Clonal hematopoiesis in apparent treatment-resistant hypertension, insights from multiple medical centers and community-based cohorts.

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) increases with age and has been linked to cardiovascular disease. Apparent treatment-resistant hypertension (aTRH) is a severe, age-associated form of hypertension with poor response to therapy. Here we show that CHIP is enriched in patients with aTRH and is independently associated with poorer treatment response and adverse cardiac remodeling. In a multicenter discovery cohort and two community-based validation cohorts, CHIP was detected in ~23% of patients with aTRH versus ~7% of matched controlled-hypertension controls. CHIP carriers exhibited larger left ventricular dimensions, lower ejection fraction, elevated proinflammatory cytokines, smaller reductions in systolic and diastolic blood pressure after medication intensification and a substantially lower likelihood of achieving clinically controlled aTRH. Higher variant allele fraction and loss-of-function variants were linked to worse outcomes. These results identify CHIP as a common, clinically relevant biomarker in aTRH and suggest that targeting CHIP-related inflammation could improve antihypertensive treatment efficacy and outcomes.