Lung Function, Coronary Artery Disease, and Mortality in HIV

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.