Abstract：
Carnitine biosynthesis has been related to fatty acid oxidation, a process probably exerting neuroprotective effects. However, the role of carnitine biosynthesis in the development of ischemic stroke (IS) remains unclear. We aimed to examine the associations between plasma markers of carnitine biosynthesis and the IS risk.
We performed a case-control study nested in a community-based cohort (2013-2018, n = 16457). The study included 321 incident cases of IS and 321 controls matched by age and gender. Carnitine, lysine, trimethyllysine (TML), glycine, and their ratios were measured/calculated in the baseline plasma samples using ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS). Conditional logistic regression analyses were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs).
Plasma carnitine, lysine, TML, and glycine were not significantly associated with the IS risk, although a gradually reduced risk was observed across the increasing tertiles of glycine. Notably, the ratios of glycine/carnitine, glycine/lysine, and glycine/TML were all inversely associated with the IS risk. Compared to the lowest tertiles, the corresponding odds ratios for the highest tertiles were 0.60 (95% CI: 0.40-0.91), 0.63 (95% CI: 0.42-0.94), and 0.63 (95% CI: 0.42-0.95), respectively, after adjustment for body mass index, smoking, hypertension, family history of stroke, estimated glomerular filtration rate and total cholesterol. Repeating the analyses by excluding the first two years of follow-up did not materially alter the risk associations for the ratios of glycine/lysine and glycine/carnitine.
Increased ratios of plasma glycine to carnitine, lysine, and TML were associated with a lower risk of incident IS. Our observational findings suggest that the homeostasis of circulating carnitine, lysine, TML, and glycine may involve in the pathogenesis of IS.
We performed a case-control study nested in a community-based cohort (2013-2018, n = 16457). The study included 321 incident cases of IS and 321 controls matched by age and gender. Carnitine, lysine, trimethyllysine (TML), glycine, and their ratios were measured/calculated in the baseline plasma samples using ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS). Conditional logistic regression analyses were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs).
Plasma carnitine, lysine, TML, and glycine were not significantly associated with the IS risk, although a gradually reduced risk was observed across the increasing tertiles of glycine. Notably, the ratios of glycine/carnitine, glycine/lysine, and glycine/TML were all inversely associated with the IS risk. Compared to the lowest tertiles, the corresponding odds ratios for the highest tertiles were 0.60 (95% CI: 0.40-0.91), 0.63 (95% CI: 0.42-0.94), and 0.63 (95% CI: 0.42-0.95), respectively, after adjustment for body mass index, smoking, hypertension, family history of stroke, estimated glomerular filtration rate and total cholesterol. Repeating the analyses by excluding the first two years of follow-up did not materially alter the risk associations for the ratios of glycine/lysine and glycine/carnitine.
Increased ratios of plasma glycine to carnitine, lysine, and TML were associated with a lower risk of incident IS. Our observational findings suggest that the homeostasis of circulating carnitine, lysine, TML, and glycine may involve in the pathogenesis of IS.
摘要：
肉碱的生物合成与脂肪酸氧化有关，一个可能发挥神经保护作用的过程.然而,肉碱生物合成在缺血性卒中(IS)发展中的作用尚不清楚.我们旨在研究肉碱生物合成的血浆标志物与IS风险之间的关联。
我们在社区队列中进行了一项病例对照研究（2013-2018年，n=16457）。该研究包括321例IS事件病例和321例年龄和性别相匹配的对照。肉碱,赖氨酸，三甲基赖氨酸（TML），甘氨酸,使用超高效液相色谱-串联质谱（UHPLC-MS/MS）在基线血浆样品中测量/计算它们的比率。使用条件逻辑回归分析来计算比值比（OR）及其95％置信区间（CI）。
血浆肉碱,赖氨酸，TML,和甘氨酸与IS风险没有显着相关，尽管在甘氨酸增加的三分位数中观察到风险逐渐降低。值得注意的是,甘氨酸/肉碱的比例，甘氨酸/赖氨酸，甘氨酸/TML均与IS风险呈负相关。与最低的三分位数相比，最高三分位数的相应比值比为0.60(95%CI：0.40-0.91)，0.63（95%CI：0.42-0.94），和0.63（95%CI：0.42-0.95），分别,调整体重指数后，吸烟,高血压,中风家族史,估计肾小球滤过率和总胆固醇。通过排除前两年的随访重复分析并没有实质性改变甘氨酸/赖氨酸和甘氨酸/肉碱比率的风险关联。
血浆甘氨酸与肉碱的比例增加，赖氨酸，和TML与较低的IS事件风险相关.我们的观察结果表明，循环肉碱的稳态，赖氨酸，TML,甘氨酸可能参与了IS的发病机制。
我们在社区队列中进行了一项病例对照研究（2013-2018年，n=16457）。该研究包括321例IS事件病例和321例年龄和性别相匹配的对照。肉碱,赖氨酸，三甲基赖氨酸（TML），甘氨酸,使用超高效液相色谱-串联质谱（UHPLC-MS/MS）在基线血浆样品中测量/计算它们的比率。使用条件逻辑回归分析来计算比值比（OR）及其95％置信区间（CI）。
血浆肉碱,赖氨酸，TML,和甘氨酸与IS风险没有显着相关，尽管在甘氨酸增加的三分位数中观察到风险逐渐降低。值得注意的是,甘氨酸/肉碱的比例，甘氨酸/赖氨酸，甘氨酸/TML均与IS风险呈负相关。与最低的三分位数相比，最高三分位数的相应比值比为0.60(95%CI：0.40-0.91)，0.63（95%CI：0.42-0.94），和0.63（95%CI：0.42-0.95），分别,调整体重指数后，吸烟,高血压,中风家族史,估计肾小球滤过率和总胆固醇。通过排除前两年的随访重复分析并没有实质性改变甘氨酸/赖氨酸和甘氨酸/肉碱比率的风险关联。
血浆甘氨酸与肉碱的比例增加，赖氨酸，和TML与较低的IS事件风险相关.我们的观察结果表明，循环肉碱的稳态，赖氨酸，TML,甘氨酸可能参与了IS的发病机制。
