Blood enzyme foretells heart attack threat.

Blood enzyme foretells heart attack threat

Elevated blood levels of a kidney-secreted enzyme may prove a potent predictor of heart attack risk among people with moderate hypertension, according to a new epidemiologic study. If further research confirms that finding, blood tests for the enzyme should help identify hypertensive people especially vulnerable to heart attack.

Years of high blood pressure can damage the heart and blood vessels. Some people with hypertension fall victim to a heart attack, while others escape that fate. Nearly 20 years ago, a retrospective study of hypertensive patients linked heart attack risk to the enzyme renin, but subsequent studies of similar patients showed no such association.

A research team in New York City has now reopened the case, adding significant weight to the renin/heart attack theory.

Renin "provides a powerful tool to identify [mild hypertensives] who are most likely to have a heart attack," says study coauthor Michael H. Alderman of the Albert Einstein College of Medicine. In the previous studies, investigators may have had trouble measuring the enzyme, he suggests.

Alderman and John H. Laragh of the Cornell University Medical College led a study of 1,717 men and women in New York City who belonged to various worker unions. All volunteers had a systolic (heart-pumping) blood pressure of at least 160 millimeters of mercury (mm Hg) and a diastolic (heart-resting) pressure of at least 95 mm Hg. (Hypertension is defined as systolic pressure of at least 140 and researchers measured blood renin at the study's start, detecting high levels in 12 percent of the volunteers. All participants received antihypertensive drugs for the next eight years.

At the end of the study period, the researchers discovered a fivefold greater incidence of heart attack in the high-renin subgroup compared with the rest of the sample. And among volunteers who had no other known cardiovascular risk factors -- such as smoking, diabetes or elevated blood cholesterol -- those with high renin levels were seven times more likely to suffer a heart attack than were those with low to normal renin, the team reports in the April 18 NEW ENGLAND JOURNAL OF MEDICINE. Indeed, these data revealed an unexpected benefit of low renin levels: Hypertensives who had no other heart risk factors remained free of heart attacks throughout the eight-year study.

Laragh suspects a link between renin and cardiac risk not just among hypertensives but in the population at large. "I wouldn't want to have high renin, having seen what I've seen here," he says.

Laragh points out that renin converts a blood protein to angiotensin II, which helps regulate blood pressure by constricting the vessels, including the coronary arteries. He suggests that too much angiotensim may trigger ischemia, or reduced blood flow to the heart, which can lead to a heart attack.

The new findings hint that high-renin hypertensives may benefit from drug therapy to lower their blood levels of renin or angiotensin II, notes Victor J. Dzau of Stanford University School of Medicine, who wrote an editorial accompanying the research report. Such drugs include beta blockers and angiotensin-converting-enzyme (ACE) inhibitors.

On the other hand, renin may prove merely a maker--rather than the cause -- of heightened heart risk, warns Michael Horan, a cardiologist at the National Heart, Lung and Blood Institute in Bethesda, Md. "Right now, it would be too soon to say we ought to be changing our drug therapy of hypertensive patients," Horan says.

Alderman and Laragh add that beta blocker drugs did not appear to lower the risk of heart attack in their study. To establish whether beta blockers or ACE inhibitors can offer hypertensives any protection against heart attack, researchers need to conduct trials specifically designed to compare different drug regimens, they say.