Friday, November 16, 2012

Why Cholesterol May Not Be the Cause Of Heart Disease - Hyman

Why Cholesterol May Not Be the Cause Of Heart Disease


WE HAVE ALL BEEN LED TO to believe that cholesterol is bad and that lowering it is good. Because of extensive pharmaceutical marketing to both doctors and patients we think that using statin drugs is proven to work to lower the risk of heart attacks and death.

But on what scientific evidence is this based, what does that evidence really show?

Roger Williams once said something that is very applicable to how we commonly view the benefits of statins. “There are liars, damn liars, and statisticians.”

We see prominent ads on television and in medical journals — things like 36% reduction in risk of having a heart attack. But we don’t look at the fine print. What does that REALLY mean and how does it affect decisions about who should really be using these drugs.

Before I explain that, here are some thought provoking findings to ponder.
  • If you lower bad cholesterol (LDL) but have a low HDL (good cholesterol) there is no benefit to statins. (i)
  • If you lower bad cholesterol (LDL) but don’t reduce inflammation (marked by a test called C-reactive protein), there is no benefit to statins. (ii)
  • If you are a healthy woman with high cholesterol, there is no proof that taking statins reduces your risk of heart attack or death. (iii)
  • If you are a man or a woman over 69 years old with high cholesterol, there is no proof that taking statins reduces your risk of heart attack or death. (iv)
  • Aggressive cholesterol treatment with two medications (Zocor and Zetia) lowered cholesterol much more than one drug alone, but led to more plaque build up in the arties and no fewer heart attacks. (v)
  • 75% of people who have heart attacks have normal cholesterol
  • Older patients with lower cholesterol have higher risks of death than those with higher cholesterol. (vi)
  • Countries with higher average cholesterol than Americans such as the Swiss or Spanish have less heart disease.
  • Recent evidence shows that it is likely statins’ ability to lower inflammation it what accounts for the benefits of statins, not their ability to lower cholesterol.
So for whom do the statin drugs work for anyway? They work for people who have already had heart attacks to prevent more heart attacks or death. And they work slightly for middle-aged men who have many risk factors for heart disease like high blood pressure, obesity, or diabetes.

So why did the 2004 National Cholesterol Education Program guidelines expand the previous guidelines to recommend that more people take statins (from 13 million to 40 million) and that people who don’t have heart disease should take them to prevent heart disease. Could it have been that 8 of the 9 experts on the panel who developed these guidelines had financial ties to the drug industry? Thirty-four other non-industry affiliated experts sent a petition to protest the recommendations to the National Institutes of Health saying the evidence was weak. It was like having a fox guard the chicken coop.
People with the lowest cholesterol as they age are in fact at highest risk of death. Under certain circumstances, higher cholesterol can actually help increase life span.
It’s all in the spin. The spin of the statistics and numbers. And it’s easy to get confused. Let me try to clear things up.

When you look under the hood of the research data you find that the touted “36% reduction” means a reduction of the number of people getting heart attacks or death from 3% to 2% (or about 30-40%).
And that data also shows that treatment only really works if you have heart disease already. In those who DON’T have documented heart disease, there is no benefit.

In those at high risk for heart disease about 50 people would need to be treated for 5 years to reduce one cardiovascular event. Just to put that in perspective: If a drug works, it has a very low NTT (number needed to treat). For example, if you have a urine infection and take an antibiotic, you will get near a 100% benefit. The number needed to treat is “1″. So if you have an NTT of 50 like statins do for preventing heart disease in 75% of the people who take them, it is basically a crap shoot.

Yet at a cost of over $28 billion a year, 75% of all statin prescriptions are for exactly this type of unproven primary prevention. Simply applying the science over 10 years would save over $200 billion. This is just one example of reimbursed but unproven care. We need not only prevent disease but also prevent the wrong type of care.

If these medications were without side effects, then you may be able to justify the risk – but they cause muscle damage, sexual dysfunction, liver and nerve damage and other problems in 10-15% of patients who take them. Certainly not a free ride.

So if lowering cholesterol is not the great panacea that we thought, how do we treat heart disease, and how do we get the right kind of cholesterol – high HDL, low LDL and low triglycerides and have cholesterol particles that are large, light and fluffy rather than small, dense and hard, which is the type that actually causes heart disease and plaque build up.

We know what causes the damaging small cholesterol particles. And it isn’t fat in the diet. It is sugar. Sugar in any form or refined carbohydrates (white food) drives the good cholesterol down, cause triglycerides to go up, creates small damaging cholesterol particles, and causes metabolic syndrome or pre-diabetes. That is the true cause of most heart attacks, NOT LDL cholesterol.

One of the reasons we don’t hear about this is because there is no good drug to raise HDL. Statin drugs lower LDL — and billions are spent advertising them, even though they are the wrong treatment.

If you’re like most of the patients I see in my practice, you’re convinced that cholesterol is the evil that causes heart disease. You may hope that if you monitor your cholesterol levels and avoid the foods that are purported to raise cholesterol, you’ll be safe from America’s number-one killer.

We are all terrified of cholesterol because for years well-meaning doctors, echoed by the media, have emphasized what they long believed is the intimate link between cholesterol and death by heart disease. If only it were so simple!

The truth is much more complex.

Cholesterol is only one factor of many — and not even the most important — that contribute to your risk of getting heart disease.

First of all, let’s take a look at what cholesterol actually is. It’s a fatty substance produced by the liver that is used to help perform thousands of bodily functions. The body uses it to help build your cell membranes, the covering of your nerve sheaths, and much of your brain. It’s a key building block for our hormone production, and without it you would not be able to maintain adequate levels of testosterone, estrogen, progesterone and cortisol.

So if you think cholesterol is the enemy, think again. Without cholesterol, you would die.

In fact, people with the lowest cholesterol as they age are at highest risk of death. Under certain circumstances, higher cholesterol can actually help to increase life span.
In reality, the biggest source of abnormal cholesterol is not fat at all — it’s sugar. The sugar you consume converts to fat in your body. And the worst culprit of all is high fructose corn syrup.
To help clear the confusion, I will review many of the cholesterol myths our culture labors under and explain what the real factors are that lead to cardiovascular disease.

Cholesterol Myths
One of the biggest cholesterol myths out there has to do with dietary fat. Although most of us have been taught that a high-fat diet causes cholesterol problems, this isn’t entirely true. Here’s why: The type of fat that you eat is more important than the amount of fat. Trans fats or hydrogenated fats and saturated fats promote abnormal cholesterol, whereas omega-3 fats and monounsaturated fats actually improve the type and quantity of the cholesterol your body produces.

In reality, the biggest source of abnormal cholesterol is not fat at all — it’s sugar. The sugar you consume converts to fat in your body. And the worst culprit of all is high fructose corn syrup.
Consumption of high fructose corn syrup, which is present in sodas, many juices, and most processed foods, is the primary nutritional cause of most of the cholesterol issues we doctors see in our patients.
So the real concern isn’t the amount of cholesterol you have, but the type of fats and sugar and refined carbohydrates in your diet that lead to abnormal cholesterol production.

Of course, many health-conscious people today know that total cholesterol is not as critical as the following:
  • Your levels of HDL “good” cholesterol vs. LDL “bad” cholesterol
  • Your triglyceride levels
  • Your ratio of triglycerides to HDL
  • Your ratio of total cholesterol to HDL
Many are also aware that there are different sizes of cholesterol particles. There are small and large particles of LDL, HDL, and triglycerides. The most dangerous are the small, dense particles that act like BB pellets, easily penetrating your arteries. Large, fluffy cholesterol particles are practically harmless–even if your total cholesterol is high. They function like beach balls and bounce off the arteries, causing no harm.

Another concern is whether or not your cholesterol is rancid. If so, the risk of arterial plaque is real.
Rancid or oxidized cholesterol results from oxidative stress and free radicals, which trigger a vicious cycle of inflammation and fat or plaque deposition under the artery walls. That is the real danger: When small dense LDL particles are oxidized they become dangerous and start the build up of plaque or cholesterol deposits in your arteries.

Now that we’ve explored when and how cholesterol becomes more problematic, let’s take a look at other factors that play a more significant role in cardiovascular disease.

Prime Contributors to Cardiovascular Disease
First of all, cardiovascular illness results when key bodily functions go awry, causing inflammation, (vii) imbalances in blood sugar and insulin and oxidative stress.

To control these key biological functions and keep them in balance, you need to look at your overall health as well as your genetic predispositions, as these underlie the types of diseases you’re most likely to develop. It is the interaction of your genes, lifestyle, and environment that ultimately determines your risks — and the outcome of your life.

This is the science of nutrigenomics, or how food acts as information to stall or totally prevent some predisposed disease risks by turning on the right gene messages with our diet and lifestyle choices. That means some of the factors that unbalance bodily health are under your control, or could be.
These include diet, nutritional status, stress levels, and activity levels. Key tests can reveal problems with a person’s blood sugar and insulin, inflammation level, level of folic acid, clotting factors, hormones, and other bodily systems that affect your risk of cardiovascular disease.

Particularly important are the causes if inflammation, which are many, and need to be assessed. Inflammation can arise from poor diet (too much sugar and trans and saturated fats), a sedentary lifestyle, stress, autoimmune disease, food allergies, hidden infections such as gum disease, and even toxins such as mercury. All of these causal factors need to be considered anytime there is inflammation.

Combined together, all of these factors determine your risk of heart disease. And I recommend that people undergo a comprehensive medical evaluation to see what their risk really is.

Zeroing in on Key Factors for Heart Disease
There’s no doubt about it, inflammation is key contributor to heart disease. A major study done at Harvard found that people with high levels of a marker called C-reactive protein (CRP) had higher risks of heart disease than people with high cholesterol. Normal cholesterol levels were NOT protective to those with high CRP. The risks were greatest for those with high levels of both CRP and cholesterol.

Another predisposing factor to heart disease is insulin resistance or metabolic syndrome, which leads to an imbalance in the blood sugar and high levels of insulin. This may affect as many as half of Americans over age 65. Many younger people also have this condition, which is sometimes called pre-diabetes.

Although modern medicine sometimes loses sight of the interconnectedness of all our bodily systems, blood sugar imbalances like these impact your cholesterol levels too. If you have any of these conditions, they will cause your good cholesterol to go down, while your triglycerides rise, which further increases inflammation and oxidative stress. All of these fluctuations contribute to blood thickening, clotting, and other malfunctions — leading to cardiovascular disease.

What’s more, elevated levels of a substance called homocysteine (which is related to your body’s levels of folic acid and vitamins B6 and B12) appears to correlate to cardiovascular illness. Although this is still somewhat controversial, I often see this inter-relationship in my practice. While genes may play a part, tests done as part of a comprehensive evaluation of cardiac risk can easily ascertain this factor. Where problematic levels occur, they can be easily addressed by adequate folic acid intake, along with vitamins B6 and B12.

Testing for Cardiovascular Risk Factors
Heart disease is not only about cholesterol. It is important to look at many factors that contribute to your overall risk. And it seems that insulin and blood sugar imbalances, and inflammation are proving to be more of a risk that cholesterol.

If you want to test your overall risk, you can consider asking your doctor to perform the following tests:
  1. Total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Your total cholesterol should be under 200. Your triglycerides should be under 100. Your HDL should be over 60. Your LDL should be ideally under 80. Your ratio of total cholesterol to HDL should be less than 3.0. Your ratio of triglycerides to HDL should be no greater than 4, which can indicate insulin resistance if elevated.
  2. NMR Lipid Profile. This looks at your cholesterol under an MRI scan to assess the size of the particles, which can determine your cardiovascular risk. This is a very important test that can further differentiate the risk of your cholesterol and can be an important factor to track as your system improves and your cholesterol transforms from being small dense and dangerous to light and fluffy and innocuous. It is done by a company called Liposcience and is also available through LabCorp.
  3. Glucose Insulin Tolerance Test. Measurements of fasting and 1 and 2 hour levels of glucose AND insulin helps identify pre-diabetes and excessively high levels of insulin, and even diabetes. Most doctors just check blood sugar and NOT insulin, which is the first thing to go up. By the time your blood sugar goes up, the train has left the station.
  4. Hemaglobin A1c. This measures your average blood sugar level over the last 6 weeks. Anything over 5.5 is high.
  5. Cardio C-reactive protein. This is a marker of inflammation in the body that is essential to understand in the context of overall risk. Your C-reactive protein level should be less than 1.
  6. Homocysteine. Your homocysteine measures your folate status and should be between 6 and 8.
  7. Lipid peroxides or TBARS test, which looks at the amount of oxidized or rancid fat. This should be within normal limits of the test and indicates whether or not you have oxidized cholesterol.
  8. Fibrinogen, which is another test looking at clotting in the blood. It should be less than 300.
  9. Lipoprotein (a), which is another factor that can promote the risk of heart disease, often in men. It should be less than 30.
  10. Genes or SNPs may also be useful in terms of assessing your situation. A number of key genes regulate cholesterol and metabolism, including Apo E genes and the cholesterol ester transfer protein gene. The MTHFR gene, which regulates homocysteine is also important and may be part of an overall workup.
  11. Get a high-speed CT or (EBT) scan of the heart if you are concerned that you have cardiovascular disease. This may be helpful to assess overall plaque burden and calcium score. A score higher than 100 is a concern, and a score higher than 400 indicates severe risk of cardiovascular disease.
Next I will review how to lower your risk of heart disease and fix your cholesterol. We’ll do this not by lowering the LDL, but by getting more light and fluffy LDL particles, which are protective and more HDL cholesterol, which is THE most important cholesterol.

(i) Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, Kastelein JJ, Bittner V, Fruchart JC; Treating to New Targets Investigators. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007 Sep 27;357(13):1301-10.
(ii) Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195-207.
(iii) Abramson J, Wright JM. Are lipid-lowering guidelines evidence-based? Lancet. 2007 Jan 20;369(9557):168-9
(iv) IBID
(v) Brown BG, Taylor AJ Does ENHANCE Diminish Confidence in Lowering LDL or in Ezetimibe? Engl J Med 358:1504, April 3, 2008 Editorial
(vi) Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet. 2001 Aug 4;358(9279):351-5.
(vii) Hansson GK Inflammation, Atherosclerosis, and Coronary Artery Disease N Engl J Med 352:1685, April 21, 2005
Read the complete article here.

Friday, November 9, 2012

Do statins really reduce the risk of cancer? - Briffa

Yesterday saw the on-line publication of a study in the New England Journal of Medicine (NEJM) that concerns statins and is getting more than its fair share of media attention. The study, conducted in Denmark, analysed the rates of death from cancer in individuals taking statins, and compared them to those in individuals not taking these drugs. Those taking statins were found to be at a statistically significant reduced risk of dying from cancer. Some seem keen to claim that statins may not only be an answer to heart disease, but our cancer woes too. Take this headline for example which you can find here: ‘Statins cut mortality in cancer patients’. The wording of this title on a website dedicated to the education of doctors strongly suggests that statins actually reduce the risk of death from cancer.

But, not so fast. The NEJM study is what is known as ‘epidemiological’ or ‘observational’ study. The study tells us that statin use is associated with a reduced risk of death from cancer, but it can’t tell us whether or not statins actually cut cancer risk.

One fundamental problem with studies of this nature is that they are subject to what is known as the ‘healthy user effect’. Basically, what this means is that healthier, often more health-conscious individuals are more likely to end up on statins than less healthy, not so health-conscious individuals. Because of this, it’s possible that the apparent benefits of statins with regard to cancer (or anything else) are not to do with the drugs themselves, but the health characteristics of those more likely to take statins.

If we really want to know if statins reduce the risk of cancer death then we need to look to what are known as ‘intervention studies’ in which, usually, roughly equivalent groups of individuals are given statins or placebo. These studies, the gold standard of which are ‘randomised controlled trials’ do have the potential of discerning the true effects of drugs and other treatments.

Single studies such as these can provide useful data, but sometimes it makes sense to amass data from several studies to get a decent overview of the impact of a drug or class of drugs. Such grouping of studies together are referred to as ‘meta-analyses’.

One meta-analysis published in 2009 found that statin use was not associated with a reduced risk of cancer [2]. A more recent meta-analysis published this year found the same thing [3]. Meta-analyses of intervention studies are not perfect, but they are much better than (crappy) single epidemiological studies like the one currently doing the rounds. And it’s perhaps worth bearing in mind that there as been at least some concern about the impact statins might have on cancer risk in the elderly. In one study, statin use (compared to placebo) increased the risk of cancer by 25 per cent (statistically significant) [4].

Put in this context, the frothing enthusiasm exhibited by some regarding this latest study seems inappropriate. And for a website dedicated to the education of doctors to proclaim that ‘Statins cut mortality in cancer patients’ is downright negligent.

1. Nielsen SF, et al. Statin Use and Reduced Cancer-Related Mortality. NEJM published online 8 October 2012
2. Brugts JJ, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ 2009;338:b2376.
3. Cholesterol treatment trialists’ collaboraton. Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy. PLoS One 2012;7(1):e29849. Epub 2012 Jan 19.
4. Shepherd J, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360(9346):1623-30
Read the complete article here.

Monday, November 5, 2012

Alzheimer’s: another reason to be sceptical about statins - Burne

Alzheimer’s: another reason to be sceptical about statins

The front page of the Daily Express on Friday led with a new warning about statins – combining them with certain blood pressure pills could raise your risk of muscle pains, lung disorders and kidney damage. Hmm yes well.

Even as a cholesterol/statin sceptic I thought that was remarkably over-hyped – statin side effects are massively underplayed and finding they go up a bit when mixed with another drug is more of a clinical technicality than front page news.

However there is a statin risk which should be a serious cause for concern – lowering cholesterol may well raise your chances of developing Alzheimer’s. I’ll come to that in a moment.
First there is one aspect of the Express story that raises a wider issue – the way the buck is subtly passed when any new risk factor is identified. The standard official response is is to say: “If you are worried discuss it with your doctor.” It seems sensible but the implications aren’t reassuring. It’s a line that’s been trotted out rather a lot recently.
Need for serious sanctions
Earlier this week it was used in response to the report that found that more women are harmed by unnecessary treatment following a mammograms than benefit from detecting a cancer. The week before, when a brilliant BMJ investigation exposed the appalling corruption involved in official EU licensing of hip implants, you were also invited to discuss how it might affect you. In both cases serious sanctions would seem appropriate.

In the case of mammograms because convincing research showing that the dangers of over-diagnosis from breast screening dates back over a decade. A clear statement of risks and benefits has taken so long because of the readiness of the mammogram establishment to ignore or denigrate evidence of harm, as I described recently in the Mail. The fact that the European Medicines Agency allows licensing bodies to behave in a way that openly favours business interests rather than the patient, should also trigger an investigation.
Shifting responsibility
There’s nothing wrong with discussing safety with your doctor, but when that’s all that happens it is a brilliant way of shifting the responsibility for producing safe products from the authorities onto you. If in the future you suffer as a result of mammograms or hip implants or indeed statins then the fact you were told about the risk, discussed it and went ahead becomes just one of those things. For a book that discusses this see here.

To appreciate how odd the response to medical dangers is, look at what happens with when something dangerous about a car is picked up. In 2010 it was found that the throttle on some Toyotas could stick in the open position. But rather than saying: “If you are worried about the “dangerous acceleration” issue, discuss it with your dealer and decide if Toyota is right for you”, the company recalled nine million cars.

The truth is that medicine is far more dangerous than the motoring. An estimated 15 people died from driving 10 million cars at risk from the acceleration issue in the USA. If all drugs and other conventional treatments had to be withdrawn at that level of mortality, medicine would become impossible.

Drugs carry serious risks because of the way they work. A single molecule, such as cholesterol that is part of a complex interlocking system, is blocked or boosted with a drug – statins. Inevitably they do things you don’t want as well as the ones you do. And the more important the system you are blocking the more likely the harm. That’s why statins could cause the sort of brain damage that shows up in Alzheimer’s.

Last week I wrote about the growing evidence for links between the raised insulin and insulin resistance that diabetics suffer from and an increased risk of Alzheimer’s. What I didn’t appreciate then was that lowering cholesterol might be equally damaging.

You may be familiar with the idea that cholesterol is involved in brain function but maybe not just how important its role is. A review article in the European Journal of Internal Medicine last year makes it clear.
Cholesterol’s vital role
“The brain represents only 2% of the body’s total mass, but contains 25% of the total cholesterol,” reads an introductory paragraph. “Cholesterol is required everywhere in the brain as an antioxidant, an electrical insulator (in order to prevent ion leakage), as a structural scaffold for the neural network, and a functional component of all membranes. Cholesterol is also utilized in the wrapping and synaptic delivery of the neurotransmitters. It also plays an important role in the formation and functioning of synapses in the brain.”

Personally I’d want to know my odds of benefiting from blocking something that vital were better than the 100 -200:1 that is on offer from stains for primary prevention. The article goes on to describe a number of specific ways cholesterol is used in the brain.

It’s directly involved in the action of a gene known as ApoE. A harmful variation – ApoE4 – is well known to raised your risk of both heart disease and Alzheimer’s . So what does ApoE do? “It has an essential role in the delivery of fat, cholesterol, and antioxidants from the liver to all the cells of the body,” writes the author Stephanie Seneff, a Senior Research Scientist in the Computer Science and Artficial Intelligence Laboratory at MIT who has recently been turning her attention to biochemistry and medicine.

The ApoE4 variation causes brain problems because it doesn’t work so well and lowers the amount of cholesterol available to the hippocampus – the brain region crucial for memory.

More evidence for the harm from having too little cholesterol comes from research showing that Alzheimer’s patients have low levels of cholesterol in their spinal fluid, along with not enough lipoproteins, triglycerides, and free fatty acids. Parkinson’s patients, who also suffer brain damage, have low levels of cholesterol in their blood.

There’s still a lot more to be done to prove definitively that too too little cholesterol damages the brain along with too much insulin and glucose.But avoiding these two highly plausible risk factors is remarkably simple and doesn’t involve adding new risks the way drugs do. It’s what we advocate in our book. Make sure you have enough good fats and eat foods that don’t push up blood sugar.

It’s what Dr Seneff’s recommends too. “Simple dietary modification, towards fewer highly-processed carbohydrates and relatively more fats and cholesterol, is likely a protective measure against Alzheimer’s disease.”
Read the complete article here.

Statin Anti-Cholesterol Drugs Revisited - DACH

Statin Anti-Cholesterol Drugs Revisited

By (about the author)     (Page 1 of 7 pages) Life Arts
This article takes a critical look at statin anti-cholesterol drugs, and asks the hard questions. Do statin drugs work? Who do they work for? Who do they harm? Who should be taking them, and who should not be taking them? Examples of Statin Drugs are Lipitor, Zocor, Simvastatin, Pravachol, Crestor, Mevacor, etc. These drugs reduce the production of cholesterol by the liver by inhibiting an enzyme called HMG-CoA. Due to a belief that cholesterol causes coronary artery disease, statin drug reduction of cholesterol is a mainstream medical treatment intended to prevent heart disease. Do statin drugs prevent coronary artery disease, heart attacks and mortality from heart disease? This article will answer that question.

Anti-Inflammatory Effect

After many decades of study and clinical trials, it has become clear that the benefit of statin drugs (if there is any) is probably not due to reduction in cholesterol, rather it is due to an anti-inflammatory effect of the drug.(link)

Reducing CoQ-10

Coincidentally, statin drugs inhibit the production of an important mitochondrial cofactor called Co-Q10, accounting for adverse effects as mitochondrial toxins. In addition, a low serum cholesterol level is a health risk for many reasons. Cholesterol is an important molecule in the body, and reducing cholesterol to low levels is associated with increased mortality and adverse effects on health. (27)

Asking A Few Questions

In this article we will revisit anti-cholesterol statin drugs while asking the following questions:

1) What is the efficacy for statin drugs in primary prevention of heart disease (in normal healthy people)?

2) What is the efficacy of statin drugs in secondary prevention (patients with known underlying heart disease)?

3) Which subgroups benefit from statin drugs, and which subgroups of the population are harmed by statin drugs?

The Elderly - Low Serum Cholesterol Predicts Increased Mortality

First, let's take a look at the medical practice of prescribing statin anti-cholesterol drugs for the elderly. Contrary to current dogma, higher cholesterol levels in the elderly are not a heath risk. Studies show that higher cholesterol in the elderly is associated with increased survival, while lower total serum cholesterol values in the elderly are a robust predictor of increased mortality. (1, 4,5)

The Prosper Study - Statins for the Elderly

When statin drugs are given to the elderly to reduce cholesterol values as was done in the PROSPER study, there was no mortality benefit for either primary or secondary prevention of heart disease. (1,6,7) True, there was a reduction in cardiac mortality of about 20% in the secondary prevention group in the Prosper study, however, this was counterbalanced by an increase in cancer mortality, yielding no over-all mortality benefit in the final analysis.

Women- No Mortality Benefit from Statins

Perhaps the best summary of the results of three decades of statin drug studies in women can be found in the Judith Walsh MD report in JAMA May 2004. (8) Again, Dr Walsh found that statin drug treatment to reduce cholesterol in women provided no mortality benefit in both primary and secondary prevention of heart disease. As we found in the PROSPER study for the elderly, statin drug use in women (with known heart disease) resulted in a reduction in mortality from heart disease, and a reduction in heart attacks in this secondary prevention group, however, this was offset by additional deaths from cancer and other mortality which yielded no over-all mortality benefit in the final analysis. (8)

MEN and Women- Primary Prevention- Dr Ray Archives of Internal Medicine
Jeffrey Dach MD is a physician and author of two books, Natural Medicine 101, and Bioidentical Hormones 101, both available on Amazon, or as a free e-book on his web sites. Dr. Dach is founder and chief medical officer of TrueMedMD, a clinic in (more...)
Read the complete article here.

Friday, November 2, 2012

New cholesterol-lowering drug is licensed despite no evidence of benefits for health - Briffa

 Another new cholesterol-lowering drug is licensed despite no evidence of benefits for health

I was reading here that there’s a new cholesterol-lowering drug in the pipeline. The Food and Drugs Administration in the US has approved the injectable agent mipomersen for the treatment of ‘homozygous familial hypercholesterolaemia – a genetic cause of raised cholesterol levels associated with cardiovascular disease developing early in life. Mipomersen has been shown to reduce low density lipoprotein (LDL) levels by about a quarter. The hope is that this will help reduce the risk of individuals suffering premature death from, most likely, heart attack.

I’ve used the word ‘hope’ in the preceding sentence but, in reality, the FDA panel that has ratified mipomersen has no idea whether it has health benefits or not. That’s because the studies used to assess this drug were not large enough in scope to detect change in ‘clinical endpoints’ such as risk of heart attack or death. In other words, the licensing of this drug has been on the basis of its impact on ‘surrogate endpoints’ (in this case, cholesterol levels), rather than clinical endpoints (the thing that really matters).

And I’m not splitting hairs either, as we already have examples in the not-too distant past of drugs that promised a lot in terms of their impact on cholesterol, but failed to deliver in terms of actual health. For example, the drug ezetimibe is a proven cholesterol-lowerer, yet not one single study to dates demonstrates it has benefits in terms of clinical endpoints. Also, the drug torcetrapib looked at one time to be a new hero of cholesterol management, until appropriately designed studies found it was killing people (it’s since been dropped).

But the principle that something that benefits cholesterol does not necessarily benefit health does seem to have been somewhat lost on the FDA. And worse still, it seems the panel may have put their faith in cholesterol modification above some quite troubling data. Here you can read how the FDA’s own review of mipomersen revealed a number of concerns about this drug. Here’s an excerpt from the article:
Serious adverse events of cardiac disorders occurred in 3.8% (10/261) of patients in the mipomersen group compared with 3.1% (4/129) in the placebo group. The reviewers concluded that “the possibility that mipomersen therapy increases the risk for cardiovascular events cannot be excluded.”
Other concerns were raised by the finding that mipomersen increased the levels of ‘liver enzymes’ and increased the amount of fat in the liver (both signs of damage to the liver). Here’s another except:
The FDA reviewers said they did not know whether long-term use of mipomersen could cause irreversible liver damage, but warned that patients could be at risk for cirrhosis and liver-related death if the observed liver changes progressed.
And perhaps worse still, there’s even concern that mipomersen might have cancer-inducing potential:
According to the review, during clinical testing neoplasms, both benign and malignant, were detected in 3.1% (23/749) of patients who received mipomersen compared with 0.9% (2/221) of patients who received placebo. However, the FDA clinical reviewer noted that there was a diversity of malignant neoplasms and that two out of nine mipomersen patients who developed a malignancy had been on mipomersen for less than a month, “making it highly unlikely that mipomersen played a role.” The review concluded that ”there are several confounding factors that make it difficult to conclude that mipomersen is playing a dominant role in this cancer imbalance.”
Forgive me, but personally I detect a hint of ‘sweeping the issue under the carpet’ here. The same thing, by the way, happened with ezetimibe, which has been shown to increase the risk of death from cancer, an effect which researchers put down to chance (even though the effect was statistically significant and therefore highly unlikely to be due to chance). See here for more about this.

The FDA panel’s vote on mipomersen was relatively close (9 v 6), so at least some members of the panel had their doubts. It is said that the severe nature of homozygous familial hypercholesterolaemia was a major determining factor in swaying the vote. That’s laudable, perhaps, but I don’t think it excuses the fact that this drug has been licensed despite an absence of data that it benefits health, as well as the presence of data which points very much in the opposite direction.
Read the complete article here.