Clinical assessment of endothelial function in patients with chronic obstructive pulmonary disease: a systematic review with meta-analysis

Patients with chronic obstructive pulmonary disease (COPD) have an increased cardiovascular morbidity and mortality. Flow-mediated (FMD) and nitrate-mediated dilatation (NMD) are considered non-invasive methods to assess endothelial function and surrogate markers of subclinical atherosclerosis. We performed a systematic review with meta-analysis and meta-regression to evaluate the impact of COPD on FMD and NMD. Studies were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. The random-effect method was used to take into account the variability among included studies. A total of eight studies were included in the final analysis, eight with data on FMD (334 COPD patients) and two on NMD (104 COPD patients). Compared to controls, COPD patients show a significantly lower FMD (MD -3.15%; 95% CI -4.89, -1.40; P < 0.001) and NMD (MD -3.53%; 95% CI -7.04, -0.02; P = 0.049). Sensitivity analyses substantially confirms the results. Meta-regression models show that a more severe degree of airway obstruction is associated with a more severe FMD impairment in COPD patients than in controls. Regression analyses confirm that the association between COPD and endothelial dysfunction is independent of baseline smoking status and most traditional cardiovascular risk factors. In conclusion, COPD is significantly and independently associated with endothelial dysfunction. These findings may be useful to plan adequate cardiovascular prevention strategies in this clinical setting, with particular regard to patients with a more severe disease.