Generally speaking, doctors have almost unbridled enthusiasm for cholesterol-reducing drugs including statins. We doctors have generally been educated to believe that cholesterol at essentially normal levels causes heart disease, and bringing levels down is of paramount importance to health. Here in the UK, doctors are even remunerated by the Government to get their patients’ cholesterol levels below a specified cut-off. With Government endorsement, surely cholesterol reduction must be a good idea?
Well, it seems not everyone agrees.
Recently, I came across a Japanese review that takes exception to cholesterol guidelines (similar to those in the UK and US) on a number of grounds. [1] The paper itself is in Japanese, but we can learn a lot, I think, from the English translation of the abstract (summary).
The authors of the review, from the Faculty of Public Health at the University of Toyama in Japan, make reference to the fact that the Japan Atherosclerosis Society recommended that low-density lipoprotein (LDL) levels be kept below 3.6 mmol/L (140 mg/dl) in 2007. This corresponds to a total cholesterol value of around 5.7 mmol/L (220 mg/dl). The authors’ main criticisms of these guidelines appear to be:
1. That the Japan Atherosclerosis Society has not provided relevance evidence regarding the relationship between LDL levels and risk of heart attacks and death due to heart disease.
2. That the recommended cholesterol level is inappropriate seeing as lowest overall risk of death (known as ‘all-cause mortality’) in Japan corresponds with a cholesterol level of 6.2 – 6.7 mmol/L (240 – 260 mg/dl).
3. That there are big differences in heart disease rates between men and women, though these were not properly considered.
4. That conflicts of interest of the individuals who issued the guidelines has never been disclosed.
These all seem like valid issues to me. Of particular importance, I think, is the attempt here for attention to be drawn to the relationship between cholesterol and all-cause mortality. The fact is, while raised cholesterol levels can be associated with an enhanced risk of heart disease in some populations, low levels of cholesterol are associated with an increased risk of death from other conditions (notably cancer). It makes sense, then, that if cholesterol guidelines are going to be issued to the country as a whole, that these recommendations should reflect overall risk of death (not just risk of heart disease).
The issue of potential conflicts of interest is pertinent too, as past events suggest that guideline-setting might have something to do with politics and money. Back in 2004, there was a significant lowering of what are regarded as acceptable levels of cholesterol, as recommended by a group known as the National Cholesterol Education Program (NCEP) expert panel in the USA. No conflicts of interest were declared at the time. However, after this it emerged that 8 out of 9 members of the panel had financial links with drugs companies making statin drugs. You can read the (belated) disclosure here. The report’s publisher described the omission of these clear conflicts of interest as an ‘oversight’. I’ll say.
Subsequently, an independent review of the guidelines, published in the Annals of Internal Medicine stated: “In this review, we found no high-quality clinical evidence to support current treatment goals for [LDL] cholesterol”. They also went on to say that the recommended practice of adjusting statin dose to achieve recommended cholesterol levels was “not scientifically proven to be beneficial or safe” [2].
Personally, I think it’s a good thing that some researchers exhibit free-thinking and independence of mind. With more researchers like these, we may end up one day having cholesterol guidelines based purely on the evidence (not vested interest).
References:
1. Inadera H, Hamazaki T.[Cholesterol controversy: cutoff point of low-density lipoprotein cholesterol level in Guidelines by Japan Atherosclerosis Society]. Nippon Eiseigaku Zasshi. 2010;65(4):506-15.
2. Hayward RA, et al. Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem. Ann Int Med 2006;145:520-530
