Role of endothelial dysfunction and insulin resistance in angina pectoris and normal coronary angiogram

Angina pectoris and a normal coronary angiogram or cardiac syndrome X is a heterogeneous syndrome that probably encompasses different pathophysiological entities. Patients affected by cardiac syndrome X are often women presenting with severe, invalidating chest pain. However, there is a significant discrepancy among the severity of symptoms, the lack of hemodynamic evidence of myocardial ischemia and the relatively benign long-term prognosis. The vascular endothelium has numerous important functions, including the regulation of vascular tone, blood flow and permeability, secreting both vasorelaxing and vasoconstricting factors. It has been found that both endothelium and non-endothelium-mediated coronary blood flow are impaired in patients with cardiac syndrome X. Interestingly, it has been shown that impaired nitric oxide-dependent vasodilation could increase coronary microvessel tone and produce spasm. It has also been reported that circulating endothelin-1 levels are elevated with a direct relationship between endothelin-1 levels and impaired coronary flow reserve in these patients. In addition, patients with high endothelin-1 levels showed a time onset of chest pain during exercise significantly lower compared to patients with low endothelin-1 concentrations. Moreover, the nitric oxide/endothelin-1 ratio was found decreased in patients with cardiac syndrome X and endothelin-1 levels were also positively correlated with fasting asymmetric dimethylarginine levels. All in all, these data suggest a role of endothelial dysfunction as a cause of regional myocardial and peripheral blood flow abnormalities. Further studies are necessary to characterize the prevailing mechanisms determining alterations in nitric oxide/endothelin-1 pathway in these patients, in order to find new therapies able to improve both quality of life and prognosis.