The predictive role of interleukin 6 trans signalling in middle aged men and women at low intermediate risk of cardiovascular events
Background Interleukin 6 trans signalling is independently associated with the risk of cardiovascular events. The aim of this study was to investigate if interleukin 6 trans signalling can identify individuals at risk for cardiovascular events (coronary artery disease and ischaemic stroke) among those at low intermediate risk. Methods In a cohort of 60 year olds (n 4232, incident cardiovascular events n 525) interleukin 6 trans signalling was estimated by a ratio between the pro inflammatory interleukin 6: soluble interleukin 6 receptor binary receptor complex and the inactivated interleukin 6: soluble interleukin 6 receptor: sgp130 ternary complex (B/T ratio) Risk associated with B/T ratio >median was investigated in individuals with low density lipoprotein cholesterol =4.0 (mmol/l) and in those at low intermediate risk according to the Framingham risk score (FRS) using Cox regression and expressed as hazard ratio and 95% confidence interval. Difference in time to event (years; 95% confidence interval) was analysed with quantile regression. The interaction between low density lipoprotein cholesterol and B/T ratio was estimated on the additive scale. Incremental discriminatory value of the B/T ratio if low density lipoprotein cholesterol =4.0 was compared to that of the FRS and interleukin 6. Results B/T ratio >median was associated with increased cardiovascular event risk when low density lipoprotein cholesterol =4.0 (hazard ratio 1.59; 95% confidence interval 1.24 2.05) or FRS 10% >10 =20% (hazard ratio 1.27; 95% confidence interval 1.00 1.61 and hazard ratio 1.78; 95% confidence interval 1.36 2.34, respectively) B/T ratio >median and low density lipoprotein cholesterol =4.0 were associated with early cardiovascular events, particularly ischaemic stroke. No interaction was observed between low density lipoprotein cholesterol and the B/T ratio, both factors increasing cardiovascular event risk by 60% In the presence of low density lipoprotein cholesterol =4.0, the B/T ratio slightly improved discrimination measures. Conclusions Interleukin 6 trans signalling increases cardiovascular event risk in middle aged men and women otherwise classified at low intermediate cardiovascular risk.
European journal of preventive cardiology