神经蝶呤和犬尿氨酸酸作为中风复发和死亡的预测因子：一项在缺血性中风后三个月测量炎症生物标志物的多中心前瞻性队列研究。

Neopterin and kynurenic acid as predictors of stroke recurrence and mortality: a multicentre prospective cohort study on biomarkers of inflammation measured three months after ischemic stroke.

机构信息

Institute of Clinical Medicine (K1), University of Bergen, Bergen, Norway.

Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.

出版信息

BMC Neurol. 2021 Dec 8;21(1):476. doi: 10.1186/s12883-021-02498-w.

DOI:10.1186/s12883-021-02498-w

PMID:34879833

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8653541/

Abstract

BACKGROUND

Chronic low-grade inflammation is associated with both ischemic stroke and sedentary behaviour. The aim of this study was to investigate the predictive abilities of biomarkers of inflammation and immune modulation associated with sedentary behaviour for ischemic stroke recurrence and mortality in a stroke population.

METHODS

Patients admitted to hospital for acute stroke were recruited to the prospective multicentre cohort study, the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study, from May 2015 until March 2017. Patients with ischemic stroke, blood samples available from the three-month follow-up, and no stroke recurrence before the three-month follow-up were included. Serum was analysed for C-reactive protein (CRP) with high-sensitive technique, and plasma for interleukin-6 (IL-6), neopterin, pyridoxic acid ratio index (PAr-index: 4-pyridoxic acid: [pyrioxal+pyridoxal-5'-phosphate]) and kynurenic acid (KA). Ischemic stroke recurrence and death were identified by the Norwegian Stroke Registry and the Cause of Death Registry until 31 December 2018.

RESULTS

The study included 354 patients, 57% male, mean age 73 (SD 11) years, mean observation time 2.5 (SD 0.6) years, and median National Institute of Health Stroke Scale of 0 (IQR 1) at three months. CRP was associated with mortality (HR 1.40, CI 1.01, 1.96, p = 0.046), and neopterin was associated with the combined endpoint (recurrent ischemic stroke or death) (HR 1.52, CI 1.06, 2.20, p = 0.023), adjusted for age, sex, prior cerebrovascular disease, modified Rankin Scale, and creatinine. When adding neopterin and KA to the same model, KA was negatively associated (HR 0.57, CI 0.33, 0.97, p = 0.038), and neopterin was positively associated (HR 1.61, CI 1.02, 2.54, p = 0.040) with mortality. Patients with cardioembolic stroke at baseline had higher levels of inflammation at three months.

CONCLUSION

Neopterin might be a valuable prognostic biomarker in stroke patients. The use of KA as a measure of anti-inflammatory capacity should be investigated further.

TRIAL REGISTRATION

The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted on 08/01/2016.

摘要

背景

慢性低度炎症与缺血性中风和久坐行为有关。本研究的目的是探讨与久坐行为相关的炎症和免疫调节生物标志物对中风患者中风复发和死亡的预测能力。

方法

从 2015 年 5 月至 2017 年 3 月，我们招募了因急性中风住院的患者参加前瞻性多中心队列研究，即挪威认知障碍后中风（Nor-COAST）研究。纳入有缺血性中风、可获得三个月随访时的血液样本且在三个月随访前无中风复发的患者。采用高灵敏度技术检测血清 C 反应蛋白（CRP），并检测血浆中白细胞介素-6（IL-6）、新蝶呤、吡啶酸比值指数（PAr-index：4-吡啶酸：[吡哆醛+吡哆醛-5'-磷酸]）和犬尿氨酸（KA）。通过挪威中风登记处和死因登记处确定中风复发和死亡，直至 2018 年 12 月 31 日。

结果

本研究共纳入 354 例患者，其中 57%为男性，平均年龄 73（11）岁，平均观察时间 2.5（0.6）年，三个月时的中位国立卫生研究院中风量表评分为 0（IQR 1）。CRP 与死亡率相关（HR 1.40，95%CI 1.01-1.96，p=0.046），新蝶呤与联合终点（复发性缺血性中风或死亡）相关（HR 1.52，95%CI 1.06-2.20，p=0.023），调整因素为年龄、性别、既往脑血管病、改良 Rankin 量表和肌酐。当将新蝶呤和 KA 加入同一模型时，KA 呈负相关（HR 0.57，95%CI 0.33-0.97，p=0.038），而新蝶呤呈正相关（HR 1.61，95%CI 1.02-2.54，p=0.040）与死亡率相关。基线时有心源性脑栓塞的患者在三个月时的炎症水平较高。