南中國海大亞灣地區(qū)海島漁民高血壓及冠脈病變特征和危險(xiǎn)因素分析
發(fā)布時(shí)間:2018-09-17 14:42
【摘要】:冠心病(coronary heart disease,CHD)是由冠狀動脈粥樣硬化引起血管狹窄或閉塞導(dǎo)致的一種血流受阻,心肌缺血性疾病。關(guān)于產(chǎn)生冠狀動脈粥樣硬化的原因尚不完全清楚,目前認(rèn)為性別、年齡、吸煙、肥胖、家族史、高血壓、糖尿病以及血脂異常等多種危險(xiǎn)因素都有可能導(dǎo)致冠心病發(fā)生。近年來,有研究進(jìn)一步發(fā)現(xiàn)冠心病的危險(xiǎn)因素及其臨床特征及誘發(fā)出冠狀動脈病變的特點(diǎn)具有地區(qū)及民族的差異性,且這種差異性與冠狀動脈病變的嚴(yán)重程度具有一定的相關(guān)性。其中高血壓是其發(fā)病的重要環(huán)節(jié),是引起冠脈病變的重要危險(xiǎn)因素。不同群體出現(xiàn)高血壓類型和程度不一樣,所誘發(fā)出血管病變的嚴(yán)重程度同樣有不一樣的差距。廣東省曾在1991年和1998年、2000年進(jìn)行了全省高血壓抽樣調(diào)查,結(jié)果表明全省高血壓患病率的增幅明顯加快,患病人群出現(xiàn)低齡趨勢,但是三次全省調(diào)查均未抽取大亞灣海島地區(qū)樣本,這對全省不同人群高血壓防治和并發(fā)癥的預(yù)防產(chǎn)生不同程度的影響。漁民是一個(gè)特殊群體,漁民飲食習(xí)慣產(chǎn)生身體內(nèi)部變化,很重要的一點(diǎn)就是同型半胱氨酸水平的提高。除營養(yǎng)狀況外,日常飲食方面由于攝入物質(zhì)不同,將影響血漿總同型半胱氨酸含量。有研究數(shù)據(jù)顯示,同型半胱氨酸水平的提高是原發(fā)性高血壓的獨(dú)立風(fēng)險(xiǎn)因素,也作為原發(fā)性肺動脈高壓的風(fēng)險(xiǎn)因素;高血壓患者的同型半胱氨酸水平往往高于普通健康人群,高同型半胱氨酸血癥提高高血壓的發(fā)生風(fēng)險(xiǎn),高同型半胱氨酸血癥和許多其他的誘發(fā)高血壓疾病因子存在效果重疊作用,但是對單獨(dú)危險(xiǎn)因子的說明和分離相當(dāng)困難。導(dǎo)致高血壓發(fā)生的重要因素之中,同型半胱氨酸引發(fā)的疾病機(jī)制,血管內(nèi)膜鈣化方面,許多體外實(shí)驗(yàn)證明尚未涉及,給同型半胱氨酸及高血壓的研究留下空白。同型半胱氨酸誘發(fā)出血管疾病,原因是同型半胱氨酸會影響人體凝血系統(tǒng),破壞血管內(nèi)皮細(xì)胞,引起炎癥反應(yīng)而產(chǎn)生血管病變和栓塞。高同型半胱氨酸血癥較為嚴(yán)重的患者往往其尿液同型半胱氨酸含量也會升高,會產(chǎn)生動脈或靜脈相關(guān)血管疾病。有體外實(shí)驗(yàn)證明導(dǎo)致冠脈病變和體內(nèi)的酸堿平衡水平可能有關(guān),但這些研究尚未進(jìn)入細(xì)胞功能及基因分析層次,給伴高同型半胱氨酸血癥的高血壓合并冠心病患者的研究留下探討的空間。本研究選擇南中國海大亞灣地區(qū)海島漁民中的高血壓病例資料,旨在探討南中國海大亞灣地區(qū)海島漁民高血壓患者臨床特點(diǎn)和冠狀動脈病變特征,以及內(nèi)環(huán)境水平變化,并從相關(guān)特異的危險(xiǎn)因素和基因?qū)用娣治銎洳∽兊奶厥庑浴D康?)了解南中國海大亞灣地區(qū)海島漁民高血壓患病基本狀況和同型半胱氨酸水平及內(nèi)環(huán)境變化。2)探討患高血壓的大亞灣地區(qū)海島漁民與大陸漢族冠心病患者臨床特點(diǎn)及冠狀動脈病變的差異,分析差異的相關(guān)原因。3)探討亞甲基四氫葉酸還原酶(MTHFR) C677T基因多態(tài)性與大亞灣地區(qū)海島漁民高血壓患者冠脈病變的關(guān)系,以期為早期發(fā)現(xiàn)高血壓及冠脈病變患者的治療提供一定的參考依據(jù)。4)通過大鼠模型實(shí)驗(yàn)驗(yàn)證同型半胱氨酸水平和pH值改變對冠狀動脈病變及微血栓形成機(jī)制及意義。方法1)利用惠州醫(yī)學(xué)會在大亞灣4個(gè)漁民居住的海島漁民進(jìn)行慢性病教育,并對該地區(qū)15~80歲的漁民進(jìn)行體檢的資料,完整者有3386人(占總?cè)丝?8%)其中男性1879例(55.5%)女性1707例(44.5%),平均年齡(40.2±9.4)歲;所有體檢對象均以面對面的方式詢問高血壓既往病史和基本情況,體檢測量體質(zhì)指數(shù)、腰圍等相關(guān)數(shù)據(jù)。均在上午測定血壓,測前安靜坐位5min,使用經(jīng)校正的汞柱臺式血壓計(jì),測量右肱動壓,Korotkoff第1音為收縮壓(SBP),第五音為舒張壓(DBP)。受檢者連續(xù)3次,每次間隔30s/次,取平均值。Hcy檢測:采集患者的空腹靜脈血,采用高效液相色譜法對患者血漿中的同型半胱氨酸進(jìn)行檢測,所運(yùn)用的儀器為Agilent 1200液相色譜儀。2)將冠心病患者分為按其來源地區(qū)分為大亞灣地區(qū)海島漁民組(觀察組)和大陸漢族組(比較組)。記錄和對比兩組患者的臨床特征和冠狀動脈病變特點(diǎn),具體內(nèi)容包括:性別、年齡、身高、體重、血壓;詢問是否有吸煙、飲酒、高血壓病、高脂血癥、2型糖尿病及心血管病家族史等;測量空腹靜脈血血糖(FBG)、血脂包括TC(總膽固醇)、TG(甘油三酯)、LDL-C(低密度脂蛋白膽固醇)、HDL-C(高密度脂蛋白膽固醇)、apo Al(載脂蛋白a1)和apo B(載脂蛋白B)以及LVEF%(左心室射血分?jǐn)?shù));檢測血管病變部位和病變數(shù)目。3)選取海島漁民高血壓患者為觀察組,冠狀動脈造影檢查,A組為造影結(jié)果陰性的高血壓患者140例;B組為造影結(jié)果為陽性的高血壓患者140例,健康體檢者140例為C組,采用聚合酶鏈反應(yīng)-限制性片段長度多態(tài)性(Polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP)法進(jìn)行基因多態(tài)性的檢測,高效液相色譜化學(xué)法檢測血漿總同型半胱氨酸(THcy)濃度,并檢測血液生化指標(biāo)等,比較分析各組基因多態(tài)性和同型半胱氨酸水平差異。4)月桂酸鈉誘導(dǎo)構(gòu)建大鼠冠狀動脈微血栓模型,通過分離血管內(nèi)皮細(xì)胞,并在不同pH條件的培養(yǎng)基中培養(yǎng)24小時(shí)oELISA檢測培養(yǎng)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及蛋白水平檢測凝血酶原酶(FGL2)的表達(dá)情況。綜合評價(jià)pH改變對大鼠冠狀動脈微血栓形成的作用。5)高同型半胱氨酸血癥對內(nèi)皮細(xì)胞和血管鈣化影響作用機(jī)制的實(shí)驗(yàn)。首先,人臍靜脈內(nèi)皮細(xì)胞(HUVEC)進(jìn)行培養(yǎng),然后進(jìn)行不同濃度的Hcy(0、0.01、0.1、1、3、5 mmol/L)及不同作用時(shí)間(3、6、12、24h)。采用流式細(xì)胞術(shù)檢測細(xì)胞凋亡率。同時(shí),建立和導(dǎo)入高同型半胱氨酸血癥以檢測總血漿Hcy水平和判斷血管鈣化程度對大鼠血管鈣化研究的模式。結(jié)果1)高血壓患病率,體檢資料完整的3386名海島漁民中,高血壓患者516人,高血壓粗患病率15.24%,標(biāo)準(zhǔn)化13.00%。血壓處于正常高值者1057人,占31.22%,其中15~39歲536人,占該年齡段總調(diào)查人口的46.21%。漁民高血壓患者中隨血壓升高Hcy水平增高,血液pH值隨血壓升高而降低。2)危險(xiǎn)因素分析,把單因素分析中具有統(tǒng)計(jì)學(xué)意義的變量納入多因素非條件Logistic回歸模型。定義進(jìn)入模型的顯著性水平為0.2,剔除變量的顯著性水平為0.05。結(jié)果表明飲酒、吸姻、婚姻狀況、高血壓家族史、鹽攝入量是高血壓的危險(xiǎn)因素。3)吸煙、飲酒以及血脂異常是大亞灣地區(qū)海島漁民冠心病患者主要危險(xiǎn)因素,OR值分別達(dá)到3.69、2.83和2.59,具有統(tǒng)計(jì)學(xué)意義(P=0.000);男性、吸煙以及飲酒冠心病比率分別達(dá)到66.0%、42.0%和57.0%,顯著高于大陸漢族冠心病患者(P=0.000),女性、肥胖、高血壓、糖尿病、以及血脂異常漁民比率均顯著低于大陸組(P=0.000);TG為(2.47±0.73)mmol/L,顯著高于大陸組(P=0.000);HDL-C為(0.89±0.32) mmol/L,顯著低于大陸組(P=0.000);冠脈單支病變例率為70.0%,顯著高于大陸組(P=0.000),多支病變例數(shù)為30.%,顯著低于大陸組(P=0.000); LCX部位病變率為30.0%,顯著高于大陸組(P=0.000),而LAD部位病變率為32.0%,顯著低于大陸組(P=0.000)。病變以鈣化為主。4)B組HCY[(21.6±9.02)μmol/L]較A組[(15.62±10.5)μmol/L]、C組[(9.7±4.19)μmol/L]顯著升高,T/T型HCY[(21.38±11.02)μmnol/L]較C/T型[(18.37±8.46)μmol/L]、C/C型[(15.51±8.24)μmol/L]顯著升高,T/T型Gensini評分(51.8±7.4)顯著高于C/C基因型、C/T基因型,B組MTHFR基因C/T型頻率(36.43%)顯著高于A組(22.86%)。5)根據(jù)ELISA實(shí)驗(yàn)結(jié)果,與對照組相比,模型組動物的內(nèi)皮細(xì)胞中vWF表達(dá)量要明顯升高,這也是血栓形成的一個(gè)標(biāo)志,進(jìn)一步在不同pH的培養(yǎng)基中培養(yǎng)分離得到的血管內(nèi)皮細(xì)胞,可以看出,在較低pH的培養(yǎng)基中,vWF的表達(dá)量要高于pH7.2-8.0組。6) ELISA檢測vWF的表達(dá)量(pg/ml, X±SD)分別是(336.67±24.95);(311.33±14.98);(359.67±39.63);(354.67±49.01);(332.00±33.42),而在模型組vWF的表達(dá)量分別是(570.00±57.94);(524.67±57.94);(437.00±95.38);(415.33±44.38);(444.67±74.31)。模型組不同pH條件培養(yǎng)下,FGL2 mRNA的相對表達(dá)量分別為:(7.93±0.93);(6.70±0.70);(5.03±0.32);(5.13±0.40);(5.57±0.83)。7)Hcy濃度的增加,細(xì)胞凋亡率和細(xì)胞均顯著增加氧自由基的產(chǎn)生,且差異均有統(tǒng)計(jì)學(xué)意義(P=0.000)。在動物鈣化模型,黑色顆粒沉積量后Von Kossa鈣化組大鼠血管染色可見。與對照組相比,鈣化組血管鈣含量、堿性磷酸酶活性和骨鈣含量均增加(p=0.000)。結(jié)論1)調(diào)查顯示大亞灣地區(qū)特定人群(海島漁民)的高血壓標(biāo)化患病率為13.00%,與全省和全國水平基本一致;高血壓患病率呈低齡化趨勢,高峰在35~39歲(37.42%),30~64歲組均呈高患病率(10%);通過Logistic回歸分析發(fā)現(xiàn),飲酒、吸煙、婚姻狀況、高鹽膳食、高血壓家族史為海島漁民高血壓患病的危險(xiǎn)因素。資料分析中發(fā)現(xiàn),大亞灣海島漁民體內(nèi)同型半胱氨酸濃度隨血壓的水平而改變,強(qiáng)烈提示漁民血壓水平與血液同型半胱氨酸濃度呈正相關(guān),意外發(fā)現(xiàn)漁民高血壓患者中,血液pH值偏低。通過分析結(jié)果,顯示大亞灣海島漁民這類群體,其血壓變化和相關(guān)病變差異性是由于體內(nèi)同型半胱氨酸濃度的變化和pH值的改變具有共同疊加作用機(jī)制。2)大亞灣地區(qū)(高血壓患病率為15.24%,標(biāo)準(zhǔn)化13.00%)漁民高血壓Logistic分析的危險(xiǎn)因素亦有所不同,但“發(fā)病年齡提前”的趨勢基本一致,并且都源于膳食結(jié)構(gòu)和生活方式。值得注意的是,調(diào)查漁民青壯年血壓值均處于正常高值,若干年后青壯年患病率不容樂觀,應(yīng)引起重視。3)與大陸漢族比較,大亞灣地區(qū)海島漁民的主要危險(xiǎn)因素是吸煙、飲酒和以TG升高以及低HDL-C為主的血脂異常,其臨床特點(diǎn)為男性患者比例高,肥胖、高血壓和糖尿病發(fā)生率低;冠狀動脈病變主要為單支病變,受累部位主要為左前降支和左回旋支,冠脈病變大多以鈣化病變?yōu)橹?呈彌漫性,雖然提示冠心病常見的危險(xiǎn)因素并沒有特異性,而冠狀動脈病變特點(diǎn)具有地域性和人群的差異性。由于尚未見相關(guān)方面的研究,因此尚無法與他人研究結(jié)果做對比。研究推斷,大亞灣域海島漁民高血壓患者冠脈病變與血液同型半胱氨酸濃度及低pH值呈正相關(guān),其血壓變化和相關(guān)病變差異性可能與體內(nèi)同型半胱氨酸濃度的變化和pH值的改變有關(guān)。4)亞甲基四氫葉酸還原酶(MTHFR) C677T基因多態(tài)性方面,高血壓合并冠心病患者HCY水平較高血壓病患者有顯著的升高,且C/T基因型頻率顯著高于單純的高血壓病患者,MTHFR C677T等位基因突變率也明顯高于單純的高血壓病患者。其中冠心病病人中,T/T基因型HCY水平、冠狀動脈的Gensini評分均明顯高于C/T基因型、C/C基因型。5)大鼠冠狀動脈微血栓的形成,可以引起vWF的高表達(dá)及分泌,同時(shí),FGL2作為凝血酶原酶,在血栓形成中也明顯上調(diào),且這種上調(diào)趨勢在低pH條件下更為明顯,提示,低pH環(huán)境是引起心血管疾病的一個(gè)因素,這個(gè)因素加速致病危險(xiǎn)因子的作用。6)同型半胱氨酸能誘導(dǎo)內(nèi)皮細(xì)胞凋亡,其影響程度取決于它的濃度和作用時(shí)間;高同型半胱氨酸血癥可促進(jìn)血管鈣化,其機(jī)制與脂質(zhì)過氧化增強(qiáng)有關(guān)。
[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.
【學(xué)位授予單位】:南方醫(yī)科大學(xué)
【學(xué)位級別】:博士
【學(xué)位授予年份】:2016
【分類號】:R541.4
本文編號: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.
【學(xué)位授予單位】:南方醫(yī)科大學(xué)
【學(xué)位級別】:博士
【學(xué)位授予年份】:2016
【分類號】:R541.4
【相似文獻(xiàn)】
相關(guān)博士學(xué)位論文 前1條
1 方快發(fā);南中國海大亞灣地區(qū)海島漁民高血壓及冠脈病變特征和危險(xiǎn)因素分析[D];南方醫(yī)科大學(xué);2016年
,本文編號:2246242
本文鏈接:http://sikaile.net/yixuelunwen/xxg/2246242.html
最近更新
教材專著