Rationale for angiotensin II receptor blockers in patients with low-renin hypertension

Abstract

African Americans outrank other ethnic groups in the United States in prevalence, early onset, and severity of hypertension. Furthermore, African Americans suffer the highest rates of mortality from cardiovascular, cerebrovascular, and end-stage renal disease. The recently concluded Heart Outcomes Prevention Evaluation (HOPE) study reports that the angiotensin-converting enzyme (ACE) inhibitor ramipril significantly reduced morbidity and mortality in a broad range of patients at high risk for cardiovascular events. These results strengthen the case for increasing the use of ACE inhibitor therapy. In accord with the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) guidelines, antihypertensive monotherapy for African Americans is based on the known ability of diuretics and calcium channel blockers to produce greater reductions in blood pressure in this population than those attainable with beta blockers and ACE inhibitors. The national guidelines also suggest ACE inhibitors for all hypertensive patients with left ventricular dysfunction or nephropathy, which implies that African Americans must cross a clinical threshold to become candidates for these agents. The rationale for delaying ACE inhibitor therapy is due in part to a perceived unique pathobiology in hypertensive African Americans: an excess prevalence of salt sensitivity, hypervolemia, and low plasma renin activity (PRA). At first glance, it would seem intuitive to avoid agents that further depress the renin-angiotensin system (RAS) and choose agents that reduce plasma volume. However, most hypertensive African Americans are not hypovolemic. Furthermore, dietary sodium restriction and diuretic therapy raise PRA and improve the response to ACE inhibitors. The overall aim of this article is to explain the rationale for expanded use of drugs that block the RAS in African Americans and low-renin populations.