Cardiovascular consequences of metabolic syndrome

Abstract

The metabolic syndrome (MetS) is defined as the concurrence of obesity-associated cardiovascular risk factors including abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, decreased HDL cholesterol, and/or hypertension. Earlier conceptualizations of the MetS focused on insulin resistance as a core feature, and it is clearly coincident with the above list of features. Each component of the MetS is an independent risk factor for cardiovascular disease and the combination of these risk factors elevates rates and severity of cardiovascular disease, related to a spectrum of cardiovascular conditions including microvascular dysfunction, coronary atherosclerosis and calcification, cardiac dysfunction, myocardial infarction, and heart failure. While advances in understanding the etiology and consequences of this complex disorder have been made, the underlying pathophysiological mechanisms remain incompletely understood, and it is unclear how these concurrent risk factors conspire to produce the variety of obesity-associated adverse cardiovascular diseases. In this review, we highlight current knowledge regarding the pathophysiological consequences of obesity and the MetS on cardiovascular function and disease, including considerations of potential physiological and molecular mechanisms that may contribute to these adverse outcomes.

Figure

Schematic diagram of the pathologic features, adverse molecular and systemic changes, and cardiovascular consequences of the metabolic syndrome. Clustering of causally inter-related risk factors including abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, decreased HDL cholesterol, and/or hypertension is associated activation of the sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS), and increased levels of pro-inflammatory adipokines and cytokines. These phenotypic changes subsequently contribute to increases in heart rate, circulating blood volume, cardiac output, vascular resistance, and changes in myocardial metabolism. The consequences of these changes include microvascular dysfunction, cardiac contractile dysfunction (augmented end-diastolic volume and systemic pressure development observed in left ventricular pressure-volume relationship (data from Sassoon et al.(52)), atherosclerotic disease (L = lumen; M = media; image of human coronary artery from Noblet et al.(170)), vascular calcification (arrow points to calcification; image provided by Dr. Michael Sturek with permission), concentric cardiac hypertrophy, myocardial infarction, and heart failure.