Body Mass Index and Adverse Cardiovascular Outcomes in Heart Failure Patients With Preserved Ejection Fraction: Results From the Irbesartan in Heart Failure With Preserved Ejection Fraction (I-PRESERVE) Trial
Open accessAbstract
Background—: Obesity is a major risk factor for incident heart failure (HF). Paradoxically, in HF with reduced left ventricular ejection fraction (HFREF), a high body mass index (BMI) appears to be beneficial. Approximately 50% of HF patients have a preserved left ventricular ejection fraction (HFPEF). However, there are few data regarding the relationship between BMI and outcomes in HFPEF. Methods and Results—: Baseline characteristics and cardiovascular outcomes were assessed in the 4109 patients (mean age, 72 years; mean follow-up, 49.5 months) in the Irbesartan in HF with Preserved Ejection Fraction (I-PRESERVE) trial. Based on the BMI distribution, 5 BMI categories were defined: <23.5, 23.5 to 26.4, 26.5 to 30.9, 31 to 34.9, and ≥35 kg/m 2 . Most patients (71%) had a BMI ≥26.5, 21% had a BMI between 23.5 and 26.4, and 8% had a BMI <23.5 kg/m 2 . Patients with higher BMI were younger, more often women, and more likely to have hypertension and diabetes and higher left ventricular ejection fraction. Patients with BMI of 26.5 to 30.9 kg/m 2 had the lowest rate for the primary composite outcome (death or cardiovascular hospitalization) and were used as reference group. After adjustment for 21 risk variables including age, sex, and N-terminal pro-brain natriuretic peptide, the hazard ratio for the primary outcome was increased in patients with BMI <23.5 (hazard ratio, 1.27; 95% confidence interval, 1.04 to 1.56; P =0.019) and in those with BMI ≥35 kg/m 2 (hazard ratio, 1.27; 95% confidence interval, 1.06 to 1.52; P =0.011) compared with the referent group. A similar relationship was found for all-cause mortality and for HF hospitalization. Conclusions—: Obesity is common in HFPEF patients and is accompanied by multiple differences in clinical characteristics. Independent of other key prognostic variables, there was a U-shaped relationship, with the greatest rate of adverse outcomes in the lowest and highest BMI categories. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT000095238.
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Epidemiologic data indicate that the majority of patients with heart failure with preserved ejection fraction have obesity.
“epidemiologic data indicate that the majority of patients with heart failure with preserved ejection fraction have obesity”
From Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (2023) · cites this paper as [4]
The Results > Baseline Characteristics section (page not specified) reports that 41.3% of the HFPEF patients had obesity (BMI >30 kg/m²), not a majority. The Discussion > Clinical and Demographic Characteristics section says more than 83% were overweight or obese combined; that figure cannot establish that a majority had obesity. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredMost people with HFpEF have obesity.
“Approximately 45% of people admitted for HFpEF have diabetes, and most people with HFpEF have obesity (320,321).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [321]
The Results > Baseline Characteristics section reports that 41.3% of the I-PRESERVE HFpEF cohort had obesity (BMI >30 kg/m²), not most patients. The Discussion > Clinical and Demographic Characteristics section says more than 83% were overweight or obese combined; that does not establish that most had obesity. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredMost people with HFpEF have obesity.
“Increasing evidence has demonstrated the benefits of GLP-1 RA or dual GIP/GLP-1 RA on symptoms and outcomes for people with HFpEF and obesity, and while most people with HFpEF have obesity, approximately 45% have diabetes (304,305).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [305]
The Results, Baseline Characteristics section (page unavailable) reports that 41.3% of the HFpEF patients in the I-PRESERVE cohort had a BMI greater than 30 kg/m²—not most. The paper’s figure of more than 83% combines overweight and obese patients, so it does not support the claim that most had obesity. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredObesity and excess adiposity may play a role in the development and progression of heart failure with preserved ejection fraction.
“growing evidence suggests that obesity and excess adiposity are not simply coexisting conditions but may play a role in the development and progression of heart failure with preserved ejection fraction. 4-8”
From Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (2023) · cites this paper as [4]
The Background calls obesity a risk factor for incident heart failure, and the Discussion links severe obesity to more adverse outcomes and hospitalizations among patients who already have HFPEF. These findings support the hedged suggestion that obesity may matter beyond coexistence, but the paper does not establish a role for excess adiposity specifically in the development or progression of HFPEF; its HFPEF analysis concerns BMI and outcomes. (LLM, conf=0.87)
Experimental — accuracy not yet measuredGrowing evidence suggests that adipose tissue may play a pivotal role in the development, progression, and adverse outcomes of heart failure with preserved ejection fraction.
“growing evidence suggests that adipose tissue may play a pivotal role in the development, progression, and adverse outcomes of heart failure with preserved ejection fraction. 4-8”
From Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (2023) · cites this paper as [4]
The Discussion (page unavailable) reports a U-shaped association between BMI and adverse outcomes in patients with HFpEF, and the paper describes obesity as a risk factor for developing heart failure generally. It does not establish a role for adipose tissue in HFpEF progression or specifically in its development; BMI is not a direct measure of adipose-tissue activity. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Approximately 45% of people admitted for HFpEF have diabetes.
“Approximately 45% of people admitted for HFpEF have diabetes, and most people with HFpEF have obesity (320,321).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [321]
The Discussion (Clinical and Demographic Characteristics; page unavailable) mentions diabetes in the HFpEF cohort but gives no 45% figure for people admitted with HFpEF. The Results (Baseline Characteristics; page unavailable) report that 41.3% of the cohort had obesity, while more than 83% had either overweight or obesity; thus the paper does not establish that most had obesity. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIncreasing evidence has demonstrated benefits of GLP-1 RA or dual GIP/GLP-1 RA on symptoms and outcomes for people with HFpEF and obesity.
“Increasing evidence has demonstrated the benefits of GLP-1 RA or dual GIP/GLP-1 RA on symptoms and outcomes for people with HFpEF and obesity, and while most people with HFpEF have obesity, approximately 45% have diabetes (304,305).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [305]
The Methods describe a BMI analysis of patients in the I-PRESERVE irbesartan trial, and the Discussion reports associations between BMI and cardiovascular outcomes. Searches for GLP-1, GIP/GLP-1, semaglutide, and tirzepatide found no passage addressing whether those treatments benefit symptoms or outcomes in people with HFpEF and obesity. Page numbers are not available in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredApproximately 45% of people with HFpEF have diabetes.
“Increasing evidence has demonstrated the benefits of GLP-1 RA or dual GIP/GLP-1 RA on symptoms and outcomes for people with HFpEF and obesity, and while most people with HFpEF have obesity, approximately 45% have diabetes (304,305).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [305]
The Discussion’s Clinical and Demographic Characteristics section says diabetes was less common in the lowest-BMI group, but gives no overall diabetes prevalence. I searched for 45%, diabetes prevalence, and the baseline characteristics in Table 1; the passages retrieved from our copy do not establish the claimed figure. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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- Authors
- Haass, M., Kitzman, D. W., Anand, I. S., Miller, A., Zile, M. R., Massie, B. M., & Carson, P. E.
- Affiliations
- San Francisco VA Medical Center (US)
- Venue
- Circulation: Heart Failure
- Published
- 2011-05
- Volume
- 4
- Issue
- 3
- Pages
- 324-331
- ISSN
- 1941-3289 (ISSN-L)
- 1941-3297
- PMC
- PMC3100162
- OpenAlex
- W2546836686
- Cited by
- 366
- References
- 28
- Citations by year
- 2026: 19 · 2025: 39 · 2024: 63 · 2023: 23 · 2022: 36 · 2021: 34 · 2020: 25 · 2019: 20 · 2018: 22 · 2017: 17 · 2016: 18 · 2015: 14 · 2014: 11 · 2013: 10 · 2012: 12
- FWCI
- 7.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Heart Failure (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Bristol-Myers Squibb
- Sanofi
- National Institutes of Health
- National Institute on Aging (P30AG21222, 37AG18915, R01AG018915, R37AG018915, P30AG021332)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- heart failure with preserved ejection fraction, body mass index, obesity, cardiovascular outcomes, all-cause mortality, heart failure hospitalization, U-shaped relationship, irbesartan, N-terminal pro-brain natriuretic peptide, left ventricular ejection fraction, hypertension, diabetes mellitus, prognostic factors, obesity paradox, cardiovascular risk factors
- MeSH terms
- Irbesartan, Aged, Biphenyl Compounds, Cardiovascular Diseases, Female, Heart Failure, Humans, Male, Middle Aged, Obesity, Prognosis, Stroke Volume, Tetrazoles, Body Mass Index, Angiotensin II Type 1 Receptor Blockers
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