很少有基于人群的队列研究（包括男性和女性）探讨了与心肌梗死 (MI) 相关的循环蛋白。本研究使用基于队列的孟德尔随机化 (MR) 分析调查了循环心脏代谢相关蛋白与 MI 风险之间的关系，并探讨了潜在的性别差异。发现队列包括 11 751 名瑞典成年人（55-93 岁）。使用了通过 Olink 邻近延伸测定、生化和基于问卷调查的信息评估的 259 种蛋白质的数据。通过与瑞典登记册的连接，对参与者的心梗事件和死亡进行了长达 8 年的跟踪调查。对英国生物银行样本 (n = 51 613) 进行了复制分析。在 MR 分析中，与蛋白质密切相关的索引顺式遗传变异被用作工具变量。 MI 的遗传关联汇总统计数据从 CARDIoGRAMplusC4D 联盟和 FinnGen 获得。在对潜在混杂因素和多重测试进行调整后，发现和复制样本中的 45 种蛋白质与 MI 事件相关。在二次分析中，13 个蛋白质关联具有性别特异性，其中大多数关联在女性中发现。在 MR 分析中，基因预测较高水平的肾素、卵泡抑素和视黄酸受体反应蛋白 2 与 MI 风险增加有关。组织因子途径抑制剂、肿瘤坏死因子受体 1 和 2、胎盘生长因子与 MI 呈负相关。这项研究发现了循环蛋白与 MI 事件之间的新关联和先前已证实的关联，并首次提出了性别特异性多种蛋白质-MI 关联中的模式。© 作者 2024。由牛津大学出版社代表欧洲心脏病学会出版。

Few population-based cohort studies, including both men and women, have explored circulating proteins associated with incident myocardial infarction (MI). This study investigated the relationships between circulating cardiometabolic-related proteins and MI risk using cohort-based and Mendelian randomization (MR) analyses and explored potential sex-specific differences.The discovery cohort included 11 751 Swedish adults (55-93 years). Data on 259 proteins assessed with Olink proximity extension assays, biochemical, and questionnaire-based information were used. Participants were followed up for incident MI and death over 8 years through linkage to Swedish registers. Replication analyses were conducted on the UK Biobank sample (n = 51 613). In MR analyses, index cis-genetic variants strongly related to the proteins were used as instrumental variables. Genetic association summary statistic data for MI were obtained from the CARDIoGRAMplusC4D consortium and FinnGen.Forty-five proteins were associated with incident MI in discovery and replication samples following adjustment for potential confounders and multiple testing. In the secondary analysis, 13 of the protein associations were sex-specific, with most associations identified among women. In MR analysis, genetically predicted higher levels of renin, follistatin, and retinoic acid receptor responder protein 2 were linked to an increased risk of MI. Tissue factor pathway inhibitor, tumor necrosis factor receptors 1 and 2, placenta growth factor had an inverse association with MI.This study identified both new and confirmed previously established associations between circulating proteins and incident MI and, for the first time, suggested sex-specific patterns in multiple protein-MI associations.© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.