Abstract 318: Circulating Neutrophils and their Secreted Mediator S100A8/A9 Correlate with Carotid Artery Disease and Predict Cardiovascular Events in Healthy Individuals

Abstract

Aims S100A8/A9 is an inflammatory mediator secreted by activated neutrophils and monocytes/macrophages. Serum S100A8/A9 levels were previously found to correlate with the severity of coronary artery disease in diabetic patients and to predict cardiovascular (CV) events in healthy postmenopausal women. Our aim was to investigate whether S100A8/A9 correlates with carotid artery disease and whether it can predict CV risk in healthy individuals. Methods We measured baseline levels of S100A8/A9 in 664 individuals with no previous history of CV disease, randomly selected from the Malmö Diet and Cancer cohort. We examined the correlation between S100A8/A9 and traditional CV risk factors, circulating cell populations, plasma cytokines, carotid intima media thickness (IMT) and area (IM area), and the incidence of CV events during a follow-up period of 16.2 years. Results We detected significant positive correlations between baseline S100A8/A9 and the number of circulating neutrophils, IFNγ, TNFα, IL-1β, smoking, BMI, systolic blood pressure and an inverse correlation with HDL. In a multivariate linear regression model adjusted for age and sex, S100A8/A9 and the neutrophil counts were correlated with IMT and IM area in the common carotid artery. The associations with IM area remained significant after further adjustment for CV risk factors. In a Cox regression model corrected for age and sex, S100A8/A9 and circulating neutrophils predicted the incidence of coronary events (fatal or non-fatal myocardial infarction) [HR (95%CI) per SD: 1.28 (1.03-1.59), P =0.026 and 1.26 (1.04-1.53), P =0.020, respectively] and CV death [1.34 (1.06-1.71), P =0.015 and 1.59 (1.33-1.90), P <0.001, respectively]. There was no relationship with stroke. Conclusions S100A8/A9 correlates strongly with circulating neutrophil numbers, but not with monocytes or monocyte sub-populations. Baseline S100A8/A9 concentrations and circulating neutrophils are significantly associated with carotid artery disease and predict coronary events and CV death in apparently healthy individuals. Our study provides further evidence for the involvement of activated neutrophils in atherogenesis and acute coronary events.