Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge.
Clin Infect Dis. 2018 Jul 2;67(2):235-242. doi: 10.1093/cid/ciy053.
It is unknown whether disrupted tryptophan catabolism is associated with cardiovascular disease (CVD) in human immunodeficiency virus (HIV)-infected individuals.
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.
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.
Plasma tryptophan-kynurenine metabolites are altered in HIV infection and associated with progression of carotid artery atherosclerosis.
目前尚不清楚色氨酸分解代谢紊乱是否与人类免疫缺陷病毒（HIV）感染者的心血管疾病（CVD）有关。
从妇女艾滋病病毒研究机构（Women's Interagency HIV Study）和多中心艾滋病队列研究（Multicenter AIDS Cohort Study）中招募了 737 名女性和男性（520 名 HIV+，217 名 HIV-），测量其血浆色氨酸和犬尿氨酸酸水平。2004 年至 2013 年期间，通过重复 B 型颈动脉超声成像对其进行了检查。我们研究了基线色氨酸、犬尿氨酸酸、犬尿氨酸酸与色氨酸的比值（KYNA/TRP）与颈动脉斑块风险之间的关系。
经过 7 年的随访，112 名参与者发生了颈动脉斑块。与未感染 HIV 的参与者相比，感染 HIV 的参与者色氨酸水平较低（P <.001），KYNA/TRP 比值较高（P =.01），犬尿氨酸酸水平相似（P =.51）。色氨酸、犬尿氨酸酸和 KYNA/TRP 与 T 细胞活化（CD38+HLA-DR+）和免疫激活标志物（血清 sCD14、半乳糖凝集素-3）相关，但与白细胞介素-6、C 反应蛋白或 CVD 危险因素（血压、血脂）相关性较低。调整人口统计学和行为因素后，色氨酸每增加一个标准差（SD），颈动脉斑块的风险降低 29%（95%置信区间 [CI]，17%-38%）（P <.001），而犬尿氨酸酸（P =.02）和 KYNA/TRP 每增加一个 SD，颈动脉斑块的风险分别增加 34%（6%-69%）和 47%（26%-73%）（P <.001）。进一步调整 CVD 危险因素和免疫激活标志物后，这些关联虽然减弱，但仍具有统计学意义。
HIV 感染患者的血浆色氨酸-犬尿氨酸代谢物发生改变，与颈动脉粥样硬化的进展有关。
