Higher serum angiopoietin 2 levels are independently associated with coronary microvascular dysfunction in patients with angina in the absence of obstructive coronary artery disease

Background: Angiopoietin-2 (Ang-2) is a type of endothelial growth factor involved in angiogenesis and vascular remodeling. Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease (CAD). This study aimed to evaluate the association between serum Ang-2 levels and coronary microvascular dysfunction in patients without obstructive CAD.Methods: A total of 125 patients with angina in the absence of obstructive CAD were included in this cross-sectional study. Coronary flow reserve (CFR) was measured in the distal left anterior descending coronary artery by trans-thoracic Doppler echocardiography. The patients were divided into the following two sub-groups according to CFR: the impaired CFR group with CFR values <2.5 and the preserved CFR group with CFR values ≥2.5. Serum Ang-2 levels were determined using enzyme-linked immunosorbent assay. Independent predictors for impaired CFR were identified by binary logistic regression analysis. The receiver-operating characteristic curve was determined to evaluate the ability of serum Ang-2 in predicting impaired CFR.Results: We found that age, percentage of female sex, N-terminal pro-B-type natriuretic peptide levels, Ang-2 levels (763.3 ± 264.9vs. 579.7 ± 169.3 pg/mL,P < 0.001), and the left atrial volume index were significantly higher in patients with impaired CFR than in patients with preserved CFR. Serum Ang-2 levels were negatively correlated with CFR (r = -0.386,P < 0.001). Binary logistic regression analysis showed that Ang-2 (odds ratio: 1.004, 95% confidence interval [CI]: 1.001-1.006,P = 0.003) and age (odds ratio: 1.088, 95% CI: 1.023-1.156,P = 0.007) were independently associated with impaired CFR. Furthermore, Ang-2 was a significant predictor of impaired CFR on the receiver-operating characteristic curve (P < 0.001). The area under the curve was 0.712 (95% CI: 0.612-0.813).Conclusions: High serum Ang-2 levels are independently associated with impaired CFR in patients with angina in the absence of obstructive CAD.