蒙古族人群脑卒中危险因素的队列研究
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摘要
研究目的：
了解农牧区蒙古族人群脑卒中发病率及其分布特征；探讨传统危险因素、炎症和内皮功能异常指标与脑卒中发病的关系；探讨危险因素的聚集与脑卒中发病的关系，为脑卒中防治策略的制定提供依据。
研究对象与方法：
1、基线调查：2002年5月和2003年6月，选择内蒙古自治区通辽市蒙古族居民集中的2个苏木（乡镇）作为本研究的现场，在这2个苏木共32个村居住的20岁及以上蒙古族居民共2589人签署知情同意书，并接受了问卷调查、体格检查、血压测量和血标本的采集。
问卷调查内容包括：社会人口学情况、高血压病史、吸烟和饮酒情况。采用标准化方法测量血压和身高、体重、腰围和臀围。采集清晨空腹静脉血，现场分离血清，血标本低温运至实验室并于-80℃保存，用于空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、胰岛素(INS)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)、肾素活性(PRA)、血管紧张素II (AngII)、一氧化氮(NO)、C-反应蛋白(CRP)、E-选择素（E-selectin）和细胞间黏附分子-1(ICAM-1)等指标的检测。
2、随访调查：调查组分别于2008年10月、2009年8月、2010年8月和2012年8月对参与基线研究的2589名研究对象进行了随访调查，收集基线以来脑卒中发病和死亡资料。
3、统计分析：应用Excel软件建立数据库，采用两次录入法进行核对检错。所有统计分析过程均由SAS9.1软件和SPSS13.0软件在计算机上完成，P<0.05为差异有统计学意义。
研究结果：
1、2589例基线调查对象平均年龄46.51岁，男性1064人（41.10%）、女性1525人（58.90%）。男性组的NO、CRP、E-selectin、ICAM-1和AngII五项炎症和内皮功能异常指标的平均水平均高于女性组。
2、随访人群中共发生124例脑卒中病例，其中缺血性脑卒中76例、出血性脑卒中46例，卒中分型不清2例；研究人群中脑卒中发病密度为519.11/10万人年，男性和女性脑卒中发病密度分别为840.89/10万人年和306.12/10万人年；缺血性脑卒中和出血性脑卒中发病密度分别为318.16/10万人年和192.57/10万人年。无论男性还是女性，缺血性脑卒中和出血性脑卒中的发病率均随年龄的增加和随访时间的增长而升高。
3、全人群Cox回归分析结果：年龄、男性、高血压、高血压家族史、脉压、平均动脉压与缺血性脑卒中和出血性脑卒中均存在关联关系；心率加快和吸烟与缺血性脑卒中均有显著的关联关系，而与出血性脑卒中无关联；而且，具有较快心率（≥80次/分）的吸烟者发生缺血性脑卒中的危险性更高，以不吸烟/心率<80为参比组，吸烟/心率≥80组发生缺血性脑卒中的风险比（HR及95%CI）在未调整和调整多因素后分别是4.12（2.07-8.17）和2.58（1.23-5.38）；CRP与缺血性脑卒中发生的HR在调整前和调整年龄、性别后分别为1.90（1.20-3.02）和1.61（1.01-2.55），但是调整多因素后HR值无统计学意义。
4、按性别分层的Cox回归分析结果：进入男性缺血性脑卒中模型的危险因素有：年龄、高血压、心率(10次/分)、吸烟和ApoA1，HR（95%CI）分别为1.11（1.08-1.43）、3.65（1.64-8.11）、1.32（1.05-1.67）、3.26（1.44-7.38）和2.13（1.08-4.18）；进入女性缺血性脑卒中模型的危险因素有：年龄、CRP、LDL-C和TG，HR（95%CI）分别为1.11（1.07-1.15）、2.41（1.06-5.49）、2.34（1.02-5.38）和0.22（0.05-0.96）。进入男性出血性脑卒中模型的危险因素有：年龄、高血压，HR（95%CI）分别为1.06(1.03-1.09)和3.31(1.32-8.32)；进入女性出血性脑卒中模型的危险因素有：高血压和饮酒，HR（95%CI）分别为28.89（3.79-220.47）和3.96（1.41-11.14）。
5、危险因素聚集性分析：调整年龄、性别后，具有2-3个、4个、≥5个传统危险因素(包括高血压、吸烟、饮酒、高血糖、血脂异常、超重或肥胖、腹部肥胖)者发生缺血性脑卒中的HR分别是具有0-1个危险因素者的2.44（1.09-5.48）、2.59（1.05-6.39）和3.67（1.48-9.07）倍。
研究结论：
1、研究现场内的蒙古族居民具有较高的脑卒中发病率，男性发病率高于女性，随着年龄的增加和随访时间的增长，脑卒中发病率均升高，脑卒中已成为威胁当地居民健康与生命的重要疾病及公共卫生问题。
2、高水平CRP是女性缺血性脑卒中发病的危险因素，提示炎症在脑卒中发生过程中可能发挥一定作用。
3、心率加快并吸烟可增加缺血性脑卒中的发病风险。
4、传统危险因素聚集与缺血性脑卒中发病风险升高有关。
Objective：
To investigate the incidence of stroke and its distribution in Mongolian populationlived in the agricultural and pastoral areas. To explore whether baseline traditional riskfactors and inflammatory and endothelial biomarkers were associated with increasedrisk of stroke. To study whether clustering of risk factors is related to the higher risk ofstroke. So a basis can be provided for the prevention and control of stroke.
Subjects and methods：
1. Baseline investigation： A cross-sectional survey was conducted between2002and2003in Tongliao City, Inner Mongolia,2589participants aged20years and olderwere recruited from32villages in2adjacent townships. Written informed consent wasobtained for all study participants. They were administered interview using a standardquestionnaire, and the related physical examination and blood samples collection wereconducted by trained staffs.
Data on demographic characteristics, family history of hypertension, smoking andalcohol consumption were obtained. Blood pressure, height, weight, waistcircumference and hip circumference were measured for all participants according tostandard methods.
Fasting blood samples were taken in the morning and separated in the field, andthen were sent to laboratory under low temperature and frozen at-80℃. Fasting plasmaglucose(FPG), insulin(INS), triglyceride(TG), total cholesterol(TC), high-densitylipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C),apolipoprotein A1(ApoA1), apolipoprotein B(ApoB), plasma rennin activity (PRA),angiotensin II(AngII), nitric oxide(NO), C-reactive protein(CRP), intercellular adhesionmolecules-1(ICAM-1) and endothelial selectin (E-selectin) were detected for all participants.
2. Follow-up survey
In October2008, August2009, August2010and August2012, follow-up surveyswere conducted for the2589subjects involved in the baseline study. Information ofoccurrence and death of stroke during the time from the baseline to the last follow-upwas collected.
3. Statistical analysis
Excel software was used to establish a database, and all data was checked afterdata entry for two times. All statistical analyses were conducted using SAS9.1andSPSS13.0statistical software, and a significance level of0.05was used.
Results：
1. A total of2589participants with a mean age of46.51years old, including1064（41.10%） males and1525（58.90%）females, were included in the analysis. Maleshad higher level of NO、CRP、E-selectin、ICAM-1and Ang II than females at thebaseline.
2. During the9.2years follow-up,124new stroke cases occurred,76cases wereischemic stroke and46cases were hemorrhagic stroke, and2cases were stroke ofunknown subtype. The incidence density of stroke was519.11/100000person-years,which were840.89/100000person-years in men and306.12/100000person-years inwomen. The incidence densities of ischemic and hemorrhagic stroke were318.16/100000person-years and192.57/100000person-years, respectively. The incidences ofischemic and hemorrhagic stroke increased with age and follow-up time both in menand women.
3. Cox regression analyses for whole study population: the results showed that bothischemic stroke and hemorrhagic stroke were associated with increasing age, male,hypertension, family history of hypertension, pulse pressure and mean artery pressure.Heart rate (every increasing10beats per minute) and smoking were positivelyassociated with ischemic stroke, while not hemorrhagic stroke. Furthermore, smokerswith faster heart rate (≥80beats/minute) were at a higher risk of ischemic stroke,compared with group with heart rate<80/nonsmokers, the hazard ratios (HRs) and 95%CI of group with heart rate≥80/smokers were4.12（2.07-8.17）and2.58(1.23-5.38)，respectively, when unadjusted and adjusted for multivariable. Unadjusted and age-andgender-adjusted HRs of ischemic stroke for CRP were1.90(1.20-3.02) and1.61(1.01-2.55), but HR became statistical insignificant after adjusted formulti-variables.
4. Multivariable Cox regression analyses for males and females, respectively: theresults showed that the risk factors for both ischemic stroke and hemorrhagic stroke inmen were somewhat different from that in women. Ischemic stroke was positivelyassociated with age, hypertension, smoking, heart rate (10beats/minute) and ApoA1inmen, the HRs（95%CI）were1.11（1.08-1.43），3.65（1.64-8.11），1.32（1.05-1.67），3.26（1.44-7.38）and2.13（1.08-4.18），respectively. Ischemic stroke was positivelyassociated with age，CRP，LDL-C and TG in women, the HRs（95%CI）were1.11(1.07-1.15)，2.41(1.06-5.49)，2.34(1.02-5.38) and0.22（0.05-0.96），respectively.Hemorrhagic stroke was positively associated with age and hypertension in men, theHRs（95%CI）were1.06(1.03-1.09) and3.31(1.32-8.32)．Hemorrhagic stroke waspositively associated with hypertension and drinking in women, the HRs（95%CI）were28.89(3.79-220.47) and3.96(1.41-11.14).
5. Compared with those with0-1risk factor，people with2-3,4,5traditional riskfactors, including hypertension, smoking，drinking, high FPG，dislipidemia, overweightor obesity, and central obesity had higher HRs for ischemic stroke after adjusting forage and gender, the HRs (95%CIs) were2.44(1.095.48),2.59(1.056.39) and3.67(1.489.07), respectively.
Conclusions：
1. The incidence of stroke was high in the Mongolian population in the study, menhad higher incidence of stroke than women, the incidence of stroke increased with ageand follow-up time. Stroke has become an important disease and public health issuethreaten to the health and live of local Mongolian.
2．Women with high level of CRP had an increased risk of ischemic strokeincidence; it suggests that inflammation may play a role in the development of ischemicstroke in women.
3. Coexistence of increased heart rate and smoking increased the risk of ischemicstroke incidence.
4. Clustering of traditional risk factors was associated with increased risk ofischemic stroke incidence.
了解农牧区蒙古族人群脑卒中发病率及其分布特征；探讨传统危险因素、炎症和内皮功能异常指标与脑卒中发病的关系；探讨危险因素的聚集与脑卒中发病的关系，为脑卒中防治策略的制定提供依据。
研究对象与方法：
1、基线调查：2002年5月和2003年6月，选择内蒙古自治区通辽市蒙古族居民集中的2个苏木（乡镇）作为本研究的现场，在这2个苏木共32个村居住的20岁及以上蒙古族居民共2589人签署知情同意书，并接受了问卷调查、体格检查、血压测量和血标本的采集。
问卷调查内容包括：社会人口学情况、高血压病史、吸烟和饮酒情况。采用标准化方法测量血压和身高、体重、腰围和臀围。采集清晨空腹静脉血，现场分离血清，血标本低温运至实验室并于-80℃保存，用于空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、胰岛素(INS)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)、肾素活性(PRA)、血管紧张素II (AngII)、一氧化氮(NO)、C-反应蛋白(CRP)、E-选择素（E-selectin）和细胞间黏附分子-1(ICAM-1)等指标的检测。
2、随访调查：调查组分别于2008年10月、2009年8月、2010年8月和2012年8月对参与基线研究的2589名研究对象进行了随访调查，收集基线以来脑卒中发病和死亡资料。
3、统计分析：应用Excel软件建立数据库，采用两次录入法进行核对检错。所有统计分析过程均由SAS9.1软件和SPSS13.0软件在计算机上完成，P<0.05为差异有统计学意义。
研究结果：
1、2589例基线调查对象平均年龄46.51岁，男性1064人（41.10%）、女性1525人（58.90%）。男性组的NO、CRP、E-selectin、ICAM-1和AngII五项炎症和内皮功能异常指标的平均水平均高于女性组。
2、随访人群中共发生124例脑卒中病例，其中缺血性脑卒中76例、出血性脑卒中46例，卒中分型不清2例；研究人群中脑卒中发病密度为519.11/10万人年，男性和女性脑卒中发病密度分别为840.89/10万人年和306.12/10万人年；缺血性脑卒中和出血性脑卒中发病密度分别为318.16/10万人年和192.57/10万人年。无论男性还是女性，缺血性脑卒中和出血性脑卒中的发病率均随年龄的增加和随访时间的增长而升高。
3、全人群Cox回归分析结果：年龄、男性、高血压、高血压家族史、脉压、平均动脉压与缺血性脑卒中和出血性脑卒中均存在关联关系；心率加快和吸烟与缺血性脑卒中均有显著的关联关系，而与出血性脑卒中无关联；而且，具有较快心率（≥80次/分）的吸烟者发生缺血性脑卒中的危险性更高，以不吸烟/心率<80为参比组，吸烟/心率≥80组发生缺血性脑卒中的风险比（HR及95%CI）在未调整和调整多因素后分别是4.12（2.07-8.17）和2.58（1.23-5.38）；CRP与缺血性脑卒中发生的HR在调整前和调整年龄、性别后分别为1.90（1.20-3.02）和1.61（1.01-2.55），但是调整多因素后HR值无统计学意义。
4、按性别分层的Cox回归分析结果：进入男性缺血性脑卒中模型的危险因素有：年龄、高血压、心率(10次/分)、吸烟和ApoA1，HR（95%CI）分别为1.11（1.08-1.43）、3.65（1.64-8.11）、1.32（1.05-1.67）、3.26（1.44-7.38）和2.13（1.08-4.18）；进入女性缺血性脑卒中模型的危险因素有：年龄、CRP、LDL-C和TG，HR（95%CI）分别为1.11（1.07-1.15）、2.41（1.06-5.49）、2.34（1.02-5.38）和0.22（0.05-0.96）。进入男性出血性脑卒中模型的危险因素有：年龄、高血压，HR（95%CI）分别为1.06(1.03-1.09)和3.31(1.32-8.32)；进入女性出血性脑卒中模型的危险因素有：高血压和饮酒，HR（95%CI）分别为28.89（3.79-220.47）和3.96（1.41-11.14）。
5、危险因素聚集性分析：调整年龄、性别后，具有2-3个、4个、≥5个传统危险因素(包括高血压、吸烟、饮酒、高血糖、血脂异常、超重或肥胖、腹部肥胖)者发生缺血性脑卒中的HR分别是具有0-1个危险因素者的2.44（1.09-5.48）、2.59（1.05-6.39）和3.67（1.48-9.07）倍。
研究结论：
1、研究现场内的蒙古族居民具有较高的脑卒中发病率，男性发病率高于女性，随着年龄的增加和随访时间的增长，脑卒中发病率均升高，脑卒中已成为威胁当地居民健康与生命的重要疾病及公共卫生问题。
2、高水平CRP是女性缺血性脑卒中发病的危险因素，提示炎症在脑卒中发生过程中可能发挥一定作用。
3、心率加快并吸烟可增加缺血性脑卒中的发病风险。
4、传统危险因素聚集与缺血性脑卒中发病风险升高有关。
Objective：
To investigate the incidence of stroke and its distribution in Mongolian populationlived in the agricultural and pastoral areas. To explore whether baseline traditional riskfactors and inflammatory and endothelial biomarkers were associated with increasedrisk of stroke. To study whether clustering of risk factors is related to the higher risk ofstroke. So a basis can be provided for the prevention and control of stroke.
Subjects and methods：
1. Baseline investigation： A cross-sectional survey was conducted between2002and2003in Tongliao City, Inner Mongolia,2589participants aged20years and olderwere recruited from32villages in2adjacent townships. Written informed consent wasobtained for all study participants. They were administered interview using a standardquestionnaire, and the related physical examination and blood samples collection wereconducted by trained staffs.
Data on demographic characteristics, family history of hypertension, smoking andalcohol consumption were obtained. Blood pressure, height, weight, waistcircumference and hip circumference were measured for all participants according tostandard methods.
Fasting blood samples were taken in the morning and separated in the field, andthen were sent to laboratory under low temperature and frozen at-80℃. Fasting plasmaglucose(FPG), insulin(INS), triglyceride(TG), total cholesterol(TC), high-densitylipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C),apolipoprotein A1(ApoA1), apolipoprotein B(ApoB), plasma rennin activity (PRA),angiotensin II(AngII), nitric oxide(NO), C-reactive protein(CRP), intercellular adhesionmolecules-1(ICAM-1) and endothelial selectin (E-selectin) were detected for all participants.
2. Follow-up survey
In October2008, August2009, August2010and August2012, follow-up surveyswere conducted for the2589subjects involved in the baseline study. Information ofoccurrence and death of stroke during the time from the baseline to the last follow-upwas collected.
3. Statistical analysis
Excel software was used to establish a database, and all data was checked afterdata entry for two times. All statistical analyses were conducted using SAS9.1andSPSS13.0statistical software, and a significance level of0.05was used.
Results：
1. A total of2589participants with a mean age of46.51years old, including1064（41.10%） males and1525（58.90%）females, were included in the analysis. Maleshad higher level of NO、CRP、E-selectin、ICAM-1and Ang II than females at thebaseline.
2. During the9.2years follow-up,124new stroke cases occurred,76cases wereischemic stroke and46cases were hemorrhagic stroke, and2cases were stroke ofunknown subtype. The incidence density of stroke was519.11/100000person-years,which were840.89/100000person-years in men and306.12/100000person-years inwomen. The incidence densities of ischemic and hemorrhagic stroke were318.16/100000person-years and192.57/100000person-years, respectively. The incidences ofischemic and hemorrhagic stroke increased with age and follow-up time both in menand women.
3. Cox regression analyses for whole study population: the results showed that bothischemic stroke and hemorrhagic stroke were associated with increasing age, male,hypertension, family history of hypertension, pulse pressure and mean artery pressure.Heart rate (every increasing10beats per minute) and smoking were positivelyassociated with ischemic stroke, while not hemorrhagic stroke. Furthermore, smokerswith faster heart rate (≥80beats/minute) were at a higher risk of ischemic stroke,compared with group with heart rate<80/nonsmokers, the hazard ratios (HRs) and 95%CI of group with heart rate≥80/smokers were4.12（2.07-8.17）and2.58(1.23-5.38)，respectively, when unadjusted and adjusted for multivariable. Unadjusted and age-andgender-adjusted HRs of ischemic stroke for CRP were1.90(1.20-3.02) and1.61(1.01-2.55), but HR became statistical insignificant after adjusted formulti-variables.
4. Multivariable Cox regression analyses for males and females, respectively: theresults showed that the risk factors for both ischemic stroke and hemorrhagic stroke inmen were somewhat different from that in women. Ischemic stroke was positivelyassociated with age, hypertension, smoking, heart rate (10beats/minute) and ApoA1inmen, the HRs（95%CI）were1.11（1.08-1.43），3.65（1.64-8.11），1.32（1.05-1.67），3.26（1.44-7.38）and2.13（1.08-4.18），respectively. Ischemic stroke was positivelyassociated with age，CRP，LDL-C and TG in women, the HRs（95%CI）were1.11(1.07-1.15)，2.41(1.06-5.49)，2.34(1.02-5.38) and0.22（0.05-0.96），respectively.Hemorrhagic stroke was positively associated with age and hypertension in men, theHRs（95%CI）were1.06(1.03-1.09) and3.31(1.32-8.32)．Hemorrhagic stroke waspositively associated with hypertension and drinking in women, the HRs（95%CI）were28.89(3.79-220.47) and3.96(1.41-11.14).
5. Compared with those with0-1risk factor，people with2-3,4,5traditional riskfactors, including hypertension, smoking，drinking, high FPG，dislipidemia, overweightor obesity, and central obesity had higher HRs for ischemic stroke after adjusting forage and gender, the HRs (95%CIs) were2.44(1.095.48),2.59(1.056.39) and3.67(1.489.07), respectively.
Conclusions：
1. The incidence of stroke was high in the Mongolian population in the study, menhad higher incidence of stroke than women, the incidence of stroke increased with ageand follow-up time. Stroke has become an important disease and public health issuethreaten to the health and live of local Mongolian.
2．Women with high level of CRP had an increased risk of ischemic strokeincidence; it suggests that inflammation may play a role in the development of ischemicstroke in women.
3. Coexistence of increased heart rate and smoking increased the risk of ischemicstroke incidence.
4. Clustering of traditional risk factors was associated with increased risk ofischemic stroke incidence.
引文
1.卫生部心血管病防治研究中心.中国心血管病报告2010.中国大百科全书出版社.2011.
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