The Association Between Lung Hyperinflation and Coronary Artery Disease in Smokers

Abstract

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.

Keywords: COPD; coronary artery disease; lung hyperinflation; smoking.

Figure 1

Scatterplot matrix depicting the correlations between various pulmonary phenotypes along with Spearman correlation coefficients in the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research cohort. The unit for each pulmonary phenotype is listed along with the name of the phenotype in the diagonal axis of the figure. For ratios, ie, FEV₁ to FVC ratio and residual volume to total lung capacity ratio, the units are 0 to 100, rather than 0 to 1. The Spearman correlation coefficient is depicted on the top of each scatterplot.

Figure 2

Forrest plots depicting the association of FEV₁ (% predicted), emphysema (visual emphysema score), and lung hyperinflation (RV to TLC ratio) with coronary artery calcium score after adjustment for CAD risk factors (top) and further adjustment for other pulmonary phenotypes listed in Tables 3 and 4 (bottom) in the SCCOR (n = 413) and COPDGene (n = 2,377) cohorts. Individuals with history of clinical CAD were excluded from these models. ORs are calculated per 20% decrease in FEV₁ % predicted, a 1-point increase in visual emphysema score (SCCOR cohort), q 1-point increase in log LAA%–950 (COPDGene cohort), and a 0.20 increase in RV to TLC ratio (SCCOR cohort) and FRV to TLC ratio (COPDGene cohort). Any association of FEV₁ % predicted (gray box) or emphysema (blue box) with calcium score was attenuated after adjustment for lung hyperinflation. In contrast, lung hyperinflation (red box) was associated with the extent of coronary artery calcium despite accounting for the FEV₁ % predicted, severity of emphysema, other pulmonary phenotypes, and CAD risk factors in both cohorts. CAD = coronary artery disease; COPDGene = Genetic Epidemiology of COPD; FRV = functional residual volume; LAA%–950 = low attenuation area with a –950-Hounsfield unit cutoff; RV = residual volume; SCCOR = University of Pittsburgh COPD Specialized Center for Clinically Oriented Research; TLC = total lung capacity.

Figure 3

Forrest plots depicting the association of FEV₁ (% predicted), emphysema (log LAA%–950), and lung hyperinflation (FRV to TLV ratio) with coronary artery calcium score after adjustment for CAD risk factors (top) and further adjustment for other pulmonary phenotypes (bottom) in participants with airflow obstruction in the COPDGene cohort (n = 1,138). Individuals with a history of clinical CAD were excluded from these models. ORs are calculated per 20% decrease in FEV₁ % predicted, a 1-point increase in log LAA%–950, and a 0.20 increase in FRV to TLV ratio. Any association of FEV₁ percent predicted (gray box) or emphysema (blue box) with calcium score was attenuated after adjustment for lung hyperinflation. In contrast, lung hyperinflation (red box) was associated with the extent of coronary artery calcium, despite accounting for the FEV₁ % predicted, severity of emphysema, other pulmonary phenotypes, and CAD risk factors. CAD = coronary artery disease; COPDGene = Genetic Epidemiology of COPD; FRV = functional residual volume; LAA%–950 = low attenuation area with a –950-Hounsfield unit cutoff; TLV = total lung volume.