Reduced six-minute walking distance is associated with endothelial dysfunction in COPD patients

Background: Endothelial dysfunction represents a key step in the increase in cardiovascular risk. We prospectively investigated the determinants of endothelial function in patients with chronic obstructive pulmonary disease (COPD). Methods: Digital pulse amplitude augmentation assessed by post-ischemic reactive hyperhemia (RH-PAT) was measured in 47 consecutive COPD patients (41 men, BMI: 25±5 kg/m 2 , age: 65±9 yrs, 35 patients in stable condition and 12 within exacerbation). RH-PAT was analyzed with the following clinical and biological covariates: body mass index (BMI), fat-free mass (FFM), pulmonary function tests, blood pressure, inflammatory and oxidative stress biomarkers, six-minute walking distance (6MWD) and peripheral muscle function, medications, diabetes and prevalent cardiovascular diseases. Results: After adjustment for age and sex, RH-PAT was linked to FFM, heart rate, prevalent hypertension and myocardial infarction history, diastolic blood pressure, FEV 1 , FEV 1 /FVC, PaCO 2 , IL6, and 6MWD. In multivariate analysis, walking distance, FFM and PaCO 2 were independent contributors of RH-PAT explaining 54% of the variance p < 0.0001. A higher FFM index was associated with higher grade of inflammation, increased oxidative stress and more severe endothelial dysfunction. RH-PAT was significantly lower in patients within exacerbation as compared with those in stable condition. Conclusion: Six-minute walking distance which is a widely available marker of severity and functional capacity in COPD patients is a main predictor of endothelial dysfunction. ClinicalTrials.gov Identifier: NCT00404430 .