Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
Implication of heart rate variability on cerebral small vessel disease: A potential therapeutic target
First author：Yu Tian
Corresponding author：Yilong Wang
essential_information
2023-02-14
Published articles
Journal：CNS Neurosci Ther
Publication type: Original Contributions
IF(IF): 7.035
PMID: 36786131 Link To Pubmed Full text Download
Background And Purpose
Autonomic nervous system(ANS) dysfunction are known to be associated with increased all-cause, cardiovascular, and cerebrovascular mortality. Heart rate variability was a non-invasive measure to reflect the function of ANS. Recent advance has suggested that autonomic nervous imbalance may be a novel mechanism of cerebral small vessel disease(CSVD). Yet, there are few evidence whether HRV parameters were associated with the total CSVD burden and different neuroimaging markers. Using the data from CNSR-III, the aim of this study was to investigate the relationship between HRV and the presence and severity of cerebral small vessel disease (CSVD).
Method
A total of 4676 participants from the Third China National Stroke Registry (CNSR-III) study were included in this cross-sectional analysis. CSVD and its markers, including white matter hyperintensity (WMH), lacunes, enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and brain atrophy (BA), were evaluated. Two common HRV parameters, including the square root of the mean of the sum of the squares of differences between adjacent N-N intervals (RMSSD) and the standard deviation of all N-N intervals (SDNN), were used to evaluate the function of the autonomic nervous system (ANS). Binary or ordinal logistic regression analyses were performed to investigate the association between HRV and CSVD. In addition, two-sample mendelian randomization (MR) analyses were performed to investigate the causality of HRV with CSVD.
Conclusion
Decreased HRV may be a potential risk factor of CSVD, implying the possible role of the ANS in the pathogenesis of CSVD.
Main results
MSSD was significantly associated with total burden of CSVD (Wardlaw's scale, common odds ratio [cOR] 0.80, 95% confidence interval [CI] 0.67-0.96, p = 0.02; Rothwell's scale, cOR 0.75, 95% CI 0.60-0.93, p = 0.008) and the presence of CSVD (Rothwell, OR 0.75, 95% CI 0.60-0.93, p = 0.008). However, no significant associations between SDNN and the presence or total burden of CSVD were observed. Moreover, RMSSD was related to WMH burden (OR 0.80, 95% CI 0.66-0.96, p = 0.02), modified WMH burden (cOR 0.82, 95% CI 0.69-0.97, p = 0.02), and Deep-WMH (OR 0.75, 95% CI 0.62-0.91, p = 0.003), while SDNN was related to Deep-WMH (OR 0.80, 95% CI 0.66-0.96, p = 0.02) and BA (cOR 0.80, 95% CI 0.68-0.95, p = 0.009). Furthermore, adding HRV to the conventional model based on vascualr risk factors enhanced the predictive performance for CSVD, as validated by the integrated discrimination index (p < 0.05). In addition, no causality between HRV and CSVD was observed in two-sample MR analyses.