Effects Of Combined Treatment Of Irbesartan And Diltiazem On Vascular Function In Essential Hypertensives

Objective:To discuss the influencing factors of vascular function and investigate the effects ofirbesartan combined with diltiazem on vascular function in essential hypertensives.Methods:Essential hypertensive and normotensive subjects, ranged from 30 to 89 years old, wereenrolled from outpatient care of the First Affiliated Hospital of Fujian MedicalUniversity between August 2000 and April 2015. Before measuring flow-mediateddilatation(FMD), the subjects’ clinical characteristics, including height, body massindex, blood pressure(BP), were recorded. Routine blood test, biochemistry test andfibrinogen(Fg) level were also determined. All subjects underwent echocardiographicexam to detect left ventricular mass index(LVMI). FMD induced by reactive hyperemiawas used to determine endothelium-dependent dilatation(EDD) andnitroglycerin-mediated dilatation(NMD) induced by nitroglycerin was used todetermine endothelium-independent dilatation(EID) respectively in brachial andanterior tibial arteries using high-resolution vascular ultrasound. Among the case withcomplete follow-up data, hypertensives were divided into 3 groups: irbesartan treated( 150 mg/day), diltiazem treated( 90 mg/day), and combined therapy( Irbesartan 150mg/day+ diltiazem 90 mg/day), and normotensives were served as controls. Thedifference of EDD and EID between baseline and after treatment among differentgroups were focused.Results:1. 1,266 subjects,including 978 hypertensives and 288 normotensives, were enrolled.315 case, including irbesartan treated group(n=46), diltiazem treated group(n=51),combined therapy group(n=53) and 40 normotensives were followed up. Totally, therewere 1581 case in the end.2. Stepwise multiple regression analysis showed that age and the course ofhypertension were important influencing factors for EDD and EID. EDD and EID weredecreased obviously with the increase of age, especially in hypertensives. BP, LVMI,Fg were higher and EDD and EID were lower in hypertensive patients than those innormotensive controls at baseline.3. After treatment, there were no significant difference in BAEDD between baselineand after treatment in irbesartan treated group and diltiazem treated group [ irbesartantreated group : baseline(9.40±4.27)% vs after treatment(10.59±4.38)%, diltiazemtreated group : baseline(9.20±4.06)% vs after treatment(10.31±4.16)%, P>0.05],while BAEDD was increased significantly after treatment in combined therapy group[ baseline(8.39±3.04)% vs after treatment(10.72±3.46)%, P<0.01]. There were nosignificant difference in TAEDD, BAEID and TAEID between baseline and aftertreatment among all groups(all P>0.05).4. In combined therapy group, BAEDD was higher significantly after treatment within1 year compared with baseline [baseline( 8.39±3.04) % vs after treatment( 10.59±3.09)%,P<0.01]. Furthermore, BAEDD was also increased significantly after over1 year treatment [ baseline(8.39±3.04)% vs after 1-3 years’ treatment(10.68±3.12)%or vs over 3 years’ treatment(10.91±3.49)%,P<0.01]. TAEDD was higher over 3years’ treatment [baseline(7.36±3.02)% vs after treatment(9.18±3.46)%,P<0.05].After stratification of age, the BAEDD of EH patients less than 65 years’ old wasincreased obviously after treatment within 1 year and over 1 year compared withbaseline. In EH patients over 65 years’ old, BAEDD was increased obviously aftercombined therapy for more than 3 years.5. After treatment, SBP was decreased significantly in three antihypertensive treatedgroup, while DBP was decreased obviously in diltiazem treated and combined therapygroup. LVMI was reduced obviously after irbesartan alone and combined therapytreatment and the reduction of LVMI was much more remarkable in combined therapygroup than in irbesartan group [irbesartan group: baseline(99.33±18.23) g/m2 vs aftertreatment(92.89±14.48) g/m2, P<0.05; combined therapy group: baseline(99.08±17.93) g/m2 vs after treatment(90.56±16.17) g/m2, P<0.01]. Fg was decreasedsignificantly after treatment in combined therapy group [ baseline(3.54±0.78) g/L vsafter treatment(3.07±0.81) g/L, P<0.05].Conclusion:Vascular function was decreased obviously with the increase of age, especially inhypertensives. Irbesartan combined with diltiazem therapy could improve theendothelium-dependent vasodilatation in essential hypertensives significantly, andreduced LVMI more obviously compared with monotherapy.