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生物标志物预测小血管病卒中的临床进展:白蛋白尿和氧化 LDL 胆固醇的预后作用。

Biomarkers to predict clinical progression in small vessel disease strokes: prognostic role of albuminuria and oxidized LDL cholesterol.

机构信息

Neurology Department, Neurovascular Research, Program of Research on Inflammatory and Cardiovascular Disorders, Municipal Institute for Medical Research, Passeig Marítim 25-29, 08003 Barcelona, Spain.

出版信息

Atherosclerosis. 2011 Nov;219(1):368-72. doi: 10.1016/j.atherosclerosis.2011.07.114. Epub 2011 Aug 4.

Abstract

OBJECTIVE

Clinical progression in lacunar strokes (LS) is an unpredictable and fearful complication. Endothelial dysfunction (ED) is believed to be the first step in the pathophysiology of LS therefore we aimed to analyze the association of three markers of ED: albuminuria, von Willebrand factor (vWF), and oxidized LDL cholesterol (ox-LDL) with LS progression.

METHODS

From December 2007 to December 2010, 127 LS patients admitted within 6 h of symptom onset were prospectively assessed. Progression was defined as initial NIHSS score worsening ≥4 points within the first 72 h. Analysis of vWF and ox-LDL was done at admission. Albuminuria was measured in the first morning spot urine. Association between 3 biomarkers and progression was tested using logistic regression analysis. Other clinical variables of interest were also studied. Discriminative power was analyzed with a receiver operator curve.

RESULTS

Twenty-two patients (17.3%) progressed. Progression was associated with worse outcome at 90 days. Albuminuria and ox-LDL were associated in univariate analysis; vWF was not. Adjusted OR were: ox-LDL [OR: 1.03; 95% CI: 1.01-1.07, p=0.019], albuminuria [OR: 2.07; 95% CI: 1.04-4.13, p=0.039]. Association was linear without a cut-off point. Clinical variables were not associated with progression. The model including albuminuria and ox-LDL had a good predictive value [AUC: 0.80 [0.70-0.89)].

CONCLUSIONS

Albuminuria and ox-LDL levels are independently associated with higher risk of progression in LS. The lack of reliable clinical predictors makes biomarker research a priority to improve progression detection in this subtype of ischemic strokes.

摘要

目的

腔隙性卒中(LS)的临床进展是一种不可预测且令人恐惧的并发症。内皮功能障碍(ED)被认为是 LS 病理生理学的第一步,因此我们旨在分析三种 ED 标志物:蛋白尿、血管性血友病因子(vWF)和氧化 LDL 胆固醇(ox-LDL)与 LS 进展的关系。

方法

从 2007 年 12 月至 2010 年 12 月,前瞻性评估了 127 例症状发作后 6 小时内入院的 LS 患者。进展定义为最初 NIHSS 评分在最初 72 小时内恶化≥4 分。入院时进行 vWF 和 ox-LDL 分析。在第一个早晨的随机尿样中测量蛋白尿。使用逻辑回归分析测试 3 种生物标志物与进展之间的关系。还研究了其他感兴趣的临床变量。通过接收者操作曲线分析鉴别力。

结果

22 例患者(17.3%)进展。进展与 90 天的不良结局相关。在单因素分析中,白蛋白尿和 ox-LDL 相关;vWF 不相关。调整后的 OR 为:ox-LDL[OR:1.03;95%CI:1.01-1.07,p=0.019],白蛋白尿[OR:2.07;95%CI:1.04-4.13,p=0.039]。关联呈线性,无截止点。临床变量与进展无关。包括白蛋白尿和 ox-LDL 的模型具有良好的预测值[AUC:0.80 [0.70-0.89)]。

结论

白蛋白尿和 ox-LDL 水平与 LS 进展的风险增加独立相关。缺乏可靠的临床预测因子使得生物标志物研究成为改善这种缺血性卒中亚型进展检测的优先事项。

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