Coronary Endothelial Dysfunction, Obesity and Metabolic Syndrome

Objective To define the impact of metabolic syndrome (MetS) and obesity on coronary vascular function, with the hypothesis that subjects with MetS will have endothelial dysfunction. Background: Obesity or the metabolic syndrome (MetS) is associated with a higher risk of diabetes and coronary artery disease (CAD). Endothelial dysfunction is a common causal pathway in the initiation and progression of CAD. Methods: A total of 418 patients (165 obese, 239 MetS) with and without angiographic evidence of CAD underwent coronary vascular function testing by measuring coronary blood flow (CBF) velocity in response to intracoronary infusion of acetylcholine (ACH) and sodium nitroprusside (SNP) and coronary flow reserve with adenosine. Results: Endothelium-dependent microvascular vasodilation correlated with BMI (r=-0.12, p=0.02), with ACH responses significantly lower in overweight, obese and MetS subjects (p=0.003). The number of MetS components correlated with the response to ACH in both the coronary microcirculation and the epicardial coronary arteries, and with impaired coronary microcirculatory responses to adenosine. No significant correlation was observed with SNP. In multivariable analysis, beyond age, only the total number of MetS components, and not BMI, emerged as an independent predictor of impaired microvascular response to ACH (CBF: β=−0.18, P<0.001). Low-grade inflammation (C-reactive protein) was higher in patients with MetS, but was not associated with coronary vascular function. Conclusions: We demonstrate that the clustering of MetS components is an important and independent determinant of coronary endothelial dysfunction in subjects with and without CAD.