LAUSR

BACKGROUND Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN & Methods: We analyzed data from the Pittsburgh SCCOR cohort (n=481), and the COPDGene cohort (n=2580). Participants were current and former smokers with >10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately due to methodological differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory/expiratory CT lung volumes in COPDGene. Sub-clinical CAD was assessed as the coronary artery calcium score, while clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV1/FVC<0.70). RESULTS Pulmonary phenotypes including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling had weak to moderate correlations (r<0.7) with each other. In multivariable models adjusted for pulmonary phenotypes and CAD risk-factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory/inspiratory CT lung-volume: OR=1.2, 95% CI 1.1-1.5, p=0.02 for coronary calcium, OR=1.6, 95% CI 1.1-2.3, p=0.01 for clinical CAD, and OR=1.7, 95% CI 1.0-2.8, p=0.05 for MI in COPDGene). FEV1 and emphysema were associated with increased CAD (p<0.05) in models adjusted for CAD risk-factors, however, these associations were attenuated upon adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION Lung hyperinflation is strongly associated with clinical and sub-clinical CAD in smokers including those with airflow obstruction. Once lung hyperinflation was accounted for, FEV1 and emphysema were no longer associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and ex-smokers.