生物衰老预测高龄人群首次脑内出血和脑梗死风险。

Biological Aging for Risk Prediction of First-Ever Intracerebral Hemorrhage and Cerebral Infarction in Advanced Age.

机构信息

Columbia University Irving Medical Center, New York, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, United States; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, United States.

出版信息

J Stroke Cerebrovasc Dis. 2022 Aug;31(8):106568. doi: 10.1016/j.jstrokecerebrovasdis.2022.106568. Epub 2022 Jun 21.

DOI:10.1016/j.jstrokecerebrovasdis.2022.106568

PMID:35749936

Abstract

BACKGROUND AND OBJECTIVES

successful interventions to prevent cerebrovascular disease and stroke require early identification of persons at risk before clinical manifestation of disease. The literature remains to be sparse on accessible plasma-based biomarkers for monitoring brain health and cerebrovascular disease in advanced age. We assessed the predictive value of biological age (BA) as an early indicator for cerebrovascular disease and risk of first-ever intracerebral hemorrhage (ICH) and cerebral infarction (CI) in advanced age and compared these relationships with chronological age (CA) and commonly used biomarkers including tau and Aβ40 and Aβ42.

METHODS

The study included Individuals who consented for blood draw and follow-up. We computed biological age using structural equation modelling. The criteria for the biomarkers included their representability of the various body systems; their availability in the Rotterdam study and their pre-hypothesized reflection of aging in other populations. The algorithm integrates biomarkers that represent six body systems involved in overall cerebrovascular health including metabolic function, cardiac function, lung function, kidney function, liver function, immunity, and inflammation. Time to event analysis was conducted using Cox-regression models. Prediction analysis was conducted using Harrel's C and Area under the receiver operating characteristic curve.

RESULTS

The sample included a total of 1699 individuals at baseline followed up over a median of 11 years. During a period of 15, 780 and 16, 172 person-years, a total of 17 first-ever intracerebral hemorrhage and 83 cerebral infarction cases occurred. In time-to-event analysis, BA showed higher magnitude of associations with ICH compared to CA (HR 2.30, 95% CI: 1.20, 4.30; HR 1.40, 95% CI: 0.76, 2.53) and higher precision with CI (HR 1.30, 95% CI: 1.01,1.75; HR1.90, 95% CI: 1.48, 2.66). BA outperformed CA for prediction of ICH (AUC: 0.68 vs 0.53; Harrel's C: 0.72 vs 0.53) and for CI (AUC:0.63 vs 0.62; Harrel's C: 0.68 vs 0.67).

CONCLUSIONS

Biological aging (delta biological aging) based on integrated physiology biomarkers provides a novel tool for monitoring and identification of persons at highest risk of cerebrovascular disease in advanced age with varying degrees of precision and magnitude for stroke subtypes. These variations are likely related to differences in pathophysiology of intracerebral hemorrhage and cerebral infarction. Wider validation and applicability require extension of these findings in other comparable samples and in clinical settings.

摘要

背景与目的

成功的预防脑血管疾病和中风的干预措施需要在疾病临床表现之前，早期识别高危人群。文献中仍然缺乏用于监测大脑健康和老年人群脑血管疾病的可及性血浆生物标志物。我们评估了生物年龄（BA）作为早期指标在老年人群中对脑血管疾病和首次颅内出血（ICH）和脑梗死（CI）风险的预测价值，并将这些关系与实际年龄（CA）和常用的生物标志物（包括 tau 和 Aβ40 和 Aβ42）进行了比较。

方法

本研究纳入了同意采血和随访的个体。我们使用结构方程模型计算生物年龄。生物标志物的标准包括它们是否代表了各种身体系统；它们在鹿特丹研究中的可用性，以及它们在其他人群中对衰老的预先假设的反映。该算法整合了代表涉及整体脑血管健康的六个身体系统的生物标志物，包括代谢功能、心脏功能、肺功能、肾功能、肝功能、免疫和炎症。使用 Cox 回归模型进行时间事件分析。使用 Harrel 的 C 和接受者操作特征曲线下的面积进行预测分析。

结果

本研究共纳入了 1699 名基线时的个体，随访中位数为 11 年。在 15、780 和 16、172 人年期间，共发生了 17 例首次颅内出血和 83 例脑梗死病例。在时间事件分析中，BA 与 CA 相比，与 ICH 的关联程度更高（HR 2.30，95%CI：1.20，4.30；HR 1.40，95%CI：0.76，2.53），与 CI 的关联程度更高（HR 1.30，95%CI：1.01，1.75；HR1.90，95%CI：1.48，2.66）。BA 在预测 ICH 方面优于 CA（AUC：0.68 与 0.53；Harrel 的 C：0.72 与 0.53）和预测 CI（AUC：0.63 与 0.62；Harrel 的 C：0.68 与 0.67）。