Context: Endothelial function is abnormal in chronic obstructive pulmonary disease (COPD); whether endothelial dysfunction causes COPD is unknown. Objective: Test associations of endothelial biomarkers with FEV1 using instrumental variables. Methods: Among 26907 participants with spirometry, ICAM-1, P-selectin, E-selectin and endothelin-1 were measured in subsets. Results: ICAM-1 and P-selectin were inversely associated with FEV1 among European-Americans (-29mL and-34mL per standard deviation of log-transformed biomarker, p<0.001), as was endothelin-1 among African-Americans (-22mL, p=0.008). Genetically-estimated ICAM-1 and P-selectin were not significantly associated with FEV1. The instrumental variable for endothelin-1 was non-informative. Conclusion: Although ICAM-1, P-selectin and endothelin-1 were inversely associated with FEV1, associations for ICAM-1 and P-selectin do not appear causal.
- Genetic polymorphisms
- Growth factors/cytokines/inflammatory mediators
- Respiratory disease