Adhesion molecules, endothelin-1 and lung function in seven population-based cohorts

Abstract

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 26 907 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 (−29 mL and −34 mL per standard deviation of log-transformed biomarker, p < 0.001), as was endothelin-1 among African-Americans (−22 mL, 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

Acknowledgements

The CARe investigators thank the National Heart, Lung, and Blood Institute and the research institutions, study investigators, and field staff for their support in creating this study. We also thank the study participants, without whom this endeavor would not have been possible. The authors thank the other investigators, staff and participants of ARIC, CARDIA, CFS, CHS, FHS, JHS, and MESA, MESA Family, MESA Air Pollution and MESA Lung studies for their valuable contributions. A full list of participating MESA Investigators and institutions can be found at http://www.mesa-nhlbi.org. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. This manuscript has been reviewed by the MESA Investigators for scientific content and consistency of data interpretation with previous MESA publications and significant comments have been incorporated prior to submission for publication.