【作者】 栗映梅；

【导师】 吴欣怡；

【作者基本信息】 山东大学 ， 眼科学（专业学位）， 2013， 博士

【摘要】 高血压病是一种常见病,目前的流行病学资料显示我国高血压病患病率高,但知晓率、治疗率和控制率水平较低,因此,一些患者出现严重的心脑血管并发症,严重危害居民健康。视网膜血管是全身血管的一部分,它的病变能够反映全身血管的病变。高血压患者早期视网膜血管变化不大,随着血压的升高和病程的延长,视网膜血管将产生管径和管壁的变化,形成特征性的视网膜病变。此外,只有视网膜的动静脉是我们通过眼底镜可以直接看到的人体血管,可以通过观察高血压患者视网膜的特征性病变,评估高血压对心、脑、肾等靶器官的损害,判断病变的严重程度并预测患者的预后。所以,进行高血压视网膜病变的流行病学调查,了解其患病率和相关危险因素,对于高血压视网膜病变及高血压病的防治工作都具有重要意义。目前有关疾病的流行病学研究调查主要有两种不同的方法：一种是以各层医院门诊或住院患者为调查对象,它容易组织、省时、费用较低,而且便于应用医院现有的各种检查设备,所获资料齐全,但是所得疾病的患病率偏高；另一种是以限定的自然居民为调查对象,它组织规模较大,需除医院外多部门协助,耗费巨大人力、财力,但所得数据真实,可以反映居民的真实患病情况。所以,我们此次通过限定人群抽样调查的方法,对山东省宁阳县城乡自然居民中高血压视网膜病变的患病情况进行了调查研究,掌握其流行病学的特点,为以后更大样本的调查奠定基础,也为我省的防盲治盲提供了科学的依据。同时我们联系了济南市多家医院,以住院高血压患者为调查对象,进一步研究这部分患者中高血压视网膜病变的患病情况,分析相关的危险因素,并对其中的部分患者进行了视网膜血管直径的定量分析,以指导治疗、监测和进一步的研究。第一部分：山东省宁阳县城乡居民高血压视网膜病变的流行病学调查目的：了解山东省宁阳县城乡居民中高血压视网膜病变的患病率,分析其相关危险因素,为确定高危人群和监测人群提供科学依据,并进行相应的健康教育,探索经济有效的防治模式,降低HR的致盲率,为进一步更大规模的调查奠定基础。方法：采取随机整群抽样(限定居民整群抽样)方法进行抽样,以宁阳县城区各社区居委会或乡镇各农村为基本抽样单位,随机抽取城区内2个社区和8个农村后按进行家庭系统抽样,抽取家庭内35岁以上的常住居民作为研究对象,对全部研究对象进行问卷调查、血压测量及相关眼科检查。问卷内容包括一般情况(姓名,性别,年龄,饮食生活习惯等),高血压病病史、家族史、治疗情况及血压控制情况,眼部疾病史,糖尿病及高血脂症疾病史等。眼科检查包括裸眼远视力、裂隙灯检查(角膜、前房、虹膜、晶体及前段玻璃体),非接触眼压计进行眼压测量,经复方托吡卡胺滴眼液散瞳后前置镜检查患者眼底,如受检者前房浅、不能排除散瞳后诱发急性闭角型青光眼的可能时在小瞳孔下用直接眼底镜检查眼底。对于屈光间质清晰者均给予检查双眼,双眼眼底病变程度不同者,记录病变相对较重的一眼,对于一眼存在严重白内障或玻璃体混浊者,记录另一眼眼底。检查医师详细、统一的记录检查结果,对临床表现不典型者,由所有参与现场眼科检查的医师共同检查后做出判断。应用SPSS13.0软件进行统计学处理,采用四格表资料X2检验进行两个样本率的比较,对于同一参数各组患病率间的比较应用X2趋势检验,检验的显著性取a=0.05,P<0.05有显著性差异。以HR为依变量,城市农村、性别、年龄、病程、收缩性高血压、舒张性高血压、混合型高血压等为自变量,进行多元回归分析。检查结果由专人负责填入表格,所有数据均由双人双次重复录入电脑以确保录入准确。结果：在全部调查对象中检出高血压患者1328例(包括新确诊为高血压病的患者,以及既往有明确高血压病史、目前服用降血压药物而血压正常的患者),其中男556例,女772例,高血压患病率为41.20%。调查出的1328例高血压患者中,242例由于眼科记录资料不全未包括在统计结果中。1086例受检者完成了全部问卷及眼科检查,其中男446例(41.07%),女640例(58.93%),男女比例为1：1.43。年龄在35～89岁之间,平均57.85岁,知道自己患高血压病变的占79.1%(859例),曾经接受药物治疗的占31.49%(342例),其中仅79例不同程度知晓HR(7.27%)。1086例受检者中303例眼底正常,783例(72.10%)出现不同程度的HR。受检的783例HR患者中,53例出现眼部并发症(6.77%),其中视网膜动脉阻塞2例,视网膜静脉阻塞5例,黄斑前膜9例,黄斑变性34例,视网膜静脉栓塞继发新生血管性青光1例,玻璃体积血2例。1.城乡患病率比较：完成全部检查的1086例受检者中农村居民779例,存在HR者581例,患病率为74.58%；城区居民307例,存在HR者为202例,患病率为65.80%；农村居民HR的患病病率明显高于城区居民,两者存在统计学差异(P<0.05)。2.性别比较：783例患者中女性456例,男性327例,其HR患病率分别为71.25%和73.32%,两者没有明显统计学差异(P>0.05)。3.不同年龄组比较：按从低到高每10岁为一个年龄组,受检者共分五组,五个不同年龄组受检者的HR患病率分别为56.69%,66.06%,71.38%,75.93%和84.54%,表明存在随着年龄增加HR患病率增加的趋势,有统计学意义(P<0.05)。4.不同血压比较：随着患者收缩压和(或)舒张压的增加,HR患病率有增加的趋势(P<0.01)5.不同病程比较：本研究表明高血压病程与HR的发生存在相关性,存在病程越长HR患病率越高的趋势(P<0.01)6.多因素分析：不同性别、年龄组、高血压病程分层分析结果显示相同年龄组者,高血压病程越长,HR患病率越高；高血压病程同组者,高年龄组中的HR患病率高于低年龄组者。经logistic有序回归分析,年龄、城区农村、高血压病程等是HR的危险因素。混合型高血压者HR患病率是血压值正常的2.44倍,高血压病程5年以上者HR患病率是病程1年以下者的2.67倍,高血压病程10年以上者HR患病率是病程1年以下者的4.15倍。结论：宁阳县城乡居民中高血压视网膜病变患病率较高,血压、年龄、城乡、高血压病程等是其相关的危险因素,存在对疾病的知晓率低、治疗率低且不规范、控制率低的情况。建立高血压视网膜病变的立体防治体系需要眼科同社区、基层医疗机构以及各级卫生在不同层面上的密切协作。第一二部分：济南市住院高血压患者高血压视网膜病变流行病学调查目的：调查济南市住院高血压患者中高血压视网膜病变的患病率,对其相关的危险因素进行分析,指导高危人群的治疗、监测,减少相关的致盲率较高的眼部疾病的发生及发展。方法：对济南市6个市级医院的300例住院的原发性高血压患者进行问卷调查、实验室检查、体格检查及眼部检查。问卷内容同第一部分,眼科检查除第一部分涉及的项目外,对部分受检者进行眼底照相及眼底荧光血管造影检查,实验室检查包括空腹血糖、总胆固醇、甘油三酯、高、低密度脂蛋白、尿微量白蛋白及超声心动图检查；体格检查包括血压、身高、体重和腰围的测量。采用SPSS13.0软件进行统计学处理,样本患病率的比较应用X2检验,两均数的比较应用u检验,多因素分析Logistic回归。对照组和患病组中年龄、高血压病程、体重指数、腰围、收缩压(mmHg)、舒张压、总胆固醇、甘油三酯,高密度脂蛋白、低密度脂蛋白、空腹血糖及尿微量白蛋白各因素的分析,检查结果由专人专项填表,收集的数据经双人双次重复输入计算机以保证准确性。采用ImageJ2x图像处理软件定量分析视网膜动静脉比。结果：此次调查中300例原发性高血压患者共236位患者有不同程度的高血压视网膜病变,济南市住院高血压病患者HR的患病率为78.67%,其中Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期的患病率分别为26.0%、33.3%、17.3%、2%。其余64人未发现有明显高血压视网膜病变。高血压视网膜病变知晓率为10.17%；8.47%的患者(20例)存在严重的眼部相关并发症,其中9例患者(12眼)存在不同程度的缺血性视乳头病变,视网膜中央静脉栓塞2例(2眼),其中一例已行全视网膜光凝；视网膜分支静脉栓塞2例(3眼),视网膜中央动脉栓塞1例,黄斑变性5例,玻璃体积血1例。1.不同性别比较：此次调查中300例原发性高血压患者中女性192例,男性108例,男女比例,1：1.77,其中84例男性高血压患者及152例女性高血压患者有不同程度的高血压视网膜病变,男性患病率为77.78%,女性患病率为79.17%,男女性别患病率没有明显差别(P>0.05)。2.不同年龄组比较：本次济南市住院高血压患者调查中受检者年龄47-86岁,平均年龄为65.96岁；按年龄分组发现随年龄增加HR患病率增加趋势不明显(P>0.05)。3.不同血压比较：按不同收缩压、舒张压分组进行患病率的比较,结果发现随着收缩压增加或舒张压的增加患者HR患病率有增加的趋势(P<0.05)。4.不同病程比较：住院患者中原发性高血压病病史从6年到27年不等,随着病程的增加,HR的患病率有增加的趋势(P<0.05)。5.各指标单因素分析：以高血压视网膜病变者作为病例组(236人),将双眼底均无HR改变的高血压患者作为对照组(64人),分别比较两组患者年龄、高血压病程、体重指数、腰围、收缩压、舒张压)、总胆固醇、甘油三酯,高密度脂蛋白、低密度脂蛋白、空腹血糖及尿微量白蛋白各指标的统计学差异。结果显示两组患者的高血压病程、舒张压,收缩压、甘油三酯及尿微量白蛋白存在明显差异,有统计学意义(P<0.05),而其他指标的差异没有统计学意义(P>0.05)。6.多因素分析：设置因变量Y：0(对照组)、1(病例组),选择年龄、体重指数、腰围、高血压病程,血糖、收缩压、舒张压,总胆固醇、甘油三酯、高低密度脂蛋白、尿微量白蛋白为自变量。将这些变量进行Logistic多因素回归分析,最终筛选出5个与HR发生、发展密切相关的因素为：高血压病程、甘油三酯、收缩压、舒张压、尿微量白蛋白。7.左心室重量比较：将HR的患者者分为轻、重度两组(轻度：Ⅰ级和Ⅱ级；重度：Ⅲ级和Ⅳ级),分别记为病例1组和病例2组,无高血压视网膜病变者记为对照组。对照组、病例1组、病例2组的左心室重量(LVH)比较,差异具有统计学意义(P<0.05)。8.视网膜动静脉比值定量分析：应用ImageJ软件分别在受检者的眼底彩照和眼底荧光造影图中测量颞上动脉和静脉、颞下动脉和静脉、鼻上动脉和静脉以及鼻下动脉和静脉的比值AVR,结果显示以上4个象限的AVR没有明显区别,而且眼底照相图片与眼底荧光血管造影图片AVR测量值也无统计学差异,但是高血压组受检者的AVR值明显小于对照组非高血压者的AVR (P<0.05)。结论：济南市住院的原发性高血压病人中高血压视网膜病变的患病率较高,程度较自然人群重,但仍以轻中度为主。血压病程、舒张压、收缩压、甘油三酯及尿微量白蛋白是HR的危险因素。高血压患者的动静脉比值明显小于非高血压患者。ImageJ软件在定量分析视网膜血管直径时有一定优势。建议把眼底检查作为高血压患者的常规检查,尤其是病程长、合并高血脂、肾功能异常的患者。结合眼科有关视网膜血管异常的评价综合评估患者的全身情况,治疗情况,为患者制定更为合适的目标血压。更多还原

【Abstract】 Hypertension is the most common systemic disease. Current epidemiological data show that the prevalence rate of hypertension in China is high, but the awareness rate, treatment rate and control rate of hypertension are relatively low. So in some patients, it can cause serious complications, such as cardiovascular and cerebrovascular diseases. Hypertention is one of the most serious diseases endangering the people’s health. The pathological changes of the retinal vessels caused by hypertension are one part of the systemic vascular changes, so it can reflect the situation of arteries in vivo to a certain degree. The retinal vascular is normal in the early stage of hypertension usually, but with the increasing of blood pressure and the course of hypertension,90%of the retinal vascular has a series change of diameter and wall gradually which is called the characteristic retinopathy. Retinal blood vessels are the only vessels which can be directly observed by ophthalmoscope. By observing the characteristic changes in retinal blood vessels of hypertension patients, we can learn about the severity of other organs’ damage caused by hypertension. So it has a certain value for us to know the severity and prognosis of hypertension. Therefore, epidemiological investigation of hypertensive retinopathy will be contributing for prevention and control of both hypertensive retinopathy and hypertension.The objects in epidemiological investigation of diseases mainly have two sources:one is the clients in hospitals, another is the natural population. The first one is easy to organize, and we can obtain much information with less time and cost, but the prevalence rate we got may be higher. The second one is difficult to organize, and it may consume a great deal of manpower and financial resources, but it can reflect the true prevalence of the residents. In this research, with the close cooperation of Shandong Province Center for Disease Control and Prevention, we conducted an epidemiology study on prevalence and related risk factors of hypertensive retinopathy in Ningyang County, Shandong Province, so as to provide a basis for enacting related policy on blinding prevention and control. At the same time, we contacted several hospitals in Ji’nan city and studied clinical epidemlology of hypertensive retinopathy in-patients with hypertension in Jinan city and analyze its related factors. Part Ⅰ:Epidemiological investigation of hypertensive retinopathy in the residents of Ningyang county in Shandong province.Objective:To study the prevalence of hypertensive retinopathy in the residents of the Ningyang county in Shandong province and analyze its related risk factors. To explore the economic and effective prevention and control mode of hypertensive retinopathy. To reduce the rate of blindness caused by hypertensive retinopathy through the corresponding health education and early diagnosis and treatment.Methods:Bying random cluster sampling (qualified residents cluster sampling), two Ningyang county urban communities and eight villages were chosed. Some people above35years old in the areas were investigated with questionnaire survey, physical and eye examinations. The contents of the questionnaire included general condition (name, gender, age, living habits, etc), the history of hypertension, family disease history, treatment and control of blood pressure, eye disease history, diabetes and hyperlipemia disease history. Eye examinations included bare eye visual acuity, slit lamp examination of corneal, iris, lens, anterior chamber and anterior vitreous, intraocular pressure measurement by non-contact tonometer and examination of fundus after mydriasis by compound tropicamide eye drops with VOLK90D lens. If the subjects had shallow anterior chamber then did direct ophthalmofundoscope through small pupil. Both two eyes were examined if binocular refractive interstitial was clear in an individual. If the retinopathy was different in right eye and left eye, we recorded the severe one. If one eye had serious cataract or vitreous opacity, we recorded another eye. If the classification was difficult in some eyes, all the ophthalmologists should be given a common diagnosis.SPSS13.0was used in statistical treatment. The four table chi-square tests were used in comparison of prevalence in two samples. Trend chi-square tests were used in comparison of prevalence in more than two groups.We took a=0.05, P<0.05as a significant test. HR was taken as the dependent variable, assigned0as normal,1as HR grade1,2as HR grade2,3as HR grade3. City/rural, sex, age, course of disease, systolic hypertension, systolic hypertension, mixed type hypertension were taken as independent variables. Multiple regression analysis was carried out. All of the data were collected by two people repeatedly in order to ensure the accuracy.Results:1328cases (566males and772females) were diagnosed as hypertension in all the subjects. Including the newly diagnosed patients and the patients already diagnosed with hypertention (they might have normal blood pressure since using antihypertensive drugs). The prevalence rate of hypertension was41.20%. Due to the incomplete information,242cases were not included in the statistical results. The other1086subjects completed questionnaires and eye examinations, including446males and640females, aged from35to89years old. The ratio of male to female was1:1.43and the average age was57.85years old.859cases (79.1%) knew that they had hypertension, and342cases(31.49%) had taken drug treatment. Only79cases(7.27%) knew that they had hypertensive retinopathy. In all the1086hypertension patients, there were303cases with normal fundus,783cases with hypertensive retinopathy of different degree.53cases (6.77%) had ocular complications, including retinal arterial obstruction(2cases), retinal vein obstruction(5cases), preretinal membrane (9cases), macular degeneration(34cases), retinal vein thrombosis complicated with neovascular glaucoma(1case), and vitreous hemorrhage(2cases).1. The prevalence of hypertensive retinopathy in county and rural population of Ningyang. The prevalence of hypertensive retinopathy in the rural residents was73.68%, which was clearly higher than that in county residents (64.82%). There was statistically significant (P<0.05).2. The prevalence of hypertensive retinopathy (HR) in residents of different sex in Ningyang. Male and female HR prevalence showed no statistically significant difference (P>0.05).3. The prevalence of hypertensive retinopathy of different age groups in Ningyang. With the increase of age, the prevalence rate of HR increased (P<0.05).4. The prevalence of hypertensive retinopathy in residents of different systolic blood pressure (SBP) and diastolic blood pressure (DBP) groups in Ningyang. With the increase of systolic blood pressure and diastolic blood pressure, the prevalence rate of HR increased (P<0.05).5. The prevalence of hypertensive retinopathy in residents of different course of hypertension in Ningyang. There was a certain correlation between the course of hypertension and the prevalence rate of HR. With the increase of hypertension course, the prevalence rate of HR increased (P<0.05).6. The results of Multiple factors analysis. In the same age group, if the duration of hypertension was longer, the prevalence rate of HR was higher. In the same course of hypertension group, the prevalence rate of HR was higher in high age group than that of in low age group. By ordinal logistic regression analysis, age, county/rural, course of hypertension were risk factors of HR. The prevalence rate of HR in mixed type hypertension group was2.44times than that of in normal blood pressure group. If the duration of hypertension was more than5years, the risk of HR would be2.67times than that of less than1year. If the duration of hypertension was more than10years, the risk of HR would be4.15times than that of less than1year.Conclusions:The prevalence of hypertensive retinopathy in Ningyang was relatively high. And it was characterized with low awareness rate, low treatment rate and low control rate. The risk factors included blood pressure, age, residential area, the course of hypertension. Ophthalmologists need to cooperate closely with the medical institutions at all levels to establish the prevention and control system of hypertensive retinopathy. PART II:Epidemiological investigation of hypertensive retinopathy in in-patients with Hypertension in Jinan city.Objective:To study the prevalence of hypertensive retinopathy in in-patients with primary hypertension in Jinan city and analyze its related factors.Methods:300inpatients with primary hypertension in several hospitals of Jinan city were investigated in detail by questionnaire investigation, laboratory and physical examinations, and ocular examinations. Questionnaire investigation and ocular examinations were similar with part Ⅰ. Besides, some inpatients had eye-ground photography and FFA. Laboratory tests were including fasting blood glucose (FBG), total cholesterol(TC), triglyceride(TG), high density lipoprotein(HDL), low density lipoprotein(LDL), urine albumin(mAlb) and ultrasound heartbeat graph examination. Physical examination including blood pressure (BP), height, weight and waist circumference were also carried out.SPSS13.0was used in statistical treatment. The four table chi-square tests were used in comparison of prevalence in two samples. HR was taken as the dependent variable age, course of hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, HDL, LDL, FBG and UA were taken as independent variables. Multiple regression analysis was carried out. The ratio of retinal arteriolar-to-venular diameter (AVR) was measured on computers with the Image J. All of the data collected were inputed by two people repeatedly in order to ensure the accuracy.Results:There were108males and192females in all the300hypertension inpatients. There were236cases of hypertensive retinopathy in all the300hypertension inpatients(84males and152females)(78.7%). And the prevalence of hypertensive retinopathy in stage Ⅰ,Ⅱ,Ⅲ, Ⅳ was26.0%,33.3%,17.3%and2%respectively.24cases(10.17%) knew that they had hypertensive retinopathy,20cases(8.47%) had ocular complications, including anterior ischemic optic neuropathy(9cases and12eyes), central retinal vein occlusion (2cases), branch retinal vein occlusion(2case), central retinal artery occlusion (1 cases), macular degeneration(5case) and vitreous hemorrhage(1case).1. The prevalence of hypertensive retinopathy (HR) in different sex of the hypertension inpatients in Jinan city. The prevalence of different sex showed no statistically significant difference (P>0.05).2. The prevalence of HR in deferent age groups of hypertension inpatients in Jinan city. The age of the subjects in this survey was from47to86years old. The average age was65.96. With the increase of age, the prevalence rate of HR increased, but there was not statistical significance (P>0.05).3. The prevalence of HR in hypertension inpatients of different systolic blood pressure (sbp) and diastolic blood pressure (dbp) groups in Jinan. With the increase of systolic blood pressure and diastolic blood pressure, the prevalence rate of HR increased (P<0.05).4. The prevalence of HR in hypertension inpatients of different course of hypertension. The course of hypertension in hypertension inpatients was from6to27years. With the increase of hypertension course, the prevalence rate of HR increased (P<0.05).5. Single factor analysis of clinical index between case and control groups. We took the hypertension inpatients with hypertensive retinopathy as case group, the hypertension inpatients without hypertensive retinopathy as control group. By single factor analysis, course of hypertension, triglyceride(TG), diastolic blood pressure(DBP), systolic blood pressure(SBP), and Urinary albumin(UA) had significantly difference between two group(P<0.05). The other clinical index had no significantly difference between two group (P>0.05)6. Multiple regression analysis.By multiple regression analysis, course of hypertension, triglyceride (TG), diastolic blood pressure(DBP), systolic blood pressure(SBP), and Urinary albumin(UA) were risk factors of HR.7. The relationship between hypertensive retinopathy and left ventricular hypertrophy. We took the hypertension inpatients without hypertensive retinopathy as control group, the hypertension inpatients with hypertensive retinopathy grade Ⅰ and grade Ⅱ as case1group, gradeⅢ and grade Ⅳ as case2group.The left ventricular weight in the three groups were significantly different (P<0.05).8. The analysis of the ratio of retinal arteriolar-to-venular diameter (AVR).The value of the AVR in4major blood vessels, the superior temporal artery and vein, the inferior temporal artery and vein, the superior nasal artery and vein,and the inferior nasal artery and vein, was no significant difference. The AVR of hypertension group was significantly lower than that of the normal group.Conclusions:The prevalence of hypertensive retinopathy was high in hypertension inpatients of Jinan city. And it was more severe than in the population sampling survey. Course of hypertension, TG, DBP, SBP, and mAlb were risk factors of HR. AVR in group with hypertension was significantly less than the normal group. Image J software had certain advantages in the quantitative analysis of retinal vessel diameters.The fundus examination should be strengthened, especially in the hypertension patients with long course and combined with hyperlipemia or renal function abnormal.To prevent or reduce the occurrence of hypertensive retinopathy, blood pressur should be under good control.更多还原