The Study On Arteriosclerosis Of Esstial Hypertension And Related Genetic Factors

Objective: Essential Hypertension (EH) is the most common cardiovascular disease, which does harm to vital organs such as the heart, brain and kidney. Up to now hypertension is still the most important cause of death resulting from cardiovascular diseases. Arteriosclerosis which is a non-inflammatory, degenerative and proliferative lesion is the primary basic pathophysiology of hypertension and is the first step causing cardiovascular disease, so detecting arteriosclerosis early and making the mechanism of Arteriosclerosis clear is the fundamental measure to prevent and control hypertension and complications. The aim of the study was to investigate the changes of arterial structure and flexibility and to explore the association between environmental factors such as age, weight, lipids, fasting plasma, and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism ,angiotensin type 1 receptor (AT1R)gene A1166C polymorphism and arteriosclerosis in patients with essential hypertension by measuring brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness(IMT) and plaque, pulse pressure which were non-invasive assessments of atherosclerosis.Methods: According to"China 2005 guideline for the treatment and Preservation of essential hypertension",the study was performed in 344 hypertensives and 342 normotensives matched in age, gender status ,and subjects with cardiovascular disease, diabetes, hypercholesterolemia and those using medication were excluded. Basic clinical data of all subjects such as age, height, weight, blood pressure and heart rate were collected; Biochemical parameters such as fasting plasma and lipids were measured; Carotid intima media thickness (IMT) and plaque were measured by ultrasoundgraphy and baPWV was evaluated by an automatic waveform analyzer; Pulse pressure was calculated. 344 hypertensives were divided into different groups according to different respects: (1) Hypertensives were divided into 1-3 stage hypertensive group based on different blood pressure. (2) Hypertensives were divided into <40 year-old group, 40-59 year-old group and≥60 year-old group based on different age levels. (3) hypertensives were divided into high baPWV group and low baPWV group based on baPWV levels.(4) Hypertensives were divided into high IMT group and normal IMT group based on different IMT.(5) Hypertensives were divided into high pulse pressure group, medium pulse pressure group and high pulse pressure group based on different pulse pressure levels. All researched factors were compared among these groups and the relations between these factors and baPWV, IMT, pulse pressure were analyzed by pearson correlation and linear regressing analysis. In addition, 126 hypertensives and 120 normotensives were randomly selected from all subjects to test the distributions of allele and genotype frequencies of AT1R and ACE by using polymerase chain reaction (PCR) and to explore their influence on blood pressure and arteriosclerosis.Results:1) There was no significant difference on age, gender, BMI, waist-hip ratio, heart rate, TC, TG, HDL-C, LDL-C and fasting plasma between normotensive and hypertensive group. Systolic blood pressure and diastolic blood pressure of hypertensives were significantly higher than normotensive group, P<0.01.2) BaPWV was significantly faster in hypertensive group than in normotensive group, P<0.01, and there were significant differences on IMT, the incidence of plaque and pulse pressure between two groups, P<0.05.3) There were significant differences on baPWV, IMT and pulse pressure among normotensive group, 1-3 hypertensive groups. The higher the blood pressure increased, the higher would be the baPWV, IMT and pulse pressure.4) There were significant differences on baPWV, IMT and pulse pressure among three different age groups. The higher the age increased, the higher would be the baPWV, IMT and pulse pressure. In every age group, baPWV, IMT, incidence of plaque and pulse pressure of hypertensives were significantly higher than normotensive group.5) Systolic blood pressure, diastolic blood pressure, pulse pressure, age, BMI, Waist-hip ratio and IMT of high baPWV group were significantly higher than low baPWV group.6) Age, systolic blood pressure, pulse pressure, LDL, HDL, baPWV, incidence of plaque and pulse pressure of high IMT group were significantly higher than low IMT group, P<0.05.7) There were significant differences on age, systolic blood pressure, diastolic blood pressure, LDL, HDL, IMT and incidence of plaque among three different pulse pressure.8) BaPWV had positive significant correlation with age, systolic blood pressure, pulse pressure, BMI, waist-hip ratio and IMT; IMT had positive significant correlation with age, systolic blood pressure, pulse pressure, LDL, baPWV, and had negative significant correlation with HDL; Pulse pressure had positive significant correlation with age, LDL, baPWV, systolic blood pressure, diastolic blood pressure, IMT, and had negative significant correlation with HDL.9) Multiple regression analysis showed that age, systolic blood pressure and BMI were main factors that influenced baPWV, baPWV(cm/s)=280.453+6.551×age+7.462×SBP(mmHg)+2.923×BMI(kg/m2). Systolic blood pressure, age and pulse pressure were main determinants for IMT, IMT (mm) =0.121+0.004×SBP (mmHg) +0.003×age+0.002×PP (mmHg). Age, baPWV, LDL, HDL were main factors that influenced pulse pressure, PP (mmHg) =7.872+0.180×age+0.024×baPWV (cm/s)-0.303×LDL (mmol/L) +0.380×LDL (mmol/L).10) There were significant differences in the distribution of genotype and allele frequency of AT1R between hypertensive group and normotensive group, P<0.05;while there was no significant difference in the distribution of genotype and allele frequency of ACE between hypertension group and normotensive group, P>0.05.11) C allele of AT1R gene had higher systolic blood pressure, diastolic blood pressure, pulse pressure, baPWV and IMT compared with the A allele, P<0.05; DD genotype of ACE gene had higher baPWV compared with the ID and II, P<0.05. When CC genetype of AT1R gene and DD genotype of ACE gene were combined, There was synergistic effect on the blood pressure and Arteriosclerosis.Conclusion: (1) Arteriosclerosis had occurred and arterial elasticity was reduced in hypertensives. (2)Age, blood pressure, BMI and Lipid were main factors that influenced arteriosclerosis. (3)Ankle-brachial pulse wave velocity (baPWV), carotid intima-media thickness (IMT) and plaque, pulse pressure were indicators of arteriosclerosis, which accessed arterial structure and function changes well. (4)There were significant differences in the distribution of genotype and allele frequency of AT1R between hypertension group and normal group, while there was no significant difference in the distribution of genotype and allele frequency of ACE between hypertension group and normal group.(5) AT1R gene A1166C and ACE gene I/D polymorphism may affect blood pressure and arteriosclerosis, but a single gene on blood pressure was limited, the synergistic effect of multiple genes could increase high blood pressure and arteriosclerosis risk.