title: Association between corrected QT interval and inflammatory cytokines in rheumatoid arthritis.
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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Adlan
authors.affiliation: 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.
authors.forename: Vasileios F
authors.initials: VF
authors.lastname: Panoulas
authors.affiliation: 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.
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Smith
authors.affiliation: 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.
authors.forename: James P
authors.initials: JP
authors.lastname: Fisher
authors.affiliation: 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.
authors.forename: George D
authors.initials: GD
authors.lastname: Kitas
mesh_terms: D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D053840:Brugada Syndrome; D000075224:Cardiac Conduction System Disease; D016207:Cytokines / Q000097:blood*; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000002:abnormalities* / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D016207:Cytokines
keywords: ARRHYTHMIA; CARDIOVASCULAR; CYTOKINES; INFLAMMATION; QTc INTERVAL; RHEUMATOID ARTHRITIS