Do you take a “statin” to reduce your risk of a heart attack? The number of people who do is enormous. Looking around today to find some statistics on how many people take these things, and how much they spend per year, I can’t find completely up-to-date numbers. But this study from 2017, including data through 2013, found that some 27.3% of adults over 40 in the U.S., or some 39.2 million people, were using them. A study by a British firm called Visiongain in 2017 estimated the total world market for statins at $19 billion per year, and continuing to grow, despite price reductions due to patent expirations and entry of generic competitors in the past several years. More or less every big pharma company has an entry in the anti-cholesterol game (e.g., AstraZeneca plc, Pfizer Inc., GlaxoSmithKline plc, Novartis International AG, Merck & Co., Inc., Biocon, Concord Biotech, and Aurobindo Pharma Ltd.).

But do statins actually do any good? Or are they a total waste of time? Or worse, might they even have negative effects on health or life expectancy? You would think that with the number of people using these things being so large, and the amount of money being spent being so huge, there would have to be definitive evidence of both positive benefit for life expectancy and of a causal relationship between blood cholesterol levels and cardiovascular disease. Wouldn’t you?

The latest entry in the Cholesterol Wars appeared last week in the peer-reviewed journal Expert Review of Clinical Pharmacology. I call this the “Cholesterol Wars” because even as the statins have become a multi-tens-of-billions-of-dollars per year business, and have swept all before them, there remains a not small group of skeptics who continue to fight on, and to point out rather compelling contrary evidence. The new article, which was posted online pre-publication in “accepted” form on September 10, is titled “LDL-C Does Not Cause Cardiovascular Disease: a comprehensive review of current literature.” (LDL-C is low-density lipoprotein cholesterol, the claimed villain in causation of heart disease on which the pro-cholesterol guys have focused their attention since the prior total cholesterol hypothesis didn’t seem to be working out.) The authors are Uffe Ravnskov and some fifteen others. You may recognize Ravnskov’s name as a long-time leader of the anti-cholesterol forces, but the co-authors are a serious group from around the world, including the U.S., Japan, France, the UK and Ireland, as well as Ravnskov’s native Sweden.

The article is rather unsparing in its critique of its adversaries, accusing them of cherry-picking data and ignoring studies where the data came out wrong. Here is the abstract:

Introduction

For half a century, a high level of total cholesterol (TC) or low-density-lipoprotein cholesterol (LDL-C) has been considered to be the major cause of atherosclerosis and cardiovascular disease (CVD), and statin treatment has been widely promoted for cardiovascular prevention. However, there is an increasing understanding that the mechanisms are more complicated, and that statin treatment, in particular when used as primary prevention, is of doubtful benefit.

Areas covered

The authors of three large reviews recently published by statin advocates have attempted to validate the current dogma. This paper delineates the serious errors in these three reviews as well as other obvious falsifications of the cholesterol hypothesis.

Expert commentary

Our search for falsifications of the cholesterol hypothesis confirms that it is unable to satisfy any of the Bradford Hill criteria for causality, and that the conclusions of the authors of the three reviews are based on misleading statistics, exclusion of unsuccessful trials and by ignoring numerous contradictory observations.

Ouch!

I won’t try to describe everything in the article, but the guts of it relate to LDL-C and its alleged causal role in the development of cardiovascular disease. For example, are people who suffer heart attacks found to have higher or lower levels of LDL-C than normal?

If high LDL-C causes CVD [cardio-vascular disease], LDL-C of untreated patients with CVD should be higher than normal. However, in a large American study [20] including almost 140,000 patients with acute myocardial infarction, their LDL-C at the time of admission to hospital was actually lower than normal. In another study with the same finding [21], the authors decided to lower the patients´ LDL-C even more, but at a follow-up three years later, total mortality among those with LDL-C below 105 mg/dl (2 mmol/l) was twice as high compared to those with a higher LDL-C, even after adjustment for confounding variables (14.8% vs. 7.1%, p = 0.005).

Or, consider total mortality rates among elderly people:

If high LDL-C was the major cause of atherosclerosis and CVD, people with the highest LDL-C should have shorter lives than people with low values. However, in a recent systematic review of 19 cohort studies including more than 68,000 elderly people (˃60 years of age) we found the opposite [26]. In the largest cohort study [27], those with the highest LDL-C levels lived even longer than those on statin treatment. In addition, numerous Japanese studies have found that high LDL-C is not a risk factor for CHD mortality in women of any age [28].

I’ll let you read the whole thing and form your own conclusions.

For myself, I think Ravnskov and his co-authors have the better side of it. If cholesterol, or maybe LDL-C, was the key causal factor for CVD, then several things should follow. Cholesterol-lowering statins should not just reduce risk by a little, but should eliminate it, or nearly so. Also, use of statins should have noticeable and significant clinical effects. Arterial plaques should not form, or should lessen, or disappear. Where are the studies showing these things? I can’t find them.

For myself, I took a statin for a few years, but kept reading on the subject, and gradually became convinced that this was nonsense. So, no more. Maybe I’m wrong, but I don’t think so.