BackgroundWe recently reported a link between plasma levels of 2 of 84 cardiovascular disease (CVD)–related proteins and the 3 major CVDs, myocardial infarction, ischemic stroke, and heart failure. The present study investigated whether measurement of almost 10 times the number of proteins could lead to discovery of additional risk markers for CVD.Methods and ResultsWe measured 742 proteins using the proximity extension assay in 826 male participants of ULSAM (Uppsala Longitudinal Study of Adult Men) who were free from CVD at the age of 70 years. Cox proportional hazards models were adjusted for age only, as well as all traditional risk factors. During a 12.5‐year median follow‐up (maximal, 22.0 years), 283 incident CVDs occurred. Forty‐one proteins were significantly (false discovery rate <0.05) related to the combined end point of incident CVD, with N‐terminal pro–brain natriuretic peptide as the top finding, while 53 proteins were related to incident myocardial infarction. A total of 13 and 16 proteins were significantly related to incident ischemic stroke and heart failure, respectively. Growth differentiation factor 15, 4‐disulfide core domain protein 2, and kidney injury molecule were related to all of the 3 major CVD outcomes. A lasso selection of 11 proteins improved discrimination of incident CVD by 5.0% (P=0.0038).ConclusionsLarge‐scale proteomics seem useful for the discovery of new risk markers for CVD and to improve risk prediction in an elderly population of men. Further studies are needed to replicate the findings in independent samples of both men and women of different ages.

中文翻译：

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突发心肌梗塞、缺血性中风和心力衰竭的大规模血浆蛋白分析

背景我们最近报道了 84 种心血管疾病 (CVD) 相关蛋白中的 2 种血浆水平与 3 种主要 CVD、心肌梗塞、缺血性中风和心力衰竭之间的联系。本研究调查了蛋白质数量的近 10 倍的测量是否会导致发现额外的 CVD 风险标志物。方法和结果我们使用邻近扩展测定法在 ULSAM（成年男性乌普萨拉纵向研究）的 826 名男性参与者中测量了 742 种蛋白质他们在 70 岁时没有患心血管疾病。Cox 比例风险模型仅针对年龄以及所有传统风险因素进行了调整。在 12.5 年的中位随访期间（最长 22.0 年），发生了 283 例心血管疾病。41 个蛋白质显着（错误发现率 <0. 05）与心血管事件的联合终点相关，以N端脑利钠肽前体为首要发现，而53个蛋白质与事件心肌梗死相关。共有 13 种和 16 种蛋白质分别与缺血性卒中和心力衰竭显着相关。生长分化因子 15、4-二硫键核心结构域蛋白 2 和肾损伤分子与所有 3 种主要 CVD 结果相关。11 种蛋白质的 lasso 选择提高了 5.0% 的突发 CVD 辨别力（和肾损伤分子与所有 3 种主要 CVD 结果有关。11 种蛋白质的 lasso 选择提高了 5.0% 的突发 CVD 辨别力（和肾损伤分子与所有 3 种主要 CVD 结果有关。11 种蛋白质的 lasso 选择提高了 5.0% 的突发 CVD 辨别力（P = 0.0038)。结论大规模蛋白质组学似乎有助于发现新的 CVD 风险标志物并改善老年人群的风险预测。需要进一步的研究来在不同年龄的男性和女性的独立样本中复制这些发现。