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Implication of heart rate variability on cerebral small vessel disease: A potential therapeutic target
Yu Tian1,2,3,4,5, Dongxiao Yao1,2,3,4,5, Yuesong Pan1,2,3,4,5
1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Insights
Decreased heart rate variability (HRV) may indicate a higher risk for cerebral small vessel disease (CSVD). Autonomic nervous system (ANS) dysfunction could play a role in CSVD development.
Area of Science:
- Neurology
- Cardiology
- Biomedical Engineering
Background:
- Cerebral small vessel disease (CSVD) is a significant contributor to stroke and cognitive decline.
- Understanding the relationship between autonomic nervous system (ANS) function and CSVD is crucial for risk stratification and prevention.
Purpose of the Study:
- To investigate the association between heart rate variability (HRV) parameters and the presence, severity, and neuroimaging markers of CSVD.
- To explore the potential causal link between HRV and CSVD using Mendelian randomization.
Main Methods:
- Cross-sectional analysis of 4676 participants from the Third China National Stroke Registry (CNSR-III).
- Evaluation of CSVD markers including white matter hyperintensity (WMH), lacunes, enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and brain atrophy (BA).
- Assessment of HRV using RMSSD and SDNN, with logistic regression and Mendelian randomization analyses.
Main Results:
- RMSSD was significantly associated with the total burden and presence of CSVD, as well as WMH burden and Deep-WMH.
- SDNN showed associations with Deep-WMH and brain atrophy (BA).
- Inclusion of HRV improved the predictive performance for CSVD in models with vascular risk factors, though no causality was found via MR analysis.
Conclusions:
- Reduced HRV, particularly RMSSD, may serve as a potential risk factor for CSVD.
- The findings suggest a possible role for ANS dysfunction in the pathogenesis of CSVD.
- HRV may enhance the prediction of CSVD beyond traditional vascular risk factors.
Objective:
This study aimed to investigate the relationships of heart rate variability (HRV) with the presence, severity, and individual neuroimaging markers 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.
Results:
RMSSD 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.
Conclusion:
Decreased HRV may be a potential risk factor of CSVD, implying the possible role of the ANS in the pathogenesis of CSVD.
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