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

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.