In this issue, author Monika Safford and Associate Editor discuss the article “Number of Social Determinants of Health and Fatal and Nonfatal Incident Coronary Heart Disease in the REGARDS Study (Reasons for Geographic and Racial Differences in Stroke).” Then authors Jennifer Ho and Timothy Churchill discuss their Research Letter “Evaluation of 2 Existing Diagnostic Scores for Heart Failure With Preserved Ejection Fraction Against a Comprehensively Phenotyped Cohort.”   TRANSCRIPT BELOW: Dr. Carolyn Lam: Welcome to Circulation On the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts, I'm Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, director of the Pauley Heart Center at VCU health in Richmond, Virginia. Dr. Carolyn Lam: Guess what, Greg? We're going to talk to a lovely friend and wonderful colleague Dr. Jennifer Ho soon regarding her research letter on the HFpEF diagnostic scoring criteria. Dr. Greg Hundley: Very nice, Carolyn. Well, I've also got another feature discussion in this issue involving the reasons for geographic and racial differences in stroke. It's from the REGARDS study. But first, how about we grab a cup of coffee and jump into the next articles in the issue. Dr. Carolyn Lam: I've got my coffee, Greg and I'm ready to tell you about acute infection and endotoxinemia. We know that infections are a well-established risk factor for cardiovascular inflammation, increasing the risk for a cardiovascular complication within the first weeks after that infection. However, what is the mechanism underlying such an association? Well here, Dr. Soehnlein from Germany and colleagues utilized a model of endotoxinemia to link acute infection and subsequent neutrophil activation with acceleration of vascular inflammation. Acute infection was mimicked by injection of a single dose of lipopolysaccharide into hypercholesterolemic mice. Dr. Greg Hundley: So, Carolyn, what did they find? Dr. Carolyn Lam: Well they found that neutrophils and specifically neutrophil extracellular traps controlled accelerated atherosclerosis during endotoxinemia. These neutrophil extracellular traps or NET-resident histone H2a, heightened arterial monocyte recruitment in endotoxinemia in a mechanism involving electrostatic charge interaction. The clinical implications are that therapeutic neutralization of NET-resident cationic molecules, including histone H2a by use of antibodies or peptides may protect patients at cardiovascular risk during an acute infection from secondary events. Dr. Greg Hundley: Wow, Carolyn. Really interesting. Well, my paper comes from Dr. David Park from New York University School of Medicine. Carolyn, elevated intracardiac pressure due to heart failure, induces electrical and structural remodeling in the left atrium that begets atrial myopathy and arrhythmias. The underlying molecular pathways that drive atrial remodeling during cardiac pressure overload are poorly defined. The authors sought in this study to characterize the response of the ETV1 signaling axis in the left atrium during cardiac pressure overload in humans and mouse models and explore the role of ETV1 in atrial electrical and structural remodeling. Dr. Carolyn Lam: Nice. And so what did they find, Greg? Dr. Greg Hundley: Well Carolyn, using the Cleveland Clinic Biobank of human left atrial specimens and their mouse models, these authors found that ETV1 is down regulated in the left atrium during cardiac pressure overload, thereby contributing to both electrical and structural remodeling of the left atrium. Dr. Carolyn Lam: Nice. Well Greg, let's talk about what else is in today's issue. There's a Perspective piece from Dr. Delgado on “Changing the Paradigm in the Management of Valvular Heart Disease: In Addition to Left Ventricular Ejection Fraction, Focus on the Myocardium. There's a Research Letter from Dr