| Part I: A cross-sectional epidemiological study of sleep-related factors in Chinese over40 years old Objective: To investigate the sleep quality of people over 40 years old in Chinese community,to analyze the risk factors of stroke among people with poor sleep quality,snoring and night shift,and to explore the relationship between sleep quality,snoring symptoms,night shift and stroke.METHODS: Based on the national screening and intervention program for high-risk population of stroke in 2016,a cross-sectional survey was conducted in 31 provinces from April 2016 to May 2017,and 423,603 community permanent residents over 40 years old completed the screening program.Among them,15,016 people completed the study “ the association between sleep and stroke”,58,696 completed the snoring questionnaire,and 58,633 completed the night shift questionnaire.In this study,demographic information,medical history information and stroke risk factors were analyzed based on the questionnaire of these three groups of people.Results:1.The proportion of poor sleep quality in community population over 40 years old was 15.9%.The proportion of poor sleep quality was higher in women,old people,widowed spouse,people with low education level,people with low income,people who had less time of physical activity,people with lack of exercise,and people with poor diet(P<0.05).Compared with the group with good sleep quality,the proportion of coronary heart disease,hypertension,hyperlipidemia,diabetes,snoring,atrial fibrillation,stroke and high-risk group of stroke risk rating were higher in the group with poor sleep quality(P<0.05).2.The proportion of snoring among people over 40 years old in the community was 35.8%.Compared to the non-snoring group,the proportion of men,people with low level of education,low income,working hours,drinking,smokeing,lack of exercise,poor eating habits,high blood pressure,uncontrolled blood pressure,hyperlipidemia,diabetes,atrial fibrillation,transient ischemic attack(TIA),liver cirrhosis,renal insufficiency or high-risk group of stroke risk rating was higher(P < 0.05)in snoring group and they were more likely to have less sleep time at night,take sleeping pill at night,and have headache or dizziness in the morning(P<0.05).The body mass index(BMI),waist circumference,neck circumference,fasting blood glucose,triglyceride(TG),total cholesterol(TC),low density lipoprotein(LDL)and homocysteine(Hcy)levels in snoring group were higher than the non-snoring group,and high density lipoprotein(HDL)levels were lower(P<0.05).The composition ratio of multiple plaques was higher in snoring group(P<0.05).3.The proportion of night shift of people over 40 years old in the community was5.9%.The proportion of men,people with higher education,higher income,long working hours,lack of exercise,using sleep pill,people who feel headache or dizziness in the morning,people with TIA,high risk for stroke,and high blood pressure were higher in night shift workers than non-night shift workers(P<0.05).The m RS score of night shift group was higher than the non-night shift group(P<0.05).The levels of BMI,fasting blood glucose,2h postprandial blood glucose,glycated hemoglobin,TG,TC,LDL,HDL and Hcy in night shift group were lower than the non-night shift group(P<0.05).The proportion of irregular plaque on the left side of CCA,low echo and strong echo plaque on both sides of CCA was higher in night shift group(P<0.05).(P<0.05).Conclusion:1.Women,widows and people with low education level,old age and low-income were more likely to suffer from poor sleep quality.Compared with the group with good sleep quality,the proportion of coronary heart disease,hypertension,hyperlipidemia,diabetes,snoring,atrial fibrillation,stroke and high-risk group in stroke risk rating were higher in the group with poor sleep quality.Sleep quality might be related to the risk factors of stroke.2.The proportion of snoring was higher in people over 40 years old in the community.Risk factors of stroke and uncontrolled blood pressure are higher in people with snoring who may have decreased sleep quality,and were more prone to have morning headache or dizziness.Snoring may be associated with risk factors of stroke.Snoring might be related to carotid atherosclerosis。3.Lack of sleep,disturbed circadian rhythms,use of sleep pills,lack of exercise and disturbed eating rhythms were common problems among night shift workers.The proportion of stroke risk factors in night shift group was higher than that in non-night shift group,which may be related to the risk factors of stroke.The adaptability increased after a long time of night shift,and the metabolic situation tended to be stable.The levels of BMI,pulse,fasting blood glucose,2h postprandial blood glucose,glycated hemoglobin,TG,TC,LDL,HDL and Hcy in night shift group were lower than the non-night shift group.The CCA plaques in the night shift group were higher than the non-night shift group,suggesting that the night shift might lead to the damage of CCA artery endothelium.Part two The relationship between sleep disturbance and prognosis of stroke Objective:To investigate the effects of sleep disorders on cognitive and neurological function after stroke,and other factors that affect cognitive and neurological function after stroke.METHODS: 1542 patients with first stroke(cerebral infarction,TIA and cerebral hemorrhage)admitted to Department of Neurology of Tianjin Huanhu Hospital from January 1,2015 to December 31,2016.Personal history,family history,and previous history of the patient were recorded.Scale simple mental state examination(MMSE)score,Montreal cognitive assessment scale(Mo CA)scores,Hamilton depression scale(HAMD)scores,the United States national institutes of health stroke scale(NIHSS)score,Pittsburgh sleep quality index(PSQI)score,ESS score,Berlin questionnaire score,STOPBANG questionnaire,Barthel index(BI),total sleep time(TST)at night were assessed before discharge.All patients were followed up at 3 months,6 months and 4 years(2019-2020)after stroke,and the scale was re-evaluated at follow-up.The sleep state,cognitive function and neurological function recovery of the patients were assessed.Results:1.The proportion of poor sleep quality was 52.5% at admission,46.8% at 3months follow-up,40.9% at 6 months follow-up,and 40.2% at 4 years follow-up.The proportion of nocturnal TST(<7h)was 50.8% at admission,49.3% at 3-month followup,46.6% at 6-month follow-up,and 43.9% at 4-year follow-up.The rate of nocturnal TST(>8h)was 13.9% at admission,12.9% at 3 months follow-up,7.6% at 6 months follow-up,and 12.6% at 4 years follow-up.The proportion of sleepiness was 21.4% at admission,21.8% at 3 months follow-up,22.3% at 6 months follow-up,and 21.6% at4 years follow-up.High risk of OSA was 74.7% at admission,75.8% at 3 months follow-up,78% at 6 months follow-up,and 77.4% at 4 years follow-up.2.Poor sleep quality(OR 2.587,95%CI 1.601-4.180,P<0.001),high risk of OSA(OR 2.788,95%CI 1.374-5.660,P=0.005)were risk factors for poor neurological recovery at 3 months after stroke.Nocturnal TST(<7h)(OR 12.853,95%CI 2.193-75.323,P=0.005)and nocturnal TST(>8h)(OR 13.293,95%CI 1.96-90.156,P= 0.008)were risk factors for poor neurological recovery 6 months after stroke;nocturnal TST(<7h)(OR 11.853,95%CI 2.213-63.475,P=0.004),wake stroke(OR 2.696,95%CI1.251-5.811,P=0.011),high risk of OSA(OR 1.756,95%CI 1.197-2.576,P=0.004)were risk factors for neurologic decline at 4 years after stroke.3.Nocturnal TST(<7h)was a risk factor for post-stroke cognitive impairment(PSCI)at 3 months(OR 5.035,95%CI 2.989-8.481,P<0.001)and 6 months(OR 7.085,95%CI 3.452-14.541,P<0.001)after stroke.Wake-up stroke(OR 2.862,95%CI1.495-5.479,P=0.002)and poor sleep quality(OR 7.265,95%CI 1.517-34.797,P=0.013)were risk factors for PSCI at 4 years after stroke.Poor sleep quality(OR1.661,95%CI 1.087-2.539,P=0.019)was a risk factor for dementia(PSD)at 3months after stroke.Nocturnal TST(>8h)(OR 8.629,95% 1.413-52.694,P=0.020)was a risk factor for PSD 4 years after stroke.Wake-up stroke(OR 2.002,95%CI1.330-3.013,P=0.001),high risk of OSA(OR 1.799,95%CI 1.432-2.261,P<0.001),drowsiness(OR 2.820,95%CI 1.777-4.476,P=0.000),nocturnal TST(<7h)(OR6.188,95%CI 2.900-13.206,P<0.001)and nocturnal TST(>8h)(OR 3.494,95%CI1.506-8.107,P=0.004)were risk factors for cognitive decline 4 years after stroke.4.Female,cerebral hemorrhage,large lesions,multiple lesions,high grade of hippocampus,high grade of leukoaraiosis,high systolic blood pressure,depression and early neurological deterioration(END)were all risk factors for poor neurological recovery(m RS >2)in early(3 months or 6 months)after stroke(P<0.05).END,depression,low Mo CA score,high score of Medial temporal lobe atrophy(MTA),internal carotid artery(ICA)stenosis,recurrent stroke,and cerebral hemorrhage were risk factors for poor neurological recovery(m RS >2)in late(4 years)post-stroke patients(P<0.05).END,recurrent stroke,and basilar artery(BA)stenosis were risk factors for poor neurological function at 4 years after stroke(P<0.05).5.Depression,poor neurological recovery(m RS >2),low education level,cerebral infarction,high grade of Fazekas,middle cerebral artery stenosis,large area lesions,critical site lesion,END were risk factors for cognitive impairment in early(3 or 6months)after stroke(P<0.05).END,worsen depression,low education level,large lesions,critical site lesion,high score of MTA,high score of Fazekas were risk factors for cognitive impairment at 4 years after stroke(P<0.05).ICA stenosis and depression were risk factors for late-onset cognitive impairment 4 years after stroke(P<0.05).6.High risk of OSA(HR 1.382,95%CI 1.125-1.699,P=0.002),old age(HR1.088,95%CI 1.059-1.119,P<0.001),microhemorrhage(HR 1.931,95%CI 1.213-3.073,P=0.006),vertebral artery(VA)stenosis(HR 1.517,95%CI 1.046-2.201,P=0.028),and BA stenosis(HR 1.678,95%CI 1.076-2.616,P=0.022)were risk factors for all-cause mortality in patients followed up for 4 years after stroke.7.In group of TIA,the prevalence of cognitive impairment at admission was79.3%(8.9% for PSD and 70.4% for PSCIND),at 3 months was 68.1%(7.4% for PSD and 60.7% for PSCIND),at 6 months was 62.1%(7.5% for PSD and 55.6% for PSCIND),at 4 years was 52.2%(8.7% for PSD and 43.5% for PSCIND).Conclusion:1.Through the follow-up of patients with stroke,sleep quality and nocturnal TST improved over time after stroke;there was no significant change in sleepiness after stroke and the high risk of OSA did not improve significantly after stroke,but showed an upward trend.2.Poor sleep quality,high risk of OSA,and short or long nocturnal TST were risk factors for poor neurological recovery after stroke.3.Short nocturnal TST,wake-up stroke and poor sleep quality were the risk factors for cognitive impairment after stroke.Poor sleep quality and long nocturnal TST were risk factors for PSD after stroke.Wake-up stroke,high risk of OSA,drowsiness,and short or long nocturnal TST were risk factors for cognitive decline at 4 years followup.4.Gender,age,depression,stroke type,stroke location,stroke characteristics and arterial stenosis were risk factors for cognitive impairment and poor neurological recovery after stroke.5.High risk of OSA,old age,microhemorrhage,VA stenosis and BA stenosis were risk factors for all-cause death in patients with stroke.6.Cognitive impairment was very common in patients with TIA,and we should pay attention to cognitive impairment after TIA.Part three Relationship between APOE,COMT gene polymorphism,subjective sleep and cognitive impairment and prognosis after cerebral infarction Objective: To investigate the effects of apolipoprotein E(APOE)and catechol-Omethyltransferase(COMT)gene polymorphism,sleep quality and nocturnal TST on cognitive impairment and neurological function recovery in patients with cerebral infarction.Methods: 634 patients with first-onset cerebral infarction were admitted to the Department of Neurology in Tianjin Huanhu Hospital from February 1,2012 to February 1,2013,Personal history,family history,previous history,NIHSS score on admission,and nocturnal TST were recorded.APOE,COMT gene were tested,PSQI questionnaire,MMSE,Mo CA,Barthel index scores were performed,and the m RS scores at discharge were evaluated.Patients were followed up at 3 months,6 months,4 years(2016-2017),and 8 years(2020-2021),with an average follow-up time of6.2±2.6 years.MMSE、MOCA score、Barthel index、 NIHSS score and m RS score were evaluated during follow-up.To analyze the factors influencing the recovery of cognitive function and neurological function after cerebral infarction.Result:1.The TG of APOE2 carriers was higher than that of APOE3 carriers(P=0.005),the TC and apolipoprotein B(Apo B)of APOE4 carriers were higher than that of APOE2(P<0.05)and APOE3(P<0.01).LDL of APOE4 carriers was higher than that of APOE2 carriers(P<0.001).LDL and Apo B of APOE3 carriers were higher than those of APOE2 carriers(P<0.001).Compared with COMT-M carriers,the levels of TG(P=0.002),TC(P<0.001),LDL(P=0.018),Apo B(P=0.001),and Hcy(P=0.006)were increased in COMT-V/V carriers.2.The proportion of poor sleep quality and short nocturnal TST time(<5h and<7h)of APOE4 carriers was higher than that of non-APOE4 carriers(P<0.001),and APOE4 carriers have higher PQSI score(P<0.001).Patients with COMT-M had a higher proportion of poor sleep quality than those with COMT-V/V(P=0.008).3.There was no significant correlation between APOE gene polymorphism,COMT gene polymorphism and neurological function recovery at discharge,3 months,6 months and 4 years after cerebral infarction(P>0.05).The APOE4 carriers(OR 0.160,95%CI 0.029-0.879,P=0.035)had better neurological recovery 8 years after cerebral infarction.Nocturnal TST(5-7h)was a risk factor for poor neurological recovery at discharge(m RS>2)(OR=0.356,95%CI 0.159-0.794,P=0.012).Sleep quality had no effect on neurological recovery after stroke(P >0.05).4.The risk factors affecting cognitive impairment in patients with cerebral infarction on admission included COMT-M genotype(OR=2.170,95%CI=1.340-3.515,P=0.002),poor sleep quality(OR=3.263,95%CI=1.450-7.342,P=0.004),nocturnal TST(8-9H)(OR=5.896,95%CI=1.818-19.116,P=0.003);risk factors for cognitive impairment at 3 months after cerebral infarction included COMT-M genotype(OR 2.006,95%CI 1.236-3.255,P=0.005),poor sleep quality(OR 2.455,95%CI1.112-5.419,P=0.026),nocturnal TST(5-7h)(OR 2.857,95%CI 1.215-6.719,P=0.016),nocturnal TST(8-9h)(0R 5.592,95%CI 1.809-17.283),P=0.003).Risk factors for cognitive impairment at 6 months after cerebral infarction included COMT-M genotype(OR 2.253,95%CI 1.383-3.672 P=0.001)and nocturnal TST(8-9H)(0R 5.572,95%CI1.803-17.221,P=0.003).The risk factors for cognitive impairment 4 years after cerebral infarction were COMT-M genotype(OR 1.940,95%CI 1.093-3.443,P=0.024),poor sleep quality(OR 4.511,95%CI 1.949-10.438,P<0.001),nocturnal TST(8-9H)(OR 11.286,95%CI 2.828-45.035,P=0.001).Risk factors for dementia 4 years after cerebral infarction included nocturnal TST(<7h)(OR 5.051,95%CI 1.103-23.140,P=0.037);Risk factors for late-onset cognitive impairment 4 years after cerebral infarction included COMT-V/V genotype(OR 3.025,95%CI 1.127-8.117,P=0.028);The risk factors for cognitive impairment 8 years after cerebral infarction were COMTM genotype(OR 2.994,95%CI 1.517-5.917,P=0.002),poor sleep quality(OR 4.863,95%CI 1.826-12.953,P=0.002),nocturnal TST(>8)(OR 21.363,95%CI 5.619-81.225,P<0.001).The risk factors for dementia 8 years after cerebral infarction were COMTV/V(OR 3.167,95%CI 1.137-8.820,P=0.027).The risk factors for late onset cognitive impairment 8 years after cerebral infarction were APOE4 genotype(OR 4.844,95%CI1.270-18.479,P=0.021)and COMT-V/V(OR 3.529,95%CI 1.445-8.622,P=0.006).The risk factors of early onset cognitive impairment 8 years after cerebral infarction were APOE2(OR 0.125,95%CI 0.021-0.754,P=0.023)and nocturnal TST(5-7h)(OR0.150,95%CI 0.042-0.535,P=0.003).5.The higher the MOCA score,the better the neurological function recovery after cerebral infarction.Older patients had poor recovery of neurological function 8 years after cerebral infarction(P<0.05).Diabetic patients had poor recovery of neurological function 4 years after cerebral infarction(P<0.05).Low education level,old age,poor neurological recovery,high blood glucose or diabetes mellitus were risk factors for cognitive impairment or dementia after cerebral infarction(P<0.05).Low education level,poor neurological recovery,hyperglycemia or diabetes mellitus were risk factors for early onset cognitive impairment(P<0.05).6.Nocturnal TST(< 5h)(HR 11.828,95%CI 1.441-97.067,P=0.021),nocturnal TST(8-9)(HR 10.345,95%CI 3.519-30.408,P<0.001),old age(HR 1.052,95%CI1.014-1.092,P=0.007),high TC(HR 2.545,95%CI 1.369-4.730,P=0.003),high Hcy(HR 1.059,95%CI 1.036-1.082,P<0.001)were risk factors for all-cause death after cerebral infarction;Patients with high TG had a lower risk of all-cause death(HR 0.584,95%CI 0.356-0.959,P=0.034),and patients with high TG had better neurological function recovery 8 years after cerebral infarction(OR 0.485,95%CI 0.243-0.969,P=0.040).Conclusion:1.In patients with acute cerebral infarction,the TC,LDL and Apo B of APOE4 carriers were significantly higher than those of non-APOE4 carriers.The APOE4 gene is closely associated with hyperlipidemia.Compared with COMT-M carriers,COMTV/V carriers had higher blood lipids and Hcy.In patients with acute cerebral infarction,the sleep quality of APOE4 carriers was poor,nocturnal TST of APOE4 carriers was short,and the sleep quality of COMT-M carriers was poor.2.There was no significant correlation between APOE4 genotype and neurological function recovery after cerebral infarction,3 months,6 months and 4 years,but APOE4 patients had better neurological function recovery 8 years after cerebral infarction.There was no significant correlation between COMT genotype,sleep quality and neurological function recovery after cerebral infarction.Short nocturnal TST is the reason for poor recovery of neurological function after cerebral infarction in short term.3.There was no significant correlation between APOE genotype and cognitive function recovery after cerebral infarction.APOE4 was a risk factor for late onset cognitive impairment after cerebral infarction.COMT-M,poor sleep quality,and nocturnal TST were risk factors for cognitive impairment after cerebral infarction.COMT-V/V was a risk factor for dementia at 8 year after cerebral infarction 8 and was a risk factor for late onset cognitive impairment.4.The higher the Mo CA score,the better the neurological function recovery.Low education level,older age,poor neurological recovery,hyperglycemia or diabetes were risk factors for cognitive impairment after cerebral infarction.Low education,poor neurological recovery,hyperglycemia or diabetes were risk factors for early onset cognitive impairment.5.Cerebral infarction patients with long nocturnal TST,short nocturnal TST,old age,high total cholesterol,and high homocysteine had higher risk of all-cause death.Patients with higher triglycerides had lower risk of all-cause death and had better neurological recovery 8 years after cerebral infarction. |
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