Effects of body size and hypertension treatments on cardiovascular event rates: subanalysis of the ACCOMPLISH randomised controlled trial
Abstract
Background In previous clinical trials in high-risk hypertensive patients, paradoxically higher cardiovascular event rates have been reported in patients of normal weight compared with obese individuals. As a prespecified analysis of the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, we aimed to investigate whether the type of hypertension treatment affects patients' cardiovascular outcomes according to their body size.Methods On the basis of body-mass index (BMI), we divided the full ACCOMPLISH cohort into obese (BMI ≥30, n=5709), overweight (≥25 to <30, n=4157), or normal weight (<25, n=1616) categories. The ACCOMPLISH cohort had already been randomised to treatment with single-pill combinations of either benazepril and hydrochlorothiazide or benazepril and amlodipine. We compared event rates (adjusted for age, sex, diabetes, previous cardiovascular events, stroke, or chronic kidney disease) for the primary endpoint of cardiovascular death or non-fatal myocardial infarction or stroke. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00170950.Findings In patients allocated benazepril and hydrochlorothiazide, the primary endpoint (per 1000 patient-years) was 30·7 in normal weight, 21·9 in overweight, and 18·2 in obese patients (overall p=0·0034). However, in those allocated benazepril and amlodipine, the primary endpoint did not differ between the three BMI groups (18·2, 16·9, and 16·5, respectively; overall p=0·9721). In obese individuals, primary event rates were similar with both benazepril and hydrochlorothiazide and benazepril and amlodipine, but rates were significantly lower with benazepril and amlodipine in overweight patients (hazard ratio 0·76, 95% CI 0·59-0·94; p=0·0369) and those of normal weight (0·57, 0·39-0·84; p=0·0037).Interpretation Hypertension in normal weight and obese patients might be mediated by different mechanisms. Thiazide-based treatment gives less cardiovascular protection in normal weight than obese patients, but amlodipine-based therapy is equally effective across BMI subgroups and thus offers superior cardiovascular protection in non-obese hypertension.Funding Novartis Pharmaceuticals.
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In hypertensive patients, diuretic treatment produces worse clinical cardiovascular outcomes in lean/normal-weight compared with obese patients at similar blood pressure reduction.
“Conversely, with diuretic administration, normalweight essential hypertension fares worse than obesityhypertension.”
From Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? (2018) · cites this paper as [108]
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- Authors
- Weber, M. A., Jamerson, K., Bakris, G. L., Weir, M. R., Zappe, D., Zhang, Y., Dahlof, B., Velazquez, E. J., & Pitt, B.
- Affiliations
- State University of New York (US)
- University of Michigan (US)
- University of Chicago (US)
- University of Maryland, Baltimore (US)
- Duke University (US)
- Corresponding author
- Weber, Michael A
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 381
- Issue
- 9866
- Pages
- 537-545
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2149410649
- Cited by
- 150
- References
- 48
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 10 · 2022: 8 · 2021: 2 · 2020: 6 · 2019: 8 · 2018: 17 · 2017: 9 · 2016: 11 · 2015: 11 · 2014: 26 · 2013: 30 · 2012: 1
- FWCI
- 14.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- body size, obesity, overweight, body mass index, antihypertensive therapy, benazepril, hydrochlorothiazide, amlodipine, combination antihypertensive therapy, cardiovascular events, cardiovascular mortality, myocardial infarction, stroke, ACCOMPLISH trial, systolic hypertension, renin-angiotensin system
- MeSH terms
- Aged, Antihypertensive Agents, Benzazepines, Body Weight, Cardiovascular Diseases, Double-Blind Method, Drug Combinations, Female, Humans, Hydrochlorothiazide, Hypertension, Male, Middle Aged, Obesity, Body Mass Index, Amlodipine, Body Size
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