….hate to see them go, but you know, their time is passing.’ Professor wipes a small tear from his eye at the thought.

I watch this stuff with a kind of morbid fascination. The marketing game is on, billions are about to be spent pushing PCSK9-inhibitors. The Key Opinion Leaders who tirelessly promoted the wonders of statins, and who told us that they were virtually side-effect free, are now singing a completely different tune.

Here is what one the panellists Prof Christie Ballantyne had to say about statin adverse effects in his book ‘Dyslipidemia & Atherosclerosis Essentials 2009’. This can be found on page 91, under the heading Adverse Effects and Monitoring.

‘Statins are very well tolerated with infrequent and reversible adverse effects. In large placebo controlled studies the frequency of adverse effects was similar to placebo (2-3%).’

Here, however, is what he said in March 2013

“Some people have hereditary disorders and have extremely high LDLs. And so the statin has some efficacy but not enough to get them down as low as they’d like. Then some people have less response than others, and we don’t understand all of that. Some of that may be genetic. And it turns out there’s an even probably larger group of people that have a hard time taking a high dose of a statin.”

Even though statins are safe for most people, there are those that can’t take them because they experience side effects.

“Many people complain of some muscle pain, soreness, weakness, excessive fatigability. There’s some slight increase in diabetes also. That can occur with high dose statins, and some people [who] say that they may have problems with their nerves or cognition.”¹

Well, that is all nice and consistent. Finally, here he is on Sunday 8^th Dec, quoted as part of a discussion on the new AHA/ACC guidelines.

“Clearly, the focus is to get people on statins,” said Dr. Christie Mitchell Ballantyne, the chief of cardiology and cardiovascular research at Baylor College of Medicine, in Houston. “But if someone has seen four doctors and tried six statins and tells me they can’t take them, what am I going to do? Tell them they are a failure?”

Ballantyne said he would give such patients a non-statin drug, despite the guidelines.’²

….Ballantyne said he would give such patients a non-statin drug, despite the guidelines.’ I wonder what he could possibly mean by this. Perhaps George Orwell had it right.

‘Four legs good, two legs bad’……becomes….’Four legs good, two legs better.’

“The creatures outside looked from pig to man, and from man to pig, and from pig to man again; but already it was impossible to say which was which.”

[A farewell to statins – Part three will arrive at some point.]

P.S. Please watch the video clip soon, as I suspect it may not last very long after this blog.

1: http://www.houstonpublicmedia.org/articles/1362665170-Promising-Baylor-Research-Reduces-Bad-Cholesterol.html

2: http://www.staradvertiser.com/news/20131114_New_cholesterol_advice_startles_even_some_doctors.html

A farewell to statins – part one

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In the end I knew that statins would be overthrown. Their time, like the dinosaurs would come to an end. I also knew it would be nothing to do with me, or any of the other critics. Nor would it have anything to do with the fact that their terrible burden of adverse effects finally came to light.

No, it would be because their patents ran out, which meant that the big pharmaceutical companies could not make eye-watering profits from them anymore. Inevitably, therefore, they would be replaced. Indeed, for years I have watched, with varying degrees of amusement, the unending efforts to unearth the ‘new’ statins. The wonder drugs to be taken by everyone, for the rest of their lives. The ones that will make billions for the pharmaceutical companies, and several millions for the key opinion leaders promoting them.

Steven Nissen had a go with apoA-1 Milano. This is a little story you may want to look up on Wikipedia. Basically, a small village was found in Italy (near Milan) where people had very low rates of heart disease, and they also had very low levels of HDL ‘good’ cholesterol.

Turning science on its head, it was therefore decreed that their HDL must be especially ‘good’ at preventing heart disease. [Rather than accept that HDL had bugger all to do with heart disease]. So attempts were made to synthesize their form of HDL, then inject it into patients. This was done in small scale clinical studies.

So brilliantly did Nissen sell the results of these studies that a start-up company called Esperion, which funded the trials, was sold to Pfizer for over a billion dollars on the back of the results. If you want to find out more, the HDL synthesized was called ETC-216, not apoA-1 Milano.

This is what Steven Nissen had to say about the trials.

“The fact that you can actually pull major amounts of plaque out of the artery in five or six weeks is an epiphany,” Nissen says. H. Bryan Brewer, chief of the molecular disease branch at the National Heart, Blood & Lung Institute, adds: “Quite to everyone’s surprise, this indicates that we might be able to be much more successful in a shorter period of time than we thought possible.”

By golly it all sounds very exciting, does it not. Pulling significant amounts of plaque out of artery walls, in six weeks! This is quite amazing, what a brilliant drug. In truth, though, that quote was from 2003. Has anything since happened since to this magical plaque munching HDL? Is it now on the market, saving lives? Well, as you ask, the answer is no.

However, several other HDL raising agents have also been developed in the last few years. Unfortunately, they also raised the risk of heart attacks and strokes – then disappeared. Torcetrapib, dalcetrapib, anacetrapib…. A yes, anacetrapib, not quite gone yet.

‘Anacetrapib has a knock-your-socks-off effect on HDL and a jaw-dropping effect on LDL,” said Chris Cannon in an AHA press release. He also said “The lipid effects are jaw dropping in both directions,” Yes, indeed, they were. Although I am not sure that ‘jaw dropping’ and ‘knock your socks-off’ are truly scientific terms.

But then Forbes ran this headline on the 22^nd October

‘Merck Heart Drug Runs Into New Worry.’ ¹

As an aside, you can find out far more about drugs in development by reading Forbes magazine than you will ever get from the scientific journals.

Anyway, I wouldn’t bet the house on anacetrapib as I suspect it will soon follow the other ‘trapibs’ into an early grave. But never mind, Lilly has yet another HDL raising agent waiting in the pipeline, evacetrapib. What is it with these unpronounceable names, and why don’t these companies just give up? However, perhaps this one has a better shot than most, because as Steven Nissen said of dalcetrapib…

“Dalcetrapib was always a long shot,” said Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic. “The worry all along was that it wouldn’t have enough effect to produce a benefit,”

Then, as he went on to say of evacetrapib

“We got everything we could hope for from this drug, and maybe more,” remarked study co-author Steven Nissen, adding that “we are going to move evacetrapib forward as rapidly as possible” into a late-stage trial.” Gosh, he is running a study on evacetrapib too. He was also lead investigator for Torcetrapib².

That Steven Nissen, what a busy chap he is? Wasn’t he the one who said about the new cardiovascular prevention guidelines. “The evidence was never there” for the LDL targets, he said. Past committees “made them up out of thin air,” he added. Why yes, I think he was.

Anyway. They have tried raising HDL…fail. They have tried a different way of lowering LDL using ezetimibe. It lowered LDL, and has had absolutely no effect on cardiovascular disease…fail. They have tried combing different HDL raising agents with statins….fail.

You know, you might even begin to think that raising HDL wasn’t that good an idea. Billions have been thrown this target, everything has miserably failed. It is also interesting that LDL lowering agents, other than statins, have failed to have any impact on cardiovascular disease. Has this had any effect on the lipid hypothesis? You must be joking.

Given this litany of disastrous drugs trials, why do I now believe that statins are about to be overthrown? What agents could be out there that are going to sweep them into the dustbin of history.

Clearly it cannot be an agent that lowers LDL even more than statins. Can it? Well, Steven Nissen has recently said the following about LDL lowering. This quote is in connection to new drugs being developed³.

“….it matters how you lower cholesterol, not just by how much.”

It matters how you lower cholesterol, not just by how much….. Interesting. Well, if cholesterol does cause heart disease, then it doesn’t really matter how you lower it, does it? The only question is, by how much? Or is Steven Nissen trying to say something else?

As a further aside, if you want to know where the really big bucks are being spent in cardiovascular research, and what is in the pipeline, all you need to do is follow Steven Nissen’s pronouncements. He is the weather vane. You don’t need to be a weather man to know which way the wind is blowing.

…… (to be continued)

1: http://www.forbes.com/sites/matthewherper/2013/10/22/merck-heart-drug-runs-into-new-worry/

2: http://online.wsj.com/news/articles/SB10001424052702304363104577389353232022644

3: http://www.forbes.com/sites/johnlamattina/2013/09/05/esperions-novel-approach-to-lowering-cholesterol-will-it-be-successful/

What is your ‘Statin by date’?

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Somewhat to my chagrin, I filled in my risk factors into the new ACC/AHA guidelines on cardiovascular disease prevention. I now find that I should have started statins eight weeks ago. Naughty, naughty, me. My blood pressure was a bit higher than the calculator liked 138/82, my cholesterol quite a bit higher at 6.0mmol/l.

Which means that I have already passed the 7.5% ten year risk score. O….M…..G. (I think my picture makes me look a bit younger than I am, although it was only taken last year – honest)

What to do?

I am now well beyond my ‘Statin by date.’ No longer can I be healthy without taking a statin. By the way, a friend came up with the concept of ‘statin by date.’ It did make me laugh, conjuring up the image of a sell by date on a can of baked beans. Or maybe Logan’s run. If you remember that film, once you reached the age of, I think it was thirty, you had to leave the colony as you had reached your sell by date. ‘No this is not au-revoir…. It is goodbye.’

Can I be reassured that my parents are both alive and healthy in their late eighties. My grandmother, on my mother’s side, lived to one hundred and two. No idea about my father’s side. WWII did for both my grandparents on that side.

Can I feel comfort in the fact that I play squash three times a week, go to the gym twice a week and walk when I can? Mind you all of this is wiped out by my excess consumption of alcohol I suppose – unfortunately. Also, I am in the overweight category with a BMI, of 28. But wait, isn’t the entire English rugby team obese, using the BMI. Must be all the training and muscle bulk that does it. Yes, the jolly old BMI.

No, I thought I was a pretty healthy chap. I have no real risk factors for heart disease at all. A resting pulse rate of 48, a reasonable blood pressure……

In truth I feel terribly sorry for the Swiss. They have the highest average cholesterol level in Europe at 6.4mmol/l (250mg/dl in those inconvenient US units). Surely the entire nation must be put on statins straight away. But, hold on, wait just one gosh darned minute. Don’t they have the second lowest rate of heart disease in Europe?

Why yes, they do. Only beaten by the French. Who have an average cholesterol levels higher than most other countries, they also eat the most saturated fat in Europe, and yet they have the lowest rate of heart disease. About one quarter that of the UK and US. I wonder how the ACC/AHA calculator works for them? Perhaps not that well. Ah oui, bonne chance. Zey must be, ‘ow you say ‘une paradox’. (Or would that be ‘un paradox’)

As you can tell I think I am grasping at straws. Who am I to attempt to stand against the massed intellectual power of the ‘experts.’ The reality is that I feel the breath of the grim reaper on the back of my neck, scythe in hand. I am now eight weeks past my statin by date, and I am not taking statins. The clock ticks in the background, I can sense the disapproval of cardiologists around the world weighing heavily upon me.

‘Forgive me father, for I haven’t statined.’

You need a statin – now what was the question?

51 Replies

As many of you are aware the American College of Cardiology (ACC) and the American Heart Association (AHA) came out with new guidelines on cardiovascular disease prevention a few days ago. As part of this, they produce a risk calculator. Using this calculator, if your risk of heart attack or stroke is greater and 7.5% over the next 10 years, you should take a statin – for the rest of your life.

I downloaded this calculator, and I have been playing around with it. I think I would tend to agree with the headline in the NY times 18^th November 2013:

Risk Calculator for Cholesterol Appears Flawed

To be frank you can fiddle around with the figures on this calculator for hours. I think my OCD is getting worse. (Maybe I should take a statin to cure my OCD). One of the questions I wanted to find an answer to was the following, at what age would a perfectly healthy man (with ‘optimal’ risk factors) have to take a statin for the rest of his life.

So, I fed in the figures, and use the ‘optimal’ figures for cholesterol and blood pressure on the risk calculator

THE PERFECTLY HEALTHY MAN

Male
Age 63
Race: WH (white)
Total cholesterol 170mg/dl [This is 4.4mmol/l in Europe i.e. very low]
HDL cholesterol 50md/dl [This is 1.3mmol/l in Europe]
Systolic blood pressure 110mmHg
Non-smoker
No treatment for high blood pressure
Non diabetic

CV risk over the next 10 years = 7.5%

So, there you are. You can do absolutely everything ‘right’ be as healthy as healthy can be – according to the AHA and ACC. Yet, by the age of sixty three you need to take a statin – for the rest of your life.

The next question I wanted to find the answer to was, at what age does a ‘normal’, very healthy man have to start using a statin? In the UK, the average total cholesterol for men is 5.0mmol/l. [this is 193mg/dl in the US]. The average blood pressure in the UK systolic is 129mmHg. (To be frank, I think the average cholesterol level for men is higher than this, but the WHO says not).

Feed these figures in, and you would need to start taking a statin, for the rest of your life, by the age of fifty eight. Which means that very healthy men, with no real risk factors for cardiovascular disease – at all – have to start statins at fifty eight.

What of women. Well, they get another seven years of statin free life. A super healthy woman, with optimal risk factors, reaches the dreaded 7.5% risk aged 70. An ‘average’ healthy women, with average BP and cholesterol levels, would have to start a statin aged sixty three.

In summary, using this risk calculator, extremely healthy men will be starting statins at fifty eight, and very healthy women at sixty three. This, then, marks the age at which life becomes a statin deficient state. You can be as healthy as healthy can be. You can do everything right, have no risk factors at all for cardiovascular disease, and yet you still need to take medication to reduce the risk of cardiovascular disease.

Sorry, what was the question again?

European cardiovascular disease statistics can be found here.

Believing in impossible things – there is a trick to it

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At times, all you can do it shake your head in amazement, and wonder at the ability of people who think of themselves as scientists to make statements that are impossible to reconcile with reality, or logic….or pretty much anything to do with science.

Yesterday, I was sent a copy of a paper called ‘High coronary plaque load: a heavy burden.’ Published in the European Heart Journal in August 2013. It looked at the use of statins to reduce the volume of plaque in arteries. I include three verbatim quotes from the paper:

Of particular interest, neither LDL cholesterol levels at baseline nor those after high dose statin treatment could independently predict major adverse cardiovascular events (MACEs)
One of the most striking results of this study is the fact that LDL levels at baseline or after statin treatment showed no predictive value for MACEs. This could lead to doubt about the beneficial effect of LDL-lowering therapy. However, as also discussed by the authors, there is overwhelming evidence for the beneficial effects of statin therapy on plaque progression and MACEs.
Currently statin therapy is so fundamentally established in clinical practice that its beneficial effect is beyond doubt. Even though it has been demonstrated that in patients receiving statin therapy LDL levels have no additional prognostic value, further lowering of LDL cholesterol levels with novel PCSK9 monoclonal antibodies could further reduce the residual risk in these patients¹.

So, the researchers discovered that LDL (‘bad’ cholesterol) levels did not predict major coronary events: angina, heart failure, heart attacks and suchlike. Neither did the degree of LDL lowering with statins have any correlation with coronary events. At this point, having very clearly established that their research flatly contradicts the cholesterol hypothesis, they finished off by remarking that when the new cholesterol agents arrive, which will lower LDL levels even more than statins, they will ‘further reduce the residual risk in these patients.’

I shall try to reduce this paper to its ineluctable essence.

We have found that LDL levels have nothing to do with cardiovascular disease
We have found that the degree of LDL lowering with statins does not correlate with cardiovascular events
We think we need to the lower the LDL more to prevent cardiovascular disease

‘Alice laughed. ‘There’s no use trying,’ she said. ‘One can’t believe impossible things.’

‘I daresay you haven’t had much practice,’ said the Queen. ‘When I was your age, I always did it for half-an-hour a day. Why, sometimes I’ve believed as many as six impossible things before breakfast. ‘Lewis Carroll – Alice in Wonderland.

I suppose it becomes easier to believe in impossible things if you have a few conflicts of interest to help you along the way…..smooth the pathway of belief, so to speak. Here follows the conflict of interest statement from the paper:

Conflict of interest:

J.W.J. receives research grants from and was a speaker at meetings sponsored by Astellas, AstraZeneca, Biotronic, Boston Scientific, Bristol-Myers Squibb, Cordis, Daiichi Sankyo, Eli Lilly and Company, Medtronic, Merck-Schering Plough, Pfizer, Orbus Neich, Novartis, Roche, Servier, the Netherlands Heart Foundation,the Interuniversity Cardiology Institute of the Netherlands, and the European Community Framework KP7 programme. M.A.dG. has no conflicts to declare. The Department of Cardiology received research grants from Biotronik, Medtronic, Boston Scientific

Corporation, St Jude Medical, Lantheus Medical Imaging, and GE Healthcare.

For those paying attention, you may have noticed the mention of PCSKP monoclonal antibodies earlier. What are these, I hear you cry. These are the next monstrous regiment of cholesterol lowering agents that are waiting in the wings, engines running smoothly. If you thought statins were heavily promoted – you ain’t seen nothing yet.

You may not be astonished to learn that one or two of the companies listed in the conflict of interest statement of that paper are developing PCSK9 monoclonal antibodies. I wonder if that could have anything to do with the statement……’further lowering of LDL cholesterol levels with novel PCSK9 monoclonal antibodies could further reduce the residual risk in these patients.’

And if that thought depresses you, as it does me, here is a little poem by W.H. Auden to cheer you up:

‘Give me a doctor partridge-plump,
Short in the leg and broad in the rump,
An endomorph with gentle hands
Who’ll never make absurd demands
That I abandon all my vices
Nor pull a long face in a crisis,
But with a twinkle in his eye
Will tell me that I have to die.’

1: Michiel A. de Graaf and J.Wouter Jukema. ‘High coronary plaque load: a heavy burden.’ European Heart Journal (2013) 34, 3168–3170

Sweden gets it right

162 Replies

I sometimes think that I should go and live in a Scandinavian country. They get so many things right about how to run healthy, equitable, societies. In addition, the people who live there seem more balanced and, well, frankly, more grown up. So it comes as no surprise to me that if a nation was to turn round and begin the process of rejecting the absolute nonsense that a high fat diet is bad for you, then it would be a country in Scandinavia.

That Scandinavian country is Sweden¹.

Now, I have been aware that there has been a movement towards a high fat low carb diet (HFLC) going on in Sweden for some years. This has been led recently by the heroic Dr Annika Dahlqvist, a General Practitioner who had been advising her diabetic patients to eat a low carb high fat diet (LCHF).

She was, of course, attacked by the idiots…sorry experts:

‘In 2007, the controversy began when two dieticians pointed out to Sweden’s National Board of Health and Welfare that LCHF dietary advice recommended to diabetic patients by general practitioner Dr Annika Dahlqvist was not compatible with either scientific evidence or conventional practice. However, following a report by diabetologist Dr Christian Berne, Dahlqvist was cleared.’

Cleared of what, exactly? Advising diabetic patients not to eat sugar. The mere fact that anyone could be dragged in front of the authorities for advising this just shows had completely mad the world of dietary advice has become. How entrenched the idiotic anti-fat dogma now is. How utterly divorced from reality and science.

As I have pointed out many times on this blog, and elsewhere, carbohydrates, at least all the carbohydrates humans can digest, are converted to sugar(s) in the GI system. They must be, because all that carbohydrates consist of are different number of sugar molecules bonded together in different ways. When you break them to bits in the digestive system, they become simple sugars.

As we all know, people with diabetes have problems with high blood sugar levels. So, dum de dum….let me think. Should diabetics eat carbohydrates/sugar, or should they eat fats. Yes, you are right, they should eat fats. This is a complete no brainer.

But, of course, the argument goes that diabetics are more likely to die of cardiovascular disease and eating fat increases cholesterol levels, and this increases your risk of cardiovascular disease. Well, this could obviously be a problem if any part of that causal chain were true. But it is all nonsense. As the latest Swedish report from the SBU (Swedish Council on Health Technology Assessment) makes clear (after reviewing 13,000 studies), a low carb diet leads to the terrible dangers of

‘…a greater increase in HDL cholesterol (“the good cholesterol”) without having any adverse effects on LDL cholesterol (“the bad cholesterol”). This applies to both the moderate low-carbohydrate intake of less than 40 percent of the total energy intake, as well as to the stricter low-carbohydrate diet, where carbohydrate intake is less than 20 percent of the total energy intake. In addition, the stricter low-carbohydrate diet will lead to improved glucose levels for individuals with obesity and diabetes, and to marginally decreased levels of triglycerides.’²

In short, when they looked at all the evidence, they found that low carb/high fat diets raise HDL cholesterol (the so-called ‘good’ cholesterol). They have no effect on LDL levels; they also lower blood sugar levels and triglyceride (VLDL) levels. All good and healthy, and all of which bascially means that insulin resistance has been reduced – the underlying cause of diabetes.

In reality all that the Swedes really ‘discovered’ is the quite astonishing fact that eating a high carbohydrate diet is bad for you, and worse for you if you are a diabetic. Well, blow me down with a feather. They have found exactly what a working knowledge of human biology/physiology would tell you would happen.

But we live in a wold controlled by entrenched stupidity, dogma, and the financial interests of massive companies who are making billions selling tasteless low fat mush. These companies know that the only way you can make low fat food, e.g. low fat yoghurt, taste like anything half palatable is to stuff it with sugar. Cheap, nasty, and damaging to health – also driving the ever increasing weight gain and diabetes in the Western World.

Why is everyone in the Western World becoming obese? Because we are replacing fat with sugar in many foodstuffs. The obesity ‘epidemic’ started at exactly the same time as the idiots, sorry experts, decreed that a healthy diet was a diet full of carbs. Which was, and remains, the exact and complete opposite of the truth.

However, anyone who dares to stand up and state the truth, gets dragged in from of organisations such as the National Board of health and Welfare. Eventually, however, the truth does emerge, as it must. Because the truth never dies. It can be stomped on, squashed, concreted over and napalmed. However, it lives on, taunting those who do everything in their power to deny its existence.

The truth is that all of the dietary advice we have been bombarded with for the last forty years about the dangers of fat consumption has been utterly and completely and damagingly wrong. Of course there will be a backlash against the Swedish report – there always is. Various powerful idiots, sorry experts, will be pushed in front of cameras to make various denunciations of the Swedes and their damaging and dangerous conclusions. The strings of these idiots will be jerked in unison by faceless marketers in companies that promote low fat spreads, and the like. Yes, you know who you are.

And yes, this stuff does make me angry. It is killing people prematurely, millions of people, all around the world.

1: http://coconutoil.com/sweden-becomes-first-western-nation-to-reject-low-fat-diet-dogma-in-favor-of-low-carb-high-fat-nutrition/

2: http://www.dietdoctor.com/swedish-expert-committee-low-carb-diet-effective-weight-loss

P.S:

Question: ‘What do you call five hundred dieticians lying at the bottom of the ocean?’
Answer: ‘A good start.’

So much for scientific debate

25 Replies

I thank Ted Hutchinson for pointing me at this article in the Irish Independent. It appeared on the 5^th of October, and I reprint it in full, here.

A LEADING vascular surgeon, whose research review concluded cholesterol-lowering medicines may do more harm than good for many otherwise healthy people, has been gagged by the Health Service Executive.

Sherif Sultan, a senior medic at University College Hospital, Galway, reviewed a range of studies of statins and found a lack of evidence to show they should be given as a means of prevention to healthy people with high cholesterol but no heart disease.

Mr Sultan and his surgeon colleague Niamh Hynes said lifestyle changes to reduce cholesterol were better because this allowed people to avoid the risk of statins’ side effects.

However, in a statement last night, Dr Pat Nash, a cardiologist and the group clinical director in University College Hospital said the recently published views of his colleagues were “not representative” of those in Galway or neighbouring hospitals.

“As group clinical director of the West/North West Hospitals Group, and a working cardiologist, I wish to reassure patients that statins are safe,” said Dr Nash.

“These are very important, well-validated drugs for the treatment of elevated cholesterol. We have extensive evidence to show their benefit and to show that they improve outcomes for patients with heart disease and stroke and that they have a role in preventing heart disease and stroke.

“As always, if patients have any concerns, they should not discontinue their medication without discussing with their GP or consultant.”

Asked to comment, Mr Sultan said: “I have received an official warning from the HSE and have been instructed not to liaise directly with the press in my capacity as a HSE consultant.” However, he said he could continue to comment as a consultant vascular surgeon at the Galway Clinic, where he has a private practice.

The HSE declined to comment on the reasons for ordering Mr Sultan not to speak as a public consultant. He said he stood by his analysis of the role of statins in otherwise healthy patients with high cholesterol. He pointed to another recently published review on exercise versus drug therapy in the management of pre-diabetes and cardiovascular disease.

“That ‘British Medical Journal’ analysis showed the superiority of exercise over drug therapy extends even to secondary prevention (where patients have developed disease)¹.

This story has been rumbling on for a while. A report on the research paper can be found in the Irish Medical Times from a couple of weeks before.

The under-reporting of findings on major adverse effects of statin therapy and the way in which they had been withheld from the public, and even concealed, is a scientific farce, claims new Irish research.

Mr Sherif Sultan, Consultant Vascular and Endovascular Surgeon, and Niamh Hynes, Clinical Lecturer In Vascular and Endovascular Surgery, claimed their study, just published in the Journal of Endocrine and Metabolic Diseases (2013, 3, 179-185) highlights the major side-effects and dangers of statins.

They said there is a categorical lack of clinical evidence to support the use of statin therapy in primary prevention. They are both based in the Western Vascular Institute at University College Hospital Galway and the Galway Clinic. “Odds are greater than 100-to-1 that if you’re taking a statin, you don’t really need it²..

I was sent the original paper by Sherif Sultan a couple of months ago, and it is very scathing about statins….. very scathing indeed. It even suggests, perish the very thought, that pharmaceutical companies may have been trying to present statins in the best light possible. I find such a suggestion almost impossible to believe. Knowing how completely ethical these companies are.

Anyway, I suppose the key phrase in all of this sorry episode is the following:

“The HSE declined to comment on the reasons for ordering Mr Sultan not to speak as a public consultant.”

If the Health Service Executive were to comment, what could they say to justify their actions?

“The hell with scientific debate. He should just damned will shut up and say what we want him to say?”

“How dare anyone criticise the sainted statins which work in mysterious ways their wonders to perform.”

“We expect utter loyalty from those who work in the glorious Irish Health Service. Those who do not support us can expect serious sanctions……”

On balance, declining to comment is probably the best policy for the HSE. Because if you start trying to justify why you are gagging a researcher for trying to tell the truth then, well, you will end up having to justify state censorship of scientific debate. Which never looks that good on the printed page, I find.

I feel I should sign off this blog with a quote from George Orwell, taken from 1984. “Being in a minority, even in a minority of one, did not make you mad. There was truth and there was untruth, and if you clung to the truth even against the whole world, you were not mad.”

1: http://www.independent.ie/irish-news/hse-gags-surgeon-after-cholesterol-drug-claims-29636095.html

2: http://www.imt.ie/news/latest-news/2013/09/study-claims-to-highlight-the-ugly-side-of-statins.html

Statins do not help you live longer – or do anything much else for that matter

53 Replies

Sometimes you read a thing quickly, and then you have to read it again to make sure you read it right. Yesterday I was sent a copy of a ‘Patient page’ from the Journal of the American Medical Association (JAMA). The page was from the April 3^rd 2013 edition, pp 1419. It is stamped ‘JAMA – copy for your patients’. JAMA is one of the highest impact medical journals in the world.

This patient page states that:

‘One question involves disagreement about whether the statin side effects are merely uncomfortable or actually pose significant health risks. The other question is whether reducing bad cholesterol will actually help you live longer than you otherwise would. Some of this disagreement involves how physicians interpret the results of studies. However, a 2010 analysis combined the results of 11 studies and found that taking statins did not lower the death rate for people who did not have heart disease. If your physician recommends taking a statin, talk to him or her about the risks and benefits for your individual situation.’

For many years I have been ridiculed by colleagues for saying that, if you do not already have established heart disease, statins do not increase your life expectancy. By which I mean that they don’t’ actually work. ‘Don’t be ridiculous.’ Is what they exclaim to me. I usually reply that the evidence is pretty clear, and always has been. But I know that they don’t believe me.

Recently, without warning, one of the most influential medical journals in the world turned round and confirmed it. JAMA has stated in black and white that if you do not have established heart disease e.g. angina, previous heart attack, you will not live any longer if you take a statin.

Frankly, I think JAMA will now come under ever increasing bombardment from the ‘experts’ and will end up retracting this statement. In fact, I am willing to bet that they will – having now seen some of the outraged letters sent in. However from time to time the truth – like a small grass shoot growing through a concrete pavement – will emerge. As it did in April.

(I should add, at this point, that around 95% of people who take statins do not have established heart disease.)

However, wrapped up in this issue, is an inevitable argument. I know this argument well, for I have heard it a thousand times. ‘Ah, but it is not just death we are talking about here…. statins prevent non-fatal heart attacks and non-fatal strokes and suchlike. These are terrible things that damage the quality of your life. Medicine is not only about getting people to live longer, it is also about quality of life. Preventing a non-fatal stroke is extremely important, and statins do this.’ In other words, statins don’t make you live longer, but they do provide other, very significant benefits, by preventing Serious Adverse Events (SEAs).

This is a good argument. At least it would be if it were true. However, we have no idea about whether it is true or not. For the simple reasons that the data on SEAs is almost entirely hidden from view. Data on SEAs are considered so commercially sensitive that, in most jurisdictions, pharmaceutical companies won’t release them (and don’t have to release them), even if you ask nicely*.

Before moving onto that issue, I know that I need to explain I am talking about here in a little more detail, and clear up a bit of confusion with the nomenclature. For in the area of adverse events/effects, we have two terms that sound very similar, but mean very different things.

Firstly, there are drug related adverse effects. These are often called ‘side-effects’. But side effects can be good, or bad. For example Viagra was developed as an angina drug but it was found to create enhanced erections, as a side-effect. [You can decide if this is a beneficial side-effect or not]. Viagra also causes headaches. This is also a side-effect, but it would be more accurate to call it a drug related adverse effect.

Drug related adverse effects = negative/unpleasant ‘side-effects’ of a drug

A Serious Adverse Event (SEA) may sound similar to a drug related adverse effect, but it means something completely different. An SEA is a significantly bad thing that a drug might prevent e.g. non-fatal heart attack. Or, it could be something that the drug causes e.g. rhabodmyolysis (muscle breakdown), followed by kidney failure. Which is something that is known to be caused by statins.

SEAs can therefore be good, or bad. Depending on whether they are caused by, or prevented by, the drug. This means that there is absolutely no point in presenting figures on SEAs prevented by statins, without knowing if they caused an equal number of SEAs at the same time.

Completely unsurprisingly, whilst we are bombarded with statistics about how many SEAs are prevented by statins, we have very little idea about how many SEAs are caused by statins. Because in most countries, these data are not released. Its’ commercially sensitive dontcha know. [Damned right it’s commercially sensitive. If the public saw these data they would stop taking half their meds overnight.]

There have, however, been glimpses of SEAs with statins – when the data escaped from the clutches of the pharmaceutical companies. When the Cochrane collaboration fist looked at primary prevention studies, two of the five major studies did report ‘negative’ SEAs (although they did not say what the SEAs were, and still won’t). In these two trials AFCPAS and PROSPER, the SEAs were:

Statin arm: 44.2%
Placebo arm: 43.9%

‘In the 2 trials where serious adverse events are reported, the 1.8% absolute reduction in myocardial infarction and stroke should be reflected by a similar absolute reduction in total serious adverse events; myocardial infarction and stroke are, by definition, serious adverse events. However, this is not the case; serious adverse events are similar in the statin group, 44.2%, and the control group, 43.9% This is consistent with the possibility that unrecognized serious adverse events are increased by statin therapy and that the magnitude of the increase is similar to the magnitude of the reduction in cardiovascular serious adverse events in these populations.’ (read more…)

In short there were slightly more SEAs in those taking statins than in those taking placebo. Slightly more harm than good.

So what do we now know? We know that if you do not have established heart disease, and you take a statin, you will:

not live any longer
not avoid major Serious Adverse Events

Which means that there is no possible improvement in either the quality, or the quantity, of life. On the other hand there is a good chance that you will suffer from significant adverse effects e.g. muscle pain, joint pain, impotence, stomach upset, rashes etc. etc. On balance therefore we can state that, if you do not have established heart disease, statins provide no benefits on any important outcome. All they can do is to give you adverse effects. ‘Oh boy, that sounds like a great deal doc. Can’t wait, can’t wait, can I get them now?’

*Please see petition that I just put up on my blog. This petition arrived coincidentally as I was writing this article. At present the European Medicines Agency (EMA), will provide SEA data if requested (with huge persistence). The UK authorities will not release these data, nor will the FDA in the states. A recent move by the pharmaceutical industry is now threatening that the EMA will be forced to hide SEAs. ‘Six months ago two US pharmaceutical companies AbbVie and InterMune took a legal action against EMA that has closed down access to all trial data for all drugs for all doctors and researchers anywhere in the world.’

Closed down all access to all trial data for all drugs for all doctors and researchers anywhere in the world.

That statement is worth repeating. Be afraid, be very afraid indeed. And sign the petition please. Oh, and write to your MEP, as I am now doing.

Please sign – most important issue

13 Replies

I received this post and felt the immediate need to post it on my blog, to allow as many people as possible to sign a petition to stop pharmaceutical companies hiding adverse event data on their drug FOREVER. This is a hugely important issue for humanity.

See below…

Sorry for the Mass Posting here but we have just posted a Swedish translation of the RxISK petition calling for Access to Clinical Trial Data.

Some of you will have signed this but even if you have read on because we have a mission for you.

Two years ago, the European Ombudsman ruled that the European Medicines Agency should open up access to Clinical Trial Data for anyone who applied from anywhere in the world.

Six months ago two US pharmaceutical companies AbbVie and InterMune took a legal action against EMA that has closed down access to all trial data for all drugs for all doctors and researchers anywhere in the world…

Some of you may not have heard of AbbVie. Until recently they were Abbott Laboratories, one of the biggest pharmaceutical companies in the world.

They make Humira, a monoclonal antibody used for Rheumatoid Arthritis, Crohn’s Disease, Psoriasis and other conditions. It is the best selling drug in the world today, and projected to be the best selling drug of all time.

This is one of the most important legal actions in Healthcare ever. At a recent meeting in Bruxelles AbbVie made it clear that a main reason to keep clinical trial data confidential was to hide adverse event data, although there may be other issues like a Trade War with China.

You can read about this and see the whole video here

Essentially AbbVie are asking the Courts to grant their Corporation the privacy rights of an individual – a very powerful wealthy individual.

But the key help is this. If this legal action succeeds Adverse Event data will be hidden for ever.

So we’d love you and anyone you know to sign a petition calling on AbbVie to drop their legal action against the EMA’s policy of open access to clinical trial data. The petition is here or in Swedish as above

This petition is as much for anyone who may be prescribed drugs as for those prescribing them – so we are hoping to spread word about it generally.

In addition to signing, we are trying to get every country in the world to sign.

We have 72 of the 187 countries in the world signed up but would love to have all. If any of you have contacts in any Eastern European, African or South East Asian countries that you could get to sign this it would be really excellent

Thanks, David

David Healy
Professor of Psychiatry, Hergest Unit,
Bangor, Wales LL57 2PW, UK

E david.healy54@googlemail.com
B davidhealy.org

Too much medicine – dementia

35 Replies

I am, in general, distinctly sceptical about mass screening programmes. Politicians, however, just love them. They use the complex scientific principle of ‘A stitch in time, save nine.’ Or else the concept of pure logical reasoning known as ‘Better to be safe than sorry.’

On a very superficial level screening is obviously a good thing. You pick up a disease early, then you ‘treat’ it, then it is gone. Huzzah! Pink ribbon anyone? Indeed, how could anyone possibly argue with such an obviously sensible thing to do? So sensible that we are drawn to this idea like moths to a flame. We flutter around it, unable to break free from its mesmerising power.

I am not suggesting that all forms of screening are useless. My favourite screening test is to take someone’s pulse. You can tell within about twenty seconds, or less, if someone has atrial fibrillation (AF). If they do, this is a condition that can be effectively managed, reducing the risk of stroke by nearly a half.

This test costs nothing, requires no great skill, is non-invasive, and…… of course it is not on any screening programme anywhere in the world (as far as I know). Strange, as it fulfils virtually all of the criteria of a successful screening test. As outlined by the WHO as far back as 1968

World Health Organization guidelines on assessing the value of a screening test

The condition should be an important health problem.
There should be a treatment for the condition.
Facilities for diagnosis and treatment should be available.
There should be a latent stage of the disease.
There should be a test or examination for the condition.
The test should be acceptable to the population.
The natural history of the disease should be adequately understood.
There should be an agreed policy on whom to treat.
The total cost of finding a case should be economically balanced in relation to medical expenditure as a whole.
Case-finding should be a continuous process, not just a “once and for all” project

Instead, we have vastly expensive, poorly sensitive tests for diseases where our treatments are poor, and our knowledge of the natural history of the disease is virtually non-existent. I am not discussing cancer screening here as that is a far more nuanced area.

What I am talking about here, specifically, is dementia screening. Which is the latest bonkers, poorly thought though, damaging bit of stupidity that the UK Govt is now intent forcing on General Practitioners in the UK – and the US. And that was the polite version of my real views.

Here is what the BMJ has to say about dementia screening:

‘Conclusions—Current policy is rolling out untested and uncontrolled experiments in the frailest people in society without a rigorous evaluation of its benefits and harms to individuals, families, service settings, and professionals.’

In fact, the entire article is a paean of common sense, and I would recommend anyone to try and get hold of it, and read it. But journals place themselves behind pay for view barriers nowadays, so you probably can’t.

However on of my favourite passages is the following

‘What will be the effect of encouraging more widespread and earlier diagnosis of dementia? A meta-analysis of the diagnostic accuracy of clinical tools used by general practitioners, including 15 studies on dementia, estimated that if, a clinician saw 100 consecutive community based patients with a prevalence of dementia of 6%, using current criteria he or she would correctly identify four of the six but would incorrectly identify dementia in a further 23 people.’

In short, if there were six out of a hundred patients in the community with early stage dementia. The average clinical would miss two of them, and state that twenty three without the condition had it. My, how fantastically accurate.

A good screening test needs to pick up (or not miss) well over ninety five per-cent of people who have the condition, and not misdiagnose more than one – or two – in a hundred. A misdiagnosis (false positive), is not a trivial thing. ‘I am sorry to tell you Mrs Smith, that you have dementia.’ The effects of being told this can be utterly devastating.

Finances, family planning, the sense of despair that you are going to end up unable to recognise your close family. Dribbling to yourself in a nursing home, doubly incontinent. These are all the things that flash through people’s minds when told they have dementia.

‘But don’t worry, we haven’t got any effective treatment for it either….. you will be glad to know….’ The doctors shall then happily inform the three out of four people that they have MISDIAGNOSED. Whilst thirty per cent of those with dementia wander off happily, reassured that they don’t have dementia – when they have actually got it.

There are times, when I look at the direction of travel in medicine, that I almost give in to despair. There is not enough money to pay for many proven and effective treatments. We are closing hospital beds and making nurses redundant. Our psychiatric services are virtually exterminated due to lack of funding, with severely distressed people unable to access any support.

Yet we can find money – it seems- to fund a completely useless. Sorry, not completely useless. Dementia screening is far more that completely useless – it is actively damaging. We have money to pour into an actively damaging, vastly expensive screening programme to pick up a disease that we cannot actually treat in any meaningful way. Gasp…thud. Noise of head hitting desk.

Luckily, there is always malt whisky to dull the pain.

’Political drive to screen for pre-dementia:
not evidence based and ignores the harms of diagnosis.’

Deadly Medicines and Organised Crime: How big pharma has corrupted healthcare

11 Replies

A bold title for a blog indeed, but not mine (I almost hasten to add). This is the title of a new book by Professor Peter Gotzsche. I have ordered it, and started to read it. Gotzsche does not hold back. As the introduction states:

We take so many drugs is that drug companies don’t sell drugs, they sell lies about drugs. This is what makes drugs so different from anything else in life…Virtually everything we know about drugs is what the companies have chosen to tell us and our doctors…the reason patients trust their medicine is that they extrapolate the trust they have in their doctors into the medicines they prescribe. The patients don’t realise that, although their doctors may know a lot about diseases and human physiology and psychology, they know very, very little about drugs that hasn’t been carefully concocted and dressed up by the drug industry…If you don’t think the system is out of control, then please email me and explain why drugs are the third leading cause of death…If such a hugely lethal epidemic had been caused by a new bacterium or a virus, or even one hundredth of it, we would have done everything we could to get it under control.

This is a short blog. The only reason I have written it is to make you aware that this book exists, and to urge you to buy it, and read it.

Disclosure of Interest (D.O.I). I have absolutely no financial interest in this book. I know Peter Gotzsche through e-mail conversations.

What is your blood pressure (BP)?

85 Replies

Central arterial blood pressure

(What is it, don’t like it. Pay attention it could save your life)

It is a pressure that is measured, almost exclusively, by placing a cuff around one arm – usually the left. The cuff is then inflated to a point whereby all blood flow is stopped. If you have placed a stethoscope over the brachial artery (artery in the arm) you will hear nothing at this point. Because there is no blood flow, and nothing to hear.

As the pressure in the cuff is lowered, a noise will be heard as the blood first starts to squeeze through. This is defined as the systolic blood pressure i.e. the point of highest arterial pressure, just after the heart contracts. A sharp tapping noise would be the best description.

As you lower the pressure in the cuff, the noise changes and muffles. Eventually, there will come a point where the blood is flowing through the brachial artery all the time …the point of ‘lowest’ blood pressure. Once this pressure is reached, the noises in the brachial artery cease. This is defined as the diastolic blood pressure. (The pressure does not reach zero, because the heart pumps once again to boost the pressure again).

All of this means that your blood pressure is presented as two figures. The highest recorded pressure (systolic) over the lowest (diastolic).

Historically, blood pressure measured in millimetres of mercury. Because, in the good old days, blood pressure meant how many millimetres of mercury could be pushed up a tube by the force of the cuff being inflated round the arm. If you used water in the tube, instead of mercury, we would measure in metres, not millimetres.

Despite the fact that mercury has nothing to do with the process any more, the measurement is still called mmHg (millimetres of mercury that can be pushed up a narrow tube). A normal blood pressure is around 120/70. If you are an Olympic weightlifter, the blood pressure can reach over 300mmHg during a lift. Which is pretty high.

In a nutshell that is what your blood pressure is…. but what does it mean? The pressure in your arm is certainly not the same as the pressure in your finger, or your brain. The pressure will be different in the right and left arms, as the blood has further to go before it reaches your right arm. It will be different if the cuff is put in a slightly different place on the arm. It will also be different if you are stressed, if the cuff is a bit small – or slightly too big.

In short, your blood pressure can be all over the place. Which is why a single measurement is not used to define high blood pressure. You need at least three. In fact, this is not nearly enough either. To diagnose someone with high blood pressure you really need to monitor the blood pressure over a twenty four hour period – using ambulatory monitoring. This helps to get rid of ‘white coat’ hypertension (high blood pressure). A phenomenon whereby the act of a healthcare professional wrapping a cuff round your arm sends your blood pressure sky high.

Because of the difficulties of measuring the blood pressure, it is estimated that around twenty five per cent of people diagnosed as having hypertension – do not actually have high blood pressure at all. Which means that they are taking drugs that they do not need. Costing the NHS at least a billion a year, and a great deal more around the world (yes, this truly is an international blog).

The other major problem with measuring the blood pressure at the arm is that it may not reflect the blood pressure just after the blood leaves the heart. The central arterial pressure. This is important, because this is the most critical pressure of all. There are a number of reasons why this is so.

Firstly, the central arterial pressure is the pressure in the aortic arch (the U bend in the aorta (biggest artery in the body)). This represents the pressure that sends blood straight up the carotid arteries and into the brain, which is clearly important with regard to stroke risk. [This where two, critically important, small BP sensing organs sit]

It is also the pressure that has the greatest impact on the kidneys. The renal arteries branch directly from the aorta itself. Therefore the central arterial pressure is closely monitored by the kidneys, which are the primary organs of blood pressure control. In addition, the central pressure has the greatest impact on the aorta itself. A relatively common cause of death is a ‘ballooning’ of the aorta (aortic aneurysm). Such aneurysms can burst, with obviously catastrophic results.

Now, there is no doubt that the pressure at the arm is related to the central arterial pressure. It must be – to a certain degree. And for most people measuring at the arm is probably a good enough estimate of the ‘true’ blood pressure.

However, if your blood pressure measurement is high, or low, or you are on blood pressure medication….then the pressure measured in the arm becomes increasingly unreliable. It can even become misleading i.e. your pressure seems to be going down in the arm – but it is not going down as much centrally¹. (It may even be going up.)

‘The results of the Conduit Artery Functional Endpoint (CAFE) study also suggest that the central aortic blood pressure may be more predictive of cardiovascular events, such as stroke and heart attack, than traditional peripheral (brachial) blood pressure measurements. CAFE was the first study to repeatedly measure central aortic pressure in a major clinical outcomes trial and the first to show that central aortic pressure is a plausible mechanism to explain the better clinical outcomes seen in patients treated with amlodipine-based therapy in ASCOT.’

Of course, central arterial blood pressure is somewhat difficult to measure. Up till fairly recently you had to insert a catheter, with a measuring device, into to the femoral artery, and push it up to the aortic arch. This would not be highly practical during a consultation with a GP. So central BP is very rarely measured. But it would be best if it could…

The anomalies of blood pressure trials

Now to introduce another thread to this discussion. Which is the fact that, if you choose to look at the clinical trials on blood pressure lowering with an objective eye, there is almost no correlation between the amount the blood pressure is lowered (at the arm) – and any clinical outcomes. By which I mean that the rate of heart attacks and strokes do not relate to the degree of blood pressure lowering.

To quote a series of bullet point in the European Journal of Cardiology entitled ‘There is a non-linear relationship between mortality and blood pressure’:

Drugs that lower the blood pressure by about the same amount have very different effects on outcomes
Cardiovascular benefits of ACE-inhibitors (Angiotensin Converting Enzyme – Inhibitors), independent of blood pressure, are not observed with calcium antagonists, despite the latter having more pronounced effects on blood pressure.
HOPE (Heart Outcomes Prevention Evaluation study) demonstrated that ACE inhibitors provided diverse and profound cardiovascular benefits, with only trivial differences in blood pressure between the treatment and control groups
ALLHAT (Antihypertensive and Lipid Lowering treatment to prevent Heart Attack Trial) showed a dramatic difference in cardiovascular risk between alpha blockers and diuretics, with essentially no difference in their effect on blood pressure. The investigators of ALLHAT concluded ‘blood pressure lowering is an inadequate surrogate marker for health benefits in hypertension.’

This is extremely important, because for many years, most of the ‘evidence’ on blood pressure treatment has been based on a statistical model known as the ‘log-linear’ model. This model states that ‘the relation of blood pressure to risk of death is continuous, graded, and strong, and there is no evidence of a threshold.’ (Stamler). The model itself, and that statement, were almost entirely based on evidence from the Framingham Heart Study. The study that your doctors will use to calculate your risk of dying of heart disease.

Essentially, according the log-linear model, the lower your blood pressure (measured at your arm), the better. And the more that drugs lower it, the better. At least this is the thinking that is currently used.

However, thirty years ago Ancel Keys (yes, him) concluded that the linear model, in terms of the relationship of overall and coronary heart disease death to blood pressure was ‘unjustified’. Ten years ago, the authors of the article ‘There is a non-linear relationship between mortality and blood pressure’ further concluded (after reviewing the Framingham data – the data upon which your doctor will determine your future risk of dying of CVD)…the following:

‘Shockingly, we have found that the Framingham data in no way supported the current paradigm to which they gave birth. In fact, these data actually statistically rejected the linear model. This fact has major consequences. Statistical theory now tells us that the paradigm MUST be false ….’ (Their italics and capital letters).

In short, the blood pressure model that is used worldwide is simply, plain damned wrong. The reality is that the amount the blood pressure is lowered in the arm bears little, or no, relationship to any benefit on heart attacks and stroke. How can this be? Well, there are two major reasons for this. One of which I am covering in this article. The other, later. Now to introduce another thread.

How do blood pressure lowering drugs work?

I am going to avoid being too technical here – which is tricky. I am also, only focussing on the four most commonly used blood pressure lowering agents/classes.

1: Diuretics. These drugs make you pass more urine, by blocking sodium re-absorption by nephrons in the kidney. This means that you pass a lot of urine (diuresis). This puts you into a state of mild dehydration, thus reducing blood volume. Exactly why this lowers your blood pressure is a moot point. (You may think you know. However, it is almost certainly far more complicated that what you are thinking – I certainly don’t understand it)

2: Beta-blockers: These, effectively, slow your heart rate and also decrease the pumping force of your heart. An unwanted effect is that they also cause peripheral blood vessel constriction.

3: Calcium channel blockers: These reduce the force of contraction of the heart, dilate blood vessels (arteries not veins), and slow the heart rate at bit. All of which lowers the blood pressure.

4: ACE-inhibitors: (a bit more explanation is required to explain how they work). The kidneys are the primary organs that control blood pressure. If they pick up that the BP is too low, they release a substance called renin. Renin triggers a whole series of other hormones into action. Ending up with increased angiotensin II levels.

This hormone has multiple effects. It reduces urine production, by increasing sodium absorption. It causes constriction of arteries, and stimulates the pituitary gland to produce anti-diuretic hormone (ADH) – thus reducing urine output. It does several other things too, all of which result in the blood pressure going up.

As is the complex way of the body, the kidney doesn’t actually produce angiotensinogen II when the blood pressure drops(which would seem logical). The kidney produces renin, the liver produces angiotensinogen. When these two hormones met, angiotensinogen is converted into angiotensin I. Then angiotensin I is further converted to angiotensin II by an enzyme called Angiotensin Converting Enzyme (ACE). (There will be an exam later)

All of this means that angiotensin II is the main, active, substance. Once it has been produced, angiotensin II goes off to do all its blood pressure raising things. If, however, you give an ACE-inhibiting drug (ACE-inhibitor), angiotensin II production is blocked, and the blood pressure will fall.

Anyway, as I hope has now become clear, the blood pressure lowering classes of drugs all work though very different mechanism. They all lower the blood pressure at the arm, but what else are they doing?

Beta blockers tend to constrict peripheral blood vessels. Calcium channel blockers and ACE-inhibitors tend to dilate them. Diuretics are mainly neutral on blood vessel diameter. ACE-inhibitors also do something else that is extremely important. They stimulate Nitric Oxide synthesis in the blood vessels themselves, which both dilates arteries, and increases blood vessel flexibility.

In short, the effect on central and peripheral blood pressure of various BP lowering medications will be very different.

Bringing these thoughts together

You may think, why now? Why is he quoting articles, and research, from many years ago? Well, you have to bear in mind that it is a long time since anyone did a placebo controlled blood pressure lowering study. It would be considered unethical to do so now (such are the alleged enormous benefits of BP lowering). So, there isn’t really any fresh information. Just the monitoring of one drug vs. another, and assuming benefit based on the degree of BP lowering – using the log-linear scale.

However, it has now become possible to measure central blood pressure by simply using a cuff placed round the arm. I have had this process explained to me many times, and cannot really understand how it is done. But the results are repeatable, and accurately reflect central blood pressure. Which is all that really matters.

When you do this, you can also measure the velocity of the pulse wave, which is an accurate indicator of arterial flexibility – and thus arterial health. If your arteries are stiff this is a worrying sign, and reflects poor arterial health. The more flexible your arteries are, the better.

At last, hoorah, instead of wrapping a simple cuff round people’s arms, we can use a complicated cuff to look at two more, really important things. The central blood pressure, and arterial flexibility. This gives us far more information.

Perhaps most importantly, we can monitor the effects that different blood pressure lowering medications have, beyond their impact on the BP measured at the arm. We can see if central pressure is increased, or decreased, or if arterial compliance (flexibility) is improved.

I think that this is a major breakthrough in medical practice. So much so, that I have acquired a machine for myself, and will be using it on a regular basis. I fear it will take the wider medical profession about twenty years or so for this to become an accepted way of measuring blood pressure. This is about the normal lead time for new ideas to become standard practice.

Sweden in 1967

It may, of course, take longer. Or never happen at all. At the risk of going off on a major tangent, I remember looking at pictures of roads Sweden in 1967. This was when they switched from driving on the left, to driving on the right. 3^rd Sept 1967

As you can see from the picture, a bit of a mess. But imagine if any country tried to do it now, with the extra number of cars and lorries, and roads, and signs. This would probably be just too difficult.

How about changing the way we look at measuring blood pressure. We have always measured blood pressure using a simple cuff on the arm. All the clinical studies on BP lowering were done using this technique. All the data, all the guidelines….everything, is now based on doing BP measurement in this way.

Just imagine what happens if someone now says. Hold on, this is not good enough. The measurement is inaccurate and potentially confusing, and it doesn’t’ really tell us what we need to know. Let us start again. Let us drive on the right, not the left.

In the meantime, whilst the medical world grapples (or chooses not to grapple) with a trillion dollar problem, you can do yourself a favour and get your blood pressure measured centrally.

How is medical data presented to the public?

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Beradinelli-Seip Syndrome – stick that in your pipe and smoke it

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We are told, ad-nauseam, that obesity is the main cause of type II diabetes. This, allegedly, follows a very simple causal chain.

Obesity > insulin resistance > raised blood sugar levels

For those not familiar with the term Insulin resistance, this is the condition whereby various organs in the body become gradually more insensitive to insulin, which forces insulin levels higher to keep the blood sugar levels down.

Eventually the resistance to insulin becomes so great that the blood sugar levels rise anyway – despite the high insulin levels. Alternatively, or in parallel, the pancreas gives up fighting against the resistance and insulin production becomes ‘burnt-out’. Whichever process is dominant, they both result in sugar levels become very high, and you will be diagnosed with type II diabetes.

At this point I have to state that I have always found it weird that a raised blood sugar level can be defined as a disease, when it is clearly nothing of the sort. In my world a ‘disease’ is the underlying malfunction which causes various signs and symptoms to occur (of which a raised blood sugar level would be one).

Everyone agrees that insulin resistance is the basic underlying cause of a raised blood sugar level a.k.a. type II diabetes. Despite this we define the blood sugar level itself as the disease.

‘A high blood sugar level is type II diabetes….end of.’

‘So, if we lower the sugar level, we have cured the disease?’

‘Yes. Now do shut up.’

Clearly bonkers, but let us not expect too much in the way of logic in medicine. Anyway, that is a slight distraction from the main theme here, which is the: obesity > insulin resistance > raised blood sugar levels discussion.

Now, for reasons that I am not going to fully bore you with here (but maybe at a later date), I have always had problems with this causal chain. Primarily, that it has never made much sense to me. Insulin resistance occurs almost exclusively in two tissues; the liver and skeletal muscle, and NOT in adipose tissue. So why would having too much adipose tissue make you insulin resistant? Answers on a post-card please*.

In order to pursue this thought further I started to look at evidence from Sumo Wrestlers. These are the most obese people on the planet. At least they are if you use BMI to define obesity. Yet, none of them have type II diabetes (at least not, whilst in training). For example:

‘Abnormally large waist circumferences, which were determined by the criteria established by the Japanese Society of Internal Medicine, were present in all Sumo wrestlers (100%), and fifteen Sumo wrestlers (83%) had high abdominal visceral fat areas (>100cm2). Only 2 subjects were categorized with high serum triglyceride levels, and 5 subjects were classified with low HDL-C levels by established criteria. None of the Sumo wrestlers had fasting hyperglycemia (high blood sugar levels) (0%)’¹

Interesting, is it not, that the most obese people on the planet do not have type II diabetes (although some of them have a degree of insulin resistance – for reasons that I may explain at a later date). Yes, I know exactly what you are now thinking. They do not have diabetes because they exercise a lot. It’s true, they do. But does that not make it more likely that a lack of exercise is the true of cause of insulin resistance, rather than obesity….yes, of course it could certainly mean that.

In truth, finding very obese people without diabetes does not rule out obesity as the cause of diabetes. But it does rule out obesity as being both ‘necessary’ and ‘sufficient’. At this point I need to explain the concept of necessary and/or sufficient.

It was Koch who first tried to determine a process of logic to describe whether or not something may be a true cause of a disease, or just a chance association. He introduced us to Koch’s postulates, and also the concept of necessary and/or sufficient.

For example, it is known that the bacteria vibrio cholarea causes cholera. In order to get all the signs and symptoms of cholera it is ‘necessary’ to be infected with this organism. However, infection with vibrio cholarea does not cause cholera in everyone. If you are a fit and healthy adult you can shrug off the infection with only mild symptoms. Koch proved this by drinking a glass of water known to be infected with vibrio cholarea and developing only mild symptoms of the disease

Thus it can be stated therefore that infection with vibrio cholarea is ‘necessary’ to cause cholera. However it is not, on its own, ‘sufficient.’ Other factors are needed. On the other hand, if you could find people with cholera who had not been infected with vibrio cholarea, then you would have to declare that vibrio cholarea was neither necessary, nor sufficient, to cause cholera. So it could NOT be the cause of cholera.

This is obvious, and inarguable.

So, moving back to type II diabetes. Can you find people with type II diabetes who are of normal weight? Or, to stretch this concept to the limit, can you find people with type II diabetes who have no adipose tissue at all? Surely not, you say. Surely impossible.

At this point I shall introduce you to ‘Berardinelli-Seip Congenital Lipodystrophy’. This condition affects about one in ten million people. So it is hardly common, but that is not the point. The point is that the primary abnormality in Berardinelli-Seip Congenital Lipodystrophy is a lack of functional adipocytes – which means that those who suffer from this condition do not have fat cells, and cannot store fat. Ergo, that they are extremely lean. The leanest of the lean, the least obese of the least obese.

From time to time I describe this condition to doctors. At which point I somewhat cheekily ask them to guess what percentage of people with Berardinelli-Seip Congenital Lipodystrophy have type II diabetes. I say cheekily, because they inevitably get the answer wrong. They always, without exception, answer pretty much as follows:

‘Obviously, none of them.’

The correct answer is, of course, ‘Every… single…one…of…them.’ [Gasp, sounds of people collapsing to the floor in shock etc.]

Now, if you can understand why this is true, you are at least one step on the road to understanding type II diabetes. Or to be more accurate, what is the true underlying cause of insulin resistance and high blood sugar levels. You will also understand that obesity has only a small and indirect part to play in this process; that BMI has no relevance to the issue, and that the simple causal chain: Obesity > insulin resistance > raised blood sugar level……is wrong.

Of course obesity is closely associated with diabetes – to state otherwise would be nuts. However it is not the cause of type II diabetes. It is caused by it. By which I mean that obesity is (in major part) caused by that the underlying process that also leads to insulin resistance and high sugar levels. There is a causal chain here, but it is not Obesity>insulin resistance>raised blood sugar levels.

More on this later, once your brain has become unscrambled.

*Yes, for those who know about this area, you can talk about visceral fat, but this is another more interesting and completely different discussion. I am also only discussion type II diabetes, not type I (which is a completely different condition altogether).

1: http://connection.ebscohost.com/c/articles/84569721/metabolic-profiles-fat-distribution-japanese-college-sumo-wrestlers

811 deaths and counting

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There is a doctor in the USA called Duane Graveline who I know well. He trained as an astronaut, when such things were seen as exciting. He was very much mainstream in his prescribing and thinking about medicine, until he was started on statins. He took them happily, until he suffered an episode of transient global amnesia. A complete loss of memory, re-booting his brain to the age of about eight.

On the first occasion he had no idea what had happened. He thought he could have had a stroke, but after investigations nothing was found. He asked if the statin could have caused this, and was told no – not a chance. So he started on statins again, and suffered another episode, the same as the last.

He then started investigating and found that thousands of others had suffered from episodes of transient global amnesia whilst on statins. A very, very, rare thing to happen to anyone, but increasingly common nowadays. I wonder why? Dr. Graveline then started to develop a neuromuscular disease, similar to amyotrophic lateral sclerosis (ALS) which he attributes to the statin. Statins can certainly cause neuropathy – but I shall say no more on this issue at present.

Dr. Graveline is not so keen on statins now, nor does he believe that cholesterol causes heart disease – having looked at the evidence again with a fresh eye. For those who do not know, he has a website www.spacedoc.com. Here are listed all of the many adverse effects of statins, and the suffering of many thousands of people.

He believes that the authorities are, basically, turning a blind eye to the many and varied problems with statins. So he has laboriously gone through the Food and Drug Administration (FDA) database of Adverse Drug Events (Medwatch), to find out just exactly how many deaths statins have caused.

This is extremely difficult to analyse as the coding system in Medwatch is complex, poorly linked and many things – frankly – do not seem to make sense. Whilst going through this stuff is an absolute nightmare, it can be done – although you have to make some assumptions along the way.

What Dr. Graveline did was to look for case of rhabdomyolysis (catastrophic breakdown of muscle tissue) linked to statins. Rhabdomyolysis is a pretty specific, and well-accepted, adverse effect of al statins. However, it is considered as so vanishingly rare as to be not worth bothering about by most doctors.

Rhabdomyolysis carries a very high mortality rate, because the waste products of dissolving muscles travel to the kidneys, where they block up the nephrons, causing acute kidney failure. In around ten per-cent of cases rhabdomyolysis is fatal. So you can assume, with reasonable accuracy, that for every ten reported cases of rhabomyolysis, you will get one death. You will also get a number of people with destroyed kidneys who end up on dialysis – hey ho.

At this point I should also point out that adverse drug events are widely known to be a massively under-reported. It is difficult to be certain on the exact figures. However, having read many papers on this subject the general feeling is that about 1 – 5% of all events are actually reported by anyone – ever. Which means that any figures in Medwatch can be pretty reliably multiplied by twenty to one hundred? Which is a topic for another day.

Anyway, with this pre-amble out of the way, I have copied Dr. Graveline’s blog on statins (with his full permission). What he has found is that, over a six year period there were 8,111 cases of rhabodmyolysis reported to Medwatch associated with statins. This represents, at least, 811 deaths in this period. [If you were to multiply this figure by twenty, this is 16,200. Multiply by one hundred and you have 81,110.]

A few years ago one of the statins called Baycol was rapidly removed by the FDA after sixty people died from rhabdomyolysis whilst taking statins. Well, all statins can cause rhabdomyolysis. Hundreds have died, probably more, since Baycol was yanked from the market. Yet there is absolute radio silence on this issue.

Below is Dr. Graveline’s blog…

Relative risk of Statin Associated Rhabdomyolysis

A recent study comparing the relative risks of muscle problems with the use of the various statin drugs has recently been reported. Generally the risk of muscle adverse effects varies with the strength of the statin used except for the statin fluvastatin (Lescol). Lescol, usually considered to be the weakest of the commonly used statins now shares with rosuvastatin (Crestor), the strongest of the statins, in being consistently linked to higher adverse muscle events relative to the other commonly used statins. Atorvastatin (Lipitor) and simvastatin (Zocor) showed intermediate risks and pravastatin (Pravachol) and lovastatin (Mevacor) had the lowest risk rates. Designating rosuvastatin’s and fluvastatin’s relative risk as 100%, comparative rates for atorvastatin, simvastatin, pravastatin, and lovastatin were, respectively, 55%, 26%, 17%, and 7.5%.

There were a total of 186,796 case reports listed within the Adverse Event database (Medwatch) during the study period 1 Jul 2005 to 31 Mar 2011. Choosing rhabdomyolysis as one of the more discrete and credible of the muscle diagnoses, a total of 8,111 cases of rhabdomyolysis were reported during this study period, averaging 1,350 cases yearly. Sidney Wolfe MD has previously estimated the statin associated rhabdomyolysis death rate to be 10 percent (giving a total of 811 deaths during this 6 year 4 month time period). Of the total number of rhabdomyolysis cases, fluvastatin was involved in 164, rosuvastatin in 1146, simvastatin in 3395, atorvastatin in 1641, pravastatin in 267 and lovastatin in 161.

Returning to the death rate estimate of 811, this strikes me as extraordinarily high and I cannot believe I am just now discovering this. Back in the Baycol crisis of 2004, sixty deaths caused FDA to rise up and Bayer to take its problematic product off the shelves. Six years later, 811 deaths do not even deserve a mention. What has happened? Where is the media uproar that we had back in 2004? I knew the Medwatch figures for Lipitor because I had obtained a copy of the Medwatch data and counted the rhabdomyolysis cases myself. I counted 2731 cases of rhabdomyolysis from the period 1997 to 2011 from Lipitor alone which fits quite well with this recently published work. So I had a heads up. I predicted the total rhabdomyolysis cases would be 6,000 for all the statins never suspecting I would underestimate by several thousand.

Medwatch exists for FDA to monitor these outrageous post marketing events and report back to the medical community. Where is the FDA report? This is incredible!

The most unutterable balls

66 Replies

A couple of night’s ago, I was watching a programme called ‘Long Live Britain’ on the BBC, co-presented by Phil Hammond. He is a UK doctor whom I greatly admire, and who mostly talks common sense. So I hesitate to criticise him. But on this programme I heard him say these very words to a volunteer on the programme (sic) ‘A lifetime of eating fatty food has made your liver fatty……’ In truth, he may have used slightly different words, but I cannot bear to watch again.

He then went on to present a lengthy clip of a very unwell lady with (I presume, though not stated), non-alcoholic steatohepatitis NASH. This is the name for a damaged, fatty, liver. A condition that can worsen and worsen and may, eventually, lead to liver failure.

Sorry Phil, but when I heard you say that eating fat caused a fatty liver, I had to switch the television off and take a few deep breaths, lest my blood pressure became too high.

What is it about diet that no-one has even the faintest damned idea what they are talking about, especially when I comes to fat consumption. I think we have demonised fat for so long that you can say anything about fat and, so long as it is sufficiently damning; no-one dares question anything you say. Science goes straight out the window.

A.N. Idiot: ‘Did you know that eating fat can make your liver explode.’

A.N. Other Idiot: ‘OMG, I never knew that.’

A.N. Idiot: ‘It’s true. It must be, I saw it on the telly.’

Well, here are a few facts that really are facts. When you eat fat it is absorbed in the small bowel, turned into triglycerides, and packaged into a lipoprotein called a chylomicron. Chylomicrons are then fed directly into the bloodstream via the thoracic duct – bypassing the liver completely. As they pass fat cells, the cells strip almost all of the fat out of them, so the chylomicrons shrink down and down in size, becoming chylomicron remnants. Once almost all fat is gone, these remnants are absorbed into the liver.

As should be clear from this, at no point in this process does the vast, vast, majority of fat we eat get anywhere near the liver. It is carried from the bowel directly into adipose tissue. So, Phil, how does eating fat make your liver fatty…exactly? When the liver has no part of play in the absorption, transport and storage of any fat we eat? Oh, sorry, you’re right, it can’t.

Carbohydrates, on the other hand, now here you are talking. All the carbohydrates we eat are converted into glucose and/or fructose in the gut [apart from fibre, and starch, which we cannot digest]. Glucose and fructose then pass directly into the liver where, if your body’s sugar stores are full, they are converted into…you guessed it…fat. [Your body can only store about fifteen hundred calories of energy as glucose/sugar before the stores are full – which is not a lot].

Imagine, if you will, a body with full sugar stores* – this would be most people, most of the time. You eat carbohydrate a.k.a. proto-sugar. With sugar stores full, there is nowhere for this excess sugar to go, so the liver converts it all into fat a.k.a. triglycerides. The liver tries to stick this excess triglyceride into a lipoprotein called a VLDL (Very Low Density Lipoprotein). However, this process is complex, so the liver starts to fill up with fat.

At the same time insulin does battle with the liver, in order to drive lipogenesis (the making of fat from sugar) in the liver. Which means that you are more likely to end up with diabetes. This is not rocket science. This is basic human metabolism/physiology. And you know what, the way to reverse this process is…TO EAT FAT.

The simple fact is that there is no way on God’s earth that eating fat can give you a fatty liver. However, the process by which eating excess carbohydrate could give you a fatty liver, and then diabetes, is simple and straightforward. Yet we have a BBC programme, with a real doctor on it, stating the exact opposite.

I suppose I don’t really blame Phil Hammond too much. We have all been fed with such unutterable balls about the dangers of eating fat for so long now that the science behind nutrition long since became an inconvenience. ‘Do not bother me with facts, for my mind is made up.’

Or ‘don’t bother me with the fats; I am going to kill myself eating carbohydrates.’ Long Live Britain indeed.

*sugar/glucose is stored in the body as glycogen, a polymer of glucose (lots and lots of glucose molecules stuck together). The body does this to reduce the amount of water required to encircle individual glucose molecules.

Who shall guard the guardians?

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(Quis custodiet ipsos custodes?)

Mainstream medicine increasingly relies on Guidelines. Well, they are called guidelines, but increasingly they carry the force of law. In many countries if you try to practice outside the wise and infallible guidelines you may lose your license to practice medicine. In the US, you may well be dragged into court, and if you have not been following the guidelines, you will be sued. You can even be gaoled (or jailed, as we say in the UK).

In short, guidelines are very serious and important things indeed, and they now rule medicine with a rod of steel. In the UK up to 50% of general practice time is spend ensuring that all patients are constantly monitored to ensure that various guidelines are rigorously followed. Is the BP low enough, the cholesterol low enough, have you checked blood sugar levels etc.

But where do guidelines come from – exactly? Who gives people the right to sit on guideline committees? What are the entrance requirements? Who shall guard the guideliners?

The answer is, perhaps shockingly, that there are almost no rules to this. If a group, such as the National Institutes for Health in the US, decides to set up a committee to decide on, for example, what is the healthy level for cholesterol lowering, what happens? They ask a number of Key Opinion Leaders to join the committee. In this case the NCEP (National Cholesterol Education Programme – which is a committee, not a programme).

In 2004 this committee decided that cholesterol levels should be lowered far more aggressively than in the past. Based on, as far as I could see, very flimsy evidence. Could it be that that committee was, in some way, biased in favour of cholesterol lowering companies? A number of people, including me, demanded to see if any of the eight invited members of this hugely important committee had financial conflicts.

With much reluctance, the conflicts were revealed (I have highlighted, in bold, the companies who marketed cholesterol lowering agents at the time.) See below

ATP III Update 2004: Financial Disclosure of NCEP members

Dr. Cleeman: (Chairman) has no financial relationships to disclose.

Dr. Grundy: has received honoraria from Merck, Pfizer, Sankyo, Bayer, Merck/Schering-Plough, Kos, Abbott, Bristol-Myers Squibb, and AstraZeneca; he has received research grants from Merck, Abbott, and Glaxo Smith Kline.

Dr. Bairey Merz: has received lecture honoraria from Pfizer, Merck, and Kos; she has served as a consultant for Pfizer, Bayer, and EHC (Merck); she has received unrestricted institutional grants for Continuing Medical Education from Pfizer, Procter & Gamble, Novartis, Wyeth, AstraZeneca, and Bristol-Myers Squibb Medical Imaging; she has received a research grant from Merck; she has stock in Boston Scientific, IVAX, Eli Lilly, Medtronic, Johnson & Johnson, SCIPIE Insurance, ATS Medical, and Biosite.

Dr. Brewer: has received honoraria from AstraZeneca, Pfizer, Lipid Sciences, Merck, Merck/Schering-Plough, Fournier, Tularik, Esperion, and Novartis; he has served as a consultant for AstraZeneca, Pfizer, Lipid Sciences, Merck, Merck/Schering-Plough, Fournier, Tularik, Sankyo, and Novartis.

Dr. Clark: has received honoraria for educational presentations from Abbott, AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer; he has received grant/research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer.

Dr. Hunninghake: has received honoraria for consulting and speakers bureau from AstraZeneca, Merck, Merck/Schering-Plough, and Pfizer, and for consulting from Kos; he has received research grants from AstraZeneca, Bristol-Myers Squibb, Kos, Merck, Merck/Schering-Plough, Novartis, and Pfizer.

Dr. Pasternak: has served as a speaker for Pfizer, Merck, Merck/Schering-Plough, Takeda, Kos, BMS-Sanofi, and Novartis; he has served as a consultant for Merck, Merck/Schering-Plough, Sanofi, Pfizer Health Solutions, Johnson & Johnson-Merck, and AstraZeneca.

Dr. Smith: has received institutional research support from Merck; he has stock in Medtronic and Johnson & Johnson.

Dr. Stone: has received honoraria for educational lectures from Abbott, AstraZeneca, Bristol-Myers Squibb, Kos, Merck, Merck/Schering-Plough, Novartis, Pfizer, Reliant, and Sankyo; he has served as a consultant for Abbott, Merck, Merck/Schering-Plough, Pfizer, and Reliant.

http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04_disclose.htm

Of course, as people have stated to me, the mere fact that there were seventy two financial conflicts of interest does not mean that the guidelines themselves were biased. But you know what, I don’t believe it. Imagine if eight Supreme Court judges, ruling on any issue, had seventy two direct financial conflicts of interest to do with that issue…..Well, the outcry would never end.

Yet doctors, it seems, are beyond any suspicion – of any sort. There is not the slightest possibility that any doctor would ever do anything wrong….We are, after all, superior beings. ‘But, what’s that you say skippy…. hold on.’

‘Despite a 2-year-old scandal discrediting key evidence, current guidelines relying on this evidence have not been revised. As a result of physicians following these guidelines, some researchers say, it is possible that thousands of patients may have died each year in the UK alone. It is unlikely that a true understanding of the damage will ever be known…..

The guidelines, which were published in 2009, were based on analyses of the available trials. The strongest evidence came from the DECREASE family of trials, which appeared to strongly support perioperative beta-blockade, and one other large trial, POISE, which raised concerns that beta-blockers might lead to an increase in deaths

In 2011, however, faith in the reliability of the DECREASE trials was shattered as a result of a scientific misconduct scandal centering on the principal investigator of the studies, the now disgraced Dutch researcher Don Poldermans. The issue was further complicated because, in addition to his key role in the trials, Poldermans was the chairman of the committee that drafted the guidelines.’ http://cardiobrief.org/2013/07/31/european-heart-guidelines-based-on-disgraced-research-may-have-caused-thousands-of-deaths/

Oh well, maybe not.

The fact is that, wherever you look, guidelines are being developed by doctors who have widespread conflicts of interest. And if you go a step further back to review the studies that the guidelines are based on, they are run by, and written up by, doctors who have enormous conflicts of interest. Although sometimes, these conflicts are just…well, forgotten about.

For example, a few opinion leader were ‘named and shamed’ by the Journal of the American Medical Association, when someone pointed out that a number of the authors of the original paper they wrote might just have slipped up in declaring their conflicts:

Unreported Financial Disclosures in: ‘Association of LDL Cholesterol, Non–HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins: A Meta-analysis.’

….the following disclosures should have been reported: “Dr Mora reports receipt of travel accommodations/meeting expenses from Pfizer; Dr Durrington reports provision of consulting services to Hoffman-La Roche, delivering lectures or serving on the speakers bureau for Pfizer, and receipt of royalties from Hodder Arnold Health Press; Dr Hitman reports receipt of lecture fees and travel expenses from Pfizer, provision of consulting services on advisory panels to GlaxoSmithKline, Merck Sharp & Dohme, Eli Lilly, and Novo Nordisk, receipt of a grant from Eli Lilly, and delivering lectures or serving on the speakers bureau for GlaxoSmithKline, Takeda, and Merck Sharp & Dohme; Dr Welch reports receipt of a grant, consulting fees, travel support, payment for writing or manuscript review, and provision of writing assistance, medicines, equipment, or administrative support from Pfizer, and provision of consultancy services to Edwards, MAP, and NuPathe; Dr Demicco reports having stock/stock options with Pfizer; Dr Clearfield reports provision of consulting services on advisory committees to Merck Sharp & Dohme and AstraZeneca; Dr Tonkin reports provision of consulting services to Pfizer, delivering lectures or serving on the speakers bureau for Novartis and Roche, and having stock/stock options with CSL and Sonic Health Care; and Dr Ridker reports board membership with Merck Sharp & Dohme and receipt of a grant or pending grant to his institution from Amgen. http://jama.ama-assn.org/content/307/16/1694.3.full?etoc

Not a bad little list. As you can see, Dr Ridker had board membership with Merck Sharp and Dohme…… a company that has made billions from selling statins. Now, here is he is authoring a paper on the benefit of statins (which will be used to develop guidelines on cholesterol lowering), and he simply forgot about this conflict of interest. As for the others, well, they’re also busy people; things must have just slipped their minds, such as thirty three separate financial conflicts.

For this terrible crime against the integrity of medical science, none of them can ever again do medical research, or author a medical paper, or sit on guideline committees. Cue, mad cackling laughter. As you may expect, absolutely nothing happened at all, apart from the publication of that statement you in the Journal in the American Medical Journal (JAMA).

I am sorry, but the system of developing guidelines is, frankly, bust. It has been for many years, but it is a very big and dangerous looking nettle to grasp, and no-one, currently has the will to do it.

Someone, somewhere, needs to ensure that guidelines, and the evidence they are based on, and the interpretation of that evidence, is of the highest quality – and free from potential bias, and financial conflicts of interest. We are about as far from this happy state of affairs as I am from being invited onto any guideline committee, ever, anywhere.

And that, my friend, is a very, very long way away indeed. You would need to Hubble telescope to see across distances as vast as that.

Dr. Malcolm Kendrick

Scottish Doctor, author, speaker, sceptic