【作者】 李红美；

【导师】 张永红；

【作者基本信息】 苏州大学 ， 卫生毒理学， 2010， 博士

【摘要】 研究目的:1.了解农牧区蒙古族人群中高血压前期以及高血压的现患率,比较高血压前期与高血压者中心血管疾病危险因素及其聚集程度。2.探讨炎症和内皮功能异常与高血压前期和高血压的关联关系及关联强度。3.阐明高血压前期人群是否比血压正常人群有更高的脑卒中发病风险。4.阐明炎症和内皮功能异常是否会增加脑卒中发病风险。对象与方法:1.基线研究:2002-2003年选择内蒙古通辽市科左后旗朝鲁吐乡和奈曼旗固日班花乡共32村作为调查现场,将居住在该地20岁及以上成年蒙古族人作为研究对象。采用统一制定的调查问卷,按标准化调查方法,由培训过的医师对研究对象进行调查、血压测量、身体指标测量和血标本采集。(1)现场调查内容包括:人口统计学特征、高血压家族史、吸烟和饮酒情况等;三次血压测量;身体指标测量:身高、体重、腰围及臀围。(2)实验室检测包括:空腹血糖、胰岛素、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)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)、C-反应蛋白(CRP)、细胞间黏附分子-1(ICAM-1)、E-选择素(E-selectin)、血管紧张素II(AngII)和血浆肾素活性(PRA)。2.随访研究:分别于2008年10月和2009年7-8月对参与基线研究的对象进行了随访,结局事件定义为从基线到最后一次随访期间首次发生的脑卒中事件。采取入户调查和查阅监测资料、医院病历记录相结合的方法,采用标准设计的调查表,对每位研究对象进行调查,收集观察期内发生脑卒中事件的相关资料。3.统计分析:采用Epidata3.0软件建立数据库,所有调查表经过双录入后进行核对,应用SAS 9.1软件进行统计分析,检验水准α设为0.05。结果:现场内共有2589人参与了本研究,其中男性有1064人,女性1525人。年龄最小为20岁,最大为84岁,平均年龄为46.5岁。1.该地高血压前期现患率为38.39%,其中男性现患率为38.44%,女性现患率为38.36%;高血压现患率为37.39%,其中男性现患率为45.58%,女性现患率为31.67%。2.高血压前期人群中饮酒(31.29%)、超重或肥胖(23.34%)、中心肥胖(37.63%)、血脂异常(25.26%)、空腹血糖受损或糖尿病(17.56%)、高CRP(23.90%)的比例均高于正常血压者;同样,高血压人群中饮酒(44.32%)、超重或肥胖(37.16%)、中心肥胖(53.52%)、血脂异常(37.89%)、空腹血糖受损或糖尿病(25.60%)、高CRP(32.63%)的比例高于血压前期及血压正常者。3.多因素的logistic回归分析结果表明,高血压前期与年龄增加、男性、超重、肥胖、高TG、高ApoB和高AngII相关联,其OR值及95%可信区间(95%CI)分别为:1.03(1.02 ~1.04)、2.04(1.50 ~2.79)、1.96(1.23 ~3.13)、2.58(1.18 ~5.52)、1.64(1.09 ~2.47)、1.99(1.03 ~3.84)和1.39(1.01 ~1.89);而高血压与年龄、男性、高血压家族史、重度饮酒、超重、肥胖、高甘油三酯、高ApoB、心动过速、高AngII和CRP存在正的关联,其OR(95%CI)分别为1.09(1.07~1.10)、2.05(1.44~2.89)、5.83(3.51~9.69)、2.10(1.31~3.35)、3.41(2.02~5.73)、8.16(3.69~18.01)、2.13(1.39 ~3.25)、2.07(1.00~4.28)、4.16 (1.29~13.44)、2.36(1.65 ~3.35)和1.57(1.03~2.37)。4.高血压前期人群超重或肥胖、中心肥胖、空腹血糖受损或糖尿病、血脂异常等4个因素中2个及2个以上因素的聚集率(31.39%)大于血压正常者(21.25%),高血压人群(49.43%)大于高血压前期及血压正常者。调整年龄、性别等其他因素后,有1个、2个及≥3个危险因素聚集的人群患有高血压前期的危险分别是无危险因素聚集人群的1.56(1.19~2.06)、1.89(1.38~2.59)和2.57(1.61~4.09)倍,患有高血压的危险分别为1.98(1.44~2.73)、3.46(2.47~4.97)和7.58(4.69~12.26)。5.高血压前期人群高AngII、高CRP、高ICAM-1和低PRA等4个因素中有2个及2个以上因素的聚集率(22.36%)大于血压正常者(13.40%),高血压人群(37.94%)大于高血压前期及血压正常者。调整年龄、性别等其他因素后,有1个、2个及≥3个危险因素聚集的人群患有高血压前期的危险分别是无危险因素聚集人群的1.17(0.93~1.49)、1.40(0.99~1.97)和2.61(1.17~5.82)倍,患有高血压的危险分别为0.85(0.64~1.13)、1.42(1.04~2.20)、4.98(2.26~11.00)。6.在7年的随访中,2589个研究对象中新发脑卒中78例,其中41例为缺血性脑卒中,35例为出血性脑卒中,2例分型不清。脑卒中的发病密度为476.91/10万人年,其中男性脑卒中的发病密度为809.19/10万人年,女性发病密度为255.28/10万人年;缺血性脑卒中的发病密度为250.80/10万人年,出血性脑卒中的发病密度为213.38/10万人年。7.正常血压者和高血压前期人群脑卒中的发病密度分别为25/10万人年和282/10万人年。与正常血压者相比,高血压前期者发生脑卒中的风险比为11.3。高血压前期人群中发生脑卒中的归因危险度百分比为91%、人群归因危险度百分比为20%;高血压人群脑卒中的发病密度为987/10万人年,高于高血压前期人群和正常血压者。与血压正常者相比,高血压者发生脑卒中的风险比为39.7。高血压中发生脑卒中的归因危险度百分比为97%,人群归因危险度百分比为74%。8.根据基线时CRP的四分位数把人群分成四组,以小于下四分位数者为参比组,CRP最高分位数组发生缺血性脑卒中的风险比(HR)为2.96(1.17~7.46),但是在调整年龄、性别后,HR值(1.89,95%CI:0.75~4.76)无统计学意义。而基线血清中的AngII、ICAM-1、E-selectin与脑卒中的发病尚未发现有统计学意义的关联。结论:1.内蒙古农牧区蒙古族人群中高血压前期和高血压的现患率均较高。高血压前期者心血管疾病危险因素的水平以及危险因素的聚集程度均高于血压正常者。因此,在高血压前期阶段已经具有心血管危险因素的存在和聚集。2.高水平的CRP和AngII者患高血压前期和高血压的危险性均有所增加,炎症或内皮功能受损在高血压的发展过程中可能发挥一定的作用。3.现场内的蒙古族居民具有较高的脑卒中发病率,脑卒中已成为威胁当地蒙古族居民健康与生命的重要疾病及公共卫生问题。4.与正常血压者相比,基线高血压前期和高血压人群具有较高的脑卒中发病率及风险比。高血压前期人群已具有发生脑卒中的较高风险,是脑卒中发病的重要危险因素。更多还原

【Abstract】 Objective: 1. To investigate the prevalence of pre-hypertension and hypertension in Mongolian population lived in the agricultural and pastoral areas, and to compare cardiovascular risk factors, clustering of these factors between pre-hypertension and hypertension. 2. To explore association between inflammation and endothelial dysfunction biomarkers and pre-hypertension and hypertension. 3. To study whether pre-hypertension individuals have more hazards developing to stroke. 4. To study whether status of inflammation and endothelial dysfunction was associated with increased risk of stroke.Subjects and methods:1. Baseline investigation: A cross sectional survey was conducted between 2002 and 2003. In the survey, study participants aged 20 years and older were recruited from 32 villages in 2 adjacent townships located in Kezuohou Banner (county) and Naiman Banner in Inner Mongolia, and they were administered interview using a standard questionnaire, and the related physical examination and blood samples collection were conducted by trained staffs.(1) Field surveyData on demographic characteristics, family history of hypertension, smoking and alcohol consumption were obtained. Height, weight, waist circumference, hip circumference and three blood pressures were measured for all participants.(2)Laboratory testsFasting plasma glucose(FPG), insulin, triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1(ApoA1), apolipoprotein B(ApoB), C-reactive protein (CRP), E-selectin, intercellular adhesion molecules-1(ICAM-1), plasma rennin activity (PRA) and angiotensin II(AngII) were detected for all participants. 2. Survey follow-up studyIn October 2008 and July to August 2009, follow-up surveys were conducted for the subjects involved in a baseline study. Failure event is defined as the first occurrence of stroke during the time from the baseline to the last follow-up. We interviewed subjects by household, reviewed monitoring data and hospital medical records to investigate stroke events using standard questionnaires.3. Statistical analysisEpidata3.0 software was used to establish a database, and all questionnaires were input after checking by two individuals. All p-values were based on a 2-sided test and a significance level of 0.05, and statistical analysis was conducted using SAS 9.1 statistical software.Results:A total of 2589 participants aged 20-84 years old, 1064 males and 1525 females, were included in the analysis.1. In the study, prehypertensives accounted for 38.39% among all participants, 38.44% in males and 38.36% in females. Hypertensives accounted for 37.39% among all participants, 45.58% in males and 31.67% in females.2. Prehypertensives had higher proportions of individuals with alcohol consumption (31.29%), overweight or obesity (23.34%), central obesity (37.63%), hyperlipidemia (25.26%), impaired fasting glucose or diabetes (17.56%) and high CRP (23.9%) than normotensives. Similarly, hypertensives had higher proportions of individuals with alcohol consumption (44.32%), overweight or obesity (37.16%), central obesity (53.52%), hyperlipidemia (37.89%), impaired fasting glucose or diabetes (25.60%) and high CRP (32.63%) than pre-hypertensives and normotensives3. Multivariate logistic regression analysis showed that pre-hypertension was associated with increasing age, male, overweight, obesity, high triglycerides, high Apolipoprotein B and high angiotensin II, and the odd ratios (ORs) and 95% confidence intervals (95% CIs) were as follows: 1.03(1.02-1.04), 2.04(1.50-2.79), 1.96(1.23 -3.13), 2.58(1.18 -5.52), 1.64(1.09-2.47), 1.99(1.03 -3.84) and 1.39(1.01 -1.89), respectively. Hypertension was positively associated with aging, male, family history of hypertension, heavy drinking, overweight, obesity, high triglycerides, Apolipoprotein B, heart rate, angiotensin II and CRP, and ORs (95%CIs) were 1.09(1.07-1.10), 2.05 (1.44 -2.89), 5.83(3.51-9.69), 2.10(1.31-3.35), 3.41(2.02-5.73), 8.16(3.69-18.01), 2.13 (1.39-3.25), 2.07(1.00-4.28), 4.16(1.29-13.44), 2.36(1.65-3.35) and 1.57(1.03-2.37), respectively.4. Prehypertensives had high clustering proportion (31.39%) of≥2 risk factors, including overweight or obesity, central obesity, impaired fasting glucose or diabetes and hyperlipidemia, than that in normotensives (21.25%), and hypertensives had high clustering proportion (49.43%) than prehypertensives and normotenives. Compared with none risk factors clustering group, 1, 2 and≥3 factors clustering groups had the ORs (95%CIs) of 1.56(1.19-2.06), 1.89(1.38-2.59) and 2.57(1.61-4.09) for pre-hypertension, respectively; and ORs(95%CIs) of 1.98(1.44-2.73), 3.46(2.47-4.97) and 7.58 (4.69-12.26) for hypertension, respectively.5. Prehypertensives had high clustering proportion (22.36%) of≥2 risk factors, including high levels of angiotensin II, high CRP, ICAM-1 and low levels of PRA, than that in normotensives (13.40%), and hypertensives had high clustering proportion (37.94%) of the biomarkers than prehypertensives and normotensives. Compared with none risk factors clustering group, 1, 2 and≥3 biomarkers clustering groups had the ORs (95%CIs) of 1.17(0.93-1.49), 1.40(0.99-1.97) and 2.61(1.17-5.82) for pre-hypertension, respectively; and ORs (95%CIs) of 0.85(0.64-1.13), 1.42(1.04-2.20) and 4.98 (2.26-11.00) for hypertension , respectively.6. During follow-up, 78 new stroke cases occurred among 2589, 41 cases were ischemic stroke and 35 cases were hemorrhagic stroke, and 2 cases of sub-type were unknown. The incidence density of stroke was 476.91/100 000 person-years, which were 809.19/100 000 person-years in men and 255.28/100 000 person-years in women. The incidence densities of ischemic and hemorrhagic stroke were 250.80/100000 person-years and 213.38/100 000 person-years, respectively.7. The incidence density of stroke was 25/100 000 person-years in normotension group, and 282/100 000 person-years in pre-hypertension group. Compared with normotensives, prehypertensive individuals had a hazard ratio (HR) of 11.3 for stroke. Attributable risk percent (ARP) was 91% and population attributable risk percent (PARP) was 20% for stroke in pre-hypertensive population. The incidence density of stroke was 987/100 000 person-years in hypertension group. And the HR for stroke was 39.7, compared to normotensives. Moreover, ARP was 97% and PARP was 74% for stroke in hypertensives. 8. The population was divided into four groups according to baseline CRP quartile, and the lowest quartile as the reference group, the highest group had the HR of 2.96(95%CI: 1.17-7.46) for ischemic stroke, but adjusted for age and sex, HR value(1.89, 95%CI: 0.75-4.76)was no more statistically significant. Association between the baseline serums AngII, ICAM-1, E-selectin and the incidence of stroke has not been found statistically significant.Conclusion:1. The prevalence rates of pre-hypertension and hypertension are relatively high in Mongolia population. Pre-hypertensive population has higher levels and aggregation extents of cardiovascular risk factors than those with normotension. Thus, cardiovascular risk factors and clustering of these factors are existed in the stage of pre-hypertension.2.Individuals with high levels of CRP and AngII have increased risk of suffering from pre-hypertension, inflammation or endothelial dysfunction may play a role in the development of hypertension.3. The incidence of stroke is high in the study, and Stroke has become an important disease and public health issues threaten to the health and lives of local Mongolian.4. Compared with normal blood pressure, baseline pre-hypertension and hypertension groups have higher incidences of stroke and hazard ratios for stroke. So, pre-hypertensive group had higher risk of stroke occurrence, and pre-hypertension is a major risk factor for stroke.更多还原