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Rationale for angiotensin II receptor blockers in patients with low-renin hypertension
1University of Michigan Medical Center, Ann Arbor, MI 48109-0357, USA. jamerson@umich.edu
Insights
African Americans experience higher rates of hypertension and related mortality. This study supports increased use of angiotensin-converting enzyme (ACE) inhibitors for this population, challenging traditional treatment guidelines.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Pharmacology
Background:
- Hypertension is more prevalent, severe, and earlier onset in African Americans, leading to higher mortality from cardiovascular, cerebrovascular, and renal diseases.
- Current guidelines recommend diuretics and calcium channel blockers for African Americans due to perceived lower response to beta blockers and ACE inhibitors.
- Existing guidelines suggest ACE inhibitors only for hypertensive patients with left ventricular dysfunction or nephropathy, creating a high threshold for African Americans.
Purpose of the Study:
- To explain the rationale for expanded use of renin-angiotensin system (RAS) blocking drugs in African Americans.
- To address the perceived unique pathobiology of hypertension in African Americans, including salt sensitivity and low plasma renin activity (PRA).
Main Methods:
- Review of existing guidelines and study findings, including the Heart Outcomes Prevention Evaluation (HOPE) study.
- Analysis of the physiological responses to ACE inhibitors in African Americans, considering factors like plasma volume and PRA.
- Evaluation of the impact of dietary sodium restriction and diuretic therapy on PRA and ACE inhibitor efficacy.
Main Results:
- The HOPE study demonstrated significant morbidity and mortality reduction with the ACE inhibitor ramipril in high-risk patients.
- Contrary to assumptions, most hypertensive African Americans are not hypovolemic.
- Dietary sodium restriction and diuretics can increase PRA, potentially enhancing the response to ACE inhibitors.
Conclusions:
- Increased use of ACE inhibitors is warranted in African Americans with hypertension.
- The perceived contraindications for ACE inhibitors in this population may be based on outdated or incomplete understanding of their pathophysiology.
- RAS blockade offers a viable therapeutic strategy for hypertensive African Americans, potentially improving cardiovascular and renal outcomes.
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.