Center for Cardiac Arrest Prevention, Smidt Heart Institute, Cedars-Sinai Health System, Los Angeles, California.
Advanced Clinical Biosystems Research Institute at Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Heart Rhythm. 2023 Mar;20(3):414-422. doi: 10.1016/j.hrthm.2022.12.014. Epub 2022 Dec 13.
The identification of circulating biomarkers specific for sudden cardiac arrest (SCA) could enhance risk prediction. Of particular interest are biomarkers specific to SCA, independent of coronary artery disease (CAD).
The purpose of this study was to identify biomarkers of SCA obtained close to the SCA event.
Twenty cases (survivors of SCA) and 40 age- and sex-matched controls were compared, with a replication analysis of 29 cases matched to 57 controls. A secondary analysis compared 20 SCA cases to 20 controls with CAD. Blood samples were obtained from SCA survivors at a median of 11 months after the SCA event. Proteins were analyzed on a mass spectrometer using data-independent acquisition; a subset of cytokines were analyzed using immunoassays; and 1153 lipids (13 classes) were analyzed. A false discovery rate P value of <.05 identified associated proteins.
Patients had a mean age of 58 years (range 25-87 years), and 70% were male. A total of 26 protein biomarkers associated with SCA when cases were compared with controls, of which 20 differentiated SCA from CAD. The replication analysis identified 8 of 26 biomarkers, of which 6 were not overlapping with CAD. The top identified biological processes involved the extracellular matrix, coagulation cascades, and platelet activation. Lipids in the lysophosphatidylcholine class were implicated in SCA through the CAD pathway.
We identified a panel of novel blood biomarkers specifically associated with SCA, including several that may be involved outside the CAD pathway. These biomarkers could have mechanistic significance and the potential to enhance clinical prediction of SCA.
识别与心脏性猝死(SCA)相关的循环生物标志物可增强风险预测。特别感兴趣的是与冠状动脉疾病(CAD)无关的、特异性针对 SCA 的生物标志物。
本研究旨在确定与 SCA 事件接近时获得的 SCA 生物标志物。
将 20 例(SCA 幸存者)和 40 例年龄和性别匹配的对照者进行比较,采用 29 例病例与 57 例对照者匹配的复制分析。二次分析比较了 20 例 SCA 病例与 20 例伴有 CAD 的对照者。在 SCA 事件后中位数为 11 个月时,从 SCA 幸存者采集血样。使用数据非依赖性采集方法在质谱仪上分析蛋白质;使用免疫测定法分析一组细胞因子;并分析 1153 种脂质(13 类)。错误发现率 P 值<0.05 鉴定出相关蛋白。
患者的平均年龄为 58 岁(范围 25-87 岁),70%为男性。与对照组相比,共有 26 种蛋白生物标志物与 SCA 相关,其中 20 种将 SCA 与 CAD 区分开来。复制分析鉴定出 26 种生物标志物中的 8 种,其中 6 种与 CAD 不重叠。确定的顶级生物学过程涉及细胞外基质、凝血级联和血小板激活。通过 CAD 途径,溶血磷脂酰胆碱类中的脂质与 SCA 相关。
我们确定了一组与 SCA 特异性相关的新型血液生物标志物,其中包括几个可能与 CAD 途径无关的标志物。这些生物标志物可能具有机制意义,并有可能增强对 SCA 的临床预测。