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

doi:10.1161/JAHA.117.007792

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 journal › Article › peer-review

60 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 language	English
Article number	e007792
Journal	Journal of the American Heart Association
Volume	7
Issue number	10
DOIs	https://doi.org/10.1161/JAHA.117.007792
State	Published - May 15 2018

Bibliographical note

Publisher Copyright:
© 2018 The Authors.

Funding

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. 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).

Funders	Funder number
VA Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment
National Institutes of Health (NIH)	HL063043, HL138579, RO1 HL074045, R21 AG051913, RO1 HL132213
National Institute of Mental Health	P30-MH062294
National Institute on Drug Abuse	R01DA035616
National Institute on Alcohol Abuse and Alcoholism	U24-AA020794, U24 AA022007, U01-AA020790, U01-AA020799, U01-AA020795, U10 AA013566-completed, U24-AA022001
National Heart, Lung, and Blood Institute (NHLBI)	K01HL134147, R01-HL090342, R01-HL095136
National Childhood Cancer Registry – National Cancer Institute	R01 CA173754
National Institute of Allergy and Infectious F32-AI286447 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI168214 Jason W. Rosch Diseases National Institute of Allergy and Infectious P30 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R00-AI166116 Christopher D. Radka Diseases National Institute of Allergy and Infectious T32-AI106700 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI192221 Jason W. Rosch Diseases National Inst...	U01-A1069918, P30AI050409
Fogarty International Center	R25TW009337
Agency for Healthcare Research and Quality	R01-HS018372
American the American Heart Association	SDG 17SDG33410716
Biomedical Laboratory Research and Development, VA Office of Research and Development	VA REA 08-266
Center for AIDS Research, Emory University	5R01HL125032

Keywords

Bilirubin
Cardiovascular disease
HIV
Heart failure
Myocardial infarction
Stroke

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1161/JAHA.117.007792

Cite this

Marconi, V. C., Duncan, M. S., So-Armah, K., Lo Re, V., Lim, J. K., Butt, A. A., Goetz, M. B., Rodriguez-Barradas, M. C., Alcorn, C. W., Lennox, J., Beckman, J. A., Justice, A., & Freiberg, M. (2018). Bilirubin is inversely associated with cardiovascular disease among HIV-positive and HIV-negative individuals in VACS (Veterans Aging Cohort Study). Journal of the American Heart Association, 7(10), Article e007792. https://doi.org/10.1161/JAHA.117.007792

@article{a6016d2aee5e47d2b3dc7be3fa6946c6,

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

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.",

keywords = "Bilirubin, Cardiovascular disease, HIV, Heart failure, Myocardial infarction, Stroke",

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

note = "Publisher Copyright: {\textcopyright} 2018 The Authors.",

year = "2018",

month = may,

day = "15",

doi = "10.1161/JAHA.117.007792",

language = "English",

volume = "7",

number = "10",

}

Marconi, VC, Duncan, MS, So-Armah, K, Lo Re, V, Lim, JK, Butt, AA, Goetz, MB, Rodriguez-Barradas, MC, Alcorn, CW, Lennox, J, Beckman, JA, Justice, A & Freiberg, M 2018, 'Bilirubin is inversely associated with cardiovascular disease among HIV-positive and HIV-negative individuals in VACS (Veterans Aging Cohort Study)', Journal of the American Heart Association, vol. 7, no. 10, e007792. https://doi.org/10.1161/JAHA.117.007792

TY - JOUR

T1 - Bilirubin is inversely associated with cardiovascular disease among HIV-positive and HIV-negative individuals in VACS (Veterans Aging Cohort Study)

AU - Marconi, Vincent C.

AU - Duncan, Meredith S.

AU - So-Armah, Kaku

AU - Lo Re, Vincent

AU - Lim, Joseph K.

AU - Butt, Adeel A.

AU - Goetz, Matthew Bidwell

AU - Rodriguez-Barradas, Maria C.

AU - Alcorn, Charles W.

AU - Lennox, Jeffrey

AU - Beckman, Joshua A.

AU - Justice, Amy

AU - Freiberg, Matthew

PY - 2018/5/15

Y1 - 2018/5/15

N2 - 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.

AB - 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.

KW - Bilirubin

KW - Cardiovascular disease

KW - HIV

KW - Heart failure

KW - Myocardial infarction

KW - Stroke

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U2 - 10.1161/JAHA.117.007792

DO - 10.1161/JAHA.117.007792

M3 - Article

C2 - 29720501

AN - SCOPUS:85046946009

SN - 2047-9980

VL - 7

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 10

M1 - e007792

ER -

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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