What is the Role of Aldosterone Excess in Resistant Hypertension and How Should It Be Investigated and Treated?

Abstract

Resistant hypertension has evolved as an important global health care problem. Primary aldosteronism is one of several potentially reversible causes of resistant hypertension. Primary aldosteronism can be effectively treated, when recognized, with a mineralocorticoid receptor antagonist, such as spironolactone and eplerenone. Each of these compounds can reduce blood pressure as monotherapy or when given with a range of other antihypertensive drug classes. These compounds have distinctive pharmacokinetic and pharmacodynamic patterns that require some forethought in their use before they are prescribed. However, as the use of mineralocorticoid-blocking agents has gradually increased, the hazards inherent to use of such drugs has become more apparent. Whereas the endocrine side effects of spironolactone are in most cases little more than a cosmetic annoyance, the potassium-sparing effects of both spironolactone and eplerenone can prove fatal if sufficient degrees of hyperkalemia develop. However, for most patients the risk of developing hyperkalemia in and of itself should not discourage the prudent clinician from bringing these compounds into play. Hyperkalemia should always be considered as a likelihood in any patient receiving one or the other of these medications. As such, steps should be taken to lessen the likelihood of it occurring if therapy is being contemplated with agents in this class.

Assessment and management of resistant hypertension

“…1,23 Elevated aldosterone levels are associated with detrimental cardiovascular physiologic effects, such as oxidative stress, endothelial dysfunction, inflammation and tissue fibrosis. 24 Elevated activity of the sympathetic nervous system is also a key contributor to resistant hypertension. This excess activity is frequently present in primary (essential) hypertension.…”

“…Eplerenone, which has fewer sex-hormonedependent adverse effects (e.g., painful gynecomastia and erectile dysfunction), is a costlier and less potent alternative. 24 Amiloride, an epithelial sodium-channel blocker (not a mineralocorticoidreceptor antagonist), is another option and is used most commonly in primary aldosteronism. 52 Table 3).…”