Recently, there have been calls for the statin-net to be widened to include all people over the age of 50, irrespective of their degree of risk of cardiovascular events such as heart attack and stroke. This idea was apparently supported by the findings of a study which was published online on 17 May in The Lancet medical journal. The study in question is a meta-analysis (grouping together of similar studies) of statin trials [1]. Part of this meta-analysis involved assessing the impact of statin therapy in individuals deemed to be at relatively low risk of cardiovascular events such as heart attacks and strokes (< 10 per cent risk of vascular events over a 5-year period).

One of the stand-out findings of this study is that statin therapy led to a statistically significant reduction in the risk of ‘major vascular events’ in those deemed at low risk. This has led to the suggestion that the use of statins might be widened to include even those at low risk of cardiovascular problems.

Before the study authors and media’s positive take on these results becomes widely accepted and part of our thinking, it is perhaps a good idea to delve more deeply into the findings of this meta-analysis to see just how effective statins are in people at low risk.

First of all, it should be borne in mind that the main outcome measure in this meta-analysis was ‘major vascular events’. This is a term that includes many different potential outcomes including fatal and non-fatal heart attacks and strokes and ‘revascularisation’ procedures (such as placing tubes called stents in the coronary arteries). When a lot of different outcomes are grouped together, it makes it much more likely that ‘statistically significant’ results will emerge.

However, when the focus of the outcomes is narrowed a little, the results are less impressive. For example, when we look at risk of death from any vascular event we find that statins did not reduce risk in individuals deemed to be at low risk of cardiovascular disease. This, by the way, was even true for those who had known vascular disease.

The ‘positive’ findings from this study have, as is often the case, been expressed as reductions in relative risk. The risk of vascular events overall was 21 per cent lower for each 1 mmol/l (39 mg/ml) reduction in levels of low density lipoprotein cholesterol (LDL-C). However, when overall risk is low, then a relative risk reduction might not amount to much in real terms.

We’re told by the authors of this meta-analysis that treating with statins prevented 11 major vascular events for every 1,000 people treated for a period of 5 years. Put another way, 91 people would need to be treated for 5 years to prevent one major vascular event. Or put another way, at this level of cholesterol reduction almost 99 per cent of people treated with statins for 5 years will not benefit from the treatment.

Overall, lowering LDL-C by 1 mmol/l was found to reduce the risk of death by 9 per cent over a 5-year period. Again, this might sound like a positive finding to some, but the actual reduction in risk of death was 0.2 per cent per year. What this means is that at this level of cholesterol reduction, 500 individuals would need to be treated with statins for a year for one person to have his/her life saved.

But what of the side effects of statins such as myopathy (muscle pain and weakness), liver damage, kidney damage and diabetes? The authors of this meta-analysis give us some reassurances here, but again seem hopelessly biased. For example, they quote of the excess incidence of myopathy as 0.5 cases per 1,000 people over 5 years. However, the source they quote is based on diagnosing myopathy once the marker for muscle damage (creatine kinase) is at least ten times the upper limit of normal.

Despite the very positive interpretation of the data by the study authors and the media, this meta-analysis shows us once again what previous evidence has revealed: statins are highly ineffective in terms of improving health and saving lives. And their risks are generally downplayed.

Here's to a healthy heart

Dr John Briffa
for The Cholesterol Truth

References:

1. Cholesterol Treatment Trialists’ (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. The Lancet epub 17th May 2012

Cholesterol in the body is carried around the bloodstream in the form of what are called ‘lipoproteins’. The two main lipoproteins are so-called low-density lipoprotein cholesterol (LDL-cholesterol) and high-density lipoprotein cholesterol (HDL-cholesterol). Conventional wisdom tells us that HDL-C is a marker for cholesterol being cleared from the inside of the arteries, while LDL-C has the capacity to deposit itself in the artery wall. Because of this, HDL-C and LDL-C are often dubbed ‘good’ and ‘bad’ cholesterol respectively.

Many doctors have been encouraged to focus on LDL-C, and ensure that their patients’ levels of this substance remain below a predetermined set point. However, the fact remains that no studies have ever tested the effect of treating LDL-C levels (with medication and/or diet) to below a certain point. It will seem far-fetched to some that the core strategy used in cholesterol management has not been adequately tested, and things get even more unbelievable when it turns out that LDL-C is not even a particularly good marker for heart disease.

While it is often said that LDL-C causes heart disease, this appears to be a gross oversimplification. To begin with, LDL-C comes in different sizes, ranging from small, dense to large ‘buoyant’ forms. The former are believed to be potentially damaging to artery walls, while the latter not so. Also, there has been increasing interest in the idea that the build-up of plaque on the inside of the arteries is promoted by the process known as inflammation. Some scientists have suggested that inflammation is the key underlying process in the development of ‘atherosclerotic plaque’.

With these concepts in mind, some have argued that measuring inflammation in the body might better identify those at risk for heart disease than measuring LDL levels. So I was interested to read a study recently which supports this concept.

In this study, blood samples were drawn from 100 individuals who had been confirmed as having had a heart attack. Blood samples were also taken for comparison from 100 individuals who had not had a heart attack. Each blood sample was tested for levels of LDL-C, as well as a marker for inflammation known as high-sensitivity C-reactive protein (HS-CRP). The results showed:

1. No significant difference in LDL-C levels between those who had had a heart attack and those that had not. Actually, LDL-C levels were almost identical between the two groups.

2. There was, however, a significant difference between the two groups with regard to HS-CRP levels. In fact, on average, levels were about six times higher in those who had had a heart attack, compared to those who had not.

This study supports the idea that LDL-C is not a very reliable indicator regarding the risk of having a heart attack. It also supports the idea that inflammation may indeed be the process that drives heart disease and perhaps should be targeted for the most effective prevention. By focusing on LDL levels, we might be looking in all the wrong places.

Here's to a healthy heart

Dr John Briffa
for The Cholesterol Truth

References:

1. Datta S, et al. Comparison between serum hsCRP and LDL cholesterol for search of a better predictor for ischemic heart disease. Ind J Clin Biochem Apr-June 2011 26(2):210-213