Pattern B another genetic heart risk?

Pattern B another genetic heart risk?

A recent study suggests that about one-third of the population in the United States carries a yet-unidentified gene associated with an increased risk of heart disease, a scientist involved in the study said last week. Other scientists, however, say that there is no satisfactory proof that the observed genetic trait actually translates into any amount of increased risk.

Speaking at the American Heart Association's 15th Science Writers Forum in New Orleans, Ronald M. Krauss of the University of California at Berkeley suggested that roughly 30 percent of the U.S. population has a preponderance of particularly heavy forms of low-density lipoproteins (LDL) circulating in their blood. Lipoproteins are complexes of lipids and proteins used by the body to transport fats, and the LDL types are considered "bad" in terms of depositing cholesterol in the blood vessels. Using a superfast centrifuge to separate LDL factions according to their size and weight, Krauss and his co-workers had previously found four major LDL subgroups. Since that discovery, they have used a more sophisticated method to measure the relative concentrations of the different LDL types in more than 2,000 individuals.

What they found were two distinct LDL patterns, or profiles. Approximately 70 percent of those tested had higher relative concentrations of the lighter, larger LDL types (a profile called the A pattern), while the remainder had more of the smaller, denser LDL types and were said to have the B pattern. Krauss says that, based on subsequent family studies among 300 Mormons in Northern California, "there appears to be a major single gene in the population...which appears to regulate, or at least influence, whether or not an individual falls into [the B] category."

The Berkeley scientists, with researchers at Harvard University, then looked at A and B patterns in about 120 patients with heart disease, as well as those in an equal number of normal controls. Their results--which have been submitted for publication--suggest that the B profile is more common among heart patients, and therefore closely tied to an increased risk of heart disease. This does not necessarily mean, however, that the B individual is definitely predisposed to cardiovascular problems, says Krauss.

He says that because a person can use diet and exercise to convert B to A, this particular factor can be controlled. In general, he says, everyone age 20 or younger appears to be an A in terms of LDL patterns. With increasing age, however, the B blood pattern begins to appear, becoming common by middle age.

Although the Berkeley/Harvard group originally concluded there was a three-fold increased risk of having heart disease among those with a B profile, the scientists have been reevaluating the magnitude of this increased risk, Krauss told SCIENCE NEWS. He says the possibility that heart drugs called beta-blockers can artificially cause a B pattern has cast some doubt on the clinical implications of A and B profiles.

Ernst J. Schaefer of Tufts University in Boston agrees that medication may indeed influence clinical findings. He said in an interview that independent studies by his research group show that, when subjects taking beta-blockers are eliminated from clinical studies, no increased risk of heart disease is evident among those with B profiles. Beta-blockers, which are used in about 80 percent of heart patients following a heart attack, can themselves increase the concentration of dense LDL, says Schaefer. Until much larger studies are completed taking into account the drugs' actions, he says, researchers will not know whether the B profile equals increased risk.

Both Krauss and Schaefer agree that there are many unanswered questions regarding the clinical importance of the new studies. While the B pattern "deserves a lot of attention," it may actually just be a marker for the impaired clearance of fats that are the true risk factors, says Krauss. Schaefer, however, says he cannot yet discount the possibility that dense LDL is somehow directly related to heart disease. His group has found significant amounts of the dense LDL in 44 percent of normal middle-aged males in one small study, as compared to only 15 percent of the study's female subjects. This sex difference, along with the fact that heart disease is more common among men, may be evidence supporting the Berkeley/Harvard data, says Schaefer.