Association of Apparent Treatment-Resistant Hypertension With Differential Risk of End-Stage Kidney Disease Across Racial Groups in the Million Veteran Program

Abstract

Apparent treatment-resistant hypertension (ATRH) has been linked to end-stage kidney disease (ESKD) and cardiovascular disease. We tested the hypothesis that the effect of ATRH on ESKD is greater in Black patients than in White patients and investigated the effect of ATRH on ESKD independent of APOL1 genotype. In a retrospective cohort of 139 685 hypertensive veterans (22% Black, 5% women) in the Million Veteran Program, ATRH was defined as failure to achieve outpatient blood pressure <140/90 mmHg with 3 antihypertensives including a thiazide or use of ≥4. Outcomes included incident ESKD, myocardial infarction, and stroke. Poisson models were used to test effect modification by race. Over a median follow-up of 10.3 years (interquartile range, 5.8–11.7), 17 521 incident ATRH cases were observed. Compared with nonresistant hypertension, patients with ATRH had higher incidence rates (per 1000-person-years) of ESKD (4.7 versus 1.6), myocardial infarction (6.7 versus 3.4), and stroke (16.7 versus 8.5). A greater attributable risk of ESKD because of ATRH was observed among Black patients (44.4/1000) compared with White patients (25.5/1000). Black patients with ATRH had a 2.3-fold higher risk of ESKD compared with Black patients with nonresistant hypertension; 3-fold the risk of White patients with ATRH, and 9-fold the risk of White patients with nonresistant hypertension ( P -interaction<0.001). Among Black patients, ATRH remained associated with a 98% (95% CI, 1.66–2.75) higher risk of ESKD after adjustment for APOL1 genotype. Patients with ATRH experienced excess ESKD and cardiovascular disease risk. This excess ATRH-related ESKD risk was magnified among Black patients independently of APOL1 genotype. Targeted treatment of ATRH could curtail ESKD and cardiovascular disease incidence.