Obesity and heart failure with preserved ejection fraction: focus on new drugs and future direction in medical treatment

Abstract

Obesity is a major risk factor for heart failure with preserved ejection fraction (HFpEF) and contributes through multiple pathophysiological pathways, including systemic inflammation, neurohormonal activation, and mechanical inhibition. The treatment of obesity has shown significant potential for improving HFpEF outcomes. Sodium-glucose cotransporter 2 inhibitors have emerged as effective treatments for improving symptoms and quality of life in patients with HFpEF while aiding in weight control. Furthermore, a recent demonstration of the clinical benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in HFpEF showed promising results in reducing weight loss, and improving symptoms and clinical outcomes. In this review article, we discuss the association between HFpEF and obesity, the emerging role of GLP-1 RAs, and future directions for medical therapies targeting obesity-associated HFpEF.

Keywords: Glucagon-like peptide-1 receptor agonists; Heart failure; Obesity.

Figure 1

Pathophysiology of obesity and HFpEF. Obesity contributes to HFpEF via several mechanisms. HFpEF, heart failure with preserved ejection fraction; CRP, C-reactive protein; TGF, transforming growth factor; IL, interleukin; SNS, sympathetic nervous system; RAAS, renin-angiotensin-aldosterone system; HTN, hypertension; DM, diabetes mellitus; CAD, coronary artery disease; SVR, systemic vascular resistance; SV, stroke volume; NP, neprilysin; LV, left ventricle.

Figure 2

Mechanisms of GLP-1 and GIP. GLP-1 and GIP are secreted by the intestine following food intake. In the brain, it promotes satiety and loss of appetite; in the pancreas, GLP-1 increases insulin levels and decreases glucagon levels, whereas GIP increases both insulin and glucagon levels. Unlike GLP-1, GIP acts on subcutaneous white adipose tissue. GLP-1 and GIP are responsible for blood sugar control, weight loss, and anti-inflammatory, anti-atherosclerotic, and endothelial functions. Ultimately, these actions play a positive role in HFpEF. GLP-1, glucagon-like peptide-1; GIP, glucose-dependent insulin-tropic polypeptide; HFpEF, heart failure with preserved ejection fraction.