Obesity/cardiometabolic phenotype of heart failure with preserved ejection fraction: mechanisms to recent trials
Abstract
PURPOSE OF REVIEW: Heart failure with preserved ejection fraction (HFpEF) is a leading and growing cause of morbidity and mortality globally. Of the various phenotypes identified, the obesity (or cardiometabolic) phenotype appears to be most common. The purpose of this review is to provide the clinician with an abridged understanding of recent developments that have elucidated obesity/visceral adiposity as a central mechanism linking inflammation/immune dysregulation to the development of the HFpEF syndrome. Recent clinical trials examining the efficacy of pharmacological treatments that target obesity in HFpEF will also be discussed. RECENT FINDINGS: Recent data indicate that visceral adiposity and insulin resistance in HFpEF serve as key mechanisms driving inflammation and immune dysregulation, which play a critical role in the development of cardiac stiffness, diastolic dysfunction and fibrosis in HFpEF. In obesity, alterations in macrophage polarization, changes in innate and adaptive immune systems and altered myocardial energetics promote metabolic inflammation in HFpEF. Finally, emerging data suggest that inflammatory biomarkers, specifically, IL-6, may provide useful information about HFpEF severity and symptom burden in obesity. SUMMARY: The obesity phenotype of HFpEF is seen in upward of 80% with HFpEF. Obesity is not just a bystander, but plays an essential role in the pathobiology and clinical course of HFpEF. Targeting overweight/obesity in HFpEF with GLP-1 receptor agonists holds promise in these patients.
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GLP-1 receptor agonists improve microvascular function, myocardial structure, insulin sensitivity, and vascular protection; and reduce inflammation, oxidative stress, and neurohormonal activation.
“GLP-1 receptor agonists improve microvascular function, 37 myocardial structure, 38 insulin sensitivity, 39 and vascular protection; 40,41 and reduce inflammation, 39,42 oxidative stress, 43 and neurohormonal activation 44”
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Butler, J., Shah, S. J., Petrie, M. C., Borlaug, B. A., Abildstrøm, S. Z., Davies, M. J., Hovingh, G. K., Kitzman, D. W., Møller, D. V., Verma, S., et al. (2024) · The Lancet · doi:10.1016/s0140-6736(24)00469-0 · Cited by 386 · see citing works
- Authors
- Verma, R., Dhingra, N. K., & Connelly, K. A.
- Affiliations
- Royal College of Surgeons in Ireland (IE)
- Division of Cardiac Surgery
- St. Michael's Hospital (CA)
- Corresponding author
- Connelly, Kim A.
- Venue
- Current Opinion in Cardiology
- Published
- 2024-01-25
- Volume
- 39
- Issue
- 2
- Pages
- 92-97
- ISSN
- 0268-4705 (ISSN-L)
- 1531-7080
- OpenAlex
- W4391386641
- Cited by
- 24
- References
- 43
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 2
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- heart failure with preserved ejection fraction, obesity phenotypes, cardiometabolic phenotypes, visceral fat, insulin resistance, metabolic inflammation, immune dysregulation, macrophage polarization, cardiac stiffness, diastolic dysfunction, myocardial fibrosis, interleukin-6, inflammatory markers, GLP-1 receptor agonists
- MeSH terms
- Heart Failure, Humans, Inflammation, Obesity, Phenotype, Stroke Volume
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