Effect Of Compound Of Valsartan And Amlodipine On Insulin Resistance In Hypertensive Patients

Objective: It is well established that the existance of IR was always accompanying with hypertensive patients.More recently, more and more researches in preclinical medicine performed indicate IR was the pathogenesis of hypertension. antihypertensive drugs are expected to improve IR better beyoud antihypertension. ARBs such as valsantan alone has been confirmed to improve IR as well as amlodipine alone, but No consistent or conclusive evidence has been found which is more efficiency between a compound of Valsartan and Amlodipine and double-fold dose of Valsartan alone. The objective of this trial was to investigate the effects of improving IR between double-fold dose of valsatan alone and a compound of Valsartan and Amlodipine in mild-moderate hypertensive patients.Methods: After a week of washout and two-week treatment of Valsartan 80mg QD, subjects whose blood pressure value were in a mild or moderate blood pressure level among a total of 110 hypertensive participates were allocated into three groups at randoms(N=75, n=25). Each Group was treated by Valsartan 80mg QD, Valsartan 160mg QD or Valsartan80mg plus Amlodipine 5mg QD for 8 weeks respectively during the whole double-blind drug period. Age, height, body weight, BMI, Waist Circumstance (WC), Hip Circumstance (HC) and Waist Hip Ratio(WHR) were detected before double-blind period. The systolic blood pressure (SBP), diastolic blood pressure (DBP), Total Cholesterol (TC), Triglycerides (TG), High-density Lipoprotein (HDL), Low-density Lipoprotein (LDL), Very-low-density Lipoprotein (VLDL), Fasting Blood Glucose (FBG) and Fasting Insulin (FINS) were detected before and after treatment. Insulin Sensitive Index(ISI) was calculated[ISI: Ln (1/FIN*FBG)]. Statistical Analysis Statistical analysis of data was performed using the SPSS statistical software package for Windows (version 10.0; Chicago, IL). Continuous variables were reported as mean±SD and compared by t test and analysis of variance (ANOVA). Intervention effects were adjusted for additional potential confounders using analysis of Logistic regression, ANOVA was also used to assess the significance among groups. A paired t test was used to compare values obtained before and after treatment, P value <0.05 was considered significant.Results : After a week of washout and two-week treatment of Valsartan 80mg QD, 75 patients satisfying the inclusion criteria were entered into the study and were randomly allocated to receive one treatment among Valsartan 80mg QD, Valsartan 160mg QD and a compound of Valsartan 80mg plus Amlodipine 5mg QD for 8 weeks respectively. Clinical characteristics including age, height, body weight, BMI, WC, HC, WHR, hemodynamic parameters or laboratory measurements such as TC, HDL, TG, LDL and VLDL at baseline did not differ significantly among the three groups.moreover, Eight weeks of therapy with any one of double-blind drug treatment did not cause significant changes in FBG(P>0.05). Compared with that of before double-blind treatment, there was a statistically significant reduction at the end of 8-week double treat in SBP (SBP: group of Valsartan 80mg 137.44±10.09mmHg VS 128.7±8.53mmHg (P<0.05), group of Valsartan 160mg135.52±15.94mmHg versus 130.8±9.98 mmHg(P<0.05), a combination with Valsartan 80mg plus Amlodipine 5mg 142.88±8.58mmHg versus 124.32±6.57 mmHg(P<0.05) and DBP (DBP: group of Valsartan 80mg 96.56±4.76mmHg versus 89.44±5.68 mmHg(P<0.05), group of Valsartan 160mg 95.56±4.83 mmHg versus 89.28±7.62 mmHg(P<0.05), a compound with Valsartan 80mg plus Amlodipine 5mg 96.56±4.42 mmHg versus 81.84±5.75 mmHg(P<0.05)) in each group. At the end of the study, reductions in SBP and DBP from baseline were a statistically significant (reduction of SBP:group of Valsartan 80mg 8.72±9.01 mmHg versus group of Valsartan 160mg 9.04±10.84 mmHg versus a compound with Valsartan 80mg plus Amlodipine 5mg 18.5±9.04 mmHg (P<0.05), reduction of DBP:group of Valsartan 80mg 7.1±4.36 mmHg versus group of Valsartan 160mg 7.28±7.15 mmHg versus a combination with Valsartan 80mg plus Amlodipine 5mg 14.7±4.96 mmHg (P<0.05)). SBP and DBP in a compound with Valsartan 80mg plus Amlodipine 5mg group were greater decrease than other two groups between which there is no significient difference within a compound with Valsartan 80mg plus Amlodipine 5mg group, FIN was significantly reduced and ISI was significantly greater from baseline , (FIN( mIU/L) , 23.76±9.04 versus 15.30±6.51(P<0.05); ISI -1.35±0.41 versus -0.91±0.39(P<0.05)). FIN was mild reduced and ISI was lightly greater from baseline in group of Valsartan 80mg and group of Valsartan 160mg ,but there is no significantly difference compared within group (FIN( mIU/L) in group of Valsartan 80mg:24.84±12.49 versus 19.76±7.68 (P>0.05), FIN( mIU/L) in group of Valsartan 160mg:21.84±9.67 versus 17.24±5.26 (P>0.05); ISI in group of Valsartan 80mg: -1.28±0.44 versus -1.15±0.35 (P>0.05), ISI in group of Valsartan 160mg:-1.25±0.42 versus -1.06±0.34 (P>0.05)).Compared among three groups after double-blind drug treatment,FINS was significantly reduced and ISI was significantly greater in a group of Valsartan 80mg plus Amlodipine 5mg(P<0.05), but there was no statistically difference between Valsartan 80mg and Valsartan 160mg groups. Even after SBP and DBP as Intervention effects were statistically analysed, there always maintain the trend invariably.Conclusion: Compound of Valsartan and Amlodipine could decrease SBP and DBP and improve the IR significiently in hypertensive patients.the effect of combination with Valsartan and Amlodipine was better than that of double-dose Valsartan alone in blood pressure control and improving insulin resistance.