Predictors and outcomes of resistant hypertension among patients with coronary artery disease and hypertension

Abstract

Objective Resistant hypertension (res-HTN) is a challenging problem, but little is known of res-HTN in patients with coronary artery disease (CAD). In this post-hoc INternational VErapamil SR-Trandolapril STudy (INVEST) analysis, we assessed prevalence, predictors, and impact on outcomes of res-HTN in CAD patients with hypertension. Methods Participants (n=17 190) were divided into three groups according to achieved blood pressure (BP): controlled (BP <140/90 mmHg on three or fewer drugs); uncontrolled (BP ≥140/90mmHg on two or fewer drugs); or resistant (BP ≥140/90 mmHg on three drugs or any patient on at least four drugs). Results The prevalence of res-HTN was 38%: significant predictors of res-HTN included heart failure [odds ratio (OR) 1.73], diabetes (OR 1.63), Black race (OR 1.50), and US residence (OR 1.50). Compared with controlled HTN, res-HTN had multivariate-adjusted association with higher risk of adverse outcomes {first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke [hazard ratio 1.27, 95% confidence interval (CI) 1.13–1.43], and individual outcomes of all-cause death (hazard ratio 1.29, 95% CI 1.13–1.48), cardiovascular mortality (hazard ratio 1.47, 95% CI 1.21–1.78), and nonfatal stroke (hazard ratio 1.61, 95% CI 1.17–2.22), but not nonfatal myocardial infarction (hazard ratio 0.98, 95% CI 0.72–1.34)}. Adverse outcomes, except nonfatal stroke, did not differ in patients with res-HTN compared to uncontrolled HTN. Conclusions Res-HTN is common in patients with CAD and hypertension, associated with poor prognosis, and linked with a number of conditions. Emphasis should be placed on recognizing those at risk for res-HTN and future studies should examine whether more aggressive treatment of res-HTN improves outcomes.

Mortality Risk Associated With Resistant Hypertension Among Women: Analysis from Three Prospective Cohorts Encompassing the Spectrum of Women's Heart Disease

“…Importantly, the median follow-up time of >14 years in this study far surpasses the vast majority of previous analyses of RH-associated outcomes, which have typically had £5 years of follow-up. [9][10][11][12][13][14][15] Finally, our findings are remarkably consistent with a recent analysis of ALLHAT data, in which RH (Vs. non-RH) was associated with a nearly 1.4-fold increased risk of all-cause mortality over *5 years among a more homogenous group of women. 9 The mechanisms underlying the association between aRH and death are not known, but it seems reasonable to presume that requiring a greater number of antihypertensive agents to achieve BP control reflects a combination of adverse underlying disease processes.…”

“…Moreover, this is one of the first studies in men or women, to our knowledge, to assess risks associated with resistant hypertension across the spectrum of underlying cardiac disease. Previous analyses have been largely limited to patients with high risk for CV events or to specific disease-based cohorts, for example, in those with underlying coronary artery disease, 12,13 subclinical or clinical atherothrombotic disease, 11 or chronic kidney disease. 10 The most important finding from this study is the very early emergence of and sustained increased risk of death associated with aRH, particularly in women with signs and symptoms of myocardial ischemia (from WISE) or CAD (from INVEST).…”

“…7,17 Multiple lines of empiric evidence suggest that women are at greater risk of developing RH than men: mean BP is demonstrably higher in postmenopausal women than agematched men 18 ; women are more likely than men to be treated with antihypertensive drugs, but less likely to achieve BP control 1,6,[19][20][21][22] ; and female sex has been repeatedly identified as an independent predictor of RH. 6,[11][12][13]23,24 Yet, most studies of RH-associated outcomes have enrolled comparatively few women, 17 consistent with CV studies in general. [25][26][27] This lack of RH outcome data in women represents a major gap in knowledge.…”

“…Additional methodological details for each study are provided in the Supplement (Supplementary Data are available online at www.liebertpub.com/jwh). 12 and others 9,15 has indicated remarkably similar risk for adverse outcomes whether or not diuretic use is required to meet criteria for RH among patients using multiple antihypertensive drugs of different classes. Finally, because we had previously demonstrated an equivalent impact on outcomes and very similar effects on BP control between the treatment strategies, 12,33 all U.S. women in INVEST were pooled, regardless of initial treatment randomization.…”

“…6 Emerging evidence suggests that RH is associated with increased risk for major adverse cardiovascular (CV) events and mortality and worse health-related quality of life, compared with nonresistant hypertension (non-RH). [9][10][11][12][13][14][15][16] Consequently, RH has been identified as a priority research area. 7,17 Multiple lines of empiric evidence suggest that women are at greater risk of developing RH than men: mean BP is demonstrably higher in postmenopausal women than agematched men 18 ; women are more likely than men to be treated with antihypertensive drugs, but less likely to achieve BP control 1,6,[19][20][21][22] ; and female sex has been repeatedly identified as an independent predictor of RH.…”