Plasma Tryptophan-Kynurenine Metabolites Are Altered in Human Immunodeficiency Virus Infection and Associated With Progression of Carotid Artery Atherosclerosis. (3rd February 2018)

• Record Type: Journal Article
• 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; Burk, Robert D; Hodis, Howard N; Landay, Alan L; Post, Wendy S; Anastos, Kathryn; Kaplan, Robert C
• Is Part Of: Clinical infectious diseases. Volume 67:Number 2(2018)
• Page Start: 235
• Page End: 242
• Publication Date: 2018-02-03
• Subjects: association study -- atherosclerosis -- HIV infection -- metabolite; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciy053
• Languages: English
• ISSNs: 1058-4838

Abstract

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. Abstract : In 2 human immunodeficiency virus (HIV) cohorts we report tryptophan catabolism and related metabolites in plasma were altered in HIV-infected individuals (decreased tryptophan and increased kynurenic acid-to-tryptophan ratio) and this disruption was associated with greater progression of carotid artery atherosclerosis.