Obesity and heart failure: exploring the cardiometabolic axis

Abstract

Obesity is one of the biggest risks to public health in both developed and developing countries, and yet incidence continues to skyrocket. Being the main risk factor for a large number of life-limiting conditions, obesity has the potential to cause enormous damage unless addressed urgently. Heart failure (HF) is the most common cardiovascular disease associated with obesity. The incidence of HF overall continues to rise and mortality rates remain high, despite the rapid and significant advances in pharmacotherapy that have recently transformed the landscape of HF treatment. Both obesity and heart failure are multisystem disorders that are closely interlinked. Obesity poses the body a number of challenges, ranging from haemodynamic, to neuroendocrine, to inflammatory, to intracellular physiology. This narrative review describes the pathophysiological 'vicious cycle' caused by the combination of obesity and HF. Management of obesity in established heart failure has for years been a controversial topic, and yet an increasing body of evidence suggests that there are numerous benefits to managing obesity and insulin resistance in heart failure. Here, we review the existing evidence base, as well as exciting new developments, suggesting that we may finally be on the brink of a revolution in managing obesity in heart failure.

Keywords: Heart failure; Metabolic syndrome; Obesity; Weight loss.

Figure 1

(A) Projected rates of obesity are expected to continue to rise (reproduced under CC BY-NC license from Lee, M. Research trends in obesity and obesogenic environments in Korea. Nutrition Research and Practice 2019;13(6):461–472). (B) Obesity is more strongly linked to the development of heart failure than coronary disease or stroke (reproduced under CC-BY-NC-CD from Ndumele et al. Obesity and Subtypes of Incident Cardiovascular Disease. JAHA 2016;5:e003921). (C) Obesity is associated with a greater degree of cardiac remodelling than normal weight in (A) dilated (DCM) and (B) hypertrophic cardiomyopathy (HCM) (reproduced under CC BY-NC-ND license from Rayner JJ et al. Obesity-related ventricular remodelling is exacerbated in dilated and hypertrophic cardiomyopathy. Cardiovascular Diagnosis and Therapy 2020. Vol 10, No 3.).

Figure 2

Very low calorie diets in individuals with obesity are associated with cardiac metabolic (A) and functional (B) changes at 1-week and 8-week timepoints. Reproduced with permission under CC BY 4.0 license from Rayner et al. Very low calorie diets are associated with transient ventricular impairment before reversal of diastolic dysfunction in obesity. Int J Obes 43, 2536–2544 (2019).

Figure 3

Increasing body mass index is associated with lower energetic status (PCr/ATP, A), but increased forward rate constant through creatine kinase (B) leading to overall compensatory resting ATP delivery (C). In HFrEF (lower panels), obesity (DCMob) is associated with greater resting ATP delivery (lower L panel) due to elevated creatine kinase enzyme activity (upper L panel) compared to DCM in normal weight (DCMnw). Upper panel reproduced under CC-BY license from Rayner et al. Myocardial energetics in obesity. Circulation 2020. 141:1152–1163. Lower panel reproduced under CC-BY-NC license from Rayner et al. Obesity modifies the energetic phenotype of dilated cardiomyopathy. EHJ 2022. 43(9); 868–877).

Figure 4

Cumulative incidence of cardiovascular disease in individuals with obesity treated with bariatric surgery (lower curve) or control (upper curve) (A–C), with mortality with those with a history of pre-existing heart failure (D). Reproduced under CC BY-NC-ND from Höskuldsdóttir et al. JAHA 2021; 10:e019323.

Figure 5

Use of weekly semaglutide is associated with improved quality of life scores (A) and reduced body weight (B) in individuals with obesity and heart failure with preserved ejection fraction (reproduced with permission from Kosiborod M.N. et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med 2023; 389:1069–1084).