Association between interleukin-6 levels and first-ever cerebrovascular events in patients with vascular risk factors.

OBJECTIVE: The objective of this study was to examine the association of inflammatory markers with risk of first-ever cerebrovascular events (CVEs), while simultaneously evaluating subclinical vascular disease. METHODS AND RESULTS: We enrolled 464 outpatients who had vascular risk factors without any preexisting cardiovascular disease. We examined the presence of silent lacunar infarction (SLI) by magnetic resonance imaging; carotid intima-media thickness by ultrasound; and measured high-sensitivity C-reactive protein, interleukin (IL)-6, and IL-18 at baseline, and assessed their associations with CVEs using Cox proportional hazards models of 4.8±2.6 years follow-up. We further calculated measures of reclassification and discrimination. In age- and sex-adjusted analysis, IL-6, but neither high-sensitivity C-reactive protein nor IL-18, was associated with CVEs. The association remained significant after adjustment for conventional risk factors, intima-media thickness, and SLI (hazard ratios: 1.80, per 1-SD increase in log IL-6, P=0.03). Compared with the patients with below median IL-6 without SLI, those with above median IL-6 and SLI had a higher risk of CVEs (hazard ratios: 4.14, P=0.0014). The combination of IL-6 and SLI resulted in the net reclassification improvement of 14.3% (P=0.04), and the integrated discrimination improvement gain of 2.1% (P=0.05). CONCLUSIONS: IL-6 levels were independently associated with CVEs and could improve reclassification in those with SLI.