Cerebral small vessel disease (cSVD) is correlated with a high risk of stroke and cognitive impairment. Previous studies between heart rate variability (HRV) and cSVD revealed paradoxical results. The authors aimed to investigate the relationship between HRV and cSVD using Mendelian randomization analysis. Genetic instruments for HRV were obtained from previous genome-wide association studies. They applied inverse variance-weighted analysis, weighted median analysis, simple median analysis, and Mendelian randomization-Egger regression to evaluate the associations of HRV with white matter hyperintensity (WMH) and small vessel stroke (SVS) in the UK Biobank neuroimaging dataset and the MEGASTROKE genome-wide association study dataset. Two genetically predicted traits of HRV (the root mean square of the successive differences of inter beat intervals [RMSSD] and the peak-valley respiratory sinus arrhythmia or high frequency power [pvRSA/HF]) were suggestively associated with WMH (β 0.26, 95% confidence interval [CI] 0.04-0.49, p = .02; β 0.14, 95% CI 0.02-0.27, p = .03, respectively). Genetically predicted traits of HRV were not significantly associated with SVS. This study provides genetic support for a suggestive causal effect of HRV (RMSSD, pvRSA/HF) on WMH but not SVS.
Keywords: Mendelian randomization; cerebral small vessel disease; heart rate variability; white matter hyperintensity.
© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.