Association Between Bilirubin, Atazanavir, and Cardiovascular Disease Events Among People Living With HIV Across the United States
Year: 2019
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: Bilirubin is an antioxidant that may suppress lipid oxidation. Elevated bilirubin is associated with decreased cardiovascular events in HIV-uninfected populations. We examined these associations in people living with HIV (PLWH). METHODS: Potential myocardial infarctions (MIs) and strokes were centrally adjudicated. We examined MI types: type 1 MI (T1MI) from atherosclerotic plaque instability and type 2 MI (T2MI) in the setting of oxygen demand/supply mismatch such as sepsis. We used multivariable Cox regression analyses to determine associations between total bilirubin levels and outcomes adjusting for traditional and HIV-specific risk factors. To minimize confounding by hepatobiliary disease, we conducted analyses limited to bilirubin values <2.1 mg/dL; among those with fibrosis-4 values <3.25; and among everyone. We repeated analyses stratified by hepatitis C status and time-updated atazanavir use. RESULTS: Among 25,816 PLWH, there were 392 T1MI and 356 T2MI during follow-up. Adjusted hazard ratios for the association of higher bilirubin levels with T1MI were not significant. Higher bilirubin levels were associated with T2MI. By contrast, among PLWH on atazanavir, higher bilirubin levels were associated with fewer T2MI (hazard ratio 0.56:0.33-1.00). Higher bilirubin levels among those on atazanavir were associated with fewer T1MI combined with ischemic stroke. LIMITATIONS: Analyses were conducted with total rather than unconjugated bilirubin. CONCLUSIONS: Among PLWH, higher bilirubin levels were associated with T2MI among some subgroups. However, among those on atazanavir, there was a protective association between bilirubin and T2MI. These findings demonstrate different associations between outcomes and elevated bilirubin due to diverse causes and the importance of distinguishing MI types.
Authors: Heidi M. Crane, Robin M. Nance, Susan R. Heckbert, Corey Ritchings, Lisa Rosenblatt, Matthew Budoff, Brian R. Wood, David L. Tirschwell, H. Nina Kim, William C. Mathews, Elvin Geng, Richard D. Moore, Peter W. Hunt, Joseph J. Eron, Greer A. Burkholder, Daniel R. Drozd, Felicia C. Chow, Kyra J. Becker, Joseph R. Zunt, Emily L. Ho, Rizwan Kalani, Andrew Huffer, Bridget M. Whitney, Michael S. Saag, Mari M. Kitahata, Joseph A. C. Delaney
Institutions: University of Washington, Bristol-Myers Squibb (United States), University of California, Los Angeles, University of California San Diego, University of California, San Francisco, Johns Hopkins University, University of North Carolina at Chapel Hill, University of Alabama at Birmingham
Language: English
Subfield: Emergency Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: American Heart Association, National Institutes of Health, Center for AIDS Research, Johns Hopkins University, Center for AIDS Research, University of Alabama at Birmingham, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, Center for AIDS Research, University of North Carolina at Chapel Hill
Awards: G1531094742, G1752886923, Johns Hopkins HIV Clinical Cohort, G2127051194, G2516619799, G378552126, The Johns Hopkins Center for AIDS Research (JHU CFAR), CFAR Network of Integrated Clinical Systems (CNICS), The University of North Carolina Center for AIDS Research, UAB Center for AIDS Research (CFAR), G97119092
OpenAlex ID: W2945110072