Hypokalemia in hypertension: Mechanistic drivers of target-organ injury and an etiology-directed framework for potassium management

Hypokalemia is common but often underrecognized in patients with hypertension. This review synthesizes clinical and mechanistic evidence suggesting that lower serum potassium levels, including values within the low-normal range, are associated with higher cardiovascular, renal, vascular, and cerebrovascular risk, with several studies suggesting that these associations persist after adjustment for blood pressure and related confounders. We use "hypokalemic hypertension" as an operational high-risk phenotype in which established hypertension coexists with persistent or recurrent hypokalemia, or with low-normal potassium in selected high-risk contexts. This phenotype is most commonly related to primary aldosteronism, diuretic exposure, renal potassium wasting, or endocrine and tubular disorders. We highlight potassium-sensitive molecular programs in the distal nephron and cardiovascular tissues that couple mineralocorticoid excess, sodium-retaining pathways, and ion-channel remodeling to target-organ injury. These processes promote sodium retention, volume expansion, salt sensitivity, endothelial dysfunction, arterial stiffening, arrhythmogenesis, and inflammatory-fibrotic remodeling, potentially aggravating target-organ injury beyond hemodynamic load alone. We propose a translational framework emphasizing systematic detection, structured etiologic evaluation, and cause-directed therapy rather than isolated potassium replacement. Serial serum potassium and creatinine monitoring, together with urinary sodium-to-potassium indices when available, may support individualized dietary and pharmacologic titration. Prospective trials stratified by etiology are needed to define actionable surveillance thresholds, individualized therapeutic ranges, and whether potassium-centered algorithms improve mechanistic and clinical outcomes.