The following is a summary of “CAUSAL RELEVANCE OF ADIPOSITY AND HEIGHT ON ECG PHENOTYPES: A MENDELIAN RANDOMIZATION STUDY,” published in the March 2023 issue of Cardiology by Ardissino, et al.
Cardiovascular disease is a leading cause of death among people with obesity. Previous studies using Mendelian randomization (MR) have established causal links between electrocardiogram (ECG) phenotypes and adverse cardiovascular outcomes such as atrial fibrillation and sudden cardiac death. In addition, observational studies suggest that body size may influence ECG phenotypes. Still, it was challenging to infer causal relationships from such data due to a high risk of residual confounding.
To address the issue, researchers employed MR to explore the causal relevance of various anthropometric measures on five ECG traits: P-wave duration (PWd), P-wave terminal force (PWTF), PR interval, QRS duration, and QT interval. To conduct the analysis, they extracted uncorrelated genome-wide significant single nucleotide polymorphisms (SNPs) (with r2 < 0.001 and P < 5 × 10-8) from genome-wide association studies (GWAS) on body mass index (BMI; n = 806,834), waist-to-hip ratio adjusted for BMI (n = 697,734), and height (n = 709,594). They also obtained genetic association estimates for the five ECG traits from GWAS on 180,574 participants for PR interval, QRS duration, and QT interval and 44,456 participants for PWd and PWTF. They used inverse-variance weighted MR as the primary analysis and weighted median MR and MR-Egger as sensitivity analyses.
The results showed that higher genetically-predicted BMI was associated with higher PWd (B coefficient 5.58 [95% CI 3.66-7.50], P < 0.001), longer PR interval (B 2.29 [95% CI 0.78-3.79], P = 0.003), and longer QT interval (B 2.34 [95% CI 0.91-3.78], P = 0.001). Still, there was no significant difference in QRS duration or PWTF after adjusting for multiple comparisons (PWTF P = 0.047). On the other hand, a higher genetically-predicted waist-to-hip ratio adjusted for BMI was not associated with any significant differences in the five ECG traits after adjusting for multiple comparisons (QT P = 0.044). Finally, higher genetically-predicted height was associated with a longer QT interval (B 2.36 [95% CI 0.40-4.32], P = 0.018).
In conclusion, the study findings suggested a causal role of body size on multiple ECG traits associated with arrhythmias, including atrial fibrillation and sudden cardiac death. The results highlighted a likely role of adiposity in determining arrhythmic risk and also revealed a novel association between height and QT interval that required further investigation.
Reference: jacc.org/doi/10.1016/S0735-1097%2823%2900445-X
