Hypertension seems root cause of heart failure in blacks

NEW YORK — Cardiovascular mortality remains higher for blacks than whites, but nontraditional therapies may be the key to reducing these mortality rates, said Elijah Saunders, MD, professor of cardiology and chief of the division of hypertension at University of Maryland School of Medicine.

“It’s hard to believe that 15 to 20 years ago there was an argument over whether blacks even had coronary heart disease,” Saunders said at the American Society of Hypertension 21st Annual Scientific Meeting and Exposition.

Although whites are more likely to have coronary disease as the cause for their heart failure, hypertension is more likely the root cause in blacks, Saunders said. “Everything is worse in blacks compared [with] whites in terms of frequency of the disease, mortality, hospitalization, sudden death and all the things that go along with heart failure.”

Most people are aware that hypertension is the major risk factor in blacks, he said. What’s striking, he added, is the age group in which it is occurring. In a slide presentation, Saunders showed that compared with whites, twice as many blacks aged 35 to 44 already had hypertension.

“This is where you’re making your coronaries, laying the ground for your diastolic dysfunction, making your systolic dysfunction for your strokes and renal disease,” Saunders said. Saunders is a member of Cardiology Today’s editorial board on the Hypertension and Vascular Disease Section.

Beyond standard treatment

According to Saunders, about 5 million Americans are diagnosed with heart failure; 750,000 are black. Total medical costs for heart failure are $26.6 billion per year.

Heart failure is becoming one of the most important problems for the black population, Saunders said. This is due to the high morbidity and also to “probable less effective treatments” for heart failure in this group, he noted.

“Since hypertension is such a significant cause of heart failure in blacks, drugs that represent the mainstay of heart therapy are not as effective in this population as in the white population,” Saunders said.

With hypertension playing such a major role, Saunders asked whether differences in the physiology and pathophysiology should require therapy for blacks to be different from conventional therapy.

One study that pointed in this direction was the African-American Heart Failure Trial (A-HeFT), Saunders said. The study was based on a theory that blacks with severe heart failure may be less responsive to ACE inhibitors. In vitro data have suggested that blacks may have a lower bioavailability of nitric oxide, a powerful natural vasodilator.

One thousand fifty self-identified black patients (61% men; mean age 56.3) with NYHA Class III or IV heart failure participated. Almost all were assigned ACE inhibitors or AII receptor antagonists, and about 75% were assigned beta-blockers.

Patients were randomized to receive either placebo or an active combination of isosorbide dinitrate and hydralazine (ISDN-H; BiDil, NitroMed Inc.) added to standard treatment. The trial was stopped after a year by A-HeFT’s data and safety and monitoring committee after finding a 43% mortality benefit in the treated group.

A-HeFT succeeded earlier studies, known as the Vasodilator-Heart Failure Trials (V-HeFT) I and II, which were conducted in Veterans Administration hospitals from 1980 through 1990.

Black patients in V-HeFT I had lower mortality when treated with ISDN-H compared with black patients assigned placebo, with annual mortality rates of 9.7% and 17.3%, respectively. White patients showed no significant differences in mortality rates for ISDN-H, prazosin and placebo groups.

Lost in the literature

“This study was kind of forgotten in the medical literature,” Saunders noted. “We really didn’t know how to interpret it and, at that time, no one recommended using ISND-H for blacks and not for whites.”

A-HeFT authors hypothesized the following: That isosorbide dinitrate is a nitric oxide donor; that hydralazine is an antioxidant that suppresses formation of reactive oxygen species that combine with and neutralize nitric oxide; and that the combination of ISDN-H improves nitric oxide bioavailability.

Ultimately, a “particular fixed dose” of ISDN-H in the A-HeFT study was responsible for the reduced mortality rate, Saunders said.

“The mechanism of the effectiveness of this therapy is believed related to more oxidative stress and reduced nitric oxide availability in African-Americans, although we can not prove that,” Saunders said. – by Rachel Eskenazi

For more information:

• Saunders E. The complicated African American hypertensive: emphasis on heart failure. Presented at the American Society of Hypertension 21st Annual Scientific Meeting and Exposition. May 16-20, 2006. New York.