Cardiovascular Phenotype in HFpEF Patients With or Without Diabetes
Open accessAbstract
Background The RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) study was a multicenter, randomized trial of sildenafil versus placebo in heart failure with preserved ejection fraction (HFpEF) with rigorous entry criteria and extensive phenotypic characterization of participants.Objectives The aim of this study was to characterize clinical features, exercise capacity, and outcomes in patients with HFpEF with or without diabetes and gain insight into contributing pathophysiological mechanisms.Methods The RELAX study enrolled 216 stable outpatients with heart failure, an ejection fraction ≥ 50%, increased natriuretic peptide or intracardiac pressures, and reduced exercise capacity. Prospectively collected data included echocardiography, cardiac magnetic resonance, a comprehensive biomarker panel, exercise testing, and clinical events over 6 months.Results Compared with nondiabetic patients (n = 123), diabetic HFpEF patients (n = 93) were younger, more obese, and more often male and had a higher prevalence of hypertension, renal dysfunction, pulmonary disease, and vascular disease (p < 0.05 for all). Uric acid, C-reactive protein, galectin-3, carboxy-terminal telopeptide of collagen type I, and endothelin-1 levels were higher in diabetic patients (p < 0.05 for all). Diabetic patients had more ventricular hypertrophy, but systolic and diastolic ventricular function parameters were similar in diabetic and nondiabetic patients except for a trend toward higher filling pressures (E/e') in diabetic patients. Diabetic patients had worse maximal (peak oxygen uptake) and submaximal (6-min walk distance) exercise capacity (p < 0.01 for both). Diabetic patients were more likely to have been hospitalized for heart failure in the year before study entry (47% vs. 28%, p = 0.004) and had a higher incidence of cardiac or renal hospitalization at 6 months after enrollment (23.7% vs. 4.9%, p < 0.001).Conclusions HFpEF patients with diabetes are at increased risk of hospitalization and have reduced exercise capacity. Multimorbidity, impaired chronotropic reserve, left ventricular hypertrophy, and activation of inflammatory, pro-oxidative, vasoconstrictor, and profibrotic pathways may contribute to adverse outcomes in HFpEF patients with diabetes. (Evaluating the Effectiveness of Sildenafil at Improving Health Outcomes and Exercise Ability in People With Diastolic Heart Failure [The RELAX Study]; NCT00763867).
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Type 2 diabetes is common in patients with HFpEF.
“Type 2 diabetes is common in patients with HFpEF. 4-6”
From Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials (2024) · cites this paper as [4]
The Introduction states that 30–40% of patients with HFpEF have diabetes, and the Results report diabetes in 93 of 216 patients (43%). These passages support that diabetes is common in HFpEF, but the paper does not identify those patients’ diabetes as type 2. (LLM, conf=0.84)
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- Authors
- Lindman, B. R., Dávila-Román, V. G., Mann, D. L., McNulty, S., Semigran, M. J., Lewis, G. D., de las Fuentes, L., Joseph, S. M., Vader, J., Hernandez, A. F., & Redfield, M. M.
- Affiliations
- Washington University in St. Louis (US)
- Duke University (US)
- Harvard University (US)
- Mayo Clinic (US)
- Corresponding author
- Lindman, Brian R.
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 64
- Issue
- 6
- Pages
- 541-549
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC4133145
- OpenAlex
- W1848919668
- Cited by
- 209
- References
- 42
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 28 · 2023: 12 · 2022: 20 · 2021: 26 · 2020: 23 · 2019: 18 · 2018: 11 · 2017: 14 · 2016: 14 · 2015: 15 · 2014: 1
- FWCI
- 10.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (KL2TR000450, UL1TR000448)
- National Heart, Lung, and Blood Institute (U10HL084904, R01HL105418, U10HL110262, U01HL084907, U10HL110309, U10HL084907, U10HL110337, K23HL116660)
- National Center for Advancing Translational Sciences
- 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 › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- heart failure with preserved ejection fraction, diabetes mellitus, cardiovascular phenotype, exercise capacity, peak oxygen uptake, 6-minute walk distance, left ventricular hypertrophy, multimorbidity, inflammatory markers, endothelin-1, galectin-3, uric acid, C-reactive protein, heart failure hospitalization, sildenafil, diastolic dysfunction, myocardial fibrosis
- MeSH terms
- Sildenafil Citrate, Aged, Diabetes Mellitus, Female, Heart Failure, Humans, Male, Middle Aged, Phenotype, Piperazines, Prospective Studies, Purines, Stroke Volume, Sulfones, Cohort Studies, Phosphodiesterase 5 Inhibitors
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