Bilirubin is inversely associated with cardiovascular disease among HIV-positive and HIV-negative individuals in VACS (Veterans Aging Cohort Study)

Vincent C. Marconi, Meredith S. Duncan, Kaku So-Armah, Vincent Lo Re, Joseph K. Lim, Adeel A. Butt, Matthew Bidwell Goetz, Maria C. Rodriguez-Barradas, Charles W. Alcorn, Jeffrey Lennox, Joshua A. Beckman, Amy Justice, Matthew Freiberg

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Background--Bilirubin may protect against cardiovascular disease (CVD) by reducing oxidative stress. Whether elevated bilirubin reduces the risk of CVD events among HIV + individuals and if this differs from uninfected individuals remain unclear. We assessed whether bilirubin independently predicted the risk of CVD events among HIV + and uninfected participants in VACS (Veterans Aging Cohort Study). Methods and Results--We conducted a prospective cohort study using VACS participants free of baseline CVD. Total bilirubin was categorized by quartiles. CVD as well as acute myocardial infarction, heart failure, and ischemic stroke events were assessed. Cox regression was used to evaluate hazard ratios of outcomes associated with quartiles of total bilirubin in HIV + and uninfected people after adjusting for multiple risk factors. There were 96 381 participants (30 427 HIV + ); mean age was 48 years, 48% were black, and 97% were men. There were 6603 total incident CVD events over a mean of 5.7 years. In adjusted models, increasing quartiles of baseline total bilirubin were associated with decreased hazards of all outcomes (hazard ratio, 0.86; 95% confidence interval, 0.80-0.91). Among HIV + participants, results persisted for heart failure, ischemic stroke, and total CVD, but nonsignificant associations were observed for acute myocardial infarction. Conclusions--VACS participants (regardless of HIV status) with elevated bilirubin levels had a lower risk of incident total CVD, acute myocardial infarction, heart failure, and ischemic stroke events after adjusting for known risk factors. Future studies should investigate how this apparently protective effect of elevated bilirubin could be harnessed to reduce CVD risk or improve risk estimation among HIV + individuals.

Original languageEnglish
Article numbere007792
JournalJournal of the American Heart Association
Volume7
Issue number10
DOIs
StatePublished - May 15 2018

Bibliographical note

Funding Information:
Thisworkwas supported by: Agency for Healthcare Research and Quality (R01-HS018372); National Institute on Alcohol Abuseand Alcoholism (U24-AA020794, U01-AA020790, U01-AA020795, U01-AA020799, U24-AA022001, U24 AA022007, U10 AA013566-completed); National Heart, Lung, and Blood Institute (R01-HL095136, R01-HL090342); National Institute of Allergy and Infectious Diseases (U01-A1069918); Fogarty International Center (R25TW009337); National Institute of Mental Health (P30-MH062294); National Institute on Drug Abuse (R01DA035616); National Cancer Institute (R01 CA173754); the Veterans Health Administration Office of Research and Development (VA REA 08-266, VA IRR Merit Award); and Office of Academic Affiliations (Medical Informatics Fellowship), Emory Center for AIDS Research (P30AI050409) for Marconi, National Heart, Lung, and Blood Institute (K01HL134147) for So-Armah and (5R01HL125032) for Freiberg.

Funding Information:
This work was supported by the National Institutes of Health (RO1 HL132213, HL138579, and R21 AG051913 to Davis and RO1 HL074045, HL063043, and HL138579 to Gyorke,); and American Heart Association (SDG 17SDG33410716 to Liu).

Publisher Copyright:
© 2018 The Authors.

Keywords

  • Bilirubin
  • Cardiovascular disease
  • HIV
  • Heart failure
  • Myocardial infarction
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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