Association Between Corrected QT Interval and Inflammatory Cytokines in Rheumatoid Arthritis

Objective. Corrected QT (QTc) interval predicts all-cause and cardiovascular mortality and may contribute to the increased mortality risk in rheumatoid arthritis (RA). Animal experiments have shown that proinflammatory cytokines [tumor necrosis factor (TNF)-a and interleukin 1 (IL-1)] can prolong cardiomyocyte action potential. We sought to determine whether elevations in circulating inflammatory cytokines were independently associated with QTc prolongation in patients with RA. Methods. One hundred twelve patients [median age 62 (interquartile range 17) yrs; 80 women (71%)] from a well-characterized RA cohort underwent baseline 12-lead electrocardiograms for QT interval measurement and contemporary blood sampling to assess concentrations of inflammatory markers including C-reactive protein (CRP), TNF-alpha, and interleukins (IL-1 alpha, IL-1 beta, IL-6, IL-10). QTc was calculated using the Bazett (QT(BAZ) = QT divided by root RR) and Framingham Heart Study (Q(TFHS) = QT + 0.154 x [1 - RR]) heart rate correction formulas. Results. Inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6, IL-10) were positively correlated with QT(BAZ) (Spearman rank correlation coefficient rho = 0.199, 0.210, 0.222, 0.333; all p < 0.05). In multivariable regression analysis, these associations were all confounded by age except IL-10, where higher tertile groups were independently and positively associated with Q(TBAZ) (beta = 0.202, p = 0.023) and QT(FHS) (beta = 0.223, p = 0.009) when compared to the lower tertile. CRP (per unit increase) was independently associated with Q(TBAZ) (beta = 0.278, p = 0.001), but not QT(FHS). Conclusion. To our knowledge, ours is the first study demonstrating a contemporary link between inflammatory cytokines and QT interval in humans. Our results suggest that a lower inflammatory burden may protect against QTc prolongation in patients with RA. However, further studies are required to confirm the effects of pro-and antiinflammatory cytokines on QTc interval.