Relationships of Measured and Genetically Determined Height with the Cardiac Conduction System in Healthy Adults

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.