An enzyme puts the 'good' in good cholesterol

May 19, 2003

DALLAS, May 20 - An oxidation-fighting enzyme called paraoxonase (PON1) can significantly reduce the risk of heart attacks, according to research reported in today's rapid access issue of Circulation: Journal of the American Heart Association.

The enzyme attaches itself to high-density lipoprotein (HDL), which is known as "good" cholesterol. When PON1 is highly active, the risk for heart attack is cut by 43 percent, says study author Michael Mackness, Ph.D., of the University Department of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom.

"This is really the story of good and bad cholesterol. The "bad" cholesterol - low-density lipoprotein (LDL) - undergoes certain changes in the walls of blood vessels that initiate atherosclerosis. HDL carries the enzyme paraoxonase, which stops these changes in LDL," he explains.

But, he adds, the protection offered by PON1 depends on its activity in the blood, not simply the levels of PON1. In the study participants, PON1 activity was 20 percent lower in men who went on to develop heart disease, than those who did not have heart disease, he says. As PON1 activity increased, the risk for heart disease decreased. When the researchers stratified the men into five groups based on PON1 activity, the relative risk for developing heart disease for the men in the highest quintile of activity was 0.57, or nearly half the risk compared to men in the lowest PON1 activity group.

Mackness says that PON1 activity is genetically determined, but there are ways to boost it. "Taking antioxidant vitamins or eating foods high in antioxidants, moderate alcohol intake and exercise all increase PON1 activity," he says.

The Caerphilly Prospective Study includes data from 1353 men who were randomly selected from voter registration records in Caerphilly, South Wales between 1984 and 1988. The men ranged in age from 49 to 65 when they were enrolled in the study. Researchers obtained blood samples, medical, lifestyle and family histories, and each participant completed a chest pain questionnaire at the beginning of the study. The men also had baseline electrocardiograms.

Blood was tested for total cholesterol and triglyceride levels. Blood PON1 activity and concentration were also measured.

During the 15-year follow-up, 163 men had a coronary event. These men had a number of well-known risk factors, including high blood pressure, high total cholesterol, family history of heart disease, and low HDL. But Mackness says the relationship between PON1 activity and likelihood of coronary events remained statistically significant after adjusting for heart disease history, smoking, diabetes, body mass index, blood pressure and total cholesterol.

He adds that PON1 activity was an even stronger prognostic factor in 313 men who had confirmed heart disease when they entered the study - a finding that has been reported in a few smaller case-control studies.

"Were it possible to increase PON1 activity by a nutritional or pharmacological intervention, the adverse effect of some of the other risk factors might be ameliorated," write the authors.

Although the study results are based on findings in men, Mackness says PON1 activity is probably just as important for women, but studies in women are needed to confirm the relationship.
Co-authors are Bharti Mackness, Ph.D.; Paul Durrington, FmedSci; Patrick McElduff, Ph.D.; John Yarnell, Ph.D.; Naheed Azam, B.Sc.; and Michael Watt, B.Sc.

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