Treatment-Resistant Hypertension and the Incidence of Cardiovascular Disease and End-Stage Renal Disease

Apparent treatment-resistant hypertension (aTRH) is defined as uncontrolled hypertension despite the use of ≥3 antihypertensive medication classes or controlled hypertension while treated with ≥4 antihypertensive medication classes. Although a high prevalence of aTRH has been reported, few data are available on its association with cardiovascular and renal outcomes. We analyzed data on 14 684 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants to determine the association between aTRH (n=1870) with coronary heart disease, stroke, all-cause mortality, heart failure, peripheral artery disease, and end-stage renal disease. We defined aTRH as blood pressure not at goal (systolic/diastolic blood pressure ≥140/90 mm Hg) while taking ≥3 classes of antihypertensive medication or taking ≥4 classes of antihypertensive medication with blood pressure at goal during the year 2 ALLHAT study visit (1996-2000). Use of a diuretic was not required to meet the definition of aTRH. Follow-up occurred through 2002. The multivariable adjusted hazard ratios (95% confidence intervals) comparing participants with versus without aTRH were as follows: coronary heart disease (1.44 1.18-1.76), stroke (1.57 1.18-2.08), all-cause mortality (1.30 1.11-1.52), heart failure (1.88 1.52-2.34), peripheral artery disease (1.23 0.85-1.79), and end-stage renal disease (1.95 1.11-3.41). aTRH was also associated with the pooled outcomes of combined coronary heart disease (hazard ratio, 1.47; 95% confidence interval, 1.26-1.71) and combined cardiovascular disease (hazard ratio, 1.46; 95% confidence interval, 1.29-1.64). These results demonstrate that aTRH increases the risk for cardiovascular disease and end-stage renal disease. Studies are needed to identify approaches to prevent aTRH and reduce risk for adverse outcomes among individuals with aTRH.