Association Between Bilirubin, Atazanavir, and Cardiovascular Disease Events Among People Living With HIV Across the United States

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. HoRizwan Kalani, Andrew Huffer, Bridget M. Whitney, Michael S. Saag, Mari M. Kitahata, Joseph A.C. Delaney

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)E141-E147
JournalJournal of acquired immune deficiency syndromes
Volume81
Issue number5
DOIs
StatePublished - Aug 15 2019

Keywords

  • HIV
  • atazanavir
  • bilirubin
  • cardiovascular disease
  • myocardial infarction
  • stroke

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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