Physiologic tailoring of treatment in resistant hypertension

Abstract

Resistant hypertension is a major opportunity for prevention of cardiovascular disease. Despite widespread dissemination of consensus guidelines, most patients are uncontrolled with approaches that assume that all patients are the same. Causes of resistant hypertension include 1) non-compliance 2) consumption of substances that aggravate hypertension (such as salt, alcohol, nonsteroidal anti-inflammatory drugs, licorice, decongestants) and 3) secondary hypertension. Selecting the appropriate therapy for a patient depends on finding the cause of the hypertension. Once rare causes have been eliminated (such as pheochromocytoma, licorice, adult coarctation of the aorta), the cause will usually be found by intelligent interpretation (in the light of medications then being taken) of plasma renin and aldosterone.If stimulated renin is low and the aldosterone is high, the problem is primary aldosteronism, and the best treatment is usually aldosterone antagonists (spironolactone or eplerenone; high-dose amiloride for men where eplerenone is not available). If the renin is high, with secondary hyperaldosteronism, the best treatment is angiotensin receptor blockers or aliskiren. If the renin and aldosterone are both low the problem is over-activity of renal sodium channels and the treatment is amiloride. This approach is particularly important in patients of African origin, who are more likely to have low-renin hypertension.

Keywords: African-American; Resistant hypertension; Stroke belt.; amiloride; primary hyperaldosteronism; renal sodium channel; renin.

Fig. (1). Central role of the renin-angiotensin-aldosterone axis in resistant hypertension

In normal homeostasis, renin is released under conditions of low blood pressure or dehydration; that activates aldosterone release, which causes salt and water retention, and excretion of potassium, magnesium, zinc and other ions. Disorders of this physiology can cause hypertension with three patterns of renin and aldosterone levels: Primary hyperaldosteronism causes salt and water retention, feeding back to suppress renin. Renal or renovascular causes of hypertension cause elevated renin with secondary hyperaldosteronism. Abnormalities of the renal tubular epithelial sodium channel (Liddle’s syndrome and other polymorphisms of the renal sodium channel, or adducin), cause salt and water retention and suppress both renin and aldosterone