Thomas Kofler1, Sébastien Thériault1, Matthias Bossard1, Stefanie Aeschbacher1, Selina Bernet1, Philipp Krisai1, Steffen Blum1, Martin Risch1, Lorenz Risch1, Christine M Albert1, Guillaume Paré1, David Conen2. 1. From the Division of Internal Medicine, Department of Medicine (T.K., S.A., P.K., S.B., D.C.), Cardiovascular Research Institute Basel (T.K., M.B., S.A., S.B., P.K., S.B., D.C.), and Cardiology Division, Department of Medicine (M.B.), University Hospital Basel, Switzerland; Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute (S.T., M.B., G.P., D.C.) and Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine (S.T., G.P.), McMaster University, Hamilton, Ontario, Canada; Division of Cardiology, Hamilton General Hospital, Hamilton Health Sciences, Canada (M.B.); Labormedizinisches Zentrum Dr. Risch, Schaan, Principality of Liechtenstein (M.R., L.R.); Division of Laboratory Medicine, Kantonspital Graubünden, Chur, Switzerland (M.R.); Division of Clinical Biochemistry, Medical University, Innsbruck, Austria (L.R.); Private University, Triesen, FL (L.R.); and Center for Arrhythmia Prevention, Division of Preventive Medicine and Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.M.A.). 2. From the Division of Internal Medicine, Department of Medicine (T.K., S.A., P.K., S.B., D.C.), Cardiovascular Research Institute Basel (T.K., M.B., S.A., S.B., P.K., S.B., D.C.), and Cardiology Division, Department of Medicine (M.B.), University Hospital Basel, Switzerland; Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute (S.T., M.B., G.P., D.C.) and Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine (S.T., G.P.), McMaster University, Hamilton, Ontario, Canada; Division of Cardiology, Hamilton General Hospital, Hamilton Health Sciences, Canada (M.B.); Labormedizinisches Zentrum Dr. Risch, Schaan, Principality of Liechtenstein (M.R., L.R.); Division of Laboratory Medicine, Kantonspital Graubünden, Chur, Switzerland (M.R.); Division of Clinical Biochemistry, Medical University, Innsbruck, Austria (L.R.); Private University, Triesen, FL (L.R.); and Center for Arrhythmia Prevention, Division of Preventive Medicine and Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.M.A.). david.conen@usb.ch.
Abstract
BACKGROUND: Increasing height is an independent risk factor for atrial fibrillation, but the underlying mechanisms are unknown. We hypothesized that height-related differences in electric conduction could be potential mediators of this relationship. METHODS AND RESULTS: We enrolled 2149 adults aged 25 to 41 years from the general population. Height was directly measured, and a resting 12-lead ECG obtained under standardized conditions. Multivariable linear regression models were used to evaluate the association between measured height and ECG parameters. Mendelian randomization analyses were then performed using 655 independent height-associated genetic variants previously identified in the GIANT consortium. Median age was 37 years, and median height was 1.71 m. Median PR interval, QRS duration, and QTc interval were 156, 88, and 402 ms, respectively. After multivariable adjustment, β-coefficients (95% confidence intervals) per 10 cm increase in measured height were 4.17 (2.65-5.69; P<0.0001) for PR interval and 2.06 (1.54-2.58; P<0.0001) for QRS duration. Height was not associated with QTc interval or the Sokolow-Lyon index. An increase of 10 cm in genetically determined height was associated with increases of 4.33 ms (0.76-7.96; P=0.02) in PR interval and 2.57 ms (1.33-3.83; P<0.0001) in QRS duration but was not related to QTc interval or Sokolow-Lyon index. CONCLUSIONS: In this large population-based study, we found significant associations of measured and genetically determined height with PR interval and QRS duration. Our findings suggest that adult height is a marker of altered cardiac conduction and that these relationships may be causal.
BACKGROUND: Increasing height is an independent risk factor for atrial fibrillation, but the underlying mechanisms are unknown. We hypothesized that height-related differences in electric conduction could be potential mediators of this relationship. METHODS AND RESULTS: We enrolled 2149 adults aged 25 to 41 years from the general population. Height was directly measured, and a resting 12-lead ECG obtained under standardized conditions. Multivariable linear regression models were used to evaluate the association between measured height and ECG parameters. Mendelian randomization analyses were then performed using 655 independent height-associated genetic variants previously identified in the GIANT consortium. Median age was 37 years, and median height was 1.71 m. Median PR interval, QRS duration, and QTc interval were 156, 88, and 402 ms, respectively. After multivariable adjustment, β-coefficients (95% confidence intervals) per 10 cm increase in measured height were 4.17 (2.65-5.69; P<0.0001) for PR interval and 2.06 (1.54-2.58; P<0.0001) for QRS duration. Height was not associated with QTc interval or the Sokolow-Lyon index. An increase of 10 cm in genetically determined height was associated with increases of 4.33 ms (0.76-7.96; P=0.02) in PR interval and 2.57 ms (1.33-3.83; P<0.0001) in QRS duration but was not related to QTc interval or Sokolow-Lyon index. CONCLUSIONS: In this large population-based study, we found significant associations of measured and genetically determined height with PR interval and QRS duration. Our findings suggest that adult height is a marker of altered cardiac conduction and that these relationships may be causal.
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