Evaluation of Large-Scale Proteomics for Prediction of Cardiovascular Events

作者：Hannes Helgason, Thjodbjorg Eiriksdottir, Magnús Ö. Úlfarsson, Abhishek Choudhary, Sigrún H. Lund, Erna V. Ivarsdottir, Grímur Hjörleifsson Eldjárn, Guðmundur Einarsson, Egil Ferkingstad, Kristjan H. S. Moore, Narimon Honarpour, Thomas Liu, Huei Wang, Thomas Hucko, Marc S. Sabatine, David A. Morrow, Robert P. Giugliano, Sisse Rye Ostrowski, Ole Birger Pedersen, Henning Bundgaard, Christian Erikstrup, Davíð O. Arnar, Guðmundur Þorgeirsson, Gísli Másson, Ólafur Þ. Magnússon, Jona Saemundsdottir, Sólveig Grétarsdóttir, Valgerður Steinthórsdóttir, Guðmar Þorleifsson, Anna Helgadóttir, Patrick Sulem, Unnur Þorsteinsdóttir, Hilma Hólm, Daníel F. Guðbjartsson, Kāri Stefánsson · 发表于：JAMA · 年份：2023 · DOI：10.1001/jama.2023.13258 · 被引用次数：122 · 研究领域：Advanced Proteomics Techniques and Applications、Lipoproteins and Cardiovascular Health、Adipokines, Inflammation, and Metabolic Diseases

Importance: Whether protein risk scores derived from a single plasma sample could be useful for risk assessment for atherosclerotic cardiovascular disease (ASCVD), in conjunction with clinical risk factors and polygenic risk scores, is uncertain. Objective: To develop protein risk scores for ASCVD risk prediction and compare them to clinical risk factors and polygenic risk scores in primary and secondary event populations. Design, Setting, and Participants: The primary analysis was a retrospective study of primary events among 13 540 individuals in Iceland (aged 40-75 years) with proteomics data and no history of major ASCVD events at recruitment (study duration, August 23, 2000 until October 26, 2006; follow-up through 2018). We also analyzed a secondary event population from a randomized, double-blind lipid-lowering clinical trial (2013-2016), consisting of individuals with stable ASCVD receiving statin therapy and for whom proteomic data were available for 6791 individuals. Exposures: Protein risk scores (based on 4963 plasma protein levels and developed in a training set in the primary event population); polygenic risk scores for coronary artery disease and stroke; and clinical risk factors that included age, sex, statin use, hypertension treatment, type 2 diabetes, body mass index, and smoking status at the time of plasma sampling. Main Outcomes and Measures: Outcomes were composites of myocardial infarction, stroke, and coronary heart disease death or cardiovascular dea...