Effects Of Losartan Combined With Amlodipine Or Hydrochlorothiazide Regimen On Blood Pressure Variation, Nitric Oxide And Endothelin In Elderly Hypertensive Patients

Objective:In this study, we tried to compare the effects of losartan combined with amlodipine or hydrochlorothiazide regimen on blood pressure, blood pressure variation, nitric oxide and endothelin in elderly hypertensive patients, in order to observe the effects of angiotensin II receptor antagonist, the second hydrogen pyridine class calcium ion antagonist, hydragogue on blood pressure variation and endothelial function and to provide evidence of experience and theory for clinical treatment of elderly hypertensive patients.Methods:According to inclusion criteria, a total of 167 patients who had been diagnosed as hypertetion level 2 or 3 in The central hospital of HanDan, were enrolled into this study from January 2010 to December 2013. All patients were randomized into amlodipine group 82 patients (male 61, female 21, average age 71.57 ± 6.09 years) or hydrochlorothiazide group 85 patients (male 66, female 19, average age 72.09±6.41 years). Amlodipine group patients were administrated of losartan 50mg qd and amlodipine 5mg qd, likewise the hydrochlorothiazide group were administrated of losartan 50mg qd and hydrochlorothiazide 12.5mg qd. All patients received 24 hours ambulatory blood pressure monitoring before the treatment and 8,16 weeks after the treatment. Nitric oxide and endothelin were monitored before the treatment and 16weeks after the treatment. Data analysis was performed by PASW 20.0 software, and P<0.05 was considered statistically significant.Results:1 Comparison of baseline clinical features between the two groups:No significant differences were found with respect to clinical features, such as age, gender, body mass index, family hypertension history, smoking history, drinking history, coronary heart disease complications and the term of hypertension (P>0.05).2 Comparison of baseline blood pressure and angiographic and drug strategy before this study:There was no significant difference between the two groups in baseline systolic blood pressure, baseline diastolic blood pressure and drug strategy before this study, including calcium channel blockers (nifedipine, long-term nifedipine preparations, nimodipine, amlodipine, felodipine), angiotensin converting enzyme inhibitor (perindopril, enalapril, benazepril, captopril), angiotensin Ⅱ receptor antagonist (valsartan, losartan, olmesartan, telmisartan, irbesartan), β receptor blocker (metoprolol, metoprolol sustained release tablets, bisoprolol) and hydragogue (furosemide, hydrochlorothiazide, spirolactone). (P>0.05).3 Comparison of the levels of blood pressure before and 16 weeks after treatment between the two groups:At 8 weeks and 16weeks after the treatment, 24h mean systolic blood pressure (24hSBP),24h mean diastolic blood pressure (24hDBP), daytime mean systolic blood pressure (dSBP), daytime mean diastolic blood pressure (dDBP), night mean systolic blood pressure (nSBP) and night mean diastolic blood pressure (nDBP) of the two groups were all lower than those before treatment (all P<0.05). Repeated measures ANOVA achieved that the effect of losartan combined with amlodipine or hydrochlorothiazide on the overall change of 24hSBP,24hDBP, dSBP, dDBP, nDBP were similar during the 16 weeks of treatment (all P<0.05). But compared with hydrochlorothiazide, losartan combined with amlodipine brought a further decrease of the overall change of nSBP (P<0.05). And t test between the two groups achieved that at 8 weeks after the treatment, the level of nSBP in amlodipine group significantly reduced compared with hydrochlorothiazide group (P<0.05). And at 16 weeks after the treatment, the levels of nSBP and nDBP in amlodipine group significantly reduced compared with hydrochlorothiazide group (P<0.05, P<0.05).4 Comparison of the levels of blood pressure variability before and 16 weeks after treatment between the two groups:At 8 weeks and 16weeks after the treatment,24h systolic blood pressure variability (24hSBPV),24h diastolic blood pressure variability (24hDBPV), daytime systolic blood pressure variability (dSBPV), daytime diastolic blood pressure variability (dDBPV), night systolic blood pressure variability (nSBPV), and night diastolic blood pressure variability (nDBPV) of the two groups were all lower than those before treatment (all P<0.05). Repeated measures ANOVA achieved that the effect of losartan combined with amlodipine could significantly reduce the overall change of 24hSBPV,24hDBPV, dSBPV, dDBPV, nDBPV, and nDBPV compared with hydrochlorothiazide (all P<0.05). And t test between the two groups achieved that at 8 weeks after the treatment, the leves of 24hDBPV, dDBPV and nDBPV in amlodipine group significantly reduced compared with hydrochlorothiazide group (all P<0.05). And at 16 weeks after the treatment, the levels of 24hSBPV,24hDBPV, dSBPV, dDBPV, nSBPV, nDBPV in amlodipine group significantly reduced compared with hydrochlorothiazide group (all P<0.05).5 Comparison of levels of nitric oxide and endothelin between the two groups:No significant differences were found with respect to nitric oxide and endothelin before the treatment (P>0.05), and at 16 weeks’treatment nitric oxide increased and endothelin decreased significantly in both amlodipine group and hydrochlorothiazide group (all P<0.05). But amlodipine group had higher level of nitric oxide and lower level of endothelin compared with hydrochlorothiazide group (P<0.05, P<0.05).Conclusion:1 Compared with hydrochlorothiazide, losartan combined with amlodipine can further reduce nocturnal blood pressure level in elder hypertension patients.2 losartan combined with both amlodipine and hydrochlorothiazide can reduce blood pressure variability in elder hypertension patients. But losartan combined with amlodipine can further reduce blood pressure variability than hydrochlorothiazide, especially diastolic blood pressure variability.3 losartan combined with amlodipine can further improve vascular endothelial function than hydrochlorothiazide, and the mechanism of decrease of blood pressure variability maybe improve vascular endothelial function.4 losartan combined with amlodipine regimen is more suitable for elder hypertension patients.