Biological plausibility and implications of obesity associated valvular heart diseases

Abstract

Obesity contributes to the development and progression of cardiovascular risk factors and diseases, but so far not much attention has been given to obesity and valvular heart disease. Several observational and mendelian randomization studies have reported an association between body mass index with aortic valve stenosis, but also with secondary functional mitral regurgitation and tricuspid regurgitation in a more indirect manner. Several mechanisms can lead to the link between obesity and valvular heart diseases: left ventricular dilation, as obesity directly contributes to ischemic heart disease and ventricular remodeling, atrial myopathy as well as atrial remodeing and arrhythmias, such as atrial fibrillation, that predispose to valvular regurgitation, but also pulmonary hypertension, which could be the consequence of obesity-related inflammation, insulin resistance, and oxidative stress, valvular calcification which is often associated with adiposity and as a direct effect of increased epicardial adipose tissue and pericardial restraint. Individuals with obesity associated valvular heart disease may experience worse symptoms, quality-of-life, exercise capacity, and risk for adverse outcomes. The effect of and the mechanism for various vavular heart diseases in relation to obesity has not been investigated in depth. Recently, incretin-based drugs and sodium-glucose cotransporter-2 inhibitors have been shown to reduce adiposity, and improve HF outcomes; however, the implications of these drugs on valvular heart diseases have not been evaluated. With innovations in therapies for obesity, several questions merit discussion. Considering the prevalence of obesity and its association with valvular heart diseases, not studying these common comorbid conditions represents a significant missed opportunity.