Often called the “bad” cholesterol, low-density lipoprotein (LDL) particles carry cholesterol through the blood. Excess cholesterol found in these particles sticks to artery walls, spurring the growth of plaque, which hardens and clogs arteries, and limits the flow of blood and oxygen to the heart, brain, and other tissues. Severe cases lead to heart attack or stroke . An elevated LDL level—greater than 160 mg/dL (4.1 mmol/L)—is a major risk factor for coronary heart disease (CHD); lowering LDL reduces this risk. The American Heart Association recommends cholesterol testing every five years starting at age 20. If LDL is high, lifestyle changes and medication may reduce it. But why wait? Will taking steps early in life to keep LDL low have a greater benefit than waiting until it reaches high and sustained levels to take action? The recent discovery of three mutations in the gene PCSK9 may help answer this question. PCSK9 is involved in regulating LDL levels. Mutations in this gene keep LDL levels low from birth onward. People who carry one of these mutations provide a sneak peak at the lifelong effect of a low LDL levels on CHD risk.
Researchers in Texas studied people with and without mutations of PCSK9 . Their findings, reported in the March 23, 2006 New England Journal of Medicine, showed that in people with a certain PCSK9 mutation, both LDL levels and CHD risk were significantly lower than in people without this mutation.
Researchers at the University of Texas Southwestern Medical Center analyzed data from the Atherosclerosis Risk in Communities (ARIC) study, which monitored 12,887 people, age 45-64, for signs of CHD over a 15-year period. Based on DNA analysis, participants were classified as carriers or noncarriers of a PCSK9 mutation. The researchers compared LDL levels and CHD risk between the two groups.
Compared with noncarriers, people carrying a PCSK9 mutation had LDL levels between 20 mg/dL (0.5 mmol/L) and 40 mg/dL (1.0 mmol/L) lower than noncarriers; and their corresponding risk of CHD was 47% to 88% lower.
It is unclear if the benefits seen in carriers will also result in a lower death rate. While there were fewer deaths in the carrier group, this finding was not statistically significant and therefore, could have been due to chance.
Should you be tested for a PCSK9 mutation? No. These mutations are uncommon, occurring in just 2.6%-3.2% of the population. And if you have one, you’re already reaping the benefits. What we can take away from this study is that acting early in life has its advantages when it comes to CHD. As the researchers explain, “lifelong reduction of LDL levels confers greater benefit than does a similar reduction instituted later in life.” Plaque build-up begins early in life, so too should efforts to protect the arteries. In his editorial, Alan Tall of Columbia University Medical Center advocates for greater efforts to promote healthy eating and reduce obesity among children. He stops short of advising childhood cholesterol screening and aggressive treatment. Although these findings hint in that direction, more study is needed before a change in population-wide guidelines is warranted. Talk with your pediatrician about your child’s risk for CHD and the best course of action.
Don’t wait for a blood test, take steps now to lower LDL and/or keep it low. For your children, offer a range of healthful foods, encourage physical activity, and most importantly, model healthful behaviors, including the following:
RESOURCES:
American Heart Association
http://www.americanheart.org
American Heart Association
Dietary Guidelines for Healthy Children
http://www.americanheart.org/presenter.jhtml?identifier=4575
National Heart, Lung, and Blood Institute
http://www.nhlbi.nih.gov/
References:
Cholesterol levels. American Heart Association website. Available at: http://www.americanheart.org/presenter.jhtml?identifier=4500 Accessed March 22, 2006.
Cohen JC, Boerwinkle E, Mosley TH, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med . 2006;354(12):1264-1272.
Tall AR. Protease variants, LDL, and coronary heart disease [editorial]. N Engl J Med . 2006;354(12):1310-1312.
Last reviewed Mar 22, 2006 by Richard Glickman-Simon, MD
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