Cardiometabolic Dysregulation and Heart Failure

Abstract

Heart failure (HF) is a complex clinical syndrome resulting from impaired myocardial function or structure, affecting approximately 56 million patients worldwide. Cardiometabolic risk factors, including hypertension, insulin resistance, obesity, and dyslipidemia play a pivotal role in both the pathogenesis and progression of HF. These risk factors frequently coexist as part of cardiometabolic syndrome and contribute to widespread organ and vascular dysfunction, leading to conditions such as coronary artery disease, chronic kidney disease, type 2 diabetes mellitus, non-alcoholic fatty liver disease, and stroke. Emerging evidence suggests that these conditions not only increase the risk of developing HF, but also negatively impact its progression and outcome. As the global burden of cardiometabolic disease continues to rise, a growing number of HF patients will exhibit multiple metabolic comorbidities. Understanding the intricate relationship between cardiometabolic risk factors and diseases and their impact on HF outcomes is therefore crucial for identifying novel therapeutic avenues. A more integrated approach to HF prevention and management-one that considers these interconnected cardiometabolic factors-offers significant potential for improving patient outcomes.

Keywords: cardiometabolic disease; cardiovascular disease; heart failure; metabolic syndrome.

Fig. 1.

Cardiometabolic risk factors, including obesity, hypertension, dyslipidemia, and insulin resistance, can contribute to the development of heart failure either directly or through the progression of specific cardiometabolic conditions, such as diabetes mellitus, coronary artery disease, non-alcoholic fatty liver disease, chronic kidney disease, and stroke. Fig. 1 was created using the image library from https://smart.servier.com/ and https://biorender.com/.

Fig. 2.

Mechanisms through which cardiometabolic diseases contribute to the development of heart failure, with particular emphasis on the bi-directional interaction between the heart and kidneys. NAFLD, non-alcoholic fatty liver disease; LV, left ventricle; LVH, left ventricular hypertrophy; RAAS, renin-angiotensin-aldosterone system; ROS, reactive oxygen species. Thick black dashed arrows represent direct mechanistic influences, while thin purple dashed arrows indicate the development of heart failure through the progression of other cardiometabolic diseases. Fig. 2 was created using the image library from https://smart.servier.com/ and https://biorender.com/.