June 12, 2016

expert reaction to systematic review reporting lack of an association between LDL cholesterol and mortality in the elderly

The contribution which different types of cholesterol make to risk of death from cardiovascular diseases is the subject of a paper published in the BMJ Open, which reports an inverse association between levels of ‘bad’ (LDL) cholesterol and mortality in most people over 60 years old.

All our previous output on this statins can be seen here.

Prof. Colin Baigent, Professor of Epidemiology & Deputy Director of the Clinical Trial Service Unit (CTSU), University of Oxford, said:

“This study has a number of serious weaknesses and, as a consequence, has reached completely the wrong conclusion. In fact, we know that cholesterol is just as important as a cause of heart disease in older people as it is in the young. We know this because of the evidence from all the randomized trials of statin therapy, which collectively have studied substantial numbers of older people, and which have shown very clearly that people benefit just as much from reducing their cholesterol when they are in their 70s as when they are younger.”

Prof. John Danesh, BHF Professor of Epidemiology and Medicine, University of Cambridge, said:

“The surprising conclusion of the report by Ravnskov and colleagues is contradicted by a vast amount of robust experimental data, most notably from large randomised drug trials [1] that clearly show reductions in the risk of heart attacks and strokes in both older and younger people who take cholesterol-lowering medications. Because Ravnskov and colleagues used crude study methods, we cannot trust the statistical correlations they have reported between cholesterol levels and cardiovascular disease risk. For example, because their analysis lacked access to data on each participant included in their analysis, they relied on limited, aggregated and inconsistent information from published sources, an approach liable to bias. By contrast, detailed analysis of comprehensive data from each participant in large studies [2,3] has previously shown that there are strongly positive correlations between LDL-cholesterol and subsequent risk of cardiovascular disease, even at older ages.”

Prof. Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said:

“This paper briefly summarises a group of published studies which consider the association between ‘bad’ LDL cholesterol levels and the overall risk of death in elderly people. Unlike studies in younger populations, these studies in the elderly did not find that high LDL cholesterol levels were associated with an increase in deaths. In some of them increased death was also associated with lower LDL cholesterol. However, this is not surprising because, as we get older, many more factors determine our overall health, making the impact of high cholesterol levels less easy to detect.

“In contrast, the evidence from large clinical trials demonstrates very clearly that lowering LDL cholesterol reduces our risk of death overall and from heart attacks and strokes, regardless of age. There is nothing in the current paper to support the authors’ suggestions that the studies they reviewed cast doubt on the idea that LDL cholesterol is a major cause of heart disease or that guidelines on LDL reduction in the elderly need re-evaluating.”

Dr Tim Chico, Reader in Cardiovascular Medicine & consultant cardiologist, University of Sheffield, said:

“Although observational data such as that summarised in this study are interesting, they are often wrong, due to so-called “confounding” influences. The literature is full of examples of this, which is why to properly examine whether cholesterol influences risk of heart disease the “gold standard” is a randomised study where some patients have their cholesterol lowered using a drug (generally a statin) and others receive a placebo.

“There have been several studies that tested whether higher cholesterol increases the risk of heart disease, by lowering cholesterol in elderly patients and observing whether this reduces their risk of heart disease (for example the PROSPER study). These have shown that lowering cholesterol using a drug does reduce the risk of heart disease in the elderly, and I find this more compelling than the data in the current study. I am surprised the authors of this study do not refer to such trials, which tends to make their own paper disappointingly unbalanced.”

‘Lack of an association or an inverse association between low-density lipoprotein cholesterol and mortality in the elderly: a systematic review’ by Ravnskovet al. published in BMJ Open on Sunday 12th June. 

Declared interests

Prof. Colin Baigent: “I jointly coordinate, with Professor Rory Collins, the Cholesterol Treatment Trialists’ Collaboration meta-analysis of all large-scale randomized trials of statin-based treatments. CTSU has received funding from the pharmaceutical industry to conduct randomized trials, including trials of statin therapy, but this work is conducted independently of the source of funding and the trials are sponsored by the University of Oxford.”

Prof. John Danesh:  “I have received research grants from, and served as a paid consultant to, pharmaceutical companies that manufacture cholesterol-lowering medication, such as Merck.”

Prof. Jeremy Pearson: No conflicts of interest

Dr Tim Chico: “I am a committee member and Treasurer of the British Atherosclerosis Society, a charity established in 1999 to promote UK atherosclerosis research.”