The Effect Of Remote Ischemic Conditioning On Blood Pressure Variability And Heart Rate Variability In Patients With Cerebral Small Vessel Disease

Background and Objective:Cerebral small vessel disease（CSVD）refers to a series of clinical,imaging,and pathological syndromes caused by pathologic changes of small arteries,arterioles,venules and capillaries due to different etiologies.The imaging features of CSVD mainly include recent small subcortical lacunar infarct,lacune,white matter hyperintensity（WMH）,enlarged perivascular space,cerebral microbleeds and brain atrophy.Patients with CSVD have twice the risk of stroke in the future and prevalence increases with age.Previous studies have found that remote ischemic conditioning（RIC）has the potential to improve the prognosis of ischemic stroke,but the mechanism is not clear.Blood pressure variability（BPV）reflects the fluctuation of blood pressure within a certain period of time.It is affected by baroreceptor sensitivity,arterial compliance and autonomic nervous system activity.Heart rate variability（HRV）as one of the basic physiological characteristics of humans,is an important measure of autonomic nervous activity.Both of them are closely related to the progression of acute lacunar infarction and WMH.It has been reported that RIC can improve HRV and BPV in healthy adults,while whether RIC can improve BPV and HRV in patients with CSVD is not clear.The aim of this study was to investigate the effect of RIC on BPV and HRV in patients with CSVD and its mechanism in order to provide new ideas for the prevention and treatment of CSVD.Materials and Methods:In our study,Patients with cerebral small vessel disease were enrolled prospectively from the Department of Neurology of the First Hospital of Jilin University from 2021 to 2022.The patients’ baseline information was recorded and patients were divided into two groups according to their wishes.Subjects in both groups received standard medical treatment,in addition,patients in the intervention group received RIC（200mm Hg）twice per day throughout the duration of hospital stay and patients in the control group received sham-RIC（60mm Hg）twice per day throughout the duration of hospital stay.Patients in both groups underwent serial beat-to-beat monitoring before RIC and after the last RIC treatment and they were followed up for 90 days.The values of BPV included standard deviation（SD）,successive variation（SV）,average real variability（ARV）and variation independent of mean（VIM）of systolic blood pressure,diastolic blood pressure,pulse pressure and mean arterial pressure.The time-domain measures of HRV include SDNN,SDANN,RMSSD,SDNNindex,HRV triangular index and TINN.The frequency-domain parameters such as total power,the power of very low frequency（VLF;0-0.04 HZ）,low-frequency（LF;0.04–0.15 Hz）,high-frequency（HF;0.15–0.40 Hz）,normalized LF,normalized HF and the ratio of LF to HF（LF/HF）were also calculated.Multivariate linear regression model was used to analyze the effect of RIC on BPV and HRV in the two groups and logistic regression model was used to analyze the effect of RIC on good outcome at90 days.Results:A total of 90 subjects completed the study,including 39 subjects（44.3%）in the intervention group and 51 subjects（56.7%）in the control group.There was no significant difference in gender,age,onset-baseline time,previous risk factors,NIHSS score and times of RIC/sham-RIC treatment between two groups at admission（P>0.05）.Multivariate linear regression model revealed a negative correlation between RIC and DBP-ARV（B=-0.181,P=0.014）;As well as a negative correlation between RIC and DBP-SV（B=-0.205,P=0.031）.We further found an excellent recovery in NIHSS score at discharge in the intervention group compared with the control group（median in intervention group: 1.00,median in control group: 1.00,P=0.037）.No significant differences were found in HRV,favorable outcome at 90 days or the variability of SBP,PP and MAP between two groups.Conclusions:（1）RIC improves neurological symptoms in the acute stage in patients with CSVD;（2）RIC can reduce beat-to-beat diastolic blood pressure variability in patients with CSVD,but has no significant effect on HRV;（3）RIC treatment as an adjunctive therapy during hospitalization may benefit patients with CSVD by reducing BPV.