Characteristics And Risk Factors Of Hypertension And Coronary Artery Disease In Sea Island Fishermen In The South China Sea, Dayawan

Coronary heart disease (CHD) is a myocardial ischemic disease caused by blood vessel stenosis or occlusion. Atherosclerosis is the underlying reason for nearly all causes of coronary artery disease. The causes of coronary atherosclerosis are not fully understood. The most common risk factors include:gender, age, smoking, obesity and family history, hypertension, diabetes, dyslipidemia and other multiple risk factors may lead to the occurrence of coronary heart disease. In recent years, more studies found the characteristics of coronary heart disease risk factors and clinical features and causes of coronary artery disease have regional and national differences, and this difference is highly correlated to the severity of coronary artery lesion. Hypertension is an important determinant of risk factors of coronary artery disease. Different groups of people have different types of hypertension, which induced by the severity of vascular lesions are also not the same gap. Guangdong Province had hypertension sampling survey among the whole population in 1991,1998 and 2000. The results showed that the morbidity rate of hypertension has increased dramatically, and also appeared in the low age tendency. However, no samples were selected from Daya Bay Island in these survives, which impacted disease prevention and treatment of complication for hypertension in different population. Fishermen are a special group of population in China due to their different eating habit and therefore causes changes in their bodies. One of the most important indicators is elevated homocysteine. In addition to the nutritional status, different diet pattern will affect the total plasma homocysteine levels. According to scientific data, elevated homocysteine is the sole risk factor of primary hypertension and primary pulmonary hypertension. Hypertensive patients have higher homocysteine level than healthy individuals. Therefore, elevated homocysteine level increases risk of hypertension. Among all hypertension risk factors, homocysteine induced vascular disease is due to effects of homocysteine on the body’s blood coagulation system, endothelial cell damage, and vascular lesions and embolism related to inflammation response. In severe Hyperhomocysteinemia patients, their urine homocysteine levels will increase, which will lead to a vein or artery related vascular diseases. Many in vitro experiments show that acid-base balance in the body is an important factor in the development of hypertension. However, these studies have not yet got further into the function of vascular endothelial cells and to the level of gene analysis, which leave a blank for in-depth study for homocysteine and hypertension. This study selected Daya Bay Island fishermen hypertension cases in the South China Sea area, aimed to discuss clinical features and characteristics of coronary artery disease in this specific group of patients, and also to determine internal environment changes in relation to the risk factors and gene analysis to review particularity of the lesions.Objective 1) To understand morbidity rate of hypertension in Dayawan Bay fishermen and homocysteine levels with changes in microenvironment 2) To investigate different clinical features of coronary artery disease between Dayawan island fishermen with hypertension and mainland Han patients with coronary heart disease, and to analyze the reasons for the differences.3) To explore the relationship between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and coronary artery physiologic changes in Daya Bay Island fishermen hypertension patients in order to provide a frame of reference for early detection of CAD in patients with hypertension.4) To verify impact of homocysteine levels and pH change on mechanism and significance of coronary artery lesions and micro thrombus formation through the establishment of rat model and experiments.Method 1) Using physical examination data from 15-80 years old fishermen who received chronic disease education which conducted by Huizhou Medical Association in Daya Bay four fishermen inhabitation areas.3386 participants completed education and physical examination (accounting for 38% of the total population), in which 1879 were male (55.5%) and 1707 were female patients (44.5%). (The average age of 40.2 ±9.4 years); all physical objects were conducted a questionnaire regarding history of hypertension and the basic situation and physical measurement of body mass index (BMI), waistline, and related data. All objects were required to have their blood pressure measured in the morning, and sitting quietly for 5 min before the test. Used calibrated mercury column type blood pressure meter to measure right brachial dynamic pressure and Korotkoff sound 1 as systolic blood pressure (SBP), the fifth for diastolic blood pressure (DBP). Pt were asked to get three consecutive readings at 30s/intervals, and then obtain an average number. Hey detection:fasting venous blood were collected, using HPLC to check on homocysteine in plasma of patients. (Used Agilent1200 instrument for liquid chromatography).2) The patients with CAD were divided into Dayawan Island fishermen group (observation group) and mainland Han group (comparison group) based on their residential status. Compared two groups of patients with clinical features and coronary artery lesion characteristics.The specific contents include:gender, age, height, weight, blood pressure; smoking and drinking history; and family history of hypertension, hyperlipidemia, type 2 diabetes and cardiovascular disease. Also, blood tests include:measurement of fasting blood glucose (FBG), blood lipids including TC (total cholesterol), TG (triglyceride), LDC-C density lipid protein cholesterol), HDC-C density lipid protein cholesterol, apolipoprotein Al (apo al) and apolipoprotein B (apo B) and LVEF%(left ventricular ejection fraction) and detection of location and quantity of vascular lesions.3) Island fishermen patients with hypertension were selected as observation group. Coronary angiocardiography test was conducted.140 cases with negative angiography results were selected into group A; 140 patients with positive contrast results were selected into group B; 140 healthy subjects were grouped in C. Using polymerase chain reaction restriction of fragment length polymorphism (polymerase chain reaction fragment length polymorphism, RFLP) method for the detection of gene polymorphism; high performance liquid phase chemical chromatographic method for detection of plasma total homocysteine (tHcy) concentration and blood biochemical indicators; comparative analysis each gene polymorphism and differences of the same type of homocysteine levels.4) The construction model of coronary artery microthrombosis in rats induced by sodium laurate, separated by vascular endothelial cells, and cultured for 24 hours in culture medium in different pH conditions. ELISA detection of medium von Willebrand factor (Von factor Willebrand, vWF) content; The use of Real-time PCR and Western blot at mRNA and protein levels of prothrombin enzyme (FGL2) expression; Comprehensive evaluation of pH changes in coronary artery microthrombosis effect in rats.5) The effects of hyperhomocysteinemia on endothelial cells and vascular calcification in experiment. First of all, human umbilical vein endothelial cells (HUVEC) were cultured with different concentrations of Hcy (0.0.01,0.1,1,3,5 mmol/L) and different time (3,6, 12,24, H). The cell apoptosis was assessed by flow cytometry. Meanwhile, established and introducedhyperhomocysteinemia to detect total plasma Hey levels and to estimate the extent of calcification on vascular calcification in rat models.Results 1) Based on complete medical data from 3386 fishermen,516 of fishermen had hypertension. The prevalence rate of hypertension was 15.24%, the standard was 13%.1057 individuals had high normal blood pressure accounting for 31.22%, and of which 536 were 15-39 years old, accounting for the 46.21% of total population in age. 2) The risk factors with statistical significance in univariate analysis of variables into multivariate non conditional Logistic regression model. The significant level definition into the model for the 0.2 level for the 0.05 eliminated variable. The results showed that drinking, smoking, marital status, family history of hypertension and salt intake were risk factors of hypertension.3) Smoking, drinking and dyslipidemia were risk factors of coronary heart disease in fishermen of Dayawan Island. The OR value reached to 3.69,2.83 and 2.59, with statistical significance (P=0.000); male, smoking and drinking rates of coronary heart disease were respectively 66%,42% and 57%, significantly higher than Han patients with coronary heart disease (P=0.000). Female, obesity, hypertension, diabetes, and dyslipidemia ratio in fishermen were significantly lower than the mainland group (P=0.000); TG was 2.47±0.73 (mmol/L), significantly higher than the mainland group (P=0.000); HDL-C was 0.89±0.32 (mmol/L), was significantly lower than that of the mainland group (P=0.000); single lesion cases rate was 70%, significantly higher than that of the mainland group (P=0.000), multi vessel disease cases was 30%, significantly lower than the mainland group (P=0.000); LCX lesions rate was 30%, significantly higher than the mainland group (P=0.000), while the LAD lesion was 32%, significantly lower than the mainland group (P=0.000).4) group B HCY[(21.6±9.02) u mol/L] compared with group A, [(15.62±10.5) u mol/L], group C [(9.7 ± 4.19) u mol/L] significantly increased, t/T genotype HCY[(21.38 ± 11.02) u mol/L] than C/T [(18.37 ±8.46) mu mol/L], C/C type [(15.51 ± 8.24) u mol/L] significantly increased, t/T genotype Gensini score (51.8 ± 7.4) was significantly higher than that of C/C genotype and C /T genotype, group B MTHFR gene C/T type frequency (36.43%) significantly higher than group A (22.86%).5) according to the results of ELISA experiment, endothelial cells VWF expression was significantly higher in model group animals compared to the control group, which was a sign of thrombosis. Further, vascular endothelial cells isolated from different pH medium culture were able to be seen in the lower pH of the culture medium. The expression of vWF to group was higher than that of Ph7.2-8.0.6) the expression of vWF were detected by ELISA respectively (PG /ml, x ±D) (336.67±24.95)(311.33±14.98); (359.67±39.63); (354.67±49.01); (332.00±33.42)，, and the expression of vWF in model group respectively (570.00±57.94); (524.67±57.94); (437.00±95.38); (415.33±44.38); (444.67±74.31). The model group cultured under different pH conditions, the relative expression of FGL2 mRNA was respectively:(7.93±0.93); (6.70±0.70); (5.03±0.32); (5.13±0.40); (5.57±0.83).7). Increase of Hey concentration, apoptosis rate will significantly increase the production of oxygen free radicals, and the differences were statistically significant (P=0.000).Conclusion 1) The survey showed that standardized prevalence rate in Daya Bay area specific populations (island fishermen) was 13.00%, basically same as the provincial and national levels. The hypertension prevalence rate in the younger age group has increased, peaks at 35-39 years old (37.42%); 30-64 years old group showed a high prevalence (> 10%). Logistic regression analysis showed that drinking, smoking, marital status, high dietary salt intake, family history of hypertension are well determined risk factors for island fishermen. Data analysis showed that homocysteine concentration was influenced by blood pressure change in island of Daya Bay fishermen. Strongly suggest the level of blood pressure blood and homocysteine concentration was positively correlated. Also accidentally discovered the fishermen with hypertension, whose blood pH value is on the low side. The results showed that the Dayawan fishermen, as a special group of population, their blood pressure change and related pathological differences are due to change common mechanism superposition effect in vivo homocysteine concentrations and pH changes.2) Dayawan area (the prevalence rate was 15.24%, the standardized prevalence rate of hypertension is 13% fishermen) Logistic analysis of the risk factors were also different, but the "age of onset" trend was basically the same as well as derived from the dietary pattern and lifestyle. It is worth noting that young fishermen blood pressure values were all in the normal high value in the survey. Young adult hypertension prevalence rate is not optimistic after several years. All health care professionals should pay attention to it.3) Compared to mainland Han population, the main risk factors for Daya Bay islands fishermen were smoking, drinking and the increase of TG and HDL-C of dyslipidemia, the clinical characteristics of high proportion of male patients, obesity, hypertension and diabetes occurred rate was low; coronary artery disease mainly single branch, affected area mainly in the left anterior descending branch and the left circumflex branch, most coronary artery lesions were in the forms of calcification and diffusion. Suggesting that the most common risk factors of coronary heart disease are not specific, and characteristics of coronary artery lesions have geographical and population differences.4) From methylene tetrahydrofolate reductase (MTHFR) gene C677T polymorphism aspects, patients with coronary heart disease (CHD) and hypertension had significantly increased Hcy levels than patients with essential hypertension alone. MTHFR genotype frequency was significantly higher than that of simple hypertension patients and MTHFR C677T allele mutation rate significantly higher than simple hypertension patients. Among the patients with coronary heart disease, coronary artery T/T genotype HCY levels, Gensini scores were significantly higher than that of the C/T genotype, C/C genotype.5) Coronary artery microthrombosis formation in rats can stimulate VWF expression and secretion. Meanwhile, FGL2 prothrombinase is also significantly increased in the formation of thrombosis, and the upward trend is more obvious under low pH conditions. Suggesting that low pH environment may be a risk factor of cardiovascular disease.6) Homocysteine can induce apoptosis of endothelial cell, and this impact depends on its concentration and action time; hyperhomocysteinemia may accelerate vascular calcification. The mechanism may be related to enhanced lipid peroxidation.