Genetic Twist May Hold Key To Why Some Arteries Narrow After Angioplasty

"A re-narrowing of the arteries occurs within six months in about one third of patients who undergo balloon angioplasty, or percutaneous transluminal coronary angioplasty [PTCA]," said Dr. Andrew P. Levy of the Technion Faculty of Medicine, who conducted a study of the procedure. "We have found a genetic trait that might predispose patients to a more rapid re-narrowing after the procedure." The results of Dr. Levy’s study are reported in the American Journal of Cardiology (Vol. 87, February 2001).

Dr. A. Michael Lincoff, an interventional cardiologist and associate professor of medicine at the Cleveland Clinic in Cleveland, Ohio, said Dr. Levy’s study may play a dual role in the field of cardiology.

"First, it may help identify patients who may be at higher risk for restenosis [re-narrowing] or for more accelerated progression for atherosclerosis," Dr. Lincoff said. "Second, it could help clarify the mechanisms behind these processes and help us design new therapies."

Balloon angioplasty is an established and effective therapy for some patients with coronary artery disease. About 70 to 90 percent of these procedures also involve the placement of a stent, a device used to keep blood vessels open in the coronary arteries.

But it has been difficult to predict which patients will develop a re-narrowing. Dr. Levy and his colleagues have identified a genetic marker that appears to predict which patients are at higher or lower risk. The marker is located in the gene for haptoglobin, an anti-oxidative protein that has been associated with coronary complications in diabetic heart patients.

There are two forms, or alleles, of the gene for haptoglobin called 1 and 2. Every gene in the human body has two copies, one from each chromosome. This means a person can have two copies of the 1 allele for haptoglobin (1-1), one copy of the 1 allele and one copy of the 2 allele (2-1), or two copies of the 2 allele (2-2). The haptoglobin protein product produced in people that are 1-1, 2-1, or 2-2 may differ in the antioxidative protection it provides. Oxidative stress plays an important role in the development of restenosis after balloon angioplasty.

Dr. Levy studied 218 patients who underwent PTCA. Follow-up examinations showed restenosis in 152 of the subjects. When their haptoglobin phenotypes were determined, 79 percent of those patients who were haptoglobin 2-2 had restenosis, compared to 67 percent of those who were haptoglobin 2-1, and 44 percent who were haptoglobin 1-1.

Dr. Lincoff also praised the study for focusing on diabetic patients, who are more likely to develop heart disease and encounter complications from the procedures used to fight heart disease. "This also helps us identify which diabetics would be at higher risk and gives us insight into how best to treat them," Dr. Lincoff said.