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Review
. 2020 Sep;22(9):1540-1550.
doi: 10.1002/ejhf.1956. Epub 2020 Aug 5.

Regional adiposity and heart failure with preserved ejection fraction

Vishal N Rao  1 , Marat Fudim  1 , Robert J Mentz  1 , Erin D Michos  2 , G Michael Felker  1
Affiliations
Review

Regional adiposity and heart failure with preserved ejection fraction

Vishal N Rao et al. Eur J Heart Fail. 2020 Sep.

Abstract

The role of obesity in the pathogenesis of heart failure (HF), and in particular HF with preserved ejection fraction (HFpEF), has drawn significant attention in recent years. The prevalence of both obesity and HFpEF has increased worldwide over the past decades and when present concomitantly suggests an obese-HFpEF phenotype. Anthropometrics, including body mass index, waist circumference, and waist-to-hip ratio, are associated with incident HFpEF. However, the cardiovascular effects of obesity may actually be driven by the distribution of fat, which can accumulate in the epicardial, visceral, and subcutaneous compartments. Regional fat can be quantified using non-invasive imaging techniques, including computed tomography, magnetic resonance imaging, and dual-energy X-ray absorptiometry. Regional variations in fat accumulation are associated with different HFpEF risk profiles, whereby higher epicardial and visceral fat have a much stronger association with HFpEF risk compared with elevated subcutaneous fat. Thus, regional adiposity may serve a pivotal role in the pathophysiology of HFpEF contributing to decreased cardiopulmonary fitness, impaired left ventricular compliance, upregulation of local and systemic inflammation, promotion of neurohormonal dysregulation, and increased intra-abdominal pressure and vascular congestion. Strategies to reduce total and regional adiposity have shown promise, including intensive exercise, dieting, and bariatric surgery programmes, but few studies have focused on HFpEF-related outcomes among obese. Further understanding the role these variable fat depots play in the progression of HFpEF and HFpEF-related hospitalizations may provide therapeutic targets in treating the obese-HFpEF phenotype.

Keywords: Heart failure; Heart failure with preserved ejection fraction; Obesity; Regional adiposity.

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Conflict of interest statement

Conflict of interest: M.F. receives research support by an American Heart Association Grant (17MCPRP33460225) and National Institute of Health T32 (5T32HL007101). He consults for Galvani and Axon Therapies. R.J.M. receives research support from the National Institutes of Health (U01HL125511–01A1, U10HL110312 and R01AG045551–01A1), Akros, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Gilead, InnoLife, Luitpold/American Regent, Medtronic, Merck, Novartis, Otsuka, and ResMed; honoraria from Abbott, Amgen, AstraZeneca, Bayer, Janssen, Luitpold Pharmaceuticals, Medtronic, Merck, Novartis, and ResMed; and has served on an advisory board for Amgen, AstraZeneca, Luitpold, Merck, Novartis and Boehringer Ingelheim. G.M.F. is supported by research grants from NHLBI, American Heart Association, Amgen, Merck, Cytokinetics, and Roche Diagnostics; he has acted as a consultant to Novartis, Amgen, BMS, Medtronic, Cardionomic, Relypsa, V-Wave, Myokardia, Innolife, EBR Systems, Arena, Abbott, Sphingotec, Roche Diagnostics, Alnylam, LivaNova, and SC Pharma. All other authors have nothing to disclose.

Figures

Figure 1
Figure 1
Baseline body mass index across heart failure with preserved ejection fraction (HFpEF) cohorts over the past two decades. These examples of HFpEF trials over the past two decades demonstrate an increase in average body mass index (BMI) across HFpEF cohorts.– The lower mean BMI in PARAGON-HF was likely due to exclusion of morbid obesity (i.e. BMI >40 kg/m2) and those with low plasma brain natriuretic peptide at the time of enrolment.
Figure 2
Figure 2
Proposed model by which regional adiposity affects heart failure with preserved ejection fraction physiology.
Figure 3
Figure 3
Thoracic and abdominal computed tomography slices and regional distribution of adiposity. Thoracic and abdominal computed tomography slice at level of T5 thoracic spine (A) and L2–L3 lumbar spine (B) demonstrating distribution of epicardial, visceral, and subcutaneous abdominal fat.
See this image and copyright information in PMC

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