Insulin resistance, endothelial function, angiogenic factors and clinical outcome in non-diabetic patients with chest pain without myocardial perfusion defects

Study investigating possible links between insulin resistance (IR) and increased CVD risk in non-diabetic patients with suspected myocardial ischemia (presenting at the clinic with angina-like chest pains). Looked at 365 patients and followed up for >5 years. 238/365 patients were found NOT to exhibit myocardial ischemia (no myocardial perfusion defects detected) and were the focus of the study. For these patients, IR was found to have a strong association with endothelial dysfunction (abnormal vasodilation/constriction) and to be an independent prognostic indicator for reduced CVD-related clinical outcome (i.e. reduced event-free survival time). They then carried out protein biomarker analysis using CVD I, with the specific intention of gaining better pathophysiological insights into these processes. Increased IR correlated with reduced expression of stem cell factor (SCF), VEGF-D, and the VEGF-induced angiogenic protein endocan. SCF is known to be involved in recruitement and stimulation of vascular endothelial progenitor cells, and in combination with the VEGF data suggest a mechanism for the endothelial dysfunction observed. Also saw that IL-6 increased in patients with high IR (confirming results from a separate study/cohort) – interesting because IL-6 over-expression is linked to impaired vasodilation. The authors conclude that these combined observations may provide a mechanistic link between increased IR and microvascular dysfunction in these patients, and hence their increased risk of cardiovascular events.