Wade T Rogers1, Lifeng Zhang2, Scott Welden2, Benjamin Krieger2, Michael Rickels3, Jonni S Moore1, Emile R Mohler2. 1. Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. 2. Section of Vascular Medicine, Division of Cardiovascular Disease, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. 3. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Abstract
BACKGROUND: We previously reported the development of a novel high dimensional cytomic assay, the Vascular Health Profile (VHP) based on measurements of angiogenic circulating hematopoietic stem and progenitor cells (CHSPCAng ) and extracellular vesicles (EVs), that discovered a unique signature, differentiating the vascular status of diabetics and normal healthy controls. Here, we present data from a 3-year follow-up to evaluate the power of the VHP to identify individuals at risk for cardiovascular (CV) events. METHODS: The original data were generated as previously described by measuring a broad panel of progenitor cells and EVs and profiled using cytometric fingerprinting. Subjects were classified into groups according to the occurrence of adjudicated CV events including myocardial infarction, stroke, major adverse cardiovascular events, revascularization, and irregular rhythm. Cross-validated Linear Discriminate Analysis (LDA) models were constructed and used to predict the occurrence of events, and were evaluated for predictive accuracy (AUC, area under the curve) using receiver operating characteristic (ROC) analysis. RESULTS: Over the period of this analysis, follow-up data was obtained on 87 subjects, with 32 events occurring overall, and only in the diabetic group. In all cases, the VHP added significant predictive power, in the form of ROC analysis, for all evaluated outcomes with the exception of irregular rhythm. CONCLUSIONS: The VHP, a relatively simple blood test, can provide sensitive and clinically relevant information on the vascular status of a patient that may be useful for a variety of applications including drug development, clinical risk assessment, and companion diagnostics.
BACKGROUND: We previously reported the development of a novel high dimensional cytomic assay, the Vascular Health Profile (VHP) based on measurements of angiogenic circulating hematopoietic stem and progenitor cells (CHSPCAng ) and extracellular vesicles (EVs), that discovered a unique signature, differentiating the vascular status of diabetics and normal healthy controls. Here, we present data from a 3-year follow-up to evaluate the power of the VHP to identify individuals at risk for cardiovascular (CV) events. METHODS: The original data were generated as previously described by measuring a broad panel of progenitor cells and EVs and profiled using cytometric fingerprinting. Subjects were classified into groups according to the occurrence of adjudicated CV events including myocardial infarction, stroke, major adverse cardiovascular events, revascularization, and irregular rhythm. Cross-validated Linear Discriminate Analysis (LDA) models were constructed and used to predict the occurrence of events, and were evaluated for predictive accuracy (AUC, area under the curve) using receiver operating characteristic (ROC) analysis. RESULTS: Over the period of this analysis, follow-up data was obtained on 87 subjects, with 32 events occurring overall, and only in the diabetic group. In all cases, the VHP added significant predictive power, in the form of ROC analysis, for all evaluated outcomes with the exception of irregular rhythm. CONCLUSIONS: The VHP, a relatively simple blood test, can provide sensitive and clinically relevant information on the vascular status of a patient that may be useful for a variety of applications including drug development, clinical risk assessment, and companion diagnostics.
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