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Tackle your cholesterol early

March 22, 2006 By Helen Pearson This article courtesy of Nature News.

US team argues for a lifelong approach to beating heart disease.

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Think you're too young to worry about cholesterol? Think again. Many people could drastically reduce their future risk of heart disease by lowering their cholesterol levels from as early as their 20s. That's the bottom line of a study showing that people born with low cholesterol are protected from heart problems.

High levels of low-density lipoprotein (LDL), a molecule that transports cholesterol in the blood, are strongly associated with heart disease. Doctors already know that reducing LDL with exercise or drugs can reduce a person's risk of heart attack. But it has been harder to find out whether heart health could be improved further by lowering LDL from a young age.

Helen Hobbs at the University of Texas Southwestern Medical Center, Dallas, and her colleagues saw an opportunity to find out. Last year, they discovered that a fraction of the population are genetically programmed to have low LDL levels, because they carry particular versions of a gene called PCSK9 that help the liver to eliminate LDL cholesterol.

To see what effect this would have over a lifetime, the team examined nearly 13,000 people enrolled in a larger study of heart disease in Mississippi, Minnesota, North Carolina and Maryland.

Born lucky

The greatest effect of the PCSK9 gene was seen in black subjects: those with a cholesterol-lowering form of the gene had LDL levels 28% below those of subjects with a normal version, and were almost 90% less likely to develop coronary heart disease over the 15 years of the study.

In white subjects, slightly different cholesterol-busting forms of the gene lowered LDL levels by around 15%. This seemed to halve their risk of heart disease.

Clinical studies that use drugs to lower LDL by comparable amounts for five years found far less heart protection than seen in Hobbs's study. The researchers say that the protection probably accrued because of the longer time over which participants had low LDL, rather than because of the different way in which their cholesterol was lowered.

The results suggest that a modest reduction in LDL over a lifetime could slash one's risk of heart disease, the number-one killer in the United States and many Western countries. "It should be thought of as early as adolescence and childhood," says Alan Tall, who studies the molecular mechanisms behind heart disease at Columbia University in New York City.

Healthy foundations

The study, published in the New England Journal of Medicine1, backs up growing evidence that the foundations for heart disease are laid down early in life.

The work is particularly significant because it focused on Americans who were at high risk of disease: many smoked, or had hypertension or diabetes. Showing a striking effect on heart health in the face of these other factors is "quite dramatic" says Scott Grundy, an expert on cholesterol also at the Southwestern Medical Center.

So how can LDL levels be kept low? A healthy lifestyle helps, including exercise, weight control and diets low in saturated fat. When these measures are not enough, another possibility is prescribing cholesterol-lowering drugs such as statins to young adults at high risk of future heart disease. But this idea has not been well tested in clinical trials.

Developing drugs that mimic the effects of the LDL-lowering version of PCSK9 might also offer a way to combat rising cholesterol, the researchers propose.

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  1. Cohen J. C., et al. NEJM, 354 . 1264 - 1272 (2006).


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