Diuretic Reduces Risk For A Type Of Heart Failure That Is More Common Among Women, Study Suggests

Heart failure is a clinical syndrome characterized by an inadequate supply of oxygen rich blood as a result of impaired cardiac pump function. More than 5 million Americans are living with heart failure and most had high blood pressure before developing this potentially deadly condition.

While much research has been focused on the impact of antihypertensive medications on the prevention of heart failure associated with reduced pumping capacity in the heart's all-important left ventricle, comparatively little research has been performed on the prevention of heart failure wherein the heart muscle is clearing a normal or preserved percentage of blood with each heart beat. This percentage is called left ventricular ejection fraction (LVEF).

"We showed that a diuretic was as good as or better than other classes of medication for high blood pressure in reducing the occurrence of heart failure in people with a wide range of left ventricular ejection fraction," said Barry Davis, M.D., Ph.D., the study's lead author, the Guy S. Parcel Chair in Public Health and director of the Coordinating Center for Clinical Trials at the UT School of Public Health.

The study involved 910 hypertensive adults who had been taking antihypertensive medications and who were subsequently diagnosed with heart failure in a hospital. Those with an ejection fraction of 50 percent or more were defined as Heart Failure Preserved Ejection Fraction (HFPEF) and those with an ejection fraction of 49 percent or less as Heart Failure Reduced Ejection Fraction (HFREF). Forty-four percent had preserved ejection fraction and 56 percent reduced ejection fraction.

Participants treated with a thiazide-type diuretic (chlorthalidone) had reduced risk of Heart Failure Preserved Ejection Fraction compared to those taking a calcium channel blocker (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), or an alpha-adrenergic blocker (doxazosin). Chlorthalidone reduced the risk in people with reduced ejection fraction compared with amlodipine or doxazosin. Chlorthalidone was similar to lisinopril in preventing heart failure with reduced ejection fraction. "On the basis of the data from many heart failure trials, a combination of the last two agents would be expected to be particularly effective in preventing heart failure in this group," the authors wrote.

"In both heart failure with preserved and reduced ejection fraction, the diuretic is helping to remove excess fluid - which can reduce both pre load and after load and thus increase ejection fraction," Davis said.

Heart failure patients with preserved ejection fraction may still have big problems, Davis said. "Let's say the heart normally should pump 70 milliliters (ml) of blood. It fills up with 100 ml and pumps 70 for an EF of 70 percent (which is good). However with reduced ejection fraction it only pumps 30 ml or has an EF of only 30 percent. On the other hand you could have preserved ejection fraction and in this case the heart fill up with just 50 ml of blood but pumps 30 ml. The EF would be 60 percent. In both cases, only 30 ml is reaching the body."

Davis said heart failure is sometimes characterized as either systolic or diastolic heart failure. In systolic heart failure, there is reduced cardiac contractility, whereas in diastolic heart failure there is impaired cardiac relaxation and abnormal ventricular filling. Heart Failure Preserved Ejection Fraction is typically associated with the filling blood phase and Heart Failure Reduced Ejection Fraction with the forcing blood out phase.

Participants with preserved ejection fraction compared to those with reduced ejection fraction were more likely to be women (52 percent versus 38 percent) and less likely to have a history of coronary heart disease (32 percent versus 39 percent). People with heart failure with preserved ejection fraction have a subsequent mortality rate almost as high as those with reduced ejection fraction, about 50 percent at five years.

Participants in the study were from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, multi-center clinical trial that compared four classes of medications for high blood pressure. More than 42,000 people 55 years of age or more with hypertension were in the trial between 1994 and 2002.

Davis' collaborators from the UT School of Public Health were Charles E. Ford, Ph.D., associate professor of biostatistics and Lara M. Simpson, Ph.D., faculty associate. Also contributing were: John B. Kostis, M.D., UMDNJ-Robert Wood Johnson Medical School, New Brunswick, N.J. ; Henry R. Black, M.D., New York University School of Medicine, New York, N.Y.; William C. Cushman, M.D., Memphis Veteran's Affairs Medical Center, Memphis, Tenn.; Paula T. Einhorn, M.D., Division of Prevention and Population Sciences, National Heart, Lung, and Blood Institute, Bethesda, Md.; Michael A. Farber, M.D., Crozer Keystone Health Network, Upland, Pa.; Daniel Levy, M.D., Framingham Heart Study/National Heart, Lung and Blood Institute Framingham, Mass.; Barry M. Massie, M.D., San Francisco Veterans Affairs Medical Center, San Francisco, Calif.; and Shah Nawaz, M.D., private practice in Sudbury, Ontario, Canada.

Research was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health and the U.S. Department of Health and Human Services, Bethesda, Md.