背景:大脑中必需氨基酸色氨酸的相对可用性,如色氨酸指数所示,这是循环中色氨酸与其竞争性氨基酸(CAA)的比例,与严重抑郁症有关。然而,目前尚不清楚色氨酸的使用是否与缺血性卒中的发病机制有关.
目的:我们旨在研究色氨酸指数与缺血性卒中风险之间的关系。
方法:我们在2013年至2018年期间在中国东部的社区队列中进行了嵌套病例对照研究。分析包括321例缺血性中风患者和321例对照患者,这些患者的性别和出生日期相匹配。血浆色氨酸和CAAs水平,包括酪氨酸,缬氨酸,苯丙氨酸,亮氨酸,和异亮氨酸,用超高效液相色谱-串联质谱法测定。使用条件逻辑回归分析来确定发病率比率(IRRs)及其95%置信区间(CIs)。
结果:调整体重指数后,目前的吸烟状况,教育程度,身体活动,中风家族史,高血压,糖尿病,高脂血症,和估计的肾小球滤过率,色氨酸指数升高以剂量-反应方式与缺血性卒中风险降低显著相关(IRR,0.76;95%CI,0.63-0.93,每标准差增量)。血浆色氨酸或CAAs与缺血性卒中的风险无关。
结论:色氨酸指数与缺血性卒中的风险呈负相关。我们的新观察表明,大脑中必需氨基酸色氨酸的可用性与缺血性中风的发病机理有关。
BACKGROUND: The relative availability of the essential amino acid tryptophan in the brain, as indicated by the tryptophan index, which is the ratio of tryptophan to its competing amino acids (CAAs) in circulation, has been related to major depression. However, it remains unknown whether tryptophan availability is involved in the pathogenesis of ischemic stroke.
OBJECTIVE: We aimed to investigate the relationship between the tryptophan index and the risk of ischemic stroke.
METHODS: We performed a nested
case-control study within a community-based cohort in eastern China over the period 2013 to 2018. The analysis included 321 cases of ischemic stroke and 321 controls matched by sex and date of birth. The plasma levels of tryptophan and CAAs, including tyrosine, valine, phenylalanine, leucine, and isoleucine, were measured by ultra-high-performance liquid chromatography-tandem mass spectrometry. Conditional logistic regression analyses were employed to determine incidence rate ratios (IRRs) and their 95% confidence intervals (CIs).
RESULTS: After adjustment for body mass index, current smoking status, educational attainment, physical activity, family history of stroke, hypertension, diabetes, hyperlipidemia, and estimated glomerular filtration rate, an elevated tryptophan index was significantly associated with a reduced risk of ischemic stroke in a dose-response manner (IRR, 0.76; 95% CI, 0.63-0.93, per standard deviation increment). The plasma tryptophan or CAAs were not separately associated with the risk of ischemic stroke.
CONCLUSIONS: The tryptophan index was inversely associated with the risk of ischemic stroke. Our novel observations suggest that the availability of the essential amino acid tryptophan in the brain is involved in the pathogenesis of ischemic stroke.