Please join authors Loren Field and Sean Reuter, as well as Associate Editor Thomas Eschenhagen as they discuss the article "Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity But Not Cardiomyocyte Proliferation." Dr. Greg Hundley: Welcome listeners, to this January 10th issue of Circulation on the Run, and I am Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Peder Myhre: I am Dr. Peder Myhre from Akershus University Hospital and University of Oslo in Norway. Dr. Greg Hundley: Well, listeners, this week's feature discussion delves into the world of preclinical science and evaluates cardiac troponin I and its impact on S phase activity in cardiomyocytes, and does that relate to cardiomyocyte proliferation. But before we get to that, how about we grab a cup of coffee and Peder and I will work through some of the other articles in the issue. Peder, how about this week I go first? Dr. Peder Myhre: Go ahead, Greg. Dr. Greg Hundley: Right. So Peder, this first study evaluated whether the burden of positive coronary artery calcification on cardiovascular disease differed by multidimensional individual characteristics, and so the investigators led by Dr. Kosuke Inoue from Kyoto University sought to investigate the heterogeneity in the association between positive coronary artery calcium and incident cardiovascular disease. And so Peder, to examine this question, the authors implemented a cohort study design that included adults aged greater than 45 years, free of cardiovascular disease, from the Multi-Ethnic Study of Atherosclerosis, or MESA, and after propensity score matching in a one-to-one ratio, they applied a machine learning causal forest model to, first, evaluate the heterogeneity in the association between positive coronary artery calcium and incident cardiovascular disease and then, second, to predict the increase in cardiovascular disease risk at 10 years when the coronary artery calcium score was greater than zero, so versus is it zero at all at the individual level? Dr. Peder Myhre: Oh, Greg, that is so cool, so using machine learning for coronary artery calcium and risk prediction, I'm very excited. What did they find? Dr. Greg Hundley: Right, Peder, so the expected increases in cardiovascular disease risk when the coronary artery calcium score was greater than zero were heterogeneous across individuals. Moreover, nearly 70% of people with low atherosclerotic cardiovascular disease risk showed a large increase in cardiovascular disease risk when the coronary calcium score was greater than zero, highlighting the need for coronary artery calcium screening among such low-risk individuals. And Peder, future studies are really needed to assess whether targeting individuals for coronary artery calcium measurements based on not only the absolute ASCVD risk, but also the expected increase in CVD risk when a CAC score is greater than zero and whether that improves overall assessment of cardiovascular outcomes. Dr. Peder Myhre: Wow, that is so clinically relevant and very interesting. And we're actually going to stay clinically relevant with the next paper which is about anti-platelet therapy after PCI. And this paper describes the long-term results of the HOST-EXAM trial. To remind you, Greg, the HOST-EXAM trial was an investigator-initiated prospective, randomized, open label, multicenter trial done at 37 sites in Korea. They enrolled patients who had undergone PCI with DES and maintained dual anti-platelet therapy without any clinical event for a mean 12 months and then they were randomized one to-one to either clopidogrel, 75 milligrams once daily, or aspirin, 100 milligram once daily. The primary results of this trial was published in Lancet in 2021 and showed superiority of clopidogrel over aspirin in prevention of the composite of MACE and major bleeding during 24 months of followup. And then, through the current paper, this describes