Lipid Disorders

Published 27 September 2004

This Editorial has been written by the specialist opinion leader, Paul Durrington, Professor of Medicine, University of Manchester Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester and published in the latest issue of the serial publication, Drugs in Context.

Within the space of a decade, the treatment of raised serum cholesterol has moved from the province of a few specialists to the very heart of everyday medical practice. Furthermore, our view of what constitutes an unhealthily high cholesterol level has undergone a radical change, as has how we select patients for statin treatment from amongst the myriad with undesirably high cholesterol levels in countries like Britain, where the average cardiovascular risk is high.

The NHS is, to some extent, the victim as well as the beneficiary of the success of statin clinical trials and the dramatic nature of their findings, which carry their own imperative for clinical implementation. Early scepticism was so great that proof was demanded that cholesterol-lowering medications would decrease not only coronary heart disease (CHD) mortality and morbidity, but also all-cause mortality, proof that had rarely, if ever, been demanded of other pharmacotherapies, except perhaps chemotherapy for malignant diseases. We now know that statin therapy will decrease not only coronary mortality and morbidity, but also reduce the incidence of stroke and all-cause mortality. Statin therapy now provides the greatest regular opportunity for doctors in general practice to prolong the lives of their patients.

Clinical trials of statins have consistently shown that the relative reduction in CHD risk is unrelated to the initial cholesterol level. This is consistent with the epidemiological evidence of a graded relationship between cholesterol and CHD risk. The relationship is exponential, with a given increment in raised cholesterol levels increasing risk by a similar proportion, whatever the starting level. In many countries, such as those of Asia and Africa, CHD occurs much less frequently than in the UK, and typically serum cholesterol levels are much lower in people in these countries. For instance, in China and Japan, where CHD is rare compared with Britain, the median serum cholesterol in middle-aged men is less than 4 mmol/L, whereas in Britain it is about 6 mmol/L. Furthermore, in these countries other risk factors such as hypertension, smoking and diabetes have much less impact on CHD risk, suggesting that high cholesterol is the permissive factor which allows them to operate. This is corroborated by statin trials - lowering serum cholesterol reduces cardiovascular risk, regardless of cause. The best plan is thus to place substantial reductions in low density lipoprotein cholesterol (LDL-C) levels at the core of CHD prevention strategy. This strategy will be most effective if those at highest risk of CHD are targeted. The current recommendations use absolute cardiovascular risk to identify these patients, who include those with:

The Joint British Societies defined high CHD risk as a greater than 15% likelihood of a CHD event over the next 10 years. The National Institute for Clinical Excellence and the UK National Service Framework (NSF) for diabetes recently endorsed this level of risk as an indication for statin therapy in people with uncomplicated diabetes. The NSF for CHD recommended that the minimum standard of care for primary prevention of CHD (i.e. in those with no clinically evident CHD or other atherosclerosis) should be to introduce statin therapy when CHD risk exceeds 30% over 10 years - higher than in many people with known CHD - and then to progress to the treatment of lower levels of risk as resources permit. This contrasts with the treatment of mild-to-moderate hypertension, for which antihypertensive therapy was advocated when CHD risk over the next 10 years was 15% or more. Ironically, many hypertensive patients receiving antihypertensive drugs would derive more benefit from statin therapy, though they benefit most, of course, from both. It is hoped that future recommendations will be clear and rational and seek to realise the success of statins by deploying them to their greatest effect in the British population.

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Lipid Disorders

Medical Opinion - Lipid Disorders