| Background :Ischemic cerebrovascular disease, is one of the major causes of hospitalization and death in affluent societies.According to World Health Organization: the incidence rate of acute cerebrovascular disease 250/10 million; and compared with other countries in the world, the recurrence rate of acute cerebrovascular disease of China predominates in the world; in Beijing, large cities, the incidence of acute cerebrovascular disease as high as 270/10 million people each year, and gradually increased. Unlike in western countries, cerebrovascular disease predominates; the number of patients who die from stroke is more than three times that from coronary heart disease. It brought a heavy burden to the community and the family. Cerebral large-artery occlusive disease represents an important cause of ischemic stroke worldwide. Therefore, the study of intracranial-extracranial atherosclerosis is very import for prevention and treatment of acute cerebrovascular diseases. With a population of 1.3 billion, China is facing a serious problem of ageing population, and the incidences of MetS and cognitive impairment are expected to substantially increase. Recent studies have demonstrated an association between MetS and cognitive impairment in elderly individuals. To date, the relationship between MetS and cognitive impairment in the Chinese population has been less frequently reported, especially in asymptomatic intra- and extracranial atherosclerotic residents.Therefore, the present study investigated the following four aspects: (1) The association between intracranial,extracranial atherosclerosis and metabolic syndrome; (2) The relationship of the distribution of cerebral atherosclerosis with the serum apolipoprotein B concentrations following acute IS/TIA and apolipoprotein B polymorphism; (3) The association between intracranial, extracranial atherosclerosis and the plasma concentrations of adipocytokine; (4) Metabolic syndrome and cognitive impairment among elderly people in asymptomatic intra- and extracranial atherosclerotic residents.Part One The association between intracranial,extracranial atherosclerosis and metabolic syndromeObjectiveTo elucidate the relationship between intracranial,extracranial atherosclerosis and metabolic syndrome.Subjects and methodsAmong the consecutive IS/TIA patients aged 60 years old and over admitted to our stroke unit between September 2008 and September 2009, 318 patients were preformed by Digital subtraction angiography (DSA). Atherosclerotic stenotic lesions on DSA were subdivided into extracranial and intracranial categories. Based on the DSA study, we selected 192 patients and divided them into two subgroups, intracranial group (105 patients with only intracranial atherosclerotic lesions) and extracranial group (87 patients with isolated extracranial atherosclerotic lesions). Atotal of 196 age- and sex-matched individuals were randomly selected as controls from health examination subjects. Controls consecutively referred to our vascular ltrasound laboratory, with no evidence of cerebral arteries stenosis at ultrasound examination. Collected demographic data, past medical history, biochemical markers and abdominal circumference corresponding situation.According to the IDF criteria to diagnosis MS. The multiple logistic regression analyses were used to study the association between MS and intra-/extracranial atherosclerosis status.Results1.The study stample consisted of 388 subjects who who underwent Digital subtraction angiography(DSA) examination at baseline examination, respectively, 250 men and 138 women. The mean age is 65.8±9.3. Compared with controls, intra- and extracranial groups showed significantly higher number of men, older, more smoker, higher prevalence of diabetes, higher prevalence of hypertension, higher BMI, larger prevalence of metabolic syndrome(P﹤0.05,P﹤0.01), but there are no significant deviation between the intra- and extracranial group; Compared with controls, intra- and extracranial groups showed significantly higher apoB and apoE concentrations, but there are no significant deviation between the intra- and extracranial group. metabolic syndrome was present in 94 (31.4%) subjects. Compared with control and extracranial group, the intracranial group had a higher level of metabolic components.2. Among the intracranial group, the prevalence of metabolic syndrome was significantly different between the 30% -69% stenosis and≥70% stenosis(P﹤0.05), and patients with≥70% stenosis had higher components of high BP and IFG, and higher number of MetS components(range from 3 to 5 ) than the patients with 30% -69% stenosis (P﹤0.05); Among the extracranial group, the prevalence of and the components of metabolic syndrome were not different between the patients with 30% -69% stenosis and with≥70% stenosis.3. After adjustment for gender, smoking and coronary artery disease,there was a strong association between intracranial atherosclerosis and metabolic syndrome, (p< 0.001), in addition, the components of metabolic syndrome, such as high BP, IFG were significantly associated with intracranial atherosclerosis. There was no significant association between extracranial atherosclerosis and metabolic syndrome after adjustment for age, smoking and coronary artery disease. In the components of metabolic syndrome, IFG was significantly associated with extracranial atherosclerosis.Conclusions1. Intracranial atherosclerosis was independently associated with MetS; 2. Among the MetS components, high BP and IFG were associated with intracranialatherosclerosis, IFG was associated with extracranial atherosclerosis.Part Two Relationship between intracranial , extracranial atherosclerosis and apolipoprotein B gene polymorphisObjectiveInvestigated the relationship of the distribution of cerebral atherosclerosis with the serum apoB concentrations and apoB polymorphism. Explore the molecular mechanism of cerebral atherosclerosis.Subjects and methodsAmong the consecutive IS/TIA patients aged 60 years old and over admitted to our stroke unit between September 2008 and September 2009, 318 patients were preformed by Digital subtraction angiography (DSA). Atherosclerotic stenotic lesions on DSA were subdivided into extracranial and intracranial categories. Based on the DSA study, we selected 192 patients and divided them into two subgroups, intracranial group (105 patients with only intracranial atherosclerotic lesions) and extracranial group (87 patients with isolated extracranial atherosclerotic lesions). Atotal of 196 age- and sex-matched individuals were randomly selected as controls from health examination subjects. Controls consecutively referred to our vascular ltrasound laboratory, with no evidence of cerebral arteries stenosis at ultrasound examination.The identification of the polymorphism was performed by Pyroseqnencing.The multiple logistic regression analyses were used to study the association between apoB polymorphism and intra-/extracranial atherosclerosis status.Results1. Compared with controls, intra- and extracranial groups showed significantly high concentrations of apoB. No significant difference was found in apoB concentrations between intra- and extracranial groups.2. ApoB A66848G genotype and allele frequencies of intra- and extracranial groups significantly higher than controls, but no significant difference was found between intra- and extracranial groups; The frequencies of A/G genotype and G allele were no difference between intra- and extracranial group with different diameter reduction; The apoB A66848G single-nucleotide polymorphism did not influence apoB serum concentrations in both patients and controls.3. ApoB G79834A genotype and allele frequencies of intra- and extracranial groups significantly higher than controls, but no significant difference was found between intra- and extracranial groups; The frequencies of G/A genotype and A allele were no difference between intra- and extracranial groups with different diameter reduction; The apoB G79834A single-nucleotide polymorphism influenced apoB serum concentrations in both patients and controls(P﹤0.05).4. No significant difference was found in apoB A47458G either both patients or controls; However, A/G genotype and G allele were significantly higher in extracranial group than that in intracranial group; The frequencies of A/G genotype and G allele were no difference between intra- and extracranial group with different diameter reduction. The apoB A47458G single-nucleotide polymorphism influenced apoB serum concentrations in both patients;5. ApoB A47458G polymorphism remained significantly associated with extracranial atherosclerosis.Conclusions1. Serum apoB is associated with cerebral atherosclerotic disease;2. ApoB G79834A,A47458G single-nucleotide polymorphism influence apoB serum concentrations;3. The apoB A47458G polymorphism is significantly associated with extracranial atherosclerosis;4. ApoB A47458G polymorphism is one possible genetic determinant for the difference between intra- and extracranial atherosclerosis.Part Three The association between intracranial,extracranial atherosclerosis and the plasma concentrations of adipocytokineObjectiveTo elucidate the association between serum APN,TNF-α,IL -6 and PAI- 1concentrations and intra-/extracranial atherosclerosis status. Subjects and methodsAmong the consecutive IS/TIA patients aged 60 years old and over admitted to our stroke unit between September 2008 and September 2009, 318 patients were preformed by Digital subtraction angiography (DSA). Atherosclerotic stenotic lesions on DSA were subdivided into extracranial and intracranial categories. Based on the DSA study, we selected 192 patients and divided them into two subgroups, intracranial group (105 patients with only intracranial atherosclerotic lesions) and extracranial group (87 patients with isolated extracranial atherosclerotic lesions). Atotal of 196 age- and sex-matched individuals were randomly selected as controls from health examination subjects. Controls consecutively referred to our vascular ltrasound laboratory, with no evidence of cerebral arteries stenosis at ultrasound examination. The serum APN, TNF-α, IL -6 and PAI-1 concentrations were measured in ELISA. T-test was used to assess difference between groups based on category. The multiple logistic regression analyses were used to study the association between serum APN, TNF-α, IL-6 and PAI-1concentrations and intra-/extracranial atherosclerosis status.Results1. Compared with control, intra- and extracranial groups showed significantly low concentrations of APN, and high concentrations of PAI-1, TNF-α, IL-6; The concentration of APN of intracranial group is lower than extracranial group.2. Diameter reduction influence serum APN concentrations in intracranial group(P<0.05 ),although, the serum PAI-1,IL-6 and TNF-αconcentrations is higher in≥70% diameter reduction than 30%-69% diameter reduction, but there was no significiant difference. In extracranial group serum APN concentrations is lower in≥70% diameter reduction than 30%-69% diameter reduction, but there was no significiant difference, the serum PAI-1,IL-6 and TNF-αconcentrations is aslo higher in≥70% diameter reduction, but no significiant difference; The serum APN concentrations were difference between intra- and extracranial group with different diameter reduction(P<0.05 ); The serum PAI-1, TNF-αand IL-6 concentrations were no difference between intra- and extracranial group with different diameter reduction3. After adjustment for gender, smoking and coronary artery disease, we found serum APN, TNF-α, IL-6 and PAI-1 concentrations were independently associated with intracranial atherosclerosis; After adjustment for gender, smoking, serum TNF-α, IL-6 and PAI-1concentrations were independently associated with intracranial atherosclerosis, excepted serum APN concentration.Conclusions1. Plasma concentrations of adipocytokine may predict the intra- and extracranial atherosclerosis;2.Intracranial atherosclerosis is independently associated with low serum adiponectin and high serum PAI-1,IL-6 and TNF-αconcentrations;3. Extracranial atherosclerosis is independently associated with high serum PAI-1,IL-6 and TNF-αconcentrations.Part Four Metabolic syndrome and cognitive impairment among elderly people in asymptomatic intra- and extracranial atherosclerotic residentsObjectiveTo elucidate the relationship between intracranial-extracranial atherosclerosis and metabolic syndrome among elderly people in asymptomatic intra- and extracranial atherosclerotic residentsSubjects and methodsWe randomly selected the participants for this investigation from the Gaoxing, Yubei and Yuzhong districts of Chongqing City. included 3,409 participants aged 60 years and over were preformed by ultrasound examination and CTA/MRA in the study. Collected demographic data, past medical history, biochemical markers and abdominal circumference corresponding situation. According to the IDF criteria to diagnosis MS. The screening procedure included the Mini-Mental State Examination (MMSE), the Activity of Daily Living (ADL) test, as well as a general condition inventory. The MMSE was extensively used to measure cognitive function The multiple logistic regression analyses were used to study the association between MS and intra-extracranial atherosclerosis status.Results1.The 3216 participants enrolled in the study had a mean age of 69.4 (±3.81) years, 45.9% were female. Cognitive impairment was observed in 470 (14.6%) individuals. MetS was present in 733 (22.8%) subjects. Among those with the MetS, 183 participants (25%) also had cognitive impairment. 422 participants had extracranial- intracranial arterial sclerosis. Participants with cognitive impairment were older and had higher prevalence of diabetes, higher prevalence of hypertension, higher BMI, larger mean waist circumference, higher systolic blood pressure, more current smokers, lower HDL cholesterol and higher fasting plasma glucose than did participants without cognitive impairment. In addition, participants had extracranial- intracranial arterial sclerosis were more likely to be cognitively impaired.2. Compared with the group without ext racranial- intracranial arterial sclerosis ,ext racranial-intracranial arterial sclerosis had lower scores in MMSE ( P < 0. 01), higher score in ADL ( P < 0. 05)。3. Cognitive impairment was directly associated with MetS after adjusting for gender, drinking and education. Age, current smoking, hypertension and diabetes were also identified as risk factors for cognitive impairment.Conclusions1. The elderly people with extracranial-intracranial arterial sclerosis have more cognitive dysfunction than those without;2. MetS is associated with cognitive impairment among elderly people in in asymptomatic intra- and extracranial atherosclerotic residents...
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