Adlan Ahmed M, Panoulas Vasileios F, Smith Jacqueline P, Fisher James P, Kitas George D
From the College of Life and Environmental Sciences, University of Birmingham, Birmingham; Imperial College London, National Heart and Lung Institute, South Kensington Campus, London; and the Department of Rheumatology, Dudley Group of Hospitals National Health Service (NHS) Trust, Russells Hall Hospital, Dudley, UK.A.M. Adlan, MBBS, MRCP, College of Environmental Sciences; J.P. Fisher, BSc (Hons), PhD, College of Life and Environmental Sciences, University of Birmingham; V.F. Panoulas, MD, PhD, Imperial College London, National Heart and Lung Institute, Department of Rheumatology, Dudley Group of Hospitals NHS Trust; J.P. Smith, BSc (Hons), MSc; G.D. Kitas, MD, PhD, FRCP, Department of Rheumatology, Dudley Group of Hospitals NHS Trust.
J Rheumatol. 2015 Mar;42(3):421-8. doi: 10.3899/jrheum.140861. Epub 2015 Jan 15.
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)-α 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.
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-α, and interleukins (IL-1α, IL-1β, IL-6, IL-10). QTc was calculated using the Bazett (QTBAZ = QT ÷ √RR) and Framingham Heart Study (QTFHS = QT + 0.154 × [1 - RR]) heart rate correction formulas.
Inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10) were positively correlated with QTBAZ (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 QTBAZ (β = 0.202, p = 0.023) and QTFHS (β = 0.223, p = 0.009) when compared to the lower tertile. CRP (per unit increase) was independently associated with QTBAZ (β = 0.278, p = 0.001), but not QTFHS.
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.
校正QT（QTc）间期可预测全因死亡率和心血管死亡率，可能是类风湿关节炎（RA）患者死亡风险增加的原因之一。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。我们试图确定循环炎症细胞因子升高是否与RA患者的QTc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（四分位间距17）岁；80例女性（71%）]接受了基线12导联心电图检查以测量QT间期，并进行了当代血液采样以评估炎症标志物的浓度，包括C反应蛋白（CRP）、TNF-α和白细胞介素（IL-1α、IL-1β、IL-6、IL-10）。使用Bazett公式（QTBAZ = QT÷√RR）和弗雷明汉心脏研究公式（QTFHS = QT + 0.154×[1 - RR]）计算QTc。
炎症细胞因子（TNF-α、IL-1β、IL-6、IL-10）与QTBAZ呈正相关（Spearman等级相关系数rho = 0.199、0.210、0.222、0.333；均p < 0.05）。在多变量回归分析中，除IL-10外，这些关联均受年龄混杂影响，与较低三分位数组相比，较高三分位数组的IL-10与QTBAZ（β = 0.202，p = 0.023）和QTFHS（β = 0.223，p = 0.009）独立且呈正相关。CRP（每单位增加）与QTBAZ独立相关（β = 0.278，p = 0.001），但与QTFHS无关。
据我们所知，我们的研究首次证明了人类炎症细胞因子与QT间期之间的当代联系。我们的结果表明，较低的炎症负担可能预防RA患者的QTc延长。然而，需要进一步研究来证实促炎和抗炎细胞因子对QTc间期的影响。
