Background:Necroptosis plays an important role in human atherosclerosis and atheroma development.Since receptor interacting protein kinase-3 (RIP3) acts as a key mediator of necroptosis,this study aimed to explore its relationship between plasma RIP3 levels and coronary artery disease (CAD) and discover a potential new biomarker for screening CAD subtypes and severity.Methods:A total of 318 patients with CAD who had coronary angiography and 166 controls in Peking Union Medical College Hospital from September 2017 to January 2018 were enrolled in this study.Patients with CAD were divided into three subgroups:patients with stable coronary artery disease (SCAD),patients with unstable angina (UA),and patients with myocardial infarction (MI).The severity of atherosclerosis was determined by Gensini score (GSS).Logistic regression was used to determine the relationship between plasma RIP3 levels and CAD.The correlation between plasma RIP3 and GSS was calculated using multiple linear regression models.Results:Overall,plasma RIP3 levels were significantly higher than serum RIP3 levels.Plasma RIP3 levels in patients with CAD were significantly higher than those in controls.Plasma RIP3 levels were strongly associated with CAD (odds ratio:6.00,95％ confidence interval 3.04-11.81;P ＜ 0.001).Plasma RIP3 levels increased linearly from controls to patients with SCAD,then patients with UA,and finally to patients with MI.We found a significantly positive correlation between proportion of cases of acute coronary syndrome in subjects and their plasma RIP3 level quartile.Plasma RIP3 levels were also associated with GSS (B 0.027;standard error 0.012;P ＜ 0.05).Conclusions:Plasma RIP3 levels were independently associated with CAD.Plasma RIP3 levels could potentially supplement clinical assessment to screen CAD and determine CAD severity.