Effect Of Hyperhomocysteine On Hypertensive Left Ventricular Hypertrophy And Study On The Intervention Effect Of Enalapril Maleate Folic Acid

Background and objective: Hypertension is a sustained increase of arterial blood pressure as the main manifestation of cardiovascular disease, which can lead to heart, brain, blood and kidney damage, is a common cause in the elderly patients. Epidemiological studies have found that, in our patients with hypertension, hypertensive patients with type H extremely high proportion.It has an interaction between plasma homocysteine(homocysteine, Hcy) level and the blood pressure, along with Hcy rising, high blood pressure, stroke, peripheral vascular and other diseases morbidity and mortality rates were increased to varying degrees. The study results show that the team in the past: high Hcy hyperlipidemia could promote endoplasmic reticulum stress(Endoplasmic reticulum stress, ERS) increase, result in the expression of proteins involved in the relevant imbalances, thereby cause hypertensive cardiac remodeling. So, what is the relationship between hypertension and left ventricular hypertrophy Hcy levels? Whether Hcy by ERS way cause or aggravate heart damage? Currently needs to be further clinical observation. Enalapril maleate folic acid( the EMFA) is a new compound antihypertensive China has independently developed the first approved for the treatment of H type hypertension, which is in accordance with the blades optimal dose(10mg / 0.8mg), which is effective and safety ratio and group parties have access to national the relevant patents, for patients with H type hypertension has a dual therapeutic effect of lowering blood pressure and Hcy. But whether the EMFA through inhibiting the ERS pathway to trigger changes associated protein, reverse left ventricular hypertrophy, improve cardiac function, it is not clear.In this clinical study, by collecting 486 cases of patients with essential hypertension, according to Hcy level is greater than 10μmol / L will be divided into Hcy normal group(130 cases) and high Hcy group(356 cases). Then according to the diagnostic criteria of left ventricular hypertrophy, selected 168 cases of H-type hypertension patients from high Hcy group and randomly divided into the enalapril group(84 cases)and the EMFA group enalapril group(84 cases), and its follow-up one year. Hcy levels Selecte immune scatter turbidimetry to detect fasting blood on of plasma homocysteine concentration,determination of cardiac function and morphological structure indexes by Vivid E9 color doppler ultrasonic diagnostic apparatus. To observe the effect of Hcy level on left ventricular hypertrophy and heart function in hypertension,study on the change of blood pressure, Hcy, left ventricular hypertrophy and cardiac function with the application the EMFA before and after treatment, explore the effect of the EMFA lowering blood pressure and plasma Hcy to reverse H-type hypertension patients. Methods:The first part: Sequential selected in 2013 April ~ 2013 December in Tangdu Hospital clinic and hospital department treatment of patients with primary hypertension in 486 cases(male 235, female 251), age ranged from 40 to 69 years old, the average age of(54.81±7.64).Diagnostic standard consults "guidelines for prevention and treatment of hypertension Chinese 2010", the blood pressure of single blind placebo of 2 week and lead-in period a washout period of 2 weeks after met the inclusion criteria. According to the plasma concentration of Hcy is greater than 10 mnol/L divided into Hcy normal group 130 case(male 63 cases, female 67), age(55.21+7.13) years old) and high Hcy group 356 case(male 172, female 184) cases, age(54.92+6.83) years. Using color Doppler ultrasonic diagnostic apparatus determinate the thickness of interventricular septum(IVST), left ventricular posterior wall thickness(LVPWT), left ventricular end diastolic diameter(LVED), ejection fraction(LVEF), the determination of left ventricular diastolic function by Doppler, in the apical four chamber view recording of mitral valve flow spectrum, the sample volume placed in the left chamber close to the mitral valve the opening, mitral early diastolic peak flow(E peak), mitral late diastolic peak flow(A peak), to calculate the ratio of E/A, according to Devereux formula tocalculate the left ventricular mass index(LVMI). To compare the difference in blood pressure, Hcy, IVST, LVPWT, LVED, LVEF, E/A values and LVMI between the two groups, and to analyze the correlation between Hcy and IVST, LVPWT, LVED, LVEF, E/A and LVMI.The second part: Selected 168 cases of patients with H type of hypertensive left ventricular hypertrophy from high Hcy group 356 cases(male 82, female 86), age ranged from 42 to 68 years old, the average age of(55.31+8.21), The selected standard: primary diagnosis standard of hypertension same as above; diagnosis of the H type hypertension standard: primary hypertension and the plasma Hcy concentration>10μmol/L; according to Devereux formula: left ventricular mass(LVM, g)=0.8*1.04[(LVED LVPWT+IVST)3-LVED3]+0.6; body surface area(BSA) =0.0061 x height(CM)+0.0128 *body mass(kg)-0.1529; left ventricular mass index(LVMI, g/m2) =LVM/BSA. The meet the conditions of the 168 patients were randomly divided into the enalapril group(84(male 41, female 43) cases, age(53.71+6.21) years old) and the EMFA group(84(male 40 cases, female 44), age(54.61+7.31) years old), random number generated by the random number table. The nalapril group: oral administration of enalapril(the commodity name: Yi Su, 10mg/plate, Yangtze River Pharmaceutical Group Limited Company products) 10 mg, 1/day; the EMFA group: oral administration of Enalapril maleate folic acid(trade name: the EMFA, 10.8mg/ plate, Osama Shenzhen pharmaceutical limited company) 10.8mg, 1/day). For all the selected patients were followed up for one year, monthly follow-up time, 12 months after treatment, to observe the changes of plasma Hcy levels, blood pressure, IVST, LVPWT, LVED, LVEF, E/A and LVMI in the two groups.Results:1.The increase of Hcy group IVST, LVPWT, LVED respectively is(1.12 + 0.11)cm,(1.11+0.12)cm,(5.19+0.31)cm, were corresponding higher than those of the normal Hcy group(0.98+0.12)cm,(0.97+0.09)cm,(4.76+0.28)cm, the difference was statistically significant(P<0.01).2. The increase of Hcy group LVMI is(126.73+11.28)g/m2, was significantly higher than the normal Hcy group LVMI(89.72+10.35)g/m2, the difference was statistically significant(P<0.01).3.The increase of Hcy group LVEF and E/A values were(65.81+1.31)% and(0.67+ 0.11),were corresponding lower than the normal Hcy group(68.35+1.27)% and(0.83+ 0.12), the difference was statistically significant(P<0.01).4. Single factor analysis showed: it was a positive correlation between the plasma Hcy level with IVST, LVPWT, LVED, LVMI(r=0.728, P<0.01;r=0.721, P<0.01;r=0.728,P<0.01;r=0.853,P<0.01);it was a negative correlation between the plasma Hcy level with LVEF, E/A values(r=-0.781, P<0.01; r=-0.591, P<0.01).5.The enalapril group and the EMFA group, systolic blood pressure(SBP) respectively by(161.35+8.27)mm Hg and(160.87+7.91)mm Hg decreased to(127.85+ 4.37)mm Hg and(120.63+4.28) mm Hg, diastolic blood pressure(DBP) respectively by(97.28+6.32)mm Hg and(98.02+7.13 mm Hg decreased to(86.57+3.41) mm Hg and(81.45+3.27)mm Hg,between before and after treatment,the SBP,DBP were very significant difference in two groups(P<0.01). After treatment,the SBP、 DBP had significant difference between the two groups(P<0.05), and the EMFA group to reduce the effect is more obvious.6. The enalapril group Hcy by(28.31+4.51) μmol/L decreased to(27.58+4.01) μmol/L, there was no significant difference compared with before treatment(P﹥0.05); the EMFA group Hcy by(27.86+4.37) μmol/L decreased to(13.25+3.46) μmol/L, there was a significant difference in comparing with the before treatment(P<0.01); After treatment, Hcy there was a significant difference between two groups(P<0.01), and the EMFA group to reduce the effect is more obvious.7. The enalapril group and the EMFA group IVST respectively by(1.15+0.13) cm and(1.14+0.14) cm decreased to(1.01+0.13) cm and(0.92+0.12) cm, LVPWT respectively by(1.10+0.12) cm and(1.11+0.10) cm decreased to(0.95+0.09) cm and(0.88 0.10) cm, LVED respectively by(5.31+0.42) cm and(5.32+0.28) cm decreased to(4.85 + 0.32) cm and(4.49+0.34) cm, between before and after treatment,the IVST, LVPWT, LVED were very significant difference in two groups(P<0.01);After treatment,the IVST, LVPWT, LVED had significant difference between the two groups(P<0.05), and the EMFA group to reduce the effect is more obvious.8. The enalapril group and the EMFA group LVMI respectively by(137.23+15.47) g/m2 and(138.61+12.79) g/m2 decreased to(113.56+13.21) g/m2 and(87.64+12.18) g/m2, between before and after treatment the LVMI were very significant difference in two groups(P<0.01);After treatment, the LVMI had significant difference between the two groups(P<0.05), and the EMFA group to reduce the effect is more obvious.9. The enalapril group and the EMFA group LVEF respectively by(64.85+1.51)% and(65.31+1.21)% up to(67.21+1.43)% and(69.15+1.32)%, E/A value respectively by(0.65 +0.15) and(0.64+0.12) up to(0.79+0.13) and(0.91+0.11), between before and after treatment,the LVEF, E/A were very significant difference in two groups(P<0.01),after treatment, the LVEF, E/A value had significant difference between the two groups(P< 0.05), and the EMFA group to increase the effect is more obvious.Conclusion:1.The increase of Hcy group of IVST, LVPWT, LVED and LVMI were significantly higher than that of the normal Hcy group,the increase of Hcy group of E/A,LVEF was significantly lower than that of the normal Hcy group, and the single factor correlation analysis showed: it was a positive correlation between the plasma Hcy level with IVST, LVPWT, LVED and LVMI, it was a negative correlation between the plasma Hcy level with LVEF, E/A values, it suggest that hyperhomocysteinemia may aggravate the degree of left ventricular hypertrophy in hypertension, leads to cardiac systolic function and diastolic function further reduces.2. The enalapril group and the EMFA group can significantly lower blood pressure in hypertensive patients, and can reverse left ventricular hypertrophy, but compared with the enalapril group, the EMFA group may better lower blood pressure and plasma Hcy level, left ventricular hypertrophy, improve heart function, it may have better protective effect on the heart.