Aldosterone and Its Role in Heart Failure

Hans Armin Dieterich, M.D., Ph.D.

Hans Armin Dieterich, MD, PhD is a Professor of Pharmacology and faculty member of the Department of Medicine and Pharmacology at the Georgetown University School of Medicine, Washington DC and the Department of Medicine and Pharmacology at the Masaryk University in Brno, Czech Republic. In addition, he is a fellow of the European Society of Cardiology (F.E.S.C.), the American College of Cardiology (F.A.C.C.), the International College of Angiology (F.I.C.A.) and the American College of Angiology (F.A.C.A.). At present, he is Vice President Cardiovascular Research and Development Worldwide at PAREXEL International, an Independent Pharmaceutical Research Organization. PAREXEL, headquartered in Boston, Massachusetts.

He is involved in the development of new medications for patients with hypertension and heart failure. His new drug is very promising also for the treatment of heart failure after a myocardial infarction. His comments have been selected from his current research findings and represent some of the most current and unique approaches to heart disease. Below is an exerpt from his recent findings:

Efforts continue to determine the underlying causes and treatments for heart attacks and strokes. In recent years, our understanding of several of the major chemical agents has also expanded, particularly in the case of aldosterone. It is now well documented that aldosterone causes myocardial and perivascular fibrosis, blocks the heart muscle’s uptake of norepinephrine, and increases plasminogen activator inhibitor levels. When taken together, these actions implicate aldosterone’s role in causing vascular damage. These recent findings also suggest aldosterone and the systems that utilize aldosterone (RAAS), play a major role in the development of both hypertension and heart failure and are therefore, a key target for therapeutic interventions.

Commonly prescribed medications for the control of hypertension and congestive heart failure are inhibitors of the RAAS, including angiotensin converting enzyme inhibitors (ACE-I) and A-II receptor antagonists. There is a well-documented increase in aldosterone levels that occurs over several months during chronic treatment with an ACE-I or A-II receptor antagonist. Such suppression of circulating aldosterone, however, is transient, as exemplified by the term “escape” used to describe the phenomenon. Following treatment, aldosterone levels can rebound and even occur when patients receive both an ACE-I and A-II receptor antagonist. In addition, ACE-I and A-II receptor antagonists are less effective in controlling blood pressure in the estimated 60% of hypertensive patients who are salt (volume) sensitive and more prone to hypertension-associated morbidity such as type 2 diabetics. Thus chronic and complete blockade of aldosterone action requires an aldosterone receptor antagonist.

Several studies have shown that different combinations of treatment, such as “cocktails” can reduce the risk of significant death due to progressive heart failure and sudden cardiac death. These findings support the pivotal role of aldosterone in progressive heart failure. Although it is an effective antialdosterone agent, widespread use of spironolactone in humans is limited by its tendency to produce undesirable sexual side effects. At standard doses, impotence and gynaecomastia (growth of breasts) can be induced in men, whereas pre-menopausal women may experience menstrual disturbances. Preliminary data on a selective aldosterone receptor antagonist, eplerenone, appear promising for treatment without the sexual disturbances of spironolactone. Eplerenone is currently under investigation for the treatment of both hypertension and heart failure. Results from these pharmaceutical trials continue to build the volume of knowledge on diseases of the heart and will no doubt lead to better treatments in the future.