Prognostic significance of raised plasma levels of interleukin-6 and C-reactive protein in atrial fibrillation

Background Atrial fibrillation (AF) is a risk factor for stroke and death. Inflammation has been associated with AF, but the prognostic significance of inflammatory mediators, such as interleukin-6 (IL-6) and C-reactive protein (CRP), among patients with AF is unknown. We hypothesized that increased plasma levels of IL-6 and CRP, as indexes of an inflammatory state, would be associated with an increased risk of stroke and death among patients with AF. Methods We undertook a pilot study to determine dates of stroke or death occurring among 77 AF cases, with stored plasma samples having initially been obtained during attendance at our specialist AF clinic between 1993 and 1995. Plasma IL-6 and CRP were measured by ELISA and a high-sensitivity latex particle turbidimetric assay, respectively. Results Patients were followed up for a median duration of 2305 days (interquartile range, 1692 to 2592) [equivalent to 6.3 (4.6 to 7.1) years]. During this period, there were 8 (10%) strokes, 22 (29%) deaths, and 28 (36%) patients who had stroke or death. Prior stroke and high (above median) IL-6 levels were independent predictors of stroke. Age was the only independent predictor of death. High (above median) IL-6 levels remained a significant predictor of stroke or death, even after adjustment for age (hazard ratio, 2.91; 95% CI, 1.20 to 6.51; P = .007), and was the only independent predictor of stroke or death. Trends toward increased risk with high plasma CRP did not reach statistical significance (P = .06 for stroke or death). Conclusions In this pilot study, high plasma IL-6 levels were an independent predictor of stroke and the composite end point of stroke or death, suggesting that inflammation in AF may predict a poor prognosis.