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Published on: June 5, 2019
A two-sample Mendelian randomization analysis of heart rate variability and cerebral small vessel disease
Danyang Tian1, Linjing Zhang1, Zhenhuang Zhuang2
1Department of Neurology, Peking University Third Hospital, Beijing, China.
Insights
This study suggests a potential causal link between heart rate variability (HRV) and white matter hyperintensities (WMH), a marker of cerebral small vessel disease (cSVD). However, no significant association was found with small vessel stroke (SVS).
Area of Science:
- Neurology
- Cardiology
- Genetics
Background:
- Cerebral small vessel disease (cSVD) increases stroke and cognitive impairment risk.
- Previous research on heart rate variability (HRV) and cSVD shows conflicting results.
Purpose of the Study:
- To investigate the causal relationship between HRV and cSVD using Mendelian randomization.
- To assess the association of HRV with white matter hyperintensity (WMH) and small vessel stroke (SVS).
Main Methods:
- Utilized genetic instruments for HRV from genome-wide association studies.
- Employed inverse variance-weighted, weighted median, simple median, and MR-Egger analyses.
- Analyzed UK Biobank neuroimaging and MEGASTROKE GWAS datasets.
Main Results:
- Genetically predicted HRV traits (RMSSD, pvRSA/HF) showed a suggestive association with WMH.
- No significant genetic association was observed between HRV and SVS.
- Suggestive causal effect of HRV on WMH, but not SVS, was identified.
Conclusions:
- Provides genetic evidence supporting a potential causal role of HRV in WMH development.
- Suggests HRV is not causally linked to small vessel stroke.
- Highlights the complex relationship between cardiac autonomic function and cerebrovascular health.
Abstract:
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.
