Many African-Americans Have a Gene That Prolongs Life After Heart Failure

About 40 percent of African-Americans have a genetic variant that can protect them after heart failure and prolong their lives, according to research conducted at Washington University School of Medicine in St. Louis and collaborating institutions.

The genetic variant has an effect that resembles that of beta blockers, drugs widely prescribed for heart failure. The new study offers a reason why beta blockers don't appear to benefit some African-Americans.

"For several years a controversy has existed in the cardiovascular field because of conflicting reports about whether beta blockers helped African-American patients," says senior author Gerald W. Dorn II, M.D., professor of medicine, associate chairman for translational research and director of the Center for Pharmacogenomics at Washington University.

"By mimicking the effect of beta blockers, the genetic variant makes it appear as if beta blockers aren't effective in these patients," he explains. "But although beta blockers have no additional benefit in heart failure patients with the variant, they are equally effective in Caucasian and African-American patients without the variant."

Co-author Stephen B. Liggett, M.D., professor of medicine and physiology at the University of Maryland School of Medicine and director of its cardiopulmonary genomics program says the discovery adds to the accumulating evidence that genetic differences contribute to the way people respond to medications and should encourage the use of genetic testing in clinical trials to identify people who can benefit from therapy tailored to their genetic makeup.

About 5 million people in the United States have heart failure, and it results in about 300,000 deaths each year. Beta blockers slow heart rate and lower blood pressure to decrease the heart's workload and prevent lethal cardiac arrhythmias.

While Caucasians with heart failure participating in clinical studies of beta blockers have shown clear benefit from the drugs, the evidence for benefit in African-Americans has been ambiguous. The current study, reported online April 20, 2008, in Nature Medicine, identified one particular race-specific gene variant that seems to account mechanistically and biologically for these indeterminate results.

The gene codes for an enzyme called GRK5, which depresses the response to adrenaline and similar hormonal substances that increase how hard the heart works. Adrenaline is a hormone released from the adrenal glands that prompts the "fight-or-flight" response — it increases cardiac output to give a sudden burst of energy.

In heart failure, decreased blood flow from the struggling heart ramps up the body's secretion of adrenaline to compensate for a lower blood flow. Overproduction of the hormone makes the weakened heart pump harder, but eventually worsens heart failure.

Beta blockers alleviate this problem by blocking adrenaline at its receptor in the heart and blood vessels. GRK enzymes mimic this effect by serving as "speed governors" that work like the governor in an engine to prevent adrenaline from over-revving the heart, says Dorn.