Endothelial dysfunction in chronic obstructive pulmonary disease: a systematic review and meta-analysis of studies using different functional assessment methods

Background Cardiovascular disease is a major cause of morbidity and mortality in chronic obstructive pulmonary disease (COPD). Endothelial dysfunction is suggested to be one of the pathogenetic mechanisms involved. This is a systematic review and meta-analysis of studies using any available functional method to examine differences in endothelial function between patients with COPD and individuals without COPD (controls). Methods Literature search involved PubMed and Scopus databases. Eligible studies included adult patients and evaluated endothelial damage via functional methods. Newcastle-Ottawa Scale was applied to evaluate the quality of retrieved studies. Subgroup analyses were performed to explore heterogeneity across the studies. Funnel-plots were constructed to evaluate publication bias. Results Of the 21 initially identified reports, 19 studies with a total of 968 participants were included in the final meta-analysis. A significantly impaired response in endothelium-dependent (weighted mean between-group difference, WMD: −2.59%, 95%CI [−3.75, −1.42]) and –independent vasodilation (WMD: −3.13, 95%CI [−5.18, −1.09]) was observed in patients with COPD compared to controls. When pooling all studies together, regardless of the technique used for assessment of vascular reactivity, pronounced endothelial dysfunction was observed in COPD compared to controls (standardised-mean-difference, SMD: −1.19, 95%CI [−1.69, −0.68]). Subgroup analysis showed that the difference was larger when patients with COPD were compared with non-smoking controls (SMD: −1.75, 95%CI [−2.58, −0.92]. Sensitivity analyses confirmed the above results. Conclusions Patients with COPD have significantly impaired endothelial function compared to controls without COPD. Future studies should delineate the importance of endothelial dysfunction towards development of cardiovascular disease in COPD.