Treatment-Resistant Hypertension and the Incidence of Cardiovascular Disease and End-Stage Renal Disease: Results From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
Abstract
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.
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The higher prevalence of apparent treatment-resistant hypertension among treated hypertensive adults in clinical trials (34%-39%) is likely explained by the selection of patients with demographic and comorbidity characteristics that place them at high risk for the fatal and nonfatal cardiovascular disease outcomes of interest.
“The higher prevalence of aTRH among treated hypertensive adults in clinical trials (34%−39%) is likely explained by the selection of patients with demographic and comorbidity characteristics that place them at high risk for the fatal and nonfatal CVD outcomes of interest.21–26”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [21]
Suboptimal medication regimens are common in patients with hypertension resistant to antihypertensive therapy.
“Suboptimal medication regimens are common in patients with hypertension resistant to antihypertensive therapy.21,60,367”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [21]
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- Authors
- Muntner, P., Davis, B. R., Cushman, W. C., Bangalore, S., Calhoun, D. A., Pressel, S. L., Black, H. R., Kostis, J. B., Probstfield, J. L., Whelton, P. K., & Rahman, M.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- ORCID
- Venue
- Hypertension
- Published
- 2014-11
- Volume
- 64
- Issue
- 5
- Pages
- 1012-1021
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2114075168
- Cited by
- 231
- References
- 26
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 15 · 2023: 16 · 2022: 11 · 2021: 18 · 2020: 30 · 2019: 26 · 2018: 21 · 2017: 19 · 2016: 36 · 2015: 17 · 2014: 2
- FWCI
- 16.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01hc35130-44-0-1)
- National Heart, Lung, and Blood Institute (N01-HC35130)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Keywords
- treatment-resistant hypertension, apparent treatment-resistant hypertension, cardiovascular disease, end-stage renal disease, coronary artery disease, stroke, all-cause mortality, heart failure, peripheral arterial disease, antihypertensive drugs, ALLHAT trial
- MeSH terms
- Aged, Antihypertensive Agents, Hypolipidemic Agents, Blood Pressure, Cardiovascular Diseases, Drug Resistance, Female, Follow-Up Studies, Humans, Hypertension, Kidney Failure, Chronic, Male, Middle Aged, Myocardial Infarction, Risk Factors, Incidence, Treatment Outcome, Treatment Failure
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