Abstract 16511: EN-RAGE: A Novel Inflammatory Marker for Coronary Heart Disease

Abstract

Introduction: Inflammation plays a key role in atherosclerosis. We hypothesized that uninvestigated inflammatory markers may predict the risk of coronary heart disease (CHD). Methods: We investigated the association of 16 inflammatory biomarkers with the risk of CHD in a random subset of 839 CHD free individuals in a prospective population-based cohort study. A Bonferroni corrected p-value of 3.1х10 -3 was used as a threshold of statistical significance. We additionally tested whether the association of any identified marker was independent of traditional CHD risk factors and previously studied inflammatory markers. Results: Mean age at baseline was 72.8 years. During a median follow-up of 10.6 years, 99 cases of incident CHD were observed. Among all novel inflammatory biomarkers, neutrophil derived human s100a12 (EN-RAGE) showed the strongest association with the risk of CHD (p-value 2.0х10 -3 ). In the age and sex adjusted model, each standard deviation increase in the natural log-transformed EN-RAGE was associated with 37% higher risk of incident CHD (Hazard ratio (HR): 1.37; 95% confidence interval (CI) CI: 1.12 - 1.67). After further adjustment for established cardiovascular risk factors, the effect estimates attenuated slightly (HR: 1.30; 95% CI: 1.06 - 1.59). Adjustment for ten previously studied inflammatory markers did not attenuate the association (HR: 1.41; 95% CI: 1.12 - 1.77). Excluding individuals with prevalent type 2 diabetes, impaired kidney function or individuals using antihypertensive medication did not change the effect estimates. Conclusions: Our results highlight EN-RAGE as a novel inflammatory marker for CHD independent of traditional CHD risk factors and inflammatory markers, suggesting a specific inflammatory risk pathway for CHD.