Obesity and cardiovascular disease: revisiting an old relationship.

A wealth of clinical and epidemiological evidence has linked obesity to a broad spectrum of cardiovascular diseases (CVD) including coronary heart disease, heart failure, hypertension, stroke, atrial fibrillation and sudden cardiac death. Obesity can increase CVD morbidity and mortality directly and indirectly. Direct effects are mediated by obesity-induced structural and functional adaptations of the cardiovascular system to accommodate excess body weight, as well as by adipokine effects on inflammation and vascular homeostasis. Indirect effects are mediated by co-existing CVD risk factors such as insulin resistance, hyperglycemia, hypertension and dyslipidemia. Adipose tissue (AT) quality and functionality are more relevant aspects for cardiometabolic risk than its total amount. The consequences of maladaptive AT expansion in obesity are local and systemic: the local include inflammation, hypoxia, dysregulated adipokine secretion and impaired mitochondrial function; the systemic comprise insulin resistance, abnormal glucose/lipid metabolism, hypertension, a pro-inflammatory and pro-thrombotic state and endothelial dysfunction, all of which provide linking mechanisms for the association between obesity and CVD. The present narrative review summarizes the major pathophysiological links between obesity and CVD (traditional and novel concepts), analyses the heterogeneity of obesity-related cardiometabolic consequences, and provides an overview of the cardiovascular impact of weight loss interventions.