Microvascular angina in different clinical conditions: Diabetes and the metabolic syndrome

Metabolic syndrome results in a pro-thrombotic, pro-inflammatory condition that markedly favours the development of diabetes and cardiovascular disease. In patients with metabolic syndrome, many interrelated factors are thought to contribute to the development of vascular alterations; however, insulin resistance is regarded as the most relevant. In fact, in addition to its well-known activity on glucose metabolism, insulin exerts a wide spectrum of non-metabolic actions, including vasodilation, inhibition of platelet aggregation and thrombosis, anti-oxidant and anti-inflammatory effects, which result in anti-atherosclerotic and vascular protective effects. In this setting, clustering of multiple cardiovascular risk factors may reinforce their pro-atherogenic potential. Metabolic syndrome is also accompanied by endothelial dysfunction, and it has become appreciated that microvascular damage is a common finding in these subjects. In diabetic patients, impairment of microcirculation is recognized at the level of all circulatory districts, including coronary microvessels, and it has an important prognostic impact. Diabetes is accompanied by profound changes in energy metabolism, increased oxidative stress, derangement of adipokines synthesis, reduced mobilization and function of endothelial progenitor cells, which may lead to microvascular dysfunction. Features of the insulin resistance syndrome, including altered glucose tolerance, are more frequent in patients with microvascular angina. Taken together, these observations suggest that diabetes, along with each of the various components of the metabolic syndrome, has the capability of profoundly altering coronary microvascular reactivity, thus predisposing to myocardial ischemia even in the absence of coronary artery stenosis. When these alterations combine in the same patient to give rise to full-blown metabolic syndrome, their negative effects on myocardial perfusion are synergistically potentiated. While the pathophysiology of this condition has become to be substantially unravelled, much research is still needed to achieve a tailored therapeutic approach.