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Baseline predictors of resistant hypertension in the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT): a risk score to identify those at high-risk
Abstract
BACKGROUND: Resistant hypertension is a well recognized clinical entity, which has been inadequately researched to date. METHODS: A multivariable Cox model was developed to identify baseline predictors of developing resistant hypertension among 3666 previously untreated Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) patients and construct a risk score to identify those at high risk. Secondary analyses included evaluations among all 19 257 randomized patients. RESULTS: One-third (1258) of previously untreated, and one-half (9333) of all randomized patients (incidence rates 75.2 and 129.7 per 1000 person-years, respectively) developed resistant hypertension during a median follow-up of 5.3 and 4.8 years, respectively. Increasing strata of baseline SBP (151-160, 161-170, 171-180, and >180 mmHg) were associated with increased risk of developing resistant hypertension [hazard ratio 1.24 (95% confidence interval, CI 0.81-1.88), 1.50 (1.03-2.20), 2.15 (1.47-3.16), and 4.43 (3.04-6.45), respectively]. Diabetes, left ventricular hypertrophy, male sex, and raised BMI, fasting glucose, and alcohol intake were other significant determinants of resistant hypertension. Randomization to amlodipine ± perindopril vs. atenolol ± thiazide [0.57 (0.50-0.60)], previous use of aspirin [0.78 (0.62-0.98)], and randomization to atorvastatin vs. placebo [0.87 (0.76-1.00)] significantly reduced the risk of resistant hypertension. Secondary analysis results were similar. The risk score developed allows accurate risk allocation (Harrell's C-statistic 0.71), with excellent calibration (Hosmer-Lemeshow χ statistics, P = 0.99). A 12-fold (8.4-17.4) increased risk among those in the highest vs. lowest risk deciles was apparent. CONCLUSION: Baseline SBP and choice of subsequent antihypertensive therapy were the two most important determinants of resistant hypertension in the ASCOT population. Individuals at high risk of developing resistant hypertension can be easily identified using an integer-based risk score.
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“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 [22]
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Metadata
- Authors
- Gupta, A. K., Nasothimiou, E. G., Chang, C. L., Sever, P. S., Dahlöf, B., & Poulter, N. R.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Gupta, Ajay K.
- Venue
- Journal of Hypertension
- Published
- 2011-10
- Volume
- 29
- Issue
- 10
- Pages
- 2004-2013
- ISSN
- 0263-6352 (ISSN-L)
- OpenAlex
- W2082072583
- Cited by
- 165
- References
- 26
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 8 · 2023: 11 · 2022: 5 · 2021: 9 · 2020: 4 · 2019: 10 · 2018: 10 · 2017: 15 · 2016: 13 · 2015: 14 · 2014: 26 · 2013: 21 · 2012: 13
- FWCI
- 13.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- National Institute for Health and Care Research (NF-SI-0508-10116)
- British Heart Foundation
- Servier
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- resistant hypertension, baseline predictors, risk score, systolic blood pressure, antihypertensive therapy, amlodipine, perindopril, atenolol, thiazide diuretics, atorvastatin, aspirin, diabetes mellitus, left ventricular hypertrophy, alcohol consumption, body mass index, hypertension incidence, ASCOT trial
- MeSH terms
- Aged, Algorithms, Antihypertensive Agents, Atenolol, Bendroflumethiazide, Diuretics, Drug Resistance, Female, United Kingdom, Humans, Hypertension, Ireland, Male, Middle Aged, Risk Factors, Scandinavian and Nordic Countries, Amlodipine, Perindopril
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