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The Study On Risk Factors For Cardiovascular Diseases And Candidate Genes For Hypertension In Shandong Population

Posted on:2008-06-16Degree:MasterType:Thesis
Country:ChinaCandidate:J M YangFull Text:PDF
GTID:2144360215476718Subject:Internal Medicine
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Background:Hypertension, coronary heart disease and stroke have become the main diseases influencing the human health, and were the first cause of death in Chinese adult population. Although the main risk factors for cardiovascular diseases are clear, the different predictive values on different aged population and different cardiovascular diseases are still uncertain. It is well acknowledged that hypertension is the main risk factors for cardiovascular diseases. Essential hypertension is a complex disorder influenced by multiple genetic and environmental factors. Genetic factors play a key role in the pathogenesis of hypertension. There are several studies on hypertension relation to GNB3, ACE and AGT polymorphisms in China, but most of them are single gene analysis and do not differentiate the subtypes of hypertension.Objectives:1) To investigate the association between pulse pressure and stroke and to explore the different association in middle-aged and senile population.2) To explore the predictive value of pulse pressure and mean arterial pressure to the incidence of stroke in middle-aged and senile population.3) To explore systolic blood pressure, diastolic blood pressure, pulse pressure,and mean arterial pressure in predicting the risk of long-time cardio-cerebro vascular death in middle-aged and senile population.4) To explore the affecting factors on cardio-cerebro vascular death events among people over 40 years of age in Shandong area, China. 5) To investigate the prevalence of the metabolic syndrome among the dwellers in Jinan, China, and the relationship between metabolic syndrome and coronary heart disease and stroke.6) To investigate the prevalence of hyperuricemia and its risk factors in the general adult population aged 35-64 years in Jinan.7) To study the singular and combined effects of the candidate genes in relation to blood pressure, hypertension in the Shandong Han population.Methods:1) Datas from shandong blood pressure survey involved 15 752 subjects aged over 40 in 2002 were analysed for the association between PP and risk of stroke ,with t-test,χ2 test and binary logistic regression.2) The baseline survey of middle-aged and senile population of shandong province was carried out in the year 1991.The correlation between the two pulse pressure and mean arterial pressure and stroke, the four blood pressure indices and cardio-cerebro vascular death, the different risk factors and cardio-cerebro vascular death were analyzed by using Cox regression model.3) We analyzed data on 4041 residents aged 35-64 years from the cross-sectional survey of Jinan. Physical examination was carried and fasting blood was tested. Data were analyzed by multivariate logistic regression models. 4) A total of 366 participants were recruited in this study. Blood pressure was measured consecutively three times. DNA, extracted from white blood cells was genotyped for polymophisms of the genes for G-proteinβ3 subunit(C825T polymorphism) ,Angiotensin converting enzyme(I/D polymorphisms) and Angiotensinogen gene(M235T polymorphism). The relationship between hypertension and the three candidate genes in the Shandong Han population were examined.Results:1) 15 752 participants were recruited in this study, including 282(1.8%) subjects with stroke and 15 450(98.2%) subjects free of stroke. The average level of pulse pressure was(47.46±11.14)mmHg.With the increase of age, the level of PP rised and arrived the peak value at about 70 years old . After adjusting age, gender, body mass index ,smoking, alcohol drinking, coronary heart disease, hypercholesteremia, diabetes, the incidence of stroke increased with the increase of PP. With each increase of 10 mmHg, the stroke risk was increased by 76.0% in the middle-aged and 44.8% in the senile population after adjusting other risk factors. After adjustment for systolic blood pressure, the association between PP and stroke was inversely significant in middle-aged population(B=-0.482,OR=0.618, P<0.01),but not significant in senile population. The association was independent of diastolic blood pressure.2) Both PP and MAP were predictors of stroke among middle-aged and senile population. In middle-aged population, for each 10 mmHg increase in PP or MAP, there was an 32.4% or 100.8% increase in the risk of stroke ,and the predictive value of MAP is independent on Systolic Blood Pressure(SBP).On the contrary, in senile population ,MAP is a weaker predictive factor than PP, and for each 10 mmHg increase in pp , there was an 9.1% increase in the risk of stroke.3) Totally 395 cardio-cerebro death events occurred among the 10 786 subjects after 8 years follow-up. After other risk factors adjusted, MAP was the strongest predictive factor for long-time cardio-cerebro vascular death in middle-aged population, and SBP in senile population. With 1-SD higer value for each blood pressure index, adjusted relative risks (RR) for cardio-cerebro vascular death were 1.837 for MAP, 1.782 for SBP, 1.775 for DBP, 1.750 for PP in middle-aged group and 1.345 for SBP, 1.343 for MAP, 1.219 for DBP and 1.215 for PP in senile group.4) Totally 434 cardio-cerebro death events occurred among the 11 008 subjects during 8 years follow-up. Cardio-cerebro death events were related to systolic blood pressure,diastolic blood pressure,smoking, stroke history and age.Cox regression analysis showed that the relative risk(RR) for cardio-cerebro vascular death events increased by 2.862 [95% confidence interval(CI): 1.976~4.144] times for those people having stroke history.When systolic blood pressure,diastolic blood pressure increased by every 10 mmHg,the relative risk for cardio-cerebro vascular death events increased by 1.171(95%CI:1.033~ 1.328),1.214(95%CI:1.044~1.413) respectively. There was 1.239(95%CI:1.088~1.553)times higher in smokers than non-smokers on relative risk for cardio-cerebro vascular death events. However,the predictive values of the influence factors for cardio-cerebro vascular death were different among population of different years of age. The relative risk for cardio-cerebro vascular death events increased by 1.366 [95% confidence interval(CI): 1.102~1.678] times for each 10 mmHg increase of diastolic blood pressure in 40~59 years old population .However,the effect was taken place by systolic blood pressure in 60~74 years old population,with a relative risk of 1.201[95% confidence interval(CI): 1.017~1.418] for each 10 mmHg increase.Age is the only significant factor for cardio-cerebro vascular death events for population aged more than 75 years old.5) The age standardized prevalence of metabolic syndrome was 14.6% in subjects aged 35-64 years in Jinan. The age standardized prevalence of obesity, high blood sugar, hypertension, high blood triglyeride and low high density lipoprotein-cholesterol were 39.6%,7.7%,42.0%,20.1% and 17.9%,respectively. The metabolic syndrome was associated with a 1.78 and 2.02 fold higher risk of coronary heart disease and stroke, respectively.6) 6.4% of men and 2.1% of women had hyperuricemia, which was defined as serum uric acid≥417 umol/L in men and≥357 umol/L in women. Multivariate logistic regression models found that hypertriglyceridemia ( OR 6.155 , 95%CI 4.354~8.701 ) , hypercholesteremia(OR 2.853,95%CI 1.796~4.531), male gender(OR 2.749 , 95%CI 1.781~4.245 ) , hypertension ( OR 1.884 , 95%CI 1.320~2.687), central obesity(OR 1.834,95%CI 1.209~2.781)were associated with increased risk of hyperuricema, however, living in rural areas(OR 0.266,95%CI 0.177~0.398)and alcohol consumption(OR 0.807,95%CI 0.706~0.892)were associated with reduced risk of hyperuricemia.7) Analysis of single-gene effect showed the GNB3 gene C825T polymorphism is not related to blood pressure level and hypertension. DD homozygosity of the Angiotensin converting enzyme had higher systolic blood pressure compared with the II homozygosity in men, but not in women. TT homozygosity of the Angiotensinogen gene had higher systolic blood pressure compared with the MM homozygosity in both men and women.8) In multigene analysis, there were synergistic effect on the relative risks of hypertension where in combination with TT genotype of GNB3 gene and DD genotype of ACE gene(R=1.82), DD genotype of ACE gene and TT genotype of AGT gene(OR=3.15).Conclusion:1) The incidence of stroke was elevated for the subjects with high PP in middle-aged and senile population.The association between PP and stroke was independent of DBP, but not of SBP. The levels of DBP in middle-aged and PP in senile population should be taken great care of when stroke risk is evaluated.2) Both PP and MAP are predictors of stroke among middle-aged and senile population. MAP is stronger independent predictive factor for stoke than PP in middle-aged population.However,PP is an independent risk factor for stroke after MAP,diastolic blood pressure(DBP) adjusted,although the predictive value is not independent on SBP.3) The predictive values of the four blood pressure indices were different among different age stages. The level of MAP should be controlled first in middle-aged population, and SBP should be taken great care in senile population.4) The predictive values of the risk factors were different among different age stages.The different risk factors should be taken great care corresponding to different age stages .5) A large proportion of adults have the metabolic syndrome. The metabolic syndrome was positively associated with the risk of coronary heart disease and stroke.6) Hypertriglyceridemia, hypercholesteremia, male gender, hypertension, central obesity are associated with increased risk of hyperuricema. Alcohol consumption and living in rural areas are associated with reduced risk of hyperuricemia.7) In single-gene analysis, polymorphism of GNB3 gene is not related to blood pressure and hypertension in this Shandong Han population .The relationship between polymorphism of ACE is affected by gender. TT homozigocity of AGT gene may have a higher systolic blood pressure.8) A synergistic effect between the ACE, GNB3 and AGT genes contribute to the increased blood pressure and the risk of hypertension.
Keywords/Search Tags:hypertension, systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure, coronary heart disease, stroke, gene polymorphism, risk factor, metabolic syndrome, Hyperuricemia
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