The Correlation Between Serum 25-hydroxyvitamin D₃ Level And Sleep Quality In Patients With Cerebral Small Vessel Disease:a Clinical Study

Background Cerebral small vessel disease（CSVD）was a clinical,imaging and pathological syndrome which caused by various factors affecting cerebral arteriovenous and capillaries and is considered to be one of the most common causes leading to cognitive decline,mental and emotional abnormalities,gait disorders and so on.Most CSVD patients were over 60 years old.Along with the development of imaging technology,the detection rate of CSVD has increased in younger people year by year.White matter hyperintensity（WMH）was found in 95%of clinical MRI images of asymptomatic patients with CSVD.Unfortunately,the exact pathogenesis of CSVD remains unclear.Currently,a number of studies have suggested that vitamin D deficiency may lead to CSVD through endothelial dysfunction,vascular injury and other mechanisms.Moreover,poor sleep quality is common in patients with CSVD.Clinical 25-hydroxyvitamin D3[25（OH）D3]as a biomarker for the assessment of vitamin D.In addition,vitamin D may play an important role in the regulation of sleep rhythm,thus affecting sleep quality.However,there is limited evidence that changes in25（OH）D3 levels affect sleep quality in patients with CSVD.Objective The purpose of this study was to investigate the changes of serum25（OH）D3 level in patients with CSVD,and to analyze the relationship between25（OH）D3 level of CSVD and different factors of sleep quality.Method From September 2019 to October 2020,142 CSVD patients in the Department of Neurology,Chaohu Hospital Affiliated to Anhui Medical University were selected and divided into three subgroups:WMH group（n=61）,NWMH group（such as lacunar cerebral infarction,cerebral microbleeds,perivascular space,etc.）（n=30）,and MWMH group（n=51）with WMH and other imaging manifestations.In addition,there were 69 patients in the health control（HC）group.General clinical data（age,gender,years of education,height,weight,past disease history and family history,etc.）and serological indexes（liver and kidney function,blood lipid,fasting blood glucose,blood coagulation,electrolytes,etc.）were collected.Pittsburgh sleep quality index（PSQI）,Ford stress insomnia response test（FIRST）,Hamilton Depression Scale（HAMD-17）,Hamilton Anxiety Scale（HAMA-14）and Montreal Cognitive Assessment Scale（Mo CA-C）were used to evaluate the sleep quality,sleep responsiveness,emotion and overall cognitive function of all subjects.Serum25（OH）D3 levels were measured by electrochemiluminescence.Results（1）Background data:there were significant differences in age（F=4.045,P=0.008）,hypertension（χ²=35.038,P=0.001）,diabetes（χ²=8.452,P=0.045）,hyperlipidemi a（χ²=9.804,P=0.025）and vitamin D deficiency（χ²=19.106,P=0.004）between CSVD group and its related subgroups and control group In terms of diabetes and hyperlipidemia,the prevalence of CSVD was higher than that of the control group;in terms of vitamin D deficiency,the prevalence of WMH was the highest,followed by NWMH,and MWMH was higher than that of the control group.There were no significant differences in gender,education years,outdoor work,body mass index（BMI）,smoking history and drinking history among the groups（all P>0.05）.（2）The comparison between CSVD subgroups and the control group showed that there were statistically significant differences in insomnia,FIRST score and PSQI score.The insomnia rate of WMH group was higher than that of the other three groups（χ²=15.007,P=0.002）.The insomnia rate of the control group was higher than that of the NWMH and MWMH groups,and that of the MWMH group was higher than that of the other C SVD group.In terms of FIRST score（F=3.085,P=0.028）,WMH group and control group were higher than NWMH group and MWMH group.For the total scores of PSQI（F=14.907,P<0.001）,CSVD subgroups were higher than that in the control group,and the MWMH group was the worst.In terms of sleep quality related factors,there were statistical differences in sleep time at night（Z=8.886,P=0.027）,sleep efficiency（Z=9.979,P=0.019）,sleep time（Z=16.821,P=0.001）,medication（Z=11.580,P=0.009）,daytime function（Z=9.316,P=0.025）and sleep quality（Z=8.002,P=0.046）.（3）Cognitive function and emotion:there were no significant differences in Mo CA-C,HAMA-14 and HAMD-17 scores between CSVD subgroups and control group（all P>0.05）.（4）The levels of serum markers:25（OH）D₃（F=5.069,P=0.002）,creatinine（Z=9.043,P=0.029）,urea（F=2.972,P=0.033）,homocysteine（F=5.751,P=0.001）,D-Dimer（Z=16.920,P=0.001）in CSVD subgroups were significantly different from those in control group.In terms of 25（OH）D₃ level,WMH group,NWMH group and MWMH group were lower than the control group;in terms of homocysteine,MWMH group and NWMH group were higher than the control group and WMH group;in terms of creatinine and urea,MWMH group was higher than the other three groups;in terms of D-dimer,CSVD subgroups were higher than the control group.（5）Correlation between serum 25（OH）D₃,sleep quality and CSVD subgroups:binary logistic regression analysis showed that hypertension,PSQI,FIRST and 25（OH）D₃levels could predict the occurrence of CSVD（all P<0.05）,and 25（OH）D₃ level was only negatively correlated with WMH（OR=0.922,95%CI:0.873-0.974,P=0.004）.At the same time,we found that WMH was related to sleep time（P=0.035）and medication（P=0.014）in PSQI,while night sleep time,medication and daytime function in PSQI were related to MWMH（all P<0.05）.（6）Correlation between sleep quality and vitamin D status of CSVD:compared with the vitamin D sufficient group,vitamin D insufficiency and vitamin D deficiency had an increased risk of cerebral small vessel disease,the value of OR were 0.309[95%CI=（0.118,0.810）,P=0.017]and 0.215[95%CI=（0.079,0.586）,P=0.003],respectively.In addition,it increased creatinine,urea and the sleep latency of PSQI scales that may lead to vitamin D deficiency（all P<0.05）.Among insomnia patients,vitamin D deficiency was associated with an increased risk of cerebral small vessel disease（OR=0.267,95%CI:0.075-0.956,P=0.043）.Conclusions The level of serum 25（OH）D₃decreased in patients with CSVD.In each CSVD subtype,25（OH）D₃ level was negatively correlated with WMH.The change of 25（OH）D₃ level had an effect on the sleep quality and insomnia of WMH subtype patients in CSVD,which was mainly manifested in the prolonged sleeping time in PSQI.