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- Title
Plasma Tryptophan-Kynurenine Metabolites Are Altered in Human Immunodeficiency Virus Infection and Associated With Progression of Carotid Artery Atherosclerosis.
- Authors
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
- 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, HIVinfected 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.
- Subjects
CORONARY heart disease risk factors; TRYPTOPHAN metabolism; AMINO acids; ANTIGENS; BIOMARKERS; BLOOD pressure; C-reactive protein; CARDIOVASCULAR diseases risk factors; CAROTID artery; CONFIDENCE intervals; HIV infections; INTERLEUKINS; LIPIDS; LONGITUDINAL method; METABOLISM; TRYPTOPHAN; DISEASE progression; T-cell lymphoma
- Publication
Clinical Infectious Diseases, 2018, Vol 67, Issue 2, p235
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1093/cid/ciy053