Inflammation and Prolonged QT Time: Results from the Cardiovascular Disease, Living and Ageing in Halle (CARLA) Study Daniel Medenwald 1 *, Jan A. Kors 2 , Harald Loppnow 3 , Joachim Thiery 4 , Alexander Kluttig 1 , Sebastian Nuding 2 , Daniel Tiller 1 , Karin H. Greiser 5 , Karl Werdan 2 , Johannes Haerting 1 1 Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany, 2 Department of Medical Informatics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands, 3 Department of Medicine III, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany, 4 Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany, 5 German Cancer Research Centre, Division of Cancer Epidemiology, Heidelberg, Germany Abstract Background: Previous research found an association of CRP with QT time in population based samples. Even more, there is evidence of a substantial involvement of the tumor necrosis factor-alpha system in the pathophysiology of cardiac arrhythmia, while the role of Interleukin 6 remains inconclusive. Objective: To determine the association between inflammation with an abnormally prolonged QT-time (APQT) in men and women of the elderly general population. Methods: Data descend from the baseline examination of the prospective, population-based Cardiovascular Disease, Living and Ageing in Halle (CARLA) Study. After exclusion of subjects with atrial fibrillation and missing ECG recording the final study cohort consisted of 919 men and 797 women. Blood parameters of inflammation were the soluble TNF-Receptor 1 (sTNF-R1), the high-sensitive C-reactive protein (hsCRP), and Interleukin 6 (IL-6). In accordance with major cardiologic societies we defined an APQT above a QT time of 460 ms in women and 450 ms in men. Effect sizes and the corresponding 95% confidence intervals (CI) were estimated by performing multiple linear and logistic regression analyses including the analysis of sex differences by interaction terms. Results: After covariate adjustment we found an odds ratio (OR) of 1.89 (95% CI: 1.13, 3.17) per 1000 pg/mL increase of sTNF-R1 in women, and 0.74 (95% CI: 0.48, 1.15) in men. In the covariate adjusted linear regression sTNF-R1 was again positively associated with QT time in women (5.75 ms per 1000 pg/mL, 95% CI: 1.32, 10.18), but not in men. Taking possible confounders into account IL-6 and hsCRP were not significantly related to APQT in both sexes. Conclusion: Our findings from cross-sectional analyses give evidence for an involvement of TNF-alpha in the pathology of APQT in women. Citation: Medenwald D, Kors JA, Loppnow H, Thiery J, Kluttig A, et al. (2014) Inflammation and Prolonged QT Time: Results from the Cardiovascular Disease, Living and Ageing in Halle (CARLA) Study. PLoS ONE 9(4): e95994. doi:10.1371/journal.pone.0095994 Editor: Andreas Zirlik, University Heart Center Freiburg, Germany Received December 9, 2013; Accepted April 2, 2014; Published April 25, 2014 Copyright: ß 2014 Medenwald et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The CARLA study was supported by a grant from the Deutsche Forschungsgemeinschaft as part of the Collaborative Research Centre 598 ‘Heart failure in the elderly – cellular mechanisms and therapy’ at the Medical Faculty of the Martin-Luther-University Halle-Wittenberg, by a grant from the Wilhelm-Roux Programme of the Martin-Luther-University Halle-Wittenberg, by the Ministry of Education and Cultural Affairs of Saxony-Anhalt, and by the Federal Employment Office. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: daniel.medenwald@uk-halle.de Introduction A prolonged QT time is one of the most important electrocar- diographic abnormalities, and an important cause of sudden cardiac death [1]. Because the QT time is generally longer in females, women are more often affected by arrhythmia due to a prolonged QT interval than men [2]. Over the last decades, research has mainly revealed insights in the genetic pathogenesis of a prolonged QT time [3]. However, the meaning of further pathophysiological mechanisms in the development of this abnormality is still the subject of research. In particular, the role of inflammation parameters and cytokines has rarely been examined. To our knowledge, there are only a few studies examining the association of inflammation and QT time [4,5]. In a population-based sample, Kim et al. found a positive association of increased blood level of C-reactive protein (CRP) and length of the heart rate-corrected QT time (QTc). This is similar to the results in Kazumi et al. [4], who revealed again a significant association of CRP and QTc in a cohort of young healthy men. While the above-mentioned studies focused mainly on CRP, data examining additional inflammation parameters are still missing. Notably, the soluble tumor necrosis factor receptor 1 (sTNF-R1) PLOS ONE | www.plosone.org 1 April 2014 | Volume 9 | Issue 4 | e95994