Is the concept of getting cholesterol down to a particular level evidence-based?

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This week there’s been a big cardiological meeting (the European Society of Cardiology) going on in Amsterdam in the Netherlands. One of the studies presented at the meeting is reported here. The research compared the number of patients achieving recommended LDL-cholesterol levels in the UK with those in Germany.

It turns out that the numbers in the Germany were far lower in than those in the UK. This, it is said, may have something to do with the fact that in the UK doctors are remunerated for ‘controlling’ their patients’ cholesterol levels. This does not happen in Germany, where such practises may be positively discouraged on the basis of cost-effectiveness (from what I can make out). So, the UK-system is better at getting people to have lower cholesterol, but is this actually better for them?

First of all, just how effective is cholesterol control? We know that low-fat diets that reduce cholesterol levels are ineffective for the purposes of prevention of heart attacks or stroke and also for reducing the risk of death.

Also, even when drugs get used, the results are far from impressive for most people. For example, if we take a group of individuals with no prior history of cardiovascular disease and treat them with a statin for 5 years, 98 per cent of them stand to gain no benefit whatsoever. But a significant number (maybe up to about 20 per cent) will have potentially debilitating side-effects such as fatigue, muscle pain, liver damage, kidney damage or diabetes. In short, for many people, statins just don’t make much sense at all.

But also, is the idea that treating people to achieve a specific cholesterol target even evidence-based?

This idea is actually based on ‘epidemiological’ evidence. For example, data drawn from studies in which individuals have been treated with, say, statins may find that lower cholesterol are found to be associated with lower risk of cardiovascular disease. From this, the conclusion is drawn that lower cholesterol levels are better and desired.

There are fundamental weaknesses in this sort of data, though. Firstly, statins reduce cholesterol, but they do other things too. They have, for example, anti-inflammatory and ‘blood thinning’ effects that might reduce the risk of cardiovascular disease. So, the cholesterol reduction they achieve may be incidental, in which case it does not necessarily make sense to use a specific cholesterol level as a goal.

The evidence base for treating to a specific LDL-cholesterol target has been comprehensively reviewed  [1]. In this review, the authors found only one study which allowed them to assess the idea that greater LDL-cholesterol reduction produces better outcomes. In this study, individuals were initially treated with a statin (simvastatin) at a fixed dose (40 mg). The benefits seen in individuals who saw relatively small LDL-reductions was the same as those who saw big reductions [2]. The logical conclusion one would draw from this is that the degree of clinical benefit is independent of the degree of cholesterol reduction.

The authors of the review also draw our attention to what is known as the ‘healthy volunteer’ effect. This relates to the fact that some people are more compliant with regard to medication-taking than others. Those who take medication tend to be more health-conscious than those who don’t. So the apparent benefits of a drug may not necessarily be due to the drug at all, but due to factors related to increased health-consciousness (e.g. healthier eating and regular exercise).

This is another major reason why the data linking lower cholesterol with improved health outcomes is unreliable. And its another example of why the idea that people should have their cholesterol controlled to a certain level is not evidence-based at all.


1. 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

2. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22 [hr]

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