Abstract
Rationale: Impaired lung function is a potent independent predictor of coronary artery disease (CAD) in individuals without human immunodeficiency virus (HIV) infection; however, the relationship between lung function and CAD in HIV remains undefined. Objectives: To examine the relationship between lung function, CAD, mortality, and circulating biomarkers in HIV. Methods: Spirometry, diffusing capacity of the lung for carbon monoxide (Dl(CO)), emphysema, coronary artery calcium, mortality, cause of death, and biomarkers were examined in HIV-infected and uninfected individuals enrolled in a cohort study at the University of Pittsburgh. Results were then validated in the Multicenter AIDS Cohort Study (MACS) cohort. Results: We examined data on 234 participants in the Pittsburgh cohort. The mean ± standard deviation age was 49.5 ± 10.2 years old, 82.1% were male, and 67.5% were ever smokers. Among the 177 of 234 individuals with HIV infection, lower Dl(CO) (not forced expiratory volume in 1 second or emphysema) was independently associated with greater coronary artery calcium (odds ratio, 1.43 per 10% lower Dl(CO); 95% confidence interval, 1.14-1.81). HIV-infected individuals with both reduced Dl(CO) and coronary artery calcium had a much higher mortality than those with either low Dl(CO) or coronary calcium alone or with neither condition. Endothelin-1, a circulating biomarker of endothelial dysfunction, was associated with both lower Dl(CO) and greater coronary artery calcium in those with HIV infection. Results were reproducible in 144 individuals enrolled in the MACS cohort; intercellular adhesion molecule 1 was the biomarker of endothelial dysfunction assessed in the MACS cohort. Conclusions: Impaired Dl(CO) and CAD were associated with each other and with higher mortality in individuals with HIV infection.