南中国海大亚湾地区海岛渔民高血压及冠脉病变特征和危险因素分析
发布时间：2018-09-17 14:42
【摘要】：冠心病(coronary heart disease,CHD)是由冠状动脉粥样硬化引起血管狭窄或闭塞导致的一种血流受阻,心肌缺血性疾病。关于产生冠状动脉粥样硬化的原因尚不完全清楚,目前认为性别、年龄、吸烟、肥胖、家族史、高血压、糖尿病以及血脂异常等多种危险因素都有可能导致冠心病发生。近年来,有研究进一步发现冠心病的危险因素及其临床特征及诱发出冠状动脉病变的特点具有地区及民族的差异性,且这种差异性与冠状动脉病变的严重程度具有一定的相关性。其中高血压是其发病的重要环节,是引起冠脉病变的重要危险因素。不同群体出现高血压类型和程度不一样,所诱发出血管病变的严重程度同样有不一样的差距。广东省曾在1991年和1998年、2000年进行了全省高血压抽样调查,结果表明全省高血压患病率的增幅明显加快,患病人群出现低龄趋势,但是三次全省调查均未抽取大亚湾海岛地区样本,这对全省不同人群高血压防治和并发症的预防产生不同程度的影响。渔民是一个特殊群体,渔民饮食习惯产生身体内部变化,很重要的一点就是同型半胱氨酸水平的提高。除营养状况外,日常饮食方面由于摄入物质不同,将影响血浆总同型半胱氨酸含量。有研究数据显示,同型半胱氨酸水平的提高是原发性高血压的独立风险因素,也作为原发性肺动脉高压的风险因素；高血压患者的同型半胱氨酸水平往往高于普通健康人群,高同型半胱氨酸血症提高高血压的发生风险,高同型半胱氨酸血症和许多其他的诱发高血压疾病因子存在效果重叠作用,但是对单独危险因子的说明和分离相当困难。导致高血压发生的重要因素之中,同型半胱氨酸引发的疾病机制,血管内膜钙化方面,许多体外实验证明尚未涉及,给同型半胱氨酸及高血压的研究留下空白。同型半胱氨酸诱发出血管疾病,原因是同型半胱氨酸会影响人体凝血系统,破坏血管内皮细胞,引起炎症反应而产生血管病变和栓塞。高同型半胱氨酸血症较为严重的患者往往其尿液同型半胱氨酸含量也会升高,会产生动脉或静脉相关血管疾病。有体外实验证明导致冠脉病变和体内的酸碱平衡水平可能有关,但这些研究尚未进入细胞功能及基因分析层次,给伴高同型半胱氨酸血症的高血压合并冠心病患者的研究留下探讨的空间。本研究选择南中国海大亚湾地区海岛渔民中的高血压病例资料,旨在探讨南中国海大亚湾地区海岛渔民高血压患者临床特点和冠状动脉病变特征,以及内环境水平变化,并从相关特异的危险因素和基因层面分析其病变的特殊性。目的1)了解南中国海大亚湾地区海岛渔民高血压患病基本状况和同型半胱氨酸水平及内环境变化。2)探讨患高血压的大亚湾地区海岛渔民与大陆汉族冠心病患者临床特点及冠状动脉病变的差异,分析差异的相关原因。3)探讨亚甲基四氢叶酸还原酶(MTHFR) C677T基因多态性与大亚湾地区海岛渔民高血压患者冠脉病变的关系,以期为早期发现高血压及冠脉病变患者的治疗提供一定的参考依据。4)通过大鼠模型实验验证同型半胱氨酸水平和pH值改变对冠状动脉病变及微血栓形成机制及意义。方法1)利用惠州医学会在大亚湾4个渔民居住的海岛渔民进行慢性病教育,并对该地区15～80岁的渔民进行体检的资料,完整者有3386人(占总人口38%)其中男性1879例(55.5%)女性1707例(44.5%),平均年龄(40.2±9.4)岁；所有体检对象均以面对面的方式询问高血压既往病史和基本情况,体检测量体质指数、腰围等相关数据。均在上午测定血压,测前安静坐位5min,使用经校正的汞柱台式血压计,测量右肱动压,Korotkoff第1音为收缩压(SBP),第五音为舒张压(DBP)。受检者连续3次,每次间隔30s/次,取平均值。Hcy检测：采集患者的空腹静脉血,采用高效液相色谱法对患者血浆中的同型半胱氨酸进行检测,所运用的仪器为Agilent 1200液相色谱仪。2)将冠心病患者分为按其来源地区分为大亚湾地区海岛渔民组(观察组)和大陆汉族组(比较组)。记录和对比两组患者的临床特征和冠状动脉病变特点,具体内容包括：性别、年龄、身高、体重、血压；询问是否有吸烟、饮酒、高血压病、高脂血症、2型糖尿病及心血管病家族史等；测量空腹静脉血血糖(FBG)、血脂包括TC(总胆固醇)、TG(甘油三酯)、LDL-C(低密度脂蛋白胆固醇)、HDL-C(高密度脂蛋白胆固醇)、apo Al(载脂蛋白a1)和apo B(载脂蛋白B)以及LVEF%(左心室射血分数)；检测血管病变部位和病变数目。3)选取海岛渔民高血压患者为观察组,冠状动脉造影检查,A组为造影结果阴性的高血压患者140例；B组为造影结果为阳性的高血压患者140例,健康体检者140例为C组,采用聚合酶链反应-限制性片段长度多态性(Polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP)法进行基因多态性的检测,高效液相色谱化学法检测血浆总同型半胱氨酸(THcy)浓度,并检测血液生化指标等,比较分析各组基因多态性和同型半胱氨酸水平差异。4)月桂酸钠诱导构建大鼠冠状动脉微血栓模型,通过分离血管内皮细胞,并在不同pH条件的培养基中培养24小时oELISA检测培养基中血管性假血友病因子(Von Willebrand因子,vWF)的含量。利用Real-time PCR和western blot在mRNA及蛋白水平检测凝血酶原酶(FGL2)的表达情况。综合评价pH改变对大鼠冠状动脉微血栓形成的作用。5)高同型半胱氨酸血症对内皮细胞和血管钙化影响作用机制的实验。首先,人脐静脉内皮细胞(HUVEC)进行培养,然后进行不同浓度的Hcy(0、0.01、0.1、1、3、5 mmol/L)及不同作用时间(3、6、12、24h)。采用流式细胞术检测细胞凋亡率。同时,建立和导入高同型半胱氨酸血症以检测总血浆Hcy水平和判断血管钙化程度对大鼠血管钙化研究的模式。结果1)高血压患病率,体检资料完整的3386名海岛渔民中,高血压患者516人,高血压粗患病率15.24%,标准化13.00%。血压处于正常高值者1057人,占31.22%,其中15～39岁536人,占该年龄段总调查人口的46.21%。渔民高血压患者中随血压升高Hcy水平增高,血液pH值随血压升高而降低。2)危险因素分析,把单因素分析中具有统计学意义的变量纳入多因素非条件Logistic回归模型。定义进入模型的显著性水平为0.2,剔除变量的显著性水平为0.05。结果表明饮酒、吸姻、婚姻状况、高血压家族史、盐摄入量是高血压的危险因素。3)吸烟、饮酒以及血脂异常是大亚湾地区海岛渔民冠心病患者主要危险因素,OR值分别达到3.69、2.83和2.59,具有统计学意义(P=0.000)；男性、吸烟以及饮酒冠心病比率分别达到66.0%、42.0%和57.0%,显著高于大陆汉族冠心病患者(P=0.000),女性、肥胖、高血压、糖尿病、以及血脂异常渔民比率均显著低于大陆组(P=0.000)；TG为(2.47±0.73)mmol/L,显著高于大陆组(P=0.000)；HDL-C为(0.89±0.32) mmol/L,显著低于大陆组(P=0.000)；冠脉单支病变例率为70.0%,显著高于大陆组(P=0.000),多支病变例数为30.%,显著低于大陆组(P=0.000); LCX部位病变率为30.0%,显著高于大陆组(P=0.000),而LAD部位病变率为32.0%,显著低于大陆组(P=0.000)。病变以钙化为主。4)B组HCY[(21.6±9.02)μmol/L]较A组[(15.62±10.5)μmol/L]、C组[(9.7±4.19)μmol/L]显著升高,T/T型HCY[(21.38±11.02)μmnol/L]较C/T型[(18.37±8.46)μmol/L]、C/C型[(15.51±8.24)μmol/L]显著升高,T/T型Gensini评分(51.8±7.4)显著高于C/C基因型、C/T基因型,B组MTHFR基因C/T型频率(36.43%)显著高于A组(22.86%)。5)根据ELISA实验结果,与对照组相比,模型组动物的内皮细胞中vWF表达量要明显升高,这也是血栓形成的一个标志,进一步在不同pH的培养基中培养分离得到的血管内皮细胞,可以看出,在较低pH的培养基中,vWF的表达量要高于pH7.2-8.0组。6) ELISA检测vWF的表达量(pg/ml, X±SD)分别是(336.67±24.95)；(311.33±14.98)；(359.67±39.63)；(354.67±49.01)；(332.00±33.42),而在模型组vWF的表达量分别是(570.00±57.94)；(524.67±57.94)；(437.00±95.38)；(415.33±44.38)；(444.67±74.31)。模型组不同pH条件培养下,FGL2 mRNA的相对表达量分别为：(7.93±0.93)；(6.70±0.70)；(5.03±0.32)；(5.13±0.40)；(5.57±0.83)。7)Hcy浓度的增加,细胞凋亡率和细胞均显著增加氧自由基的产生,且差异均有统计学意义(P=0.000)。在动物钙化模型,黑色颗粒沉积量后Von Kossa钙化组大鼠血管染色可见。与对照组相比,钙化组血管钙含量、碱性磷酸酶活性和骨钙含量均增加(p=0.000)。结论1)调查显示大亚湾地区特定人群(海岛渔民)的高血压标化患病率为13.00%,与全省和全国水平基本一致；高血压患病率呈低龄化趋势,高峰在35～39岁(37.42%),30～64岁组均呈高患病率(10%)；通过Logistic回归分析发现,饮酒、吸烟、婚姻状况、高盐膳食、高血压家族史为海岛渔民高血压患病的危险因素。资料分析中发现,大亚湾海岛渔民体内同型半胱氨酸浓度随血压的水平而改变,强烈提示渔民血压水平与血液同型半胱氨酸浓度呈正相关,意外发现渔民高血压患者中,血液pH值偏低。通过分析结果,显示大亚湾海岛渔民这类群体,其血压变化和相关病变差异性是由于体内同型半胱氨酸浓度的变化和pH值的改变具有共同叠加作用机制。2)大亚湾地区(高血压患病率为15.24%,标准化13.00%)渔民高血压Logistic分析的危险因素亦有所不同,但“发病年龄提前”的趋势基本一致,并且都源于膳食结构和生活方式。值得注意的是,调查渔民青壮年血压值均处于正常高值,若干年后青壮年患病率不容乐观,应引起重视。3)与大陆汉族比较,大亚湾地区海岛渔民的主要危险因素是吸烟、饮酒和以TG升高以及低HDL-C为主的血脂异常,其临床特点为男性患者比例高,肥胖、高血压和糖尿病发生率低；冠状动脉病变主要为单支病变,受累部位主要为左前降支和左回旋支,冠脉病变大多以钙化病变为主,呈弥漫性,虽然提示冠心病常见的危险因素并没有特异性,而冠状动脉病变特点具有地域性和人群的差异性。由于尚未见相关方面的研究,因此尚无法与他人研究结果做对比。研究推断,大亚湾域海岛渔民高血压患者冠脉病变与血液同型半胱氨酸浓度及低pH值呈正相关,其血压变化和相关病变差异性可能与体内同型半胱氨酸浓度的变化和pH值的改变有关。4)亚甲基四氢叶酸还原酶(MTHFR) C677T基因多态性方面,高血压合并冠心病患者HCY水平较高血压病患者有显著的升高,且C/T基因型频率显著高于单纯的高血压病患者,MTHFR C677T等位基因突变率也明显高于单纯的高血压病患者。其中冠心病病人中,T/T基因型HCY水平、冠状动脉的Gensini评分均明显高于C/T基因型、C/C基因型。5)大鼠冠状动脉微血栓的形成,可以引起vWF的高表达及分泌,同时,FGL2作为凝血酶原酶,在血栓形成中也明显上调,且这种上调趋势在低pH条件下更为明显,提示,低pH环境是引起心血管疾病的一个因素,这个因素加速致病危险因子的作用。6)同型半胱氨酸能诱导内皮细胞凋亡,其影响程度取决于它的浓度和作用时间；高同型半胱氨酸血症可促进血管钙化,其机制与脂质过氧化增强有关。
[Abstract]:Coronary heart disease (CHD) is a coronary artery atherosclerosis caused by vascular stenosis or occlusion caused by a blocked blood flow, myocardial ischemic disease. The causes of coronary atherosclerosis is not fully understood, currently considered as sex, age, smoking, obesity, family history, hypertension, diabetes and dyslipidemia, etc. In recent years, studies have further found that the risk factors and clinical characteristics of coronary heart disease and the characteristics of coronary artery lesions have regional and ethnic differences, and this difference has a certain correlation with the severity of coronary artery lesions. The incidence of hypertension in Guangdong Province was investigated in 1991, 1998 and 2000. The results showed that hypertension was prevalent in the whole province. The increase of the rate was obviously accelerated and the prevalence of the disease population showed a trend of younger age. However, no samples were taken from Daya Bay Island area in the three provincial surveys, which affected the prevention and treatment of hypertension and the prevention of complications in different populations in the province to varying degrees. In addition to nutritional status, dietary intake of different substances will affect plasma total homocysteine levels. Studies have shown that increased homocysteine levels are an independent risk factor for essential hypertension and a high risk factor for primary pulmonary hypertension. Hyperhomocysteinemia raises the risk of hypertension. Hyperhomocysteinemia has overlapping effects with many other factors that induce hypertension, but it is difficult to explain and isolate individual risk factors. Homocysteine induces hemorrhagic vessel disease because homocysteine affects the blood coagulation system and destroys vascular endothelium. Cells, which cause inflammation, produce angiopathy and embolism. Severe patients with hyperhomocysteinemia tend to have elevated urinary homocysteine levels, which can lead to arterial or venous-related vascular disease. In vitro studies have shown that coronary artery disease and the level of acid-base balance in the body may be involved, but these studies are still ongoing. The data of hypertension cases among fishermen in Daya Bay area of South China Sea were selected to investigate the clinical characteristics of hypertension patients in Daya Bay area of South China Sea. Objective 1) To investigate the prevalence of hypertension, homocysteine and internal environment changes in fishermen in Daya Bay, South China Sea. 2) To explore the Daya Bay area with hypertension. To explore the relationship between methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and coronary artery lesion in hypertensive patients of island fishermen in Daya Bay area, so as to early detect hypertension and coronary artery lesion. 4) To verify the mechanism and significance of changes of homocysteine and pH on coronary artery lesion and microthrombosis by rat model experiment. Methods 1) To educate fishermen of four fishermen living in Daya Bay by Huizhou Medical Association on chronic diseases, and to carry out physical examination on fishermen aged 15-80 in this area. The data were collected from 3 386 persons (38% of the total population) including 1 879 males (55.5%) and 1 707 females (44.5%) with an average age of (40.2 + 9.4) years. Right brachial arterial pressure was measured at 5 min using a corrected mercury column table sphygmomanometer. Systolic blood pressure (SBP) was recorded at the first tone of Korotkoff, and diastolic blood pressure (DBP) was measured at the fifth tone. The instrument used was Agilent 1200 liquid chromatography. 2) The patients with coronary heart disease were divided into Daya Bay Islands Fishermen Group (observation group) and Mainland Han nationality Group (comparison group) according to their origin. The clinical characteristics and coronary artery lesion characteristics of the two groups were recorded and compared, including sex, age, height, weight, blood pressure. Ask if you have a family history of smoking, drinking, hypertension, hyperlipidemia, type 2 diabetes and cardiovascular disease; measure fasting blood glucose (FBG), blood lipids including TC (total cholesterol), TG (triglyceride), LDL-C (low density lipoprotein cholesterol), HDL-C (high density lipoprotein cholesterol), apo Al (apolipoprotein a1) and apo B (apolipoprotein B) to And LVEF (left ventricular ejection fraction); the location of vascular lesions and the number of lesions. 3) selected islands fishermen with hypertension as the observation group, coronary angiography, group A for the angiographic results of 140 patients with hypertension negative; group B for the angiographic results of 140 patients with hypertension, 140 healthy people for the C group, using polymerase chain reaction Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect gene polymorphism, total homocysteine (THcy) concentration in plasma was detected by high performance liquid chromatography (HPLC) and blood biochemical parameters were detected. Genome polymorphism and homocysteine were compared among different groups. Cystine level difference. 4) Rat coronary microthrombosis model was induced by sodium laurate. Vascular endothelial cells were isolated and cultured in different pH medium for 24 hours to detect the content of von Willebrand factor (vWF) in the medium. Real-time PCR and Western blot were used to detect the expression of mRNA and protein. Levels of prothrombin 2 (FGL2) were measured. The effects of pH on coronary microthrombosis in rats were evaluated comprehensively. 5) The mechanism of hyperhomocysteinemia on endothelial cells and vascular calcification was studied. First, human umbilical vein endothelial cells (HUVEC) were cultured, and then Hcy (0,0.01,0.1,1,3) at different concentrations were performed. 5 mmol/L and different action time (3,6,12,24 h). The apoptosis rate was detected by flow cytometry. Meanwhile, the model of hyperhomocysteinemia was established and introduced to detect the total plasma Hcy level and judge the degree of vascular calcification in rats. Results 1) The prevalence of hypertension and the data of physical examination were complete in 3 386 fishermen on island. There were 516 hypertensive patients, the crude prevalence of hypertension was 15.24%, standardized 13.00%. 1 057 people with normal high blood pressure, accounting for 31.22%, of whom 536 were aged 15-39, accounting for 46.21% of the total population. The Hcy level of fishermen with hypertension increased with the increase of blood pressure, blood pH value decreased with the increase of blood pressure. 2) Risk factors were analyzed. Statistically significant variables were included in the multivariate unconditional logistic regression model. Significance was defined as 0.2 for entry and 0.05 for exclusion. The results showed that drinking, marriage, marital status, family history of hypertension, salt intake were risk factors for hypertension. 3) Smoking, drinking and dyslipidemia were risk factors for hypertension. The main risk factors of coronary heart disease were OR 3.69, 2.83 and 2.59 (P = 0.000), respectively. The prevalence of coronary heart disease in male, smoking and drinking was 66.0%, 42.0% and 57.0% respectively, which was significantly higher than that in Han Chinese (P = 0.000), female, obesity, hypertension, diabetes mellitus, and blood lipid differences. The ratio of normal fishermen was significantly lower than that of mainland group (P = 0.000), TG was (2.47.73) mmol/L, significantly higher than that of mainland group (P = 0.000), HDL-C was (0.89.32) mmol/L, significantly lower than that of mainland group (P = 0.000), single coronary artery lesion rate was 70.0%, significantly higher than that of mainland group (P = 0.000), multiple coronary artery lesion rate was 30.0%, significantly lower than that of mainland group (P = 0.000). (30.0%) was 30.0%, significantly higher than the continental group (P = 0.000), and 32.0% was 32.0%, significantly lower than the contcontinental group (P = 0.000). The leslesleslescalccalccalccalcification was the main lesleslesleslesleslesions. HCY [(21.6 [(21.6 (9.02 9.02) 0 0 0/ Gensini score of T/T type was significantly higher than that of C/C genotype and C/T genotype. The frequency of MTHFR genotype C/T in group B (36.43%) was significantly higher than that of group A (22.86%). According to the results of ELISA, the expression of vWF in endothelial cells of model group was significantly higher than that of control group, which was also associated with thrombosis. One marker was that the expression of vWF in lower pH medium was higher than that in pH 7.2-8.0 group.6. The expression of vWF in ELISA (pg/ml, X+SD) was (336.67 + 24.95); (311.33 + 14.98); (359.67 + 39.63); (354.67 + 49.01); (332.00 + 3.00 + 3. The relative expression of FGL2 mRNA in the model group was (7.93+0.93), (6.70+0.70), (5.03+0.32), (5.13+0.40), (5.57+0.7) H, and (415.33+44.38), (444.67+74.31) respectively. Cell apoptosis rate and the production of oxygen free radicals were significantly increased (P = 0.000). Vascular staining was observed in the Von Kossa calcified group after calcification in the animal model, and the calcium content, alkaline phosphatase activity and bone calcium content were increased in the calcified group compared with the control group (P = 0.000). The survey showed that the standardized prevalence rate of hypertension was 13.00% in the specific population (island fishermen) in Daya Bay area, which was basically consistent with the provincial and national levels; the prevalence rate of hypertension was younger, peaking at 35-39 years old (37.42%) and was higher in 30-64 years old group (10%); the logistic regression analysis showed that drinking, smoking, marital status and high salt were found. Diet and family history of hypertension were risk factors for hypertension in fishermen. Data analysis showed that homocysteine concentration in fishermen of Daya Bay changed with blood pressure level, strongly suggesting that blood pressure level was positively correlated with blood homocysteine concentration. The results showed that the differences of blood pressure and related pathological changes in fishermen in Daya Bay were due to the co-overlapping mechanism of homocysteine concentration and pH value. 2) The risk of hypertension in Daya Bay area (prevalence of hypertension was 15.24%, standardized 13.00%) was related to the risk of hypertension Logistic analysis in fishermen. It is noteworthy that the blood pressure values of young and middle-aged fishermen are at normal high levels, and the prevalence rate of young and middle-aged fishermen after several years is not optimistic, which should be paid attention to. 3) Compared with Han nationality in mainland China, the blood pressure of fishermen in Daya Bay area is higher than that of other islands. The main risk factors were smoking, alcohol consumption, and abnormal blood lipids with elevated TG and low HDL-C. The clinical features were high proportion of male patients and obesity.
【学位授予单位】：南方医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R541.4
本文编号：2246242
[Abstract]:Coronary heart disease (CHD) is a coronary artery atherosclerosis caused by vascular stenosis or occlusion caused by a blocked blood flow, myocardial ischemic disease. The causes of coronary atherosclerosis is not fully understood, currently considered as sex, age, smoking, obesity, family history, hypertension, diabetes and dyslipidemia, etc. In recent years, studies have further found that the risk factors and clinical characteristics of coronary heart disease and the characteristics of coronary artery lesions have regional and ethnic differences, and this difference has a certain correlation with the severity of coronary artery lesions. The incidence of hypertension in Guangdong Province was investigated in 1991, 1998 and 2000. The results showed that hypertension was prevalent in the whole province. The increase of the rate was obviously accelerated and the prevalence of the disease population showed a trend of younger age. However, no samples were taken from Daya Bay Island area in the three provincial surveys, which affected the prevention and treatment of hypertension and the prevention of complications in different populations in the province to varying degrees. In addition to nutritional status, dietary intake of different substances will affect plasma total homocysteine levels. Studies have shown that increased homocysteine levels are an independent risk factor for essential hypertension and a high risk factor for primary pulmonary hypertension. Hyperhomocysteinemia raises the risk of hypertension. Hyperhomocysteinemia has overlapping effects with many other factors that induce hypertension, but it is difficult to explain and isolate individual risk factors. Homocysteine induces hemorrhagic vessel disease because homocysteine affects the blood coagulation system and destroys vascular endothelium. Cells, which cause inflammation, produce angiopathy and embolism. Severe patients with hyperhomocysteinemia tend to have elevated urinary homocysteine levels, which can lead to arterial or venous-related vascular disease. In vitro studies have shown that coronary artery disease and the level of acid-base balance in the body may be involved, but these studies are still ongoing. The data of hypertension cases among fishermen in Daya Bay area of South China Sea were selected to investigate the clinical characteristics of hypertension patients in Daya Bay area of South China Sea. Objective 1) To investigate the prevalence of hypertension, homocysteine and internal environment changes in fishermen in Daya Bay, South China Sea. 2) To explore the Daya Bay area with hypertension. To explore the relationship between methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and coronary artery lesion in hypertensive patients of island fishermen in Daya Bay area, so as to early detect hypertension and coronary artery lesion. 4) To verify the mechanism and significance of changes of homocysteine and pH on coronary artery lesion and microthrombosis by rat model experiment. Methods 1) To educate fishermen of four fishermen living in Daya Bay by Huizhou Medical Association on chronic diseases, and to carry out physical examination on fishermen aged 15-80 in this area. The data were collected from 3 386 persons (38% of the total population) including 1 879 males (55.5%) and 1 707 females (44.5%) with an average age of (40.2 + 9.4) years. Right brachial arterial pressure was measured at 5 min using a corrected mercury column table sphygmomanometer. Systolic blood pressure (SBP) was recorded at the first tone of Korotkoff, and diastolic blood pressure (DBP) was measured at the fifth tone. The instrument used was Agilent 1200 liquid chromatography. 2) The patients with coronary heart disease were divided into Daya Bay Islands Fishermen Group (observation group) and Mainland Han nationality Group (comparison group) according to their origin. The clinical characteristics and coronary artery lesion characteristics of the two groups were recorded and compared, including sex, age, height, weight, blood pressure. Ask if you have a family history of smoking, drinking, hypertension, hyperlipidemia, type 2 diabetes and cardiovascular disease; measure fasting blood glucose (FBG), blood lipids including TC (total cholesterol), TG (triglyceride), LDL-C (low density lipoprotein cholesterol), HDL-C (high density lipoprotein cholesterol), apo Al (apolipoprotein a1) and apo B (apolipoprotein B) to And LVEF (left ventricular ejection fraction); the location of vascular lesions and the number of lesions. 3) selected islands fishermen with hypertension as the observation group, coronary angiography, group A for the angiographic results of 140 patients with hypertension negative; group B for the angiographic results of 140 patients with hypertension, 140 healthy people for the C group, using polymerase chain reaction Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect gene polymorphism, total homocysteine (THcy) concentration in plasma was detected by high performance liquid chromatography (HPLC) and blood biochemical parameters were detected. Genome polymorphism and homocysteine were compared among different groups. Cystine level difference. 4) Rat coronary microthrombosis model was induced by sodium laurate. Vascular endothelial cells were isolated and cultured in different pH medium for 24 hours to detect the content of von Willebrand factor (vWF) in the medium. Real-time PCR and Western blot were used to detect the expression of mRNA and protein. Levels of prothrombin 2 (FGL2) were measured. The effects of pH on coronary microthrombosis in rats were evaluated comprehensively. 5) The mechanism of hyperhomocysteinemia on endothelial cells and vascular calcification was studied. First, human umbilical vein endothelial cells (HUVEC) were cultured, and then Hcy (0,0.01,0.1,1,3) at different concentrations were performed. 5 mmol/L and different action time (3,6,12,24 h). The apoptosis rate was detected by flow cytometry. Meanwhile, the model of hyperhomocysteinemia was established and introduced to detect the total plasma Hcy level and judge the degree of vascular calcification in rats. Results 1) The prevalence of hypertension and the data of physical examination were complete in 3 386 fishermen on island. There were 516 hypertensive patients, the crude prevalence of hypertension was 15.24%, standardized 13.00%. 1 057 people with normal high blood pressure, accounting for 31.22%, of whom 536 were aged 15-39, accounting for 46.21% of the total population. The Hcy level of fishermen with hypertension increased with the increase of blood pressure, blood pH value decreased with the increase of blood pressure. 2) Risk factors were analyzed. Statistically significant variables were included in the multivariate unconditional logistic regression model. Significance was defined as 0.2 for entry and 0.05 for exclusion. The results showed that drinking, marriage, marital status, family history of hypertension, salt intake were risk factors for hypertension. 3) Smoking, drinking and dyslipidemia were risk factors for hypertension. The main risk factors of coronary heart disease were OR 3.69, 2.83 and 2.59 (P = 0.000), respectively. The prevalence of coronary heart disease in male, smoking and drinking was 66.0%, 42.0% and 57.0% respectively, which was significantly higher than that in Han Chinese (P = 0.000), female, obesity, hypertension, diabetes mellitus, and blood lipid differences. The ratio of normal fishermen was significantly lower than that of mainland group (P = 0.000), TG was (2.47.73) mmol/L, significantly higher than that of mainland group (P = 0.000), HDL-C was (0.89.32) mmol/L, significantly lower than that of mainland group (P = 0.000), single coronary artery lesion rate was 70.0%, significantly higher than that of mainland group (P = 0.000), multiple coronary artery lesion rate was 30.0%, significantly lower than that of mainland group (P = 0.000). (30.0%) was 30.0%, significantly higher than the continental group (P = 0.000), and 32.0% was 32.0%, significantly lower than the contcontinental group (P = 0.000). The leslesleslescalccalccalccalcification was the main lesleslesleslesleslesions. HCY [(21.6 [(21.6 (9.02 9.02) 0 0 0/ Gensini score of T/T type was significantly higher than that of C/C genotype and C/T genotype. The frequency of MTHFR genotype C/T in group B (36.43%) was significantly higher than that of group A (22.86%). According to the results of ELISA, the expression of vWF in endothelial cells of model group was significantly higher than that of control group, which was also associated with thrombosis. One marker was that the expression of vWF in lower pH medium was higher than that in pH 7.2-8.0 group.6. The expression of vWF in ELISA (pg/ml, X+SD) was (336.67 + 24.95); (311.33 + 14.98); (359.67 + 39.63); (354.67 + 49.01); (332.00 + 3.00 + 3. The relative expression of FGL2 mRNA in the model group was (7.93+0.93), (6.70+0.70), (5.03+0.32), (5.13+0.40), (5.57+0.7) H, and (415.33+44.38), (444.67+74.31) respectively. Cell apoptosis rate and the production of oxygen free radicals were significantly increased (P = 0.000). Vascular staining was observed in the Von Kossa calcified group after calcification in the animal model, and the calcium content, alkaline phosphatase activity and bone calcium content were increased in the calcified group compared with the control group (P = 0.000). The survey showed that the standardized prevalence rate of hypertension was 13.00% in the specific population (island fishermen) in Daya Bay area, which was basically consistent with the provincial and national levels; the prevalence rate of hypertension was younger, peaking at 35-39 years old (37.42%) and was higher in 30-64 years old group (10%); the logistic regression analysis showed that drinking, smoking, marital status and high salt were found. Diet and family history of hypertension were risk factors for hypertension in fishermen. Data analysis showed that homocysteine concentration in fishermen of Daya Bay changed with blood pressure level, strongly suggesting that blood pressure level was positively correlated with blood homocysteine concentration. The results showed that the differences of blood pressure and related pathological changes in fishermen in Daya Bay were due to the co-overlapping mechanism of homocysteine concentration and pH value. 2) The risk of hypertension in Daya Bay area (prevalence of hypertension was 15.24%, standardized 13.00%) was related to the risk of hypertension Logistic analysis in fishermen. It is noteworthy that the blood pressure values of young and middle-aged fishermen are at normal high levels, and the prevalence rate of young and middle-aged fishermen after several years is not optimistic, which should be paid attention to. 3) Compared with Han nationality in mainland China, the blood pressure of fishermen in Daya Bay area is higher than that of other islands. The main risk factors were smoking, alcohol consumption, and abnormal blood lipids with elevated TG and low HDL-C. The clinical features were high proportion of male patients and obesity.
【学位授予单位】：南方医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R541.4
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1 方快发;南中国海大亚湾地区海岛渔民高血压及冠脉病变特征和危险因素分析[D];南方医科大学;2016年
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