Association Between Novel Arterial Wall Atherogenesis Markers with Incident Myocardial Infarction: Observations from the Dallas Heart Study

Traditional risk factors and inflammatory markers do not adequately capture the risk of myocardial infarction (MI) despite these pathways being drivers of coronary artery disease. This is likely due to their nonspecific nature and inability to accurately capture atherogenesis potential at the arterial wall. To address these gaps, we developed an ex vivo arterial wall model that can determine atherogenesis potential by testing a person’s plasma in assays that directly reflect key early steps of atherosclerosis. In this study, we aimed to demonstrate clinical relevance of these arterial wall markers with incident MI.

At #AHA25, we presented our study investigating the association between novel arterial wall atherogenesis markers with incident MI in participants from the Dallas Heart Study. We measured atherogenesis potential in baseline plasma samples in 34 incident MI cases and 34 controls that were matched for age, sex, and race/ethnicity. We used an ex-vivo atherogenesis assay to quantify atherogenesis potential using stored plasma from participants at baseline, single-cell flow cytometry, and standardized peripheral blood mononuclear cells (pBMCs). We assessed the following arterial wall markers to determine the atherogenesis potential: 1) monocyte subset profile, 2) monocyte transendothelial migration and reverse migration of macrophages, and 3) foam cell formation in endothelial cells and macrophages.

We found that plasma at baseline in those with incident MI induced lower classical monocytes, higher pro-inflammatory monocytes, higher monocyte transendothelial migration, and higher foam cell formation versus controls. Further, plasma from incident MI cases induced less reverse migration of macrophages versus controls. Our findings suggest higher atherogenesis potential at baseline in individuals who developed incident MI as compared to those who did not. These arterial wall markers may serve as ideal candidates to accurately assess risk, monitor therapy, and test novel therapeutic agents to lower the burden of CAD.