Up in smoke: Smokers blow away antioxidants that protect against heart disease

May 14, 2000

Cigarette smoking is hard on the arteries, according to a study that finds smokers have low levels of a chemical "weapon" in the blood that helps prevent artery clogging. The study appears in today's Circulation: Journal of the American Heart Association.

Smokers' risk of heart attack is more than twice that of nonsmokers. The new study points to a potential explanation for this increased risk.

In a study of 596 people with heart disease, researchers found that smokers had much lower concentrations of an antioxidant, paraoxonase, than nonsmokers or ex-smokers, says Richard W. James, Ph.D., head of the lipid laboratory at Geneva University Hospital and the study's lead author.

Antioxidants counteract oxygen free-radicals, which are unstable molecules produced during a process called oxidation. Free-radicals can damage cells in the body. When fats in the body, such as low-density lipoprotein (LDL cholesterol, the "bad" cholesterol) are oxidized, they are more likely to form fatty plaques that block blood vessels.

"Because smokers' blood contains smaller amounts of paraoxonase, they have more oxidation, which could result in more cholesterol in the blood vessels," he says. "The excess cholesterol in the blood vessels can lead to blockages, or plaque, that can trigger a heart attack or stroke." Paraoxonase helps prevent LDL oxidation.

The good news is that ex-smokers paraoxonase levels increased dramatically over time. "Within two years of smoking cessation, paraoxonase concentration and activity in former smokers is comparable to individuals who have never smoked," says James.

All of the people studied had coronary artery disease. All participants completed a questionnaire on lifestyle and were asked if they were current smokers or nonsmokers. Nonsmokers were classified as either never-smokers or ex-smokers. Researchers used blood samples to test for paraoxonase. Of study participants, 139 had never smoked; 315 were former smokers and 142 were current smokers.

Significantly lower levels of paraoxonase activity occurred among current smokers and ex-smokers who had stopped for less than three months. The activity correlates with the concentration of the enzyme in the blood. This is one of the methods used to compare levels within the two populations.

Never-smokers and ex-smokers had an activity of 292 U/ml compared to 248 U/ml for current smokers. U/ml is a unit of measurement that refers to the biological activity of paraoxonase.

Researchers already knew that cigarette smoke contains free-radicals that can oxidize cholesterol in the blood. However, the new study finds that smoking lowers the activity of paraoxonase, the body's natural weapon against oxidation.

"Smoking is firmly established as one of the principal risk factors for heart disease, and free-radical damage is considered the major pathological mechanism associated with smoking. But the novelty of our study is that it shows smoking not only makes LDL cholesterol more toxic by producing free-radicals, but also weakens one of the means of limiting oxidation of LDL cholesterol."

Besides smoking, diabetes and older age are associated with lower levels of paraoxonase, says James. "Diabetic patients appear to be subject to greater free-radical damage, which may also be an important causative factor in aging."
-end-
Co-authors are Ilia Leviev, Ph.D. and Alberto Righetti, M.D.

Contact:
For journal copies only, please call: 214-706-1173
For other information, call:
Carole Bullock: 214-706-1279, caroleb@heart.org
Karen Hunter: 214-706-1330

American Heart Association

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