Can lipoprotein(a) foretell heart trouble?

A new study casts doubt on a cholesterol carrier's ability to predict the future risk of a heart attack -- at least for middleaged white men. However, many researchers believe the carrier, lipoprorein(a), remains a potent independent risk factor for cardiovascular disease in certain groups. Indeed, a second new study suggests that this carrier can identify children at high risk of developing heart disease later in life.

Lipoprotein(a) belongs to a class of cholesterol-carrying molecules that circulate in the bloodstream. This lipidprotein conjugate, whose function remains mysterious, was discovered in 1963. Since then, study after study has shown that people with high concentrations of the substance in their blood have a heightened risk of heart attack and stroke. However, most of those reports were conducted retrospectively.

Now, cardiologist Paul M. Ridker of Harvard Medical School in Boston and his colleagues have conducted a prospective study of Lp(a)'s connection to risk of cardiovascular disease. The team studied 14,916 male physicians between the ages of 40 and 84 who had no history of heart attack or stroke and were part of a larger research effort known as the Physicians' Health Study.

The investigators measured the concentrations of Lp(a) and other lipids in blood samples that had been frozen at the start of the study. The team then kept track of the participants for an average of five years. During that time, they recorded the number of heart attacks suffered by the physicians.

When Ridker and his co-workers compared the men who remained healthy during the study period to those who developed a heart attack, they found no difference in the concentrations of Lp(a) in their blood. Even when the team took into account other risk factors, such as age and smoking, Lp(a) failed to emerge as an independent risk factor. The researchers detailed their findings in the Nov. 10 JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION. They also presented their data this week at the 66th Scientific Sessions of the American Heart Association (AHA), held in Atlanta.

Ridker was surprised that the team found no relationship between Lp(a) concentrations measured at the start of the study and the appearance of carcliovascular problems later in the study. They had expected their findings to back up previous reports of a link between this cholesterol carrier and the risk of heart attack.

However, the study doesn't rule out the possibility that Lp(a) will prove a predictor of heart disease risk for people in certain groups. The Physicians' Health Study analyzed data that came mostly from middle-aged white men, notes Elliot S. Barnathan of the University of Pennsylvania School of Medicine in Philadelphia in an accompanying editorial. It may be that Lp(a) readings can foretell heart disease risk for people under age 40, he says.

Another research effort, this one led by Charles J. Glueck of Jewish Hospital in Cincinnati, reveals that Lp(a) does indeed predict the likelihood of cardiovascular disease for young, high-risk individuals.

Glueck's team studied 49 children age 10 to 14 from families in which one parent had suffered a heart attack before age 45. They measured the concentrations of Lp(a) in the children's bloodstreams and compared those values to Lp(a) concentrations recorded in 49 children in the same age range whose parents reported no heart disease. All the children in this study were evaluated at the University of the Andes in Merida, Venezuela.

The team discovered that the Lp(a) concentrations of children with a family history of heart problems were nearly twice as high as those of children from families without such a history. Glueck also reported his data at the AHA meeting.