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.
Bibliographical noteFunding Information:
The authors report no declarations of interest with the following exception: Dr. Barr was reimbursed for conference travel by Boehringer Ingelheim, and Cenetra Health provided in-kind donation for an NIH-sponsored clinical trial. Dr. London is supported by the Division of Intramural Research, NIEHS, NIH, DHHS. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The NHLBI cohorts were funded by contracts from NIH/NHLBI: ARIC: HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN 268201100008C, HHSN268201100009C, HHSN26820 1100010C, HHSN268201100011C, and HHSN268201 100012C, R01-HL-087641, R01-HL-059367 and R01-HL-086694; NIH/NHGRI contract U01-HG-004402 and National Institutes of Health contract HHSN 268200625226C; carotid MRI data was funded by U01-HL-075572-01; neurocognitive data is collected by U01-HL-096812, HL-096814, HL-096899, HL-096902 and HL-096917, with previous brain MRI examinations funded by R01-HL-70825; CARDIA: HHS-N2-68201200036-C, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095, N01-HC-45204, N01-HC-45205, N01-HC-05187, N01-HC-45134, N01-HC-95100; the Young Adult Longitudinal Trends in Antioxidants (YALTA) ancillary study was funded by R01-HL-53560; CFS: R01-HL-46380-01-16; CHS: N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-75150, N01-HC-45133, N01-HC-55222, U01-HL-080295; AG-023629, AG-15928, AG-20098 and AG-027058; FHS: N01-HC-25195; JHS: N01-HC-95170, N01-HC-95171, N01-HC-95172; MESA: N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, N01-HC-65226, RC1-HL-100543, R01-HL-077612, N01-HC-95159-HC-95169 and RR-024156. R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258, R01-HL-071259, EPA grant RD-831697.
- Genetic polymorphisms
- Growth factors/cytokines/inflammatory mediators
- Respiratory disease