Taking steps to lower levels of harmful LDL cholesterol at a much earlier stage than current medical practice indicates could be a far more effective way to reduce the risk of future heart attacks and strokes, according to a major new analysis by researchers from Imperial College London.
The findings show that reducing LDL levels by just 0.36 mmol/litre (the British Heart Foundation says that we should aim for an LDL concentration under 3 mmol/litre) in those currently deemed to be at lower risk leads to a 25 per cent reduction in the long-term threat of severe cardiac events.
But to get the same risk reduction in higher-risk groups treated at a much later stage, LDL cholesterol has to come down by nearly eight times as much, more than 3 mmol/litre, requiring much larger doses of cholesterol-lowering drugs such as statins, which may not always be tolerated by some.
LDL is a type of lipoprotein particle that carries cholesterol through the bloodstream. High levels can be caused by a combination of genetics, ageing, and an unhealthy lifestyle.
An estimated 8 million people in the UK have heart disease. The number is expected to reach 10m by 2040, in line with an ageing population.
Under current treatment guidelines from the National Institute for Health and Care Excellence (NICE), UK General Practitioners calculate a person's 10-year risk of a heart attack or stroke by assessing a number of factors including cholesterol levels. For those at high risk, statins are usually prescribed as a form of prevention.
In those at lower risk, with a less than 10 per cent chance of a heart attack or stroke in the next decade, statins are often deferred, as the number of patients who would have to be treated in order to prevent one heart attack or stroke often appears much higher.
However, the latest research, due to be presented on Monday 25 May at the European Atherosclerosis Society (EAS) Congress in Athens and published simultaneously in the American Journal of Preventive Cardiology, shows that intervening at a much earlier stage means the risk of cardiac events can be significantly reduced with only a small decline in LDL cholesterol, requiring much smaller doses of statins or alternative medications for those who might not be able to tolerate statins.
Researchers from Imperial College London and University Hospital Aachen, Germany, analysed data from 17 clinical trials, involving more than 100,000 people mostly without prior heart disease or strokes, to see how the risk of heart attacks and strokes varied between those treated with LDL-cholesterol lowering drugs at a relatively early stage and those treated later on.
Cholesterol is deposited in artery walls, forming plaques, a process called atherosclerosis. Even small elevations in risk factors like blood pressure, diabetes and smoking accelerate this process so plaques can form silently at much lower LDL cholesterol levels than people suspect. Problems arise when the plaques become unstable and fragments break off, leading to clotting when they come into contact with blood, which can then block the blood supply to the heart or brain.
Current NICE guidance means many NHS patients only get statins when this silent disease process is already well underway.
The analysis showed there had been 6,076 major adverse cardiovascular events (MACE) – such as heart attacks or strokes – across the 17 clinical trials analysed and that the lower the patient's risk, the smaller the reduction needed in LDL cholesterol to achieve a 25 per cent reduced chance of a heart attack or stroke. If the risk was allowed to accumulate, the required lowering of LDL needed to achieve the same benefit was considerably higher.
Dr Irene Karungi, from the School of Public Health at Imperial College London, who is the first author of the study, said the findings could lead to a sea change in the treatment of cardiovascular disease.
"Current practice relies on 10-year risk to determine when to initiate treatment but this delays therapy until atherosclerosis is often already established," she said. "Our analysis shows the benefit of reducing LDL in people who are low risk is much greater than waiting until they might become high risk. Once disease is established, treatment has to be much more intensive - with higher doses of drugs and greater risk of side-effects or the need for more than one drug."
The researchers said although the results could mean a rise in NHS statins prescriptions, the cost increase would be relatively small as generic versions of the drugs can be as little as 2p per pill. "You would need a smaller dose of statins to get the same effect," added Dr Karungi.
Professor Kausik Ray, the senior study author from the School of Public Health at Imperial College London, said it shows the importance of addressing atherosclerosis risk sooner rather than later, and the benefits of cholesterol lowering in people prone to develop atherosclerosis.
"It's like a pension scheme – the earlier you start, the bigger the long-term benefits. Nobody has shown this before using clinical trial data. But now we know the earlier you intervene, the more problems you can avoid down the line. This approach is more efficient potentially delaying the need for multiple therapies when the process is more advanced."
The researchers stressed the findings need to be validated in further, large-scale studies but said if those studies replicate their results, they expect clinical guidance to change further in the next few years to reflect the need to get LDL levels under control as soon as possible.
This research was not supported by any external funding or by funding from the pharmaceutical industry.
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'Cardiovascular event rate modifies response to pharmacologic LDL-C lowering in primary prevention: implications of a systematic review and meta-analysis for clinical practice' is published in the American Journal of Preventive Cardiology.
