Plasminogen activator inhibitor 1 (PAI-1) level and lung function over 30 years: the CARDIA study
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Michael G. Sherenian, MD, Michael J Cuttica, MD, Sadiya S Khan, MD, Laura A Colangelo, MS, Joan Cook-Mills, PhD, Seong Ho Cho, MD FAAAAI, Myriam Fornage, PhD, Myron Gross, PhD, David Jacobs, PhD, Pamela Schreiner, PhD, Douglas Vaughn, MD, Donald Lloyd-Jones, MD ScM, Ravi Kalhan, MD, Rajesh Kumar, MD FAAAAI
RATIONALE: Elevated PAI-1 levels are associated with worse outcomes in COPD. It is unknown whether elevated PAI-1 affects lung function, or risk of COPD / emphysema in healthy adults.

METHODS: We included 996 randomly sampled participants and an additional 197 subjects with obesity from the Coronary Artery Risk Development in Young Adults cohort, recruited at a mean age of 25 years and followed for 30 years. We used ANCOVA to determine the adjusted association of serum PAI-1 level, measured at years 7 and 20 (n=1180), with FEV1 %-predicted at year 30 and FEV1 decline from peak. Secondary outcomes included odds of COPD (post-bronchodilator FEV1:FVC <0.70 at year 30) and emphysema (CT scan measures).

RESULTS: Compared to the first tertile of PAI-1 levels, those within the highest tertile of PAI-1 level at either year 7 (-36 mL/yr vs -33 mL/yr, p=0.03) or year 20 (-36 mL/yr vs -33 mL/yr, p=0.01) had the greatest FEV1 decline. Individuals within the highest tertile of PAI-1 at both year 7 and 20 had the lowest post bronchodilator FEV1 %-predicted at year 30 (90.4% vs. 98.1%, p<0.0001), but no association with incident COPD. Higher log PAI-1 levels at years 7 (OR:0.73, CI: 0.55,0.97) and 20 (OR:0.67, CI:0.51,0.88) showed lower odds of emphysema, but lost significance with inclusion of BMI. Sensitivity analyses limited to the random sample showed minimal change in direction or significance.

CONCLUSIONS: Generally healthy subjects with higher PAI-1 were more likely to have greater lung function decline over 30 years, but did not have higher odds of COPD.