Comprehensive Peroxidase-Based Hematologic Profiling for the Prediction of 1-Year Myocardial Infarction and Death

Abstract

Background— Recognition of biological patterns holds promise for improved identification of patients at risk for myocardial infarction (MI) and death. We hypothesized that identifying high- and low-risk patterns from a broad spectrum of hematologic phenotypic data related to leukocyte peroxidase-, erythrocyte- and platelet-related parameters may better predict future cardiovascular risk in stable cardiac patients than traditional risk factors alone. Methods and Results— Stable patients (n=7369) undergoing elective cardiac evaluation at a tertiary care center were enrolled. A model (PEROX) that predicts incident 1-year death and MI was derived from standard clinical data combined with information captured by a high-throughput peroxidase-based hematology analyzer during performance of a complete blood count with differential. The PEROX model was developed using a random sampling of subjects in a derivation cohort (n=5895) and then independently validated in a nonoverlapping validation cohort (n=1474). Twenty-three high-risk (observed in ≥10% of subjects with events) and 24 low-risk (observed in ≥10% of subjects without events) patterns were identified in the derivation cohort. Erythrocyte- and leukocyte (peroxidase)-derived parameters dominated the variables predicting risk of death, whereas variables in MI risk patterns included traditional cardiac risk factors and elements from all blood cell lineages. Within the validation cohort, the PEROX model demonstrated superior prognostic accuracy (78%) for 1-year risk of death or MI compared with traditional risk factors alone (67%). Furthermore, the PEROX model reclassified 23.5% ( P <0.001) of patients to different risk categories for death/MI when added to traditional risk factors. Conclusion— Comprehensive pattern recognition of high- and low-risk clusters of clinical, biochemical, and hematologic parameters provided incremental prognostic value in stable patients having elective diagnostic cardiac catheterization for 1-year risks of death and MI.