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The Association Between Lung Hyperinflation and Coronary Artery Disease in Smokers

      Background

      Smokers manifest varied phenotypes of pulmonary impairment.

      Research Question

      Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers?

      Study Design and Methods

      We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas 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 to FVC ratio, < 0.70).

      Results

      Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate 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 and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV1 and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts.

      Interpretation

      Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV1 and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

      Key Words

      Abbreviations:

      CAD (coronary artery disease), COPDGene (Genetic Epidemiology of COPD), FRV (functional residual volume), IPA (index of prediction accuracy), LAA%–950 (low attenuation area with a –950-Hounsfield unit cutoff), MI (myocardial infarction), RV (residual volume), SCCOR (University of Pittsburgh COPD Specialized Center for Clinically Oriented Research), TLC (total lung capacity), TLV (total lung volume)
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