Association Between Corrected QT Interval and Inflammatory Cytokines in Rheumatoid Arthritis
Association Between Corrected QT Interval and Inflammatory Cytokines in Rheumatoid Arthritis
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DOI：
10.3899/jrheum.140861
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发表时间：
2015-03-01
影响因子：
3.9
通讯作者：
Kitas, George D.
中科院分区：
文献类型：
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作者：
Adlan, Ahmed M.;Panoulas, Vasileios F.;Kitas, George D.
Objective.校正QT（QTc）间期可预测全因和心血管死亡率，并可能导致类风湿关节炎（RA）死亡风险增加。动物实验表明，促炎细胞因子[肿瘤坏死因子（TNF）-α和白细胞介素1（IL-1）]可延长心肌细胞动作电位。我们试图确定RA患者循环中炎性细胞因子的升高是否与QTc间期延长独立相关。来自一个特征明确的RA队列的112例患者[中位年龄62（四分位距17）岁; 80例女性（71%）]接受了基线12导联心电图QT间期测量和同期血样采集，以评估炎症标志物（包括C反应蛋白（CRP）、TNF-α和白细胞介素（IL-1 α、IL-1 β、IL-6、IL-10））的浓度。使用Bazett（QT（BAZ）= QT除以RR根）和Fragrance Heart Study（Q（TFHS）= QT + 0.154 x [1 - RR]）心率校正公式计算QTc。炎性细胞因子（TNF-α、IL-1 β、IL-6、IL-10）与QT（BAZ）正相关（斯皮尔曼等级相关系数rho = 0.199、0.210、0.222、0.333;所有p < 0.05）。在多变量回归分析中，除IL-10外，这些相关性均受到年龄的混淆，其中与低三分位数相比，高三分位数组与Q（TBAZ）（β = 0.202，p = 0.023）和QT（FHS）（β = 0.223，p = 0.009）独立且正相关。CRP（每单位增加）与Q（TBAZ）独立相关（β = 0.278，p = 0.001），而与QT（FHS）无关。据我们所知，我们的研究是第一个证明人类炎症细胞因子和QT间期之间存在当代联系的研究。我们的研究结果表明，较低的炎症负荷可能会保护与RA患者的QTc间期延长。然而，需要进一步的研究来证实前和后细胞因子对QTc间期的影响。
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.