Health for life

If you read my last post about cholesterol-lowering drugs, then you understand some of the problems that can arise from their use.  Statins can produce some nasty side effects.  But side effects aside, statins save lives right?  I mean, doctors prescribe them to just about everyone, they must be effective.  Not quite... the story is not as simple as it may seem.

When looking at the statin drug clinical trials, its important to keep a few things in mind.  Firstly, and most importantly... total mortality is more important than heart disease mortality.  If a drug prevents you from dying of heart disease but doesnt affect your chances of dying in general, then that drug is not worth taking.  Whats most important is whether or not the drug will extend your life.  Secondly, you must consider that different groups of people may respond differently to the drug.  Women, middle-aged men, the elderly, and those with preexisting heart disease may all respond differently to treatment. 

Id like to begin by talking about women... both because I like women, and because they dont respond well to statins.  Although many statin studies notoriously neglect to reveal the all-cause death data for women, there are a few studies that do.  Check out the Scandinavian Simvastatin Survivial Study (4S), which was one of the most positive trials to date.  The big pharma folks must have been partying it up when this one came out.  This was a secondary prevention trial, meaning that participants all had pre-existing heart disease (previous heart attack or angina).  For future erence, a primary prevention trial would be an experiment in which the participants did not have pre-existing heart disease.  So, half of them took simvastatin and half of them took a placebo.  The results were great across the board: heart attack numbers were reduced, along with deaths from heart disease and all-cause mortality.  But there was one group that clearly didnt benefit:  women.  Over the duration of the 5.4 years of the trial, 27 (6.6%) of the women taking the statin died, while only 25 (6%) of the women taking the placebo died.  So despite the rest of the data, which was very supportive of statins, there was actually a slight increased risk of death in women from taking the statin.  As youll soon see, this finding is consistent throughout all of the statin trials, yet it is completely ignored by mainstream medicine.  These drugs simply dont work for women.


Now, men are a bit of a different story.  Its important to split men up into two distinct groups:  those with diagnosed heart disease (previous heart attack or angina), and those without diagnosed heart disease.  In those without heart disease, statins appear to be largely ineffective.  Both the University of British Columbia and Dr. Graham Jackson in the UK have published review articles looking at many of the primary prevention statin trials.  These were both reviews of the existing research, and they did not pick and choose studies that would support one side or the other.  Heres a key statistic from the UBC paper:  "71 primary prevention patients with cardiovascular risk factors have to be treated with a statin for 3 to 5 years to prevent one myocardial infarction or stroke."  And heres one from Dr. Jacksons study:  "Long term use of statins for primary prevention of heart disease produced a 1% greater risk of death over ten years versus placebo when the result of all the big controlled trials reported before 2000 were combined."  Although both studies showed reduction of cardiovascular deaths in those taking statins, overall deaths were either the same or higher.  Oh, and they also found zero effect on cardiovascular deaths in women.  Sounds like statins arent so effective in those without pre-existing heart disease. 

And Ive got more.  In 2005, a study called ASCOT-LLA, which studied Lipitor on high blood pressure patients, was stopped early due to the supposed "massive" reduction in cardiovascular deaths experienced by the Lipitor group.  The researchers considered the benefits so great that it was unethical to continue to deprive the placebo group of proper treatment. This study is considered to be one of those landmark trials that proved once and for all the life-saving benefits of statins.  Well, lets look at the data... youll have to click to enlarge it.



In that first set of data, Id like to draw your attention to the "all-cause mortality" graph in the bottom right.  See that vertical line there that Ive drawn in?  Thats a little trick I learned from Dr. Malcolm Kendrick in his book The Great Cholesterol Con.  The reason that line is drawn in there is because the trial ended at 3.3 years.  The graphs, however, show data until 3.5 years.  If you look closely at the graph, at 3.3 years there is almost no difference between the Lipitor group and the control group, but for the last 0.2 years of the study, the two lines begin to suddenly separate.  WTF mate?  How does one acquire data for a study after the study has ended?  Something seems fishy to me...  tampering of evidence perhaps?  No way to know for sure, but I can say with certainty that there was no reason to shut down this study early.  Theres virtually no difference in the all-cause mortality data.  Oh, and that second graph... thats showing the effectiveness of Lipitor on cardiovascular mortality (note: NOT all-cause mortality).  Notice women in this trial had an increased risk of dying from heart disease on the drug.

To sum up the statin drug data, heres a convenient table copied again from Dr. Malcolm Kendrick:


You can see here that the 4S trial, which I discussed earlier, was overall very supportive of statin use.  This trial was purely a secondary prevention trial.  And I must admit that statins do appear to save lives in men with previous heart disease.  But that is the ONLY group for which they save lives.  Purely primary prevention trials, like EXCEL, actually showed in increase in all-cause death on statins.  And then there are trials like WOSCOPS, which was a mix of primary and secondary prevention, and those trials typically yield results somewhere in the middle of the extremes.  Even in the most positive statin data for those with pre-existing heart disease, however, the results are really underwhelming.  You would think that with all the hype surrounding these supposed "life-saving" drugs, the data would be a little stronger.  Even if you do have pre-existing heart disease, and are a man, you can only expect about a 3% reduction in the chance of dying over the next several years.  That is just unimpressive to me.

So despite the relentless pushing of these drugs by big pharmaceutical companies, mainstream doctors, and my Anatomy and Physiology professor, caul examination of the data shows a surprising lack of evidence to support their use.  Statins decrease the risk of dying of heart disease; thats good.  But they dont decrease the risk of dying overall in the majority of the population; thats bad.  So then, if heart disease deaths are decreasing but overall deaths are not, statins must be increasing the risk that youll die of something other than heart disease.  Im even going to go as far as to say that they cause these non-cardiovascular-related deaths. Unfortunately, most studies fail to specify exactly what these non-cardiovascular deaths are, but take a look at my previous post for an idea.  If youre a woman, statins wont even reduce your risk for heart disease, and they actually increase your risk of dying overall.  The only population for which statins can save lives is men with pre-existing heart disease, which is less than 5% of the population.  If youre one of those people, take your statin if youre so inclined.  But if youre anyone else, especially a woman, you are barking up the wrong tree.

Researchers at the Linda Crnic Institute for Down Syndrome and the University of Colorado School of Medicine have found that a single mechanism may underlie the damaging effect of cholesterol on the brain and on blood vessels.

High levels of blood cholesterol increase the risk of both Alzheimers disease and heart disease, but it has been unclear exactly how cholesterol damages the brain to promote Alzheimers disease and blood vessels to promote atherosclerosis.

Using insights gained from studying two much rarer disorders, Down Syndrome and Niemann Pick-C disease, researchers at the Linda Crnic Institute for Down Syndrome and the Department of Neurology of the University of Colorado School of Medicine found that cholesterol wreaks havoc on the orderly process of cell division, leading to defective daughter cells throughout the body.

In the new study published this week in the on-line journal PLOS ONE, Antoneta Granic, PhD, and Huntington Potter, PhD, show that cholesterol, particularly in the LDL form, called bad cholesterol, causes cells in both humans and mice to divide incorrectly and distribute their already-duplicated chromosomes unequally to the next generation. The result is an accumulation of defective daughter cells with the wrong number of chromosomes and theore the wrong number of genes. Instead of the correct two copies of each chromosome, and thus two copies of each gene, some cells acquired three copies and some only one.

Granic and Potters study of the effects of cholesterol on cell division included a prominent finding of cells carrying three copies of the chromosome (#21 in humans and #16 in mice) that encodes the amyloid peptide that is the key component of the neurotoxic amyloid filaments that accumulate in the brains of Alzheimer patients.

Human trisomy 21 cells are significant because people with Down syndrome have trisomy 21 in all of their cells from the moment of conception, and they all develop the brain pathology and many develop the dementia of Alzheimers disease by age 50. Earlier studies by Granic, Potter and others have shown that as many as 10% of cells in an Alzheimer patient, including neurons in the brain, have three copies of chromosome 21 instead of the usual two. Thus, Alzheimers disease is, in some ways, a form of acquired Down syndrome. Furthermore, mutant genes that cause inherited Alzheimers disease cause the same defect in chromosome segregation as does cholesterol, thus indicating the presence of a common cell division problem in both familial and sporadic (non-familial) Alzheimers disease.

The new research also found trisomy 21 neurons in the brains of children with what, until now, was thought to be an unrelated neurodegenerative disease (Niemann Pick type C), caused by a mutation affecting cholesterol physiology. This result suggests that neurodegeneration itself might be linked to chromosome missegregation.

Such a model is supported by the finding of Thomas Arendt, MD, and colleagues at the University of Leipzig that 90% of the neuronal cell death observed at autopsy in Alzheimer patients is due to the creation and selective loss of neurons with the wrong number of chromosomes.

Identifying the specific problem caused by cholesterol will lead to completely new approaches to therapy for many human diseases, including Alzheimers disease, atherosclerosis and possibly cancer, all of which show signs of defective cell division. Granic and Potter already have found a potentially simple approach to preventing cholesterol from causing cells to distribute their chromosomes unequally into their new daughter cells. Specifically, when cells in culture were first treated with ethanol, the subsequent exposure to bad cholesterol was without effect on cell division: Each daughter cell received the correct number of chromosomes.

Its been too long since Ive spoken about cholesterol, too long I tell you. For those of you who dont know, I would sum up my view on cholesterol like this: its the most overhyped risk factor for heart disease there is. All you hear in the media is "Watch your cholesterol!" or "Cheerios lower cholesterol!" or "This food is cholesterol-free, so its good for you!". Bollocks. Bollocks I say.

First of all, the cholesterol in the food you eat barely has any effect on the cholesterol in your blood, if it has any effect at all. And second, lets set the record straight on "high cholesterol"... please for the love of God, quit worrying about it. Your total cholesterol is just about meaningless unless its taken in context with your triglycerides, HDL, and LDL... even better, your LDL particle number. Despite having no real, accurate clinical implications though, "high cholesterol" has taken on this sort-of boogey man role, scaring every health-conscious person into Lipitor land.

Anyway, I came across something today that was just too good not to write about; this stuff needs to be shared. This study was designed to analyze lipid-lowering therapy, but thats not the part I want to talk about here; its the cholesterol levels of the patients that piqued my interest. The researchers examined 65,396 patients hospitalized for heart disease (heart attack or angina) across the United States. Below youll find a screenshot of the baseline blood lipid data, taken within the first 24 hours of admission. You would expect, based on what you think you know, that heart disease patients must have had high cholesterol, right?

Average blood lipid values upon admission among all study participants.

Nope. On average, their cholesterol was 170.1 mg/dl, well below the high limit of 200. If any of these people had visited the doctor for a check-up a week before their hospitalization, the doc would have looked at these numbers and said "Steve, your cholesterol is great! Keep up the great work!" Assuming his name is Steve.

But things werent great. Each of these people experienced an acute coronary event that required hospitalization and very well could have ended their lives. Its irresponsible that were putting so much stock into cholesterol values when they clearly are NOT a good indicator of heart disease risk.

Sometimes it only takes one little piece of data, like this one, to completely change your beliefs on cholesterol and heart disease. I hope this provided the baseball to your brand new home window.

But what does this mean??
Now, theres an excellent chance that many of these people were already taking a cholesterol-lowering drug. Theres no data in the study to show whether this is true, but since so many people are on them, its very likely. So lets say for a moment that they were on statins. Say their normal cholesterol levels are around 220 mg/dl, and the statins bring it down to a more friendly-looking 170. Well, this only destroys the cholesterol and heart disease connection even more doesnt it? First off, it doesnt say much about the efficacy of the drugs. But also, it shows that reducing cholesterol from "high" back into "normal", at least via these mechanisms, is useless.

Okay, let me say it another way... if high cholesterol is the cause of our problems, lowering it should reduce our risk, regardless of the manner by which we do so. If it is not the cause, and it is just an indicator of a problem, then pharmacologically lowering it will NOT reduce our risk. It will, in fact, just make things appear to be fine when they are not.

Its sort of like when we get sick and we get a fever. We may take over-the-counter meds to reduce the fever; it makes us feel better and it takes away one of the symptoms of our illness. But we forget that the fever is an important part of our bodys defense mechanism to fight a bacterial infection... bacteria dont like the heat. We may feel a little better, but we remain just as sick as we were before, and weve now likely prolonged our sickness by messing with our bodys natural defense mechanisms.

The fever is like cholesterol, the symptom. The bacterial infection is the root cause. Got it? Okay its not a perfect analogy, but you get the point.


What is the root cause of heart disease then? If not total cholesterol, what should we focus on? Well thats a big can of worms... there are many factors that go into it. Stay tuned next week for a comprehensive guide on how to prevent heart disease!