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N Engl J Med. 2017 Sep 21;377(12):1119-1131. doi: 10.1056/NEJMoa1707914. Epub 2017 Aug 27.
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白细胞介素-6 和脂蛋白相关磷脂酶 A2 与功能轨迹相关。

Interleukin-6 and lipoprotein-associated phospholipase A2 are associated with functional trajectories.

机构信息

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United States of America.

出版信息

PLoS One. 2019 Apr 1;14(4):e0214784. doi: 10.1371/journal.pone.0214784. eCollection 2019.

DOI:10.1371/journal.pone.0214784
PMID:30934019
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6443177/
Abstract

BACKGROUND/OBJECTIVES: Inflammatory biomarkers have been associated with stroke and mortality, but inflammation may also have detrimental effects beyond acute events. We hypothesized that serum concentrations of interleukin-6 (IL6) and lipoprotein-associated phospholipase A2 (LpPLA2) were inversely associated with long-term functional decline independently of vascular risk factors, stroke and myocardial infarction (MI) occurring during follow-up.

DESIGN

Prospective population based cohort study.

SETTING

The Northern Manhattan Study.

PARTICIPANTS (INCLUDING THE SAMPLE SIZE): Race/ethnically diverse stroke-free individuals in northern Manhattan aged ≥40 years (n = 3298).

INTERVENTION

None.

MEASUREMENTS

Annual functional assessments with the Barthel index (BI), for a median of 13 years. BI was analyzed as a continuous variable (range 0-100). Baseline demographics, risk factors, and laboratory studies were collected, including IL6 (n = 1679), LpPLA2 mass (n = 1912) and activity (n = 1937). Separate mixed models estimated standardized associations between each biomarker and baseline functional status and change over time, adjusting for demographics, vascular risk factors, social variables, cognition, and depression measured at baseline, and stroke and MI occurring during follow-up.

RESULTS

Mean age was 69 (SD 10) years, 35% were male, 53% Hispanic, 74% hypertensive, and 16-24% diabetic. LogIL6 was associated with decline in BI over time (-0.13 points per year, 95% CI -0.24, -0.02) and marginally with baseline BI (-0.20, 95% CI -0.40, 0.01). LpPLA2 activity levels were associated with baseline BI (-0.36, 95% CI -0.68, -0.04) but not change over time, and LpPLA2 mass levels were not associated with either.

CONCLUSION

In this large population-based study, higher serum inflammatory biomarker levels were associated with disability, even when adjusting for baseline covariates and stroke and MI occurring during follow-up.

摘要

背景/目的:炎症生物标志物与中风和死亡率相关,但炎症可能在急性事件之外产生有害影响。我们假设,白细胞介素 6(IL6)和脂蛋白相关磷脂酶 A2(LpPLA2)的血清浓度与血管危险因素、随访期间发生的中风和心肌梗死(MI)无关,与长期功能下降呈负相关。

设计

前瞻性人群为基础的队列研究。

地点

北曼哈顿研究。

参与者(包括样本量):年龄≥40 岁的北曼哈顿无中风的种族/民族多样化个体(n=3298)。

干预

无。

测量

中位数为 13 年的年度功能评估,采用巴氏指数(BI)。BI 作为连续变量进行分析(范围 0-100)。收集基线人口统计学、风险因素和实验室研究,包括 IL6(n=1679)、LpPLA2 质量(n=1912)和活性(n=1937)。单独的混合模型估计了每个生物标志物与基线功能状态之间的标准化关联以及随时间的变化,调整了基线时测量的人口统计学、血管危险因素、社会变量、认知和抑郁,以及随访期间发生的中风和 MI。

结果

平均年龄为 69(SD 10)岁,35%为男性,53%为西班牙裔,74%为高血压,16-24%为糖尿病。LogIL6 与 BI 随时间的下降相关(每年减少 0.13 分,95%CI -0.24,-0.02),与基线 BI 相关(-0.20,95%CI -0.40,0.01)。LpPLA2 活性水平与基线 BI 相关(-0.36,95%CI -0.68,-0.04),但与随时间的变化无关,而 LpPLA2 质量水平与两者均无关。

结论

在这项大型基于人群的研究中,较高的血清炎症生物标志物水平与残疾相关,即使在调整了基线协变量和随访期间发生的中风和 MI 后也是如此。