Ahmed M Adlan1, Vasileios F Panoulas2, Jacqueline P Smith2, James P Fisher2, George D Kitas2. 1. 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. adlan.ahmed@gmail.com. 2. 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.
Abstract
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)-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. 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-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. RESULTS: 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. 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.
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)-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. 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-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. RESULTS: 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. 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.
Authors: Nino Isakadze; Marc C Engels; Dominik Beer; Rebecca McClellan; Lisa R Yanek; Bahareh Mondaloo; Allison G Hays; Thomas S Metkus; Hugh Calkins; Andreas S Barth Journal: Front Cardiovasc Med Date: 2022-06-23
Authors: Laura Geraldino-Pardilla; Yevgeniya Gartshteyn; Paloma Piña; Marina Cerrone; Jon T Giles; Afshin Zartoshti; Joan M Bathon; Anca D Askanase Journal: Lupus Sci Med Date: 2016-12-16
Authors: Ricardo Rivera-López; Juan Jiménez-Jáimez; José Mario Sabio; Mónica Zamora-Pasadas; José Antonio Vargas-Hitos; Josefina Martínez-Bordonado; Nuria Navarrete-Navarrete; Ricardo Rivera Fernández; E Sanchez-Cantalejo; Juan Jiménez-Alonso Journal: PLoS One Date: 2016-04-11 Impact factor: 3.240