Oxygen dependence of endothelium-dependent vasodilation: importance in chronic obstructive pulmonary disease

Introduction: Epidemiological studies have shown increased morbidity and mortality in patients with coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD). We aimed to characterize the oxygen dependence of endothelial function in patients with CAD and coexisting COPD. Material and methods: In CAD patients with and without COPD (n = 33), we non-invasively measured flow-mediated dilation (FMD) and intima-media thickness (IMT) of the brachial artery (BA), forearm blood flow (FBF), and perfusion of the cutaneous microcirculation with laser Doppler perfusion imaging (LDPI). In an experimental setup, vascular function was assessed in healthy volunteers (n = 5) breathing 12% oxygen or 100% oxygen in comparison to room air. Results: COPD was associated with impaired FMD (3.4 +/- 0.5 vs. 4.2 +/- 0.6%; p < 0.001) and increased IMT (0.49 +/- 0.04 vs. 0.44 +/- 0.04 mm; p < 0.01), indicating functional and structural alterations of the BA in COPD. Forearm blood flow and LDPI were comparable between the groups. Flow-mediated dilation correlated with capillary oxygen pressure (pO(2), r = 0.608). Subgroup analysis in COPD patients with pO(2) > 65 mm Hg and pO(2) = 65 mm Hg revealed even lower FMD in patients with lower pO(2) (3.0 +/- 0.5 vs. 3.7 +/- 0.4%; p < 0.01). Multivariate analysis showed that pO(2) was a predictor of FMD independent of the forced expiratory volume and pack years. Exposure to hypoxic air led to an acute decrease in FMD, whereby exposure to 100% oxygen did not change vascular function. Conclusions: Our data suggest that in CAD patients with COPD, decreased systemic oxygen levels lead to endothelial dysfunction, underlining the relevance of cardiopulmonary interaction and the potential importance of pulmonary treatment in secondary prevention of vascular disease.