Smoking, Gene Variants Triple Risk of Heart Disease

Nasty combination packs wallop for men in British study

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HealthDay Reporter

THURSDAY, July 12, 2001 (HealthDayNews) -- Depending on which genes they inherit, men who smoke almost triple their risk for coronary heart disease, a new British study shows.

Along with high cholesterol, lack of exercise, obesity and high blood pressure, family history is a strong predictor of the risk for coronary heart disease, says lead study author Dr. Steve E. Humphries, professor of cardiovascular genetics at University College London Medical School.

Humphries says he's planning another study to confirm his suspicions that the combination of smoking and particular gene variations has a similar effect on women.

Humphries says his study focused on variations of the gene called apolipoprotein E (ApoE), which plays a role in controlling fat levels in the blood.

"It comes in three flavors: E3, which is the most common, E2 and E4," says Humphries. Everyone has two copies of the gene, one from each parent. The most common pairing is E3 and E4, he says.

Humphries and his colleagues followed 3,052 healthy men, ages 50 to 61, for eight years. The team determined each man's pair of the ApoE variations, his cholesterol level and other risk factors for heart disease.

The team also kept track of any fatal or non-fatal heart attacks, coronary artery surgeries or "silent" heart attacks.

Humphries says smoking nearly doubles the risk of heart disease, and previous studies have shown that people with at least the E4 variant are at even higher risk. However, he says his study shows that "if you've got two [variants] together, it's very bad for you."

Even after factoring in other risk factors, 26 percent of the men in the study who carried one or two copies of the E4 variant and smoked had nearly three times the risk of coronary heart disease. "It's a significantly high risk," he says.

"It gives us some very interesting insight into the causes of heart disease. Obviously, the more we know about what causes it, the better we can try to prevent it," he says.

Why does the E4 variant have this effect in male smokers?

Humphries says smoking is known to cause damage by adding a harmful molecule of oxygen to cholesterol. ApoE genes are natural antioxidants, and are supposed to prevent this damage.

"It turns out that E2 is very good, E3 is not bad and E4 is absolutely terrible [as an antioxidant]," says Humphries. "What's happened here is that if you've got an oxidant stress because you smoke, and you've got a bad antioxidant."

Dr. Xing Li Wang, head of the Vascular Molecular Genetics Laboratory at the Southwest Foundation for Biomedical Research in San Antonio, Texas, says the effect may be more indirect.

"Subjects with [E4] may have a higher proportion of small LDL cholesterol, which is more susceptible to oxidation," says Wang, co-author of a commentary accompanying a report on the study in the July issue of The Lancet.

Wang says if you smoke, more than 3,000 chemicals produced by burning cigarettes produce enormous amounts of oxidizing free radicals, damaging the cholesterol and contributing to atherosclerosis.

"Cigarettes are a toxin, regardless of your [genetic makeup]. That's a fact," says Wang. "But certain genotypes will be more susceptible to develop this damage much earlier than some others."

Humphries says you can improve your odds.

"We already know some easy things you can do to improve your antioxidants in your blood, and that's by taking fresh fruits and vegetables. "Vitamin C and vitamin E are both natural antioxidants, so any diet that contains high amounts of those should be beneficial," he says.

"The best thing to do is to stop smoking," says Humphries. He says men who stopped smoking before the study started lowered their risk almost as low as nonsmokers.

"The very good news is that if you do stop smoking, your risk falls," he says.

What To Do

The American Heart Association and the Non-Smokers' Movement of Australia both provide information on smoking and heart disease.

The National Heart, Lung and Blood Institute also has information on the subject.

SOURCES: Interviews with Steve E. Humphries, M.D., professor, Centre for Cardiovascular Genetics, Department of Medicine, Royal Free and University College London Medical School, London, United Kingdom; Xing Li Wang, M.D., Ph.D., director, Vascular Molecular Genetics Laboratory, associate scientist, Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio; July 14, 2001, The Lancet

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