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老年人促凝血因子水平和凝血酶生成峰值与痴呆风险的关系:心血管健康研究

Levels of procoagulant factors and peak thrombin generation in relation to dementia risk in older adults: The Cardiovascular Health Study.

作者信息

Harrington Laura B, Ehlert Alexa N, Thacker Evan L, Jenny Nancy S, Lopez Oscar, Cushman Mary, Olson Nels C, Fitzpatrick Annette, Mukamal Kenneth J, Jensen Majken K

机构信息

Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA, USA.

Division of Pharmaceutical Outcomes and Policy, University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Chapel Hill, NC, USA.

出版信息

Thromb Res. 2024 Mar;235:148-154. doi: 10.1016/j.thromres.2024.01.024. Epub 2024 Feb 4.

Abstract

INTRODUCTION

Markers of hemostasis such as procoagulant factors and peak thrombin generation are associated with cardiovascular outcomes, but their associations with dementia risk are unclear. We aimed to evaluate prospective associations of selected procoagulant factors and peak thrombin generation with dementia risk.

METHODS

We measured levels of 7 hemostatic factors (fibrinogen, factor VII coagulant activity [FVIIc], activated factor VII [FVIIa], factor VIIa-antithrombin [FVIIa-AT], factor XI antigen [FXI], peak thrombin generation, and platelet count) among participants in the Cardiovascular Health Study, a cohort of older adults free of dementia in 1992/1993 (n = 3185). Dementia was adjudicated and classified by DSM-IV criteria through 1998/1999. Cox proportional hazards models estimated hazard ratios (HRs) for any dementia associated with 1-standard deviation (SD) differences, adjusting for sociodemographic and clinical factors and APOE genotype. Secondary analyses separately evaluated the risk of vascular dementia, Alzheimer's disease, and mixed dementia.

RESULTS

At baseline, participants had a median age of 73 years. Over 5.4 years of follow-up, we identified 448 dementia cases. There was no evidence of linear associations between levels of these hemostatic factors with any dementia risk (HRs per 1-SD difference ranged from 1.0 to 1.1; 95 % confidence intervals included 1.0). Results of secondary analyses by dementia subtype were similar.

CONCLUSIONS

In this prospective study, there was no strong evidence of linear associations between levels of fibrinogen, FVIIc, FVIIa, FVIIa-AT, FXI, peak thrombin generation, or platelet count with dementia risk. Despite their associations with cardiovascular disease, higher levels of these biomarkers measured among older adults may not reflect dementia risk.

摘要

引言

凝血因子和凝血酶生成峰值等止血标志物与心血管疾病结局相关,但其与痴呆风险的关联尚不清楚。我们旨在评估特定凝血因子和凝血酶生成峰值与痴呆风险的前瞻性关联。

方法

我们在心血管健康研究的参与者中测量了7种止血因子(纤维蛋白原、凝血因子VII促凝活性[FVIIc]、活化凝血因子VII[FVIIa]、FVIIa-抗凝血酶[FVIIa-AT]、凝血因子XI抗原[FXI]、凝血酶生成峰值和血小板计数),该研究是一个1992/1993年时无痴呆的老年人队列(n = 3185)。通过1998/1999年依据《精神疾病诊断与统计手册》第四版(DSM-IV)标准判定并分类痴呆。Cox比例风险模型估计与1个标准差(SD)差异相关的任何痴呆的风险比(HR),并对社会人口统计学和临床因素以及载脂蛋白E(APOE)基因型进行调整。二次分析分别评估血管性痴呆、阿尔茨海默病和混合性痴呆的风险。

结果

在基线时,参与者的中位年龄为73岁。在5.4年的随访期间,我们确定了448例痴呆病例。这些止血因子水平与任何痴呆风险之间均无线性关联的证据(每1-SD差异的HR范围为1.0至1.1;95%置信区间包含1.0)。按痴呆亚型进行的二次分析结果相似。

结论

在这项前瞻性研究中,没有强有力的证据表明纤维蛋白原、FVIIc、FVIIa、FVIIa-AT、FXI、凝血酶生成峰值或血小板计数水平与痴呆风险之间存在线性关联。尽管这些生物标志物与心血管疾病相关,但在老年人中测得的这些生物标志物较高水平可能无法反映痴呆风险。

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