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Exploring the Mechanistic Link Between Obesity and Heart Failure

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Abstract

Purpose of Review

Among subtypes of cardiovascular disease, obesity has a potent and unique association with heart failure (HF) that is unexplained by traditional cardiovascular risk mediators. The concomitant rise in the prevalence of obesity and HF necessitates better understanding of their relationship to develop effective prevention and treatment strategies. The purpose of this review is to provide mechanistic insight regarding the link between obesity and HF by elucidating the direct and indirect pathways linking the two conditions.

Recent Findings

Several direct pathophysiologic mechanisms contribute to HF risk in individuals with excess weight, including hemodynamic alterations, neurohormonal activation, hormonal effects of dysfunctional adipose tissue, ectopic fat deposition with resulting lipotoxicity and microvascular dysfunction. Obesity further predisposes to HF indirectly through causal associations with hypertension, dyslipidemia, and most importantly, diabetes via insulin resistance. Low levels of physical activity and fitness further influence HF risk in the context of obesity. These various processes lead to myocardial injury and cardiac remodeling that are reflected by abnormalities in cardiac biomarkers and cardiac function on myocardial imaging.

Summary

Understanding and addressing obesity-associated HF is a pressing clinical and public health challenge which can be informed by a deeper understanding of the complex pathways linking these two conditions together.

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Abbreviations

ACC:

American College of Cardiology

ACEi:

Angiotensin converting enzyme inhibitor

AHA:

American Heart Association

ARB:

Angiotensin receptor blocker

ARIC:

The Atherosclerosis Risk in Communities (study)

ARNi:

Angiotensin receptor-neprilysin inhibitor

BMI:

Body mass index

BNP:

Brain natriuretic peptide

CHF:

Congestive heart failure

CV:

Cardiovascular

CVD:

Cardiovascular disease

EF:

Ejection fraction

GIP:

Glucose-dependent insulinotropic polypeptide

hs-cTnT:

High-sensitive cardiac troponin T

HF:

Heart failure

HFpEF:

Heart failure with preserved ejection fraction

HFrEF:

Heart failure with reduced ejection fraction

LV:

Left ventricle

LVEF:

Left ventricular ejection fraction

LVEDV:

Left ventricular end-diastolic volume

MESA:

The Multi-Ethnic Study of Atherosclerosis (study)

NT-proBNP:

N-terminal pro-brain natriuretic peptide

PA:

Physical activity

RAAS:

Renin-angiotensin-aldosterone system

RV:

Right ventricle

SAT:

Subcutaneous adipose tissue

SD:

Standard deviation

SGLT2i:

Sodium-glucose cotransporter-2 inhibitors

VAT:

Visceral adipose tissue

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Funding

BO and CEN were supported by the American Heart Association grant AHA20SFRN35120152. CEN was also supported by NIH/NHLBI grant R01HL146907.

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  1. Division of Cardiology, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, 600 N Wolfe St, Carnegie, Baltimore, MD, 568, USA

    Bige Ozkan & Chiadi E. Ndumele

  2. Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Bige Ozkan & Chiadi E. Ndumele

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Ozkan, B., Ndumele, C.E. Exploring the Mechanistic Link Between Obesity and Heart Failure. Curr Diab Rep 23, 347–360 (2023). https://doi.org/10.1007/s11892-023-01526-y

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