Relationship between total bilirubin and endothelial function, inflammation and oxidative stress in HIV‐infected adults on stable antiretroviral therapy

• Published in: HIV medicine Vol. 13; no. 10; pp. 609 - 616
• Main Authors: Hileman, CO, Longenecker, CT, Carman, TL, Milne, GL, Labbato, DE, Storer, NJ, White, CA, McComsey, GA
• Format: Journal Article
• Language: English
• Published: England 01-11-2012
• Subjects: Adult; Antioxidants; antiretroviral therapy; Arteries; Atazanavir Sulfate; Bilirubin; Bilirubin - blood; biomarkers; Blood Flow Velocity; Brachial Artery - physiopathology; C-reactive protein; C-Reactive Protein - metabolism; Cell Adhesion Molecules - blood; Coagulation; Coronary heart disease; Cross-Sectional Studies; endothelial function; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; F2-Isoprostanes - blood; Female; Fibrin Fibrinogen Degradation Products - metabolism; Fibrinogen; Fibrinogen - metabolism; HIV infection; HIV Protease Inhibitors - pharmacology; HIV Seropositivity - blood; HIV Seropositivity - drug therapy; HIV Seropositivity - physiopathology; Homeostasis; Human immunodeficiency virus; Humans; Infection; Inflammation; Inflammation - blood; Insulin; Interleukin 6; Interleukin-6 - blood; Male; Middle Aged; Oligopeptides - pharmacology; Oxidative stress; Oxidative Stress - drug effects; Pyridines - pharmacology; Regression analysis; Retrospective Studies; total bilirubin; Tumor necrosis factor receptors; Tumor Necrosis Factor-alpha - blood; Vasodilation
• ISSN: 1464-2662; 1468-1293
• DOI: 10.1111/j.1468-1293.2012.01026.x

Objectives
Enhanced inflammation is evident in HIV infection, even with virological suppression. Outside HIV infection, studies show an independent association between higher total bilirubin and better endothelial function as well as a lower prevalence of coronary heart disease, possibly as a consequence of the anti‐inflammatory and antioxidant effect of bilirubin. The aim of this study was to determine whether such an association exists in HIV‐infected individuals.
Methods
A cross‐sectional study was performed in HIV‐1‐infected adults on stable antiretroviral therapy (ART) to determine if a relationship exists between total bilirubin and endothelial function [flow‐mediated dilation (FMD) of the brachial artery], inflammation [interleukin‐6 (IL‐6), soluble tumour necrosis factor receptors, C‐reactive protein, and adhesion molecules], coagulation markers (fibrinogen and D‐dimer) and oxidative stress (F
2‐isoprostanes). Endpoints were compared based on total bilirubin levels and atazanavir status using distributionally appropriate, two‐sample tests. Correlation coefficients were determined between total bilirubin and endpoints. Linear regression was used to model the relationship between total bilirubin (and atazanavir status) and FMD.
Results
A total of 98 adults were included in the study. Total bilirubin was higher in the atazanavir group when compared to the non‐atazanavir group [median (interquartile range) 1.8 (1.1–2.6) vs. 0.6 (0.4–1.4) mg/dL; P < 0.01] as were insulin, the homeostasis model assessment of insulin resistance (HOMA‐IR) and fibrinogen. Total bilirubin was positively correlated with fibrinogen and was not correlated with other outcomes. After adjustment, neither total bilirubin nor atazanavir status was associated with FMD.
Conclusions
In virologically suppressed, HIV‐infected adults on stable ART, neither total bilirubin nor atazanavir use was associated with improved endothelial function as measured using FMD, inflammation or oxidative stress as measured using biomarkers.