The Concept of CMR

Endothelial dysfunction

Endothelial dysfunction is a disturbance in the normal balance between vasoconstrictors and vasodilators, growth promoters and inhibitors, pro- and anti-atherogenic processes, and pro- and anti-coagulant factors (33). Endothelial dysfunction is central to the development and progression of atherosclerosis and enhances the risk of future cardiovascular events (33). Endothelial dysfunction is present in overweight patients, especially those with intra-abdominal obesity and insulin resistance, and weight loss can improve endothelial function (27). As described above, low levels of adipocyte-derived circulating adiponectin may cause endothelial damage, possibly by lowering nitric oxide (NO) production while increasing ROS (31). Not only does NO reduce inflammation, platelet aggregation, vascular smooth muscle cell migration and growth, and monocyte and macrophage adhesion, it also encourages vasodilatation (33). Low NO production may therefore help increase platelet activation, arterial thrombosis (Figure), and atherogenesis.

Several new features have been added to the metabolic syndrome because they frequently accompany the syndrome’s traditional features. A pro-thrombotic state has been found in obese, insulin-resistant subjects likely to have abdominal obesity. Moreover, increased PAI-1 levels, the main hemostatic disorder linked to insulin resistance, is now considered part of the cluster of abnormalities of the metabolic syndrome. In addition, intervention studies have shown that weight loss through a hypocaloric diet and exercise or treatment with insulin-sensitizing agents are effective in reducing this procoagulant state. This evidence lends weight to the notion that obesity is a modifiable risk factor for thrombosis.