Association Between Plasma Trimethyllysine and Prognosis of Patients With Ischemic Stroke.
Association Between Plasma Trimethyllysine and Prognosis of Patients With Ischemic Stroke.
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血浆三甲基赖氨酸与缺血性中风患者预后的关系
DOI：
10.1161/jaha.121.020979
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发表时间：
2021-12-07
影响因子：
5.4
通讯作者：
Wang, Yongjun
中科院分区：
文献类型：
--
作者：
Xu, Jie;Zhao, Mingming;Wang, Anxin;Xue, Jing;Cheng, Si;Cheng, Aichun;Gao, Jianing;Zhang, Qi;Zhan, Rui;Meng, Xia;Xu, Ming;Li, Hao;Zheng, Lemin;Wang, Yongjun
三甲基赖氨酸是一种三甲基胺氮氧化物前体，已被确定为急性冠状动脉综合征的独立心血管风险因素。然而，有限的数据可用于检查三甲基赖氨酸在中风人群中的作用。我们的目的是研究缺血性卒中或短暂性脑缺血发作患者血浆三甲基赖氨酸水平与卒中结局之间的关系。分析了CNSR-III（第三次中国国家卒中登记研究）中10 027例缺血性卒中/短暂性脑缺血发作患者的数据和卒中结局的1年随访数据。用质谱法测量三甲基赖氨酸的血浆水平。使用考克斯回归模型分析三甲基赖氨酸与卒中结局之间的相关性。进行中介分析，以检查风险因素对三甲基赖氨酸和卒中结局之间关系的中介作用。在多变量考克斯回归模型中，三甲基赖氨酸水平升高与心血管死亡（四分位数4与四分位数1：校正风险比[HR]，1.72; 95% CI，1.03-2.86）和全因死亡（四分位数4与四分位数1：HR，1.97; 95% CI，1.40-2.78）风险增加相关。然而，三甲基赖氨酸与非致命性卒中复发或非致命性心肌梗死之间没有相关性。三甲基赖氨酸与心血管死亡相关，与N-氧化三甲胺无关。估计的肾小球滤过率和hs-CRP（高敏C反应蛋白）对三甲基赖氨酸与心血管死亡的关联具有显著的中介作用，中介作用分别为37.8%和13.4%。三甲基赖氨酸水平升高与缺血性卒中/短暂性脑缺血发作患者的心血管死亡相关中介分析表明，三甲基赖氨酸通过炎症和肾功能导致心血管死亡，表明可能的病理机制联系。
Trimethyllysine, a trimethylamine N‐oxide precursor, has been identified as an independent cardiovascular risk factor in acute coronary syndrome. However, limited data are available to examine the role of trimethyllysine in the population with stroke. We aimed to examine the relationship between plasma trimethyllysine levels and stroke outcomes in patients presenting with ischemic stroke or transient ischemic attack. Data of 10 027 patients with ischemic stroke/transient ischemic attack from the CNSR‐III (Third China National Stroke Registry) and 1‐year follow‐up data for stroke outcomes were analyzed. Plasma levels of trimethyllysine were measured with mass spectrometry. The association between trimethyllysine and stroke outcomes was analyzed using Cox regression models. Mediation analysis was performed to examine the mediation effects of risk factors on the associations of trimethyllysine and stroke outcomes. Elevated trimethyllysine levels were associated with increased risk of cardiovascular death (quartile 4 versus quartile 1: adjusted hazard ratio [HR], 1.72; 95% CI, 1.03–2.86) and all‐cause mortality (quartile 4 versus quartile 1: HR, 1.97; 95% CI, 1.40–2.78) in multivariate Cox regression model. However, no associations were found between trimethyllysine and nonfatal stroke recurrence or nonfatal myocardial infarction. Trimethyllysine was associated with cardiovascular death independent of trimethylamine N‐oxide. Both estimated glomerular filtration rate and hs‐CRP (high‐sensitivity C‐reactive protein) had significant mediation effects on the association of trimethyllysine with cardiovascular death, with a mediation effect of 37.8% and 13.4%, respectively. Elevated trimethyllysine level is associated with cardiovascular death among patients with ischemic stroke/transient ischemic attack. Mediation analyses propose that trimethyllysine contributes to cardiovascular death through inflammation and renal function, suggesting a possible pathomechanistic link.