Aldosterone and Resistant Hypertension

Refractory or resistant hypertension, defined as the failure to control systolic (<140 mmHg) and/or diastolic blood pressure (< 90 mmHg) despite the use of three or more different classes of antihypertensive agents, is a common problem in clinical practice. Several factors induce treatment resistance, especially secondary hypertension, such as primary aldosteronism. Some authors have argued for a direct role of aldosterone autonomy as a mechanism for drug resistance and have recommended the search for primary aldosteronism in cases of severe or resistant hypertension. This proposal is further supported by the demonstration of antihypertensive efficacy of aldosterone antagonists in patients with refractory hypertension. Recently, we have demonstrated a direct role of aldosterone excess as a mechanism for drug resistance, since patients with elevated aldosterone plasma levels develop resistant hypertension, even in the absence of clinically diagnosed primary aldosteronism. The mechanism of resistance may be ascribed to increased plasma volume, regardless of renal function, and cardiovascular remodeling. The present review highlights the role of aldosterone excess as a cause of treatment resistance beyond true primary aldosteronism and provides a conceptual framework for the use of aldosterone antagonists in patients with resistant hypertension.