December 3, 2019

expert reaction to study estimating link between cholesterol levels and risk of heart disease and stroke

Research, published in The Lancet, reports on long term estimates which suggest links between cholesterol levels and risk of heart disease and stroke.

This roundup of comments accompanied an SMC briefing.

Prof Colin Baigent, Director of the MRC Population Health Research Unit, and Professor of Epidemiology, Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, said:

“This is an important paper because it shows what could be achieved if, starting early in their 40s, healthy people were to start taking a statin so that their bad cholesterol is​ halved for the rest of their lives.  It shows that, if they did this, their risk of having a heart attack or stroke by the time they are 75 would fall dramatically, and the earlier they start the larger the reduction in risk would be.  The benefit of taking a statin to achieve a 50% reduction in bad cholesterol would be very much greater than any modest reduction in cholesterol that can be achieved by dietary change, and that is why the impact of taking a statin lifelong would add substantially to healthy eating on its own.

“Of course, despite the fact that statins are safe and well tolerated, many healthy people would be reluctant to take a statin from early middle age.  But the striking findings of this study show that a policy of recommending such treatment might be a long-term investment that leads to a substantial improvement in the health of older people in the years to come.”

Prof Jane Armitage, Professor of Clinical Trials and Epidemiology and Honorary Consultant in Public Health Medicine, University of Oxford, said:

“This study adds usefully to the evidence from genetic and other sources that treating cholesterol at a younger age will protect against heart attacks and strokes in later life.  The study models the effect of lowering cholesterol by 50% (which is easily achievable with cheap, safe statin drugs) using information from about 400,000 people followed for many years.  The authors predict the long-term benefits of lowering cholesterol, with the key message that benefits are substantial and greatest the earlier the treatment is started.

Is this good quality research?  Are the conclusions backed up by solid data?

“Yes.

How does this work fit with the existing evidence?

“Consistent with other evidence.

Have the authors accounted for confounders?  Are there important limitations to be aware of?

“They make assumptions about the long-term effects of lipid lowering treatment, i.e. extrapolating beyond the 5-7 years that trials typically last for but the observational data are consistent with the effects of treatment continuing in the long-term, so this is not unreasonable.  The challenge would be keeping people on treatment over many years.

What are the implications in the real world?  Is there any overspeculation?

“It would be difficult to achieve the benefits of 50% non-HDL cholesterol at a population level for a variety of reasons but this data illustrates that the earlier the treatment the better and allows individuals and their doctors to make informed choices about when to start treatment.”

Prof Paul Leeson, Professor of Cardiovascular Medicine, University of Oxford, said:

“Everyone knows high cholesterol is associated with an increased risk of having a stroke or heart attack.  What has been demonstrated for the first time in this paper is that having a high cholesterol when you are below the age of 45 disproportionately increases your risk of having a problem during your lifetime.  That suggests it is not just the cholesterol level but how long you have high cholesterol that puts you at risk.

“They have developed a useful tool that shows just how much risk could be reduced if you lower your cholesterol and the findings support the idea that getting cholesterol controlled early in life may have more benefit than waiting till you are older.  Exactly how to reduce cholesterol effectively in young people and, in particular, whether you would need to take drugs for decades to do this is not explored but will be important to consider before these findings can be included into medical guidance.”

Prof Sir Nilesh Samani, Medical Director at the British Heart Foundation, said:

“This large study again emphasises the importance of cholesterol as a major risk factor for heart attacks and stroke.  It also shows that for some people, taking measures at a much earlier stage to lower cholesterol, for example by taking statins, may have a substantial benefit in reducing their lifelong risk from these diseases.  The authors also provide a useful tool to help doctors have a conversation with patients about their risk and how it might be lowered.”

‘Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium’ by Fabian J Brunner et al. was published in the Lancet at 23:30 UK time on Tuesday 3 December 2019.

DOI: 10.1016/S0140-6736(19)32519-X

Declared interests

Prof Colin Baigent: “Professor Colin Baigent works in the Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU) at the University of Oxford.  The CTSU has received research grants from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Merck, The Medicines Company, Novartis, Pfizer, Roche, Schering, and Solvay that are governed by University of Oxford contracts that protect its independence, and it has a staff policy of not taking personal payments from industry (with reimbursement sought only for the costs of travel and accommodation to attend scientific meetings).  The CTT Collaboration, which is coordinated by CTSU with colleagues from the University of Sydney, does not receive industry funding.”

Prof Jane Armitage: “I am a co-applicant on a grant to Oxford University for a trial of a cholesterol-lowering small interfering RNA and have been a lead investigator in earlier trials of statins.  I am also a co-applicant on HTA grant for the STATINwise Trial which is assessing the effects of statins in people who have reported muscle symptoms.  The Clinical Trial Service Unit at the University of Oxford has a policy of not accepting honoraria or other personal payments from the pharmaceutical industry.”

Prof Paul Leeson: “No conflicts of interest relevant to this work.”

Prof Sir Nilesh Samani: “None.”