Plasma tryptophan-kynurenine metabolites are altered in human immunodeficiency virus infection and associated with progression of carotid artery atherosclerosis

Qibin Qi, Simin Hua, Clary B. Clish, Justin M. Scott, David B. Hanna, Tao Wang, Sabina A. Haberlen, Sanjiv J. Shah, Marshall J. Glesby, Jason M. Lazar, Robert D. Burk, Howard N. Hodis, Alan L. Landay, Wendy S. Post, Kathryn Anastos, Robert C. Kaplan

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background It is unknown whether disrupted tryptophan catabolism is associated with cardiovascular disease (CVD) in human immunodeficiency virus (HIV)-infected individuals. Methods Plasma tryptophan and kynurenic acid were measured in 737 women and men (520 HIV+, 217 HIV?) from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Repeated B-mode carotid artery ultrasound imaging was obtained from 2004 through 2013. We examined associations of baseline tryptophan, kynurenic acid, and kynurenic acid-to-tryptophan (KYNA/TRP) ratio, with risk of carotid plaque. Results After a 7-year follow-up, 112 participants developed carotid plaque. Compared to those without HIV infection, HIV-infected participants had lower tryptophan (P <.001), higher KYNA/TRP (P =.01), and similar kynurenic acid levels (P =.51). Tryptophan, kynurenic acid, and KYNA/TRP were correlated with T-cell activation (CD38+HLA-DR+) and immune activation markers (serum sCD14, galectin-3) but had few correlations with interleukin-6, C-reactive protein, or CVD risk factors (blood pressure, lipids). Adjusted for demographic and behavioral factors, each standard deviation (SD) increment in tryptophan was associated with a 29% (95% confidence interval [CI], 17%-38%) decreased risk of carotid plaque (P <.001), while each SD increment in kynurenic acid (P =.02) and KYNA/TRP (P <.001) was associated with a 34% (6%-69%) and a 47% (26%-73%) increased risk of carotid plaque, respectively. After further adjustment for CVD risk factors and immune activation markers, these associations were attenuated but remained significant. Conclusions Plasma tryptophan-kynurenine metabolites are altered in HIV infection and associated with progression of carotid artery atherosclerosis.

Original languageEnglish (US)
Pages (from-to)235-242
Number of pages8
JournalClinical Infectious Diseases
Volume67
Issue number2
DOIs
StatePublished - Jul 2 2018

Fingerprint

Kynurenine
Carotid Artery Diseases
Kynurenic Acid
Virus Diseases
Carotid Arteries
Tryptophan
HIV
Cardiovascular Diseases
Biomarkers
Galectin 3
HLA-DR Antigens
C-Reactive Protein
Multicenter Studies
Interleukin-6
Ultrasonography
Acquired Immunodeficiency Syndrome
Cohort Studies
Odds Ratio

Keywords

  • association study
  • atherosclerosis
  • HIV infection
  • metabolite

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Plasma tryptophan-kynurenine metabolites are altered in human immunodeficiency virus infection and associated with progression of carotid artery atherosclerosis. / Qi, Qibin; Hua, Simin; Clish, Clary B.; Scott, Justin M.; Hanna, David B.; Wang, Tao; Haberlen, Sabina A.; Shah, Sanjiv J.; Glesby, Marshall J.; Lazar, Jason M.; Burk, Robert D.; Hodis, Howard N.; Landay, Alan L.; Post, Wendy S.; Anastos, Kathryn; Kaplan, Robert C.

In: Clinical Infectious Diseases, Vol. 67, No. 2, 02.07.2018, p. 235-242.

Research output: Contribution to journalArticle

Qi, Qibin ; Hua, Simin ; Clish, Clary B. ; Scott, Justin M. ; Hanna, David B. ; Wang, Tao ; Haberlen, Sabina A. ; Shah, Sanjiv J. ; Glesby, Marshall J. ; Lazar, Jason M. ; Burk, Robert D. ; Hodis, Howard N. ; Landay, Alan L. ; Post, Wendy S. ; Anastos, Kathryn ; Kaplan, Robert C. / Plasma tryptophan-kynurenine metabolites are altered in human immunodeficiency virus infection and associated with progression of carotid artery atherosclerosis. In: Clinical Infectious Diseases. 2018 ; Vol. 67, No. 2. pp. 235-242.
@article{c4292de373d74f7c91eed9648420f4ea,
title = "Plasma tryptophan-kynurenine metabolites are altered in human immunodeficiency virus infection and associated with progression of carotid artery atherosclerosis",
abstract = "Background It is unknown whether disrupted tryptophan catabolism is associated with cardiovascular disease (CVD) in human immunodeficiency virus (HIV)-infected individuals. Methods Plasma tryptophan and kynurenic acid were measured in 737 women and men (520 HIV+, 217 HIV?) from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Repeated B-mode carotid artery ultrasound imaging was obtained from 2004 through 2013. We examined associations of baseline tryptophan, kynurenic acid, and kynurenic acid-to-tryptophan (KYNA/TRP) ratio, with risk of carotid plaque. Results After a 7-year follow-up, 112 participants developed carotid plaque. Compared to those without HIV infection, HIV-infected participants had lower tryptophan (P <.001), higher KYNA/TRP (P =.01), and similar kynurenic acid levels (P =.51). Tryptophan, kynurenic acid, and KYNA/TRP were correlated with T-cell activation (CD38+HLA-DR+) and immune activation markers (serum sCD14, galectin-3) but had few correlations with interleukin-6, C-reactive protein, or CVD risk factors (blood pressure, lipids). Adjusted for demographic and behavioral factors, each standard deviation (SD) increment in tryptophan was associated with a 29{\%} (95{\%} confidence interval [CI], 17{\%}-38{\%}) decreased risk of carotid plaque (P <.001), while each SD increment in kynurenic acid (P =.02) and KYNA/TRP (P <.001) was associated with a 34{\%} (6{\%}-69{\%}) and a 47{\%} (26{\%}-73{\%}) increased risk of carotid plaque, respectively. After further adjustment for CVD risk factors and immune activation markers, these associations were attenuated but remained significant. Conclusions Plasma tryptophan-kynurenine metabolites are altered in HIV infection and associated with progression of carotid artery atherosclerosis.",
keywords = "association study, atherosclerosis, HIV infection, metabolite",
author = "Qibin Qi and Simin Hua and Clish, {Clary B.} and Scott, {Justin M.} and Hanna, {David B.} and Tao Wang and Haberlen, {Sabina A.} and Shah, {Sanjiv J.} and Glesby, {Marshall J.} and Lazar, {Jason M.} and Burk, {Robert D.} and Hodis, {Howard N.} and Landay, {Alan L.} and Post, {Wendy S.} and Kathryn Anastos and Kaplan, {Robert C.}",
year = "2018",
month = "7",
day = "2",
doi = "10.1093/cid/ciy053",
language = "English (US)",
volume = "67",
pages = "235--242",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Plasma tryptophan-kynurenine metabolites are altered in human immunodeficiency virus infection and associated with progression of carotid artery atherosclerosis

AU - Qi, Qibin

AU - Hua, Simin

AU - Clish, Clary B.

AU - Scott, Justin M.

AU - Hanna, David B.

AU - Wang, Tao

AU - Haberlen, Sabina A.

AU - Shah, Sanjiv J.

AU - Glesby, Marshall J.

AU - Lazar, Jason M.

AU - Burk, Robert D.

AU - Hodis, Howard N.

AU - Landay, Alan L.

AU - Post, Wendy S.

AU - Anastos, Kathryn

AU - Kaplan, Robert C.

PY - 2018/7/2

Y1 - 2018/7/2

N2 - Background It is unknown whether disrupted tryptophan catabolism is associated with cardiovascular disease (CVD) in human immunodeficiency virus (HIV)-infected individuals. Methods Plasma tryptophan and kynurenic acid were measured in 737 women and men (520 HIV+, 217 HIV?) from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Repeated B-mode carotid artery ultrasound imaging was obtained from 2004 through 2013. We examined associations of baseline tryptophan, kynurenic acid, and kynurenic acid-to-tryptophan (KYNA/TRP) ratio, with risk of carotid plaque. Results After a 7-year follow-up, 112 participants developed carotid plaque. Compared to those without HIV infection, HIV-infected participants had lower tryptophan (P <.001), higher KYNA/TRP (P =.01), and similar kynurenic acid levels (P =.51). Tryptophan, kynurenic acid, and KYNA/TRP were correlated with T-cell activation (CD38+HLA-DR+) and immune activation markers (serum sCD14, galectin-3) but had few correlations with interleukin-6, C-reactive protein, or CVD risk factors (blood pressure, lipids). Adjusted for demographic and behavioral factors, each standard deviation (SD) increment in tryptophan was associated with a 29% (95% confidence interval [CI], 17%-38%) decreased risk of carotid plaque (P <.001), while each SD increment in kynurenic acid (P =.02) and KYNA/TRP (P <.001) was associated with a 34% (6%-69%) and a 47% (26%-73%) increased risk of carotid plaque, respectively. After further adjustment for CVD risk factors and immune activation markers, these associations were attenuated but remained significant. Conclusions Plasma tryptophan-kynurenine metabolites are altered in HIV infection and associated with progression of carotid artery atherosclerosis.

AB - Background It is unknown whether disrupted tryptophan catabolism is associated with cardiovascular disease (CVD) in human immunodeficiency virus (HIV)-infected individuals. Methods Plasma tryptophan and kynurenic acid were measured in 737 women and men (520 HIV+, 217 HIV?) from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Repeated B-mode carotid artery ultrasound imaging was obtained from 2004 through 2013. We examined associations of baseline tryptophan, kynurenic acid, and kynurenic acid-to-tryptophan (KYNA/TRP) ratio, with risk of carotid plaque. Results After a 7-year follow-up, 112 participants developed carotid plaque. Compared to those without HIV infection, HIV-infected participants had lower tryptophan (P <.001), higher KYNA/TRP (P =.01), and similar kynurenic acid levels (P =.51). Tryptophan, kynurenic acid, and KYNA/TRP were correlated with T-cell activation (CD38+HLA-DR+) and immune activation markers (serum sCD14, galectin-3) but had few correlations with interleukin-6, C-reactive protein, or CVD risk factors (blood pressure, lipids). Adjusted for demographic and behavioral factors, each standard deviation (SD) increment in tryptophan was associated with a 29% (95% confidence interval [CI], 17%-38%) decreased risk of carotid plaque (P <.001), while each SD increment in kynurenic acid (P =.02) and KYNA/TRP (P <.001) was associated with a 34% (6%-69%) and a 47% (26%-73%) increased risk of carotid plaque, respectively. After further adjustment for CVD risk factors and immune activation markers, these associations were attenuated but remained significant. Conclusions Plasma tryptophan-kynurenine metabolites are altered in HIV infection and associated with progression of carotid artery atherosclerosis.

KW - association study

KW - atherosclerosis

KW - HIV infection

KW - metabolite

UR - http://www.scopus.com/inward/record.url?scp=85046347771&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046347771&partnerID=8YFLogxK

U2 - 10.1093/cid/ciy053

DO - 10.1093/cid/ciy053

M3 - Article

VL - 67

SP - 235

EP - 242

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 2

ER -