Resistant Hypertension

Resistant hypertension is defined as blood pressure remaining above goal (≥ 130/80) despite concurrent use of 3 optimally dosed antihypertensive medications from different classes, one of which must be a diuretic, or BP controlled on ≥ 4 medications. Pseudo-resistance must be excluded first: white coat hypertension (confirm with ambulatory BP monitoring or home monitoring), medication non-adherence (most common cause of apparent resistance — verify with refill history, drug levels, or directly observed therapy), suboptimal dosing, and improper BP measurement technique. True resistant hypertension has identifiable secondary causes in up to 20% of cases: primary aldosteronism (most common — screen with aldosterone-to-renin ratio), obstructive sleep apnea (most common comorbid condition), renal artery stenosis, CKD, pheochromocytoma, Cushing syndrome, coarctation of the aorta, and thyroid disorders. Pathophysiological mechanisms include volume expansion (excess sodium intake, inadequate diuretic therapy, aldosterone excess), sympathetic overactivity, arterial stiffness, and RAAS activation. The cornerstone of management is adding spironolactone as the fourth agent (PATHWAY-2 trial demonstrated superiority of spironolactone over other fourth-line options), which addresses the frequent occult aldosterone excess in resistant hypertension.