Ruixin Ma

Effect of felodipine with irbesartan or metoprolol on sexual function and oxidative stress in women with essential hypertension.

Objective To evaluate the impact of felodipine with irbesartan on sexual function compared with felodipine with metoprolol in hypertensive women. Methods This was a prospective, randomized, parallel, active-controlled, open-label study (ClinicalTrials.org: NCT01238705) in 160 women (18–60 years) with mild or moderate hypertension, randomized to a once-daily treatment with felodipine combined with irbesartan or metoprolol for 48 weeks. Patients’ sexual function was evaluated using a female sexual function index (FSFI) questionnaire at baseline and after 24 and 48 weeks of therapy. Levels of serum estradiol, testosterone, 8-hydroxy-2’-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) were measured. Results The two combination regimens were similarly effective in lowering blood pressure. After 48 weeks, in felodipine–irbesartan group, total scores of FSFI improved (P < 0.001). Items showing improvement in scores corresponded to desire, arousal and orgasm (P < 0.001; P = 0.002; P = 0.049, respectively). Levels of estradiol increased under treatment with felodipine–irbesartan (P = 0.003) and decreased under felodipine–metoprolol treatment (P < 0.001). The concentration of testosterone declined after felodipine–irbesartan therapy (P < 0.001) and increased under felodipine–metoprolol treatment (P < 0.001). In the felodipine–irbesartan group, decreases of 8-OHdG, 4-HNE (P < 0.001) and MDA (P < 0.001) were observed. The felodipine–irbesartan combination resulted in less oxidative stress. The differences in changes in 8-OHdG, 4-HNE and MDA between the two groups were significant (P < 0.05). Conclusion These results suggested that the felodipine–irbesartan combination regimen improved sexual function in hypertensive women, whereas felodipine–metoprolol regiment did not. The reason for the different influence of these two combination therapy on female sexual function might be their different impacts on oxidative stress and hormone levels.

The Effect of Combined Antihypertensive Treatment (Felodipine with Either Irbesartan or Metoprolol) on Erectile Function: A Randomized Controlled Trial

Objectives: This study aimed to determine whether combining a calcium channel blocker with either an angiotensin II receptor blocker or a β-blocker would have similar effects on sexual function in men with hypertension. Methods: This prospective, randomized study (ClinicalTrials.gov: NCT01238705) included 218 male participants with untreated hypertension. Patients were randomized to treatment with felodipine combined with irbesartan or metoprolol for 48 weeks. Sexual function was evaluated at baseline and after 48 weeks of therapy. The levels of serum sex hormones and markers of oxidative stress were measured at the same time. Results: There was no significant difference in the prevalence of erectile dysfunction before and after treatment in either group (p > 0.05). There were also no differences in the levels of serum testosterone, sex hormone-binding globulin or 4-hydroxynonenal before and after treatment in either group (p > 0.05). In the felodipine-irbesartan group, sexual desire scores rose after treatment (p = 0.022) and the concentrations of serum 8-hydroxy-2′-deoxyguanosine and malondialdehyde declined (p < 0.001 and p = 0.002, respectively). The between-group differences for 8-hydroxy-2′-deoxyguanosine and malondialdehyde were not significant (p > 0.05, respectively). Conclusion: The results suggest that felodipine-irbesartan may be more beneficial to the sexual desire of hypertensive male patients than felodipine-metoprolol. This effect was possibly relevant to irbesartan, which prevents oxidative stress to some extent.

The Effects of LCZ696 in Patients With Hypertension Compared With Angiotensin Receptor Blockers: A Meta-Analysis of Randomized Controlled Trials

LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, has been demonstrated to have greater advantages in the treatment of heart failure compared with angiotensin-converting enzyme inhibitors, enalapril, or angiotensin receptor blockers (ARBs). However, studies that compared the efficacy and safety of LCZ696 against valsartan in patients with hypertension are limited. To provide further evidence for the benefits of LCZ696 and to make this assessment, a meta-analysis of randomized controlled trials (RCTs) was performed. The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, PubMed, and ClinicalTrials.gov were searched for RCTs. Twelve studies involving 3816 patients were eligible for inclusion. Seven studies compared LCZ696 with valsartan, and 5 studies compared LCZ696 with olmesartan. LCZ696 showed a significantly greater reduction in systolic blood pressure (BP; mean difference [MD] = −5.43 mm Hg; 95% confidence interval [CI]: −6.36 to −4.49 mm Hg; P < .001), diastolic BP (MD = −2.34 mm Hg; 95% CI: −2.67 to −2.01 mm Hg; P < .001), 24-hour ambulatory systolic BP (MD = −3.57 mm Hg, 95% CI: −4.29 to −2.85 mm Hg; P < .001), and 24-hour ambulatory diastolic BP (MD = −1.32 mm Hg, 95% CI: −1.77 to −0.78 mm Hg; P < .001) from the baseline than ARBs. LCZ696 was more effective in reducing BP (odds ratio [OR] = 5.34; 95% CI: 4.49-6.36; P < .01) and had a higher rate of BP control compared with ARBs (OR = 1.52; 95% CI: 1.37-1.69; P < .01). LCZ696 had no difference in the incidence of adverse events (OR = 1.05; 95% CI: 0.94-1.18; P = .38) or serious adverse events (OR = 0.80; 95% CI: 0.51-1.24; P = .31) compared to ARBs. This meta-analysis revealed that LCZ696 has a greater antihypertensive efficacy and an equal tolerability profile.

Astragalus Membranaceus Improving Asymptomatic Left Ventricular Diastolic Dysfunction in Postmenopausal Hypertensive Women with Metabolic Syndrome: A Prospective, Open-Labeled, Randomized Controlled Trial

Background: Postmenopausal women with metabolic syndrome (MetS) have increased cardiovascular morbidity and left ventricular diastolic dysfunction (LVDD). The various protective effects of astragalus membranaceus (AM) have been described in previous studies. Therefore, this study aimed to evaluate the effects of different doses of AM on diastolic function in postmenopausal hypertensive women with MetS. Methods: This was a prospective, randomized controlled study. The postmenopausal hypertensive patients with MetS were enrolled from Lanzhou University Second Hospital from March 2014 to April 2015. Patients were divided into three groups: control group (received conventional medical treatment), AM Group 1 (received AM capsules at 5 g/d additionally), and AM Group 2 (received AM capsules at 10 g/d additionally). Echocardiographic and clinical characteristics were evaluated before and 12 months after treatment. Quantitative data were analyzed using unpaired t-test, analysis of variance, and multiple linear regression analysis. Results: A total of 154 patients were subjected to final analysis. In the AM Group 2, significant improvements were noted in diastolic function 12 months after treatment than those of the control group, including the early diastolic mitral annular velocity (E’; 0.065 ± 0.007 m/s vs. 0.061 ± 0.008 m/s, P = 0.014), the ratio of the early diastolic mitral peak flow velocity to the late diastolic mitral peak flow velocity (E/A; 0.81 ± 0.05 vs. 0.80 ± 0.06, P = 0.012), the ratio of E’ to the late diastolic mitral annular velocity (E’/A’; 0.56 ± 0.12 vs. 0.51 ± 0.13, P = 0.048), and the ratio of the early diastolic mitral peak flow velocity (E) to E’ (E/E’; 10.70 ± 1.30 vs. 11.37 ± 1.73, P = 0.031). After treatment, E/E’ (10.70 ± 1.30 vs. 11.24 ± 1.56, P = 0.021), deceleration time (DT; 261.49 ± 44.41 ms vs. 268.74 ± 53.87 ms, P = 0.046), and E’/A’ (0.56 ± 0.12 vs. 0.52 ± 0.13, P = 0.019) values improved more significantly than those of AM Group 2 before treatment. Besides, waist circumference was positively correlated with E’ (r = 0.472; P = 0.003) and E’/A’ (r = 0.321; P = 0.047). In addition, the waist-to-hip ratio was a significant predictor of DT (r = 0.276; P = 0.041), E’ (r = −0.590; P < 0.001), E/E’ (r = 0.454; P = 0.004), and E’/A’ (r = −0.377; P = 0.018). Conclusions: Conventional medical plus AM therapy improved diastolic function. Moreover, WC and WHR might be risk factors for LVDD. Chinese Clinical Trial Register: ChiCTR-TRC-11001747. http://www.chictr.org.cn/showprojen.aspx?proj=7798.

PS 10-07 TETRAHYDROBIOPTERIN EFFECTS LEFT VENTRICULAR DIASTOLIC FUNCTION BY UPREGULATING PROTEIN KINASE Cε SIGNALING PATHWAY IN DESOXYCORTICOSTERONE ACETATE-SALT HYPERTENSIVE MICE:

Objective: To identify the influence of tetrahydrobiopterin (BH4) on left ventricular diastolic function and the expression of protein kinase C &egr;(PKC&egr;) in desoxycorticosterone acetate (DOCA)-salt hypertensive mice. Design and method: We used the DOCA-salt mouse model, which demonstrates mild hypertension, myocardial oxidative stress, and diastolic dysfunction. Mice were divided into DOCA group(n = 22), DOCA + BH4 group(n = 22), SHAM group(n = 20) and SHAM + BH4 group(n = 20). Arterial pressure, echocardigraphy and hemodynamic method were used to investigate the DOCA model establishment, cardiac structure and function. Cyclic guanosine monophosphate(cGMP), malonaldehydeby, BH4 and PKC &egr; were detected by enzyme linked immunosorbent assay(ELASA), western-blot or high-performance liquid chromatography(HPLC) in cardiac tissues of all groups. Results: Compared to Sham group, systolic blood pressure (SBP) and diastolic blood pressure (DBP) in DOCA group were increased (P < 0.05), but between DOCA + BH4 group and DOCA group, there was no significant statistical differences in blood pressure (P > 0.05). The ratio of left-ventricular early diastolic filling velocity to early diastolic mitral annular velocity (E/E’), end-diastolic pressure-volume relation (EDPVR) and Tau index were increased in DOCA group when compared with Sham group [(14.27 ± 0.79) vs (10.6 ± 0.52) ms, (38.49 ± 3.91) vs (25.77 ± 5.21), (0.22 ± 0.05) vs (0.15 ± 0.02) mm, all P < 0.05]. After BH4 treatment in DOCA mice, EDPVR and Tau index were reduced [(0.17 ± 0.04) vs (0.22 ± 0.05), (12.05 ± 1.35) vs (14.27 ± 0.79), P < 0.05]. Superoxide dismutase (SOD) and nitric oxide (NO) in DOCA group were reduced when compared with Sham group. After BH4 treatment in DOCA mice, SOD and NO were increased. Compared to Sham group, the protein level of PKC &egr; in DOCA group was decreased (P < 0.05), while it was increased in DOCA + BH4 group as compared with DOCA group (P < 0.05). Conclusions: BH4 had little effect on BP, but it could improve left ventricular diastolic dysfunction in hypertensive mice, which was related to lowering the levels of oxidative stress, increasing amounts of NO by upregulating PKC &egr; signaling pathway.

OS 07-04 HOME BLOOD PRESSURE MONITORING IMPROVED SAFETY IN PATIENTS WITH SEVERE HYPERTENSION.

Objective: Home blood pressure monitoring (HBPM) is more likely to reflect the patients underlying blood pressure (BP), than measurements in the clinic. HBPM coupled with titration of medications under the guidance of doctors, is a viable intervention to control hypertension. The purpose of this study is to evaluate whether HBPM can increase the safety of the combination therapy of three or more different classes of antihypertensive drugs. Design and Method: We enrolled patients with severe (grade 3) hypertension, whose BP remain uncontrolled under combination treatment with standard doze of an angiotensin II receptor blocker and hydrochlorothiazide. The third drug amlodipine 5 mg daily was prescribed before patients were randomly assigned to the BP management only in clinic, or HBPM for 8 weeks. Office visits at baseline, 4th and 8th week were required to all the patients. Patients under HBPM management took BP measurement twice daily, with a memory-equipped device in the morning and evening, and allowed to titrate the doze following the doctors instruction. Results: One hundred and eighty patients average aged 69 ± 8.4 years were enrolled. 20% patents in the HBPM group titrated amlodipine to 2.5 mg daily or stop taking if there is hypotension, or intolerance to the lowing BP. There was no difference in the BP control rate at 8th week office visit between two groups. However, The reductions in systolic BP were greater under office BP management at 8th weeks(P = 0.025). Patients under HBPM management complained less about dizziness or fatigue compared with office BP management in 8 weeks (P = 0.032). Conclusions: HBPM combined with titration under guidance of doctors encourages patient-centered care and reduces the side-affect caused by BP lowing. It has advantage to prevent hypotension in the management of severe hypertension need three kinds of antihypertensive drugs or above, thus improve the safety of the combined treatment, especially in the elderly.

[PP.33.11] COMPARATIVE EFFECTIVENESS OF ANGIOTENSIN II RECEPTOR BLOCKERS VERSUS ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN LEFT VENTRICULAR STRUCTURE AND FUNCTION

Objective: Angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor 1 antagonists (ARB) ameliorate oxidative stress and fibrosis of myocardium through inhibiting the renin angiotensin system (RAS) in different ways, but if there is difference between this two kind of agents in protection to organ damages remains controversial. The purpose of this study is to study if irbesartan and benazepril alone and in combination would have different protective effects on left ventricular structure, systolic and diastolic function. Design and method: Sixteen-weeks old female spontaneously hypertensive rats (SHR) (n = 8) were treated with irbesartan (Irb,), benazepril (Ben), combination of low irbesartan and benazepril (Irb+Ben) and vehicle for 12 weeks. Wistar Kyoto (WKY) rats (n = 8) receive vehicle. Echocardiography was performed for evaluation of left ventricular structure, systolic and diastolic function at 12 weeks. Results: Systolic blood pressure were significantly lower in Irb+Ben rats than in untreated SHR, and demonstrated greater improvement than irbesartan or benazepril alone. IVSd was significantly lower in the Irb+Ben rats, Irb rats and Ben rats than untreated SHR (P = 0.010, P = 0.035, P = 0.028, separately). There was no difference in the LVEDD, LVEF and FS between SHR in each group and WKY. E/A showed no statistical difference between groups. E/E’ decreased in Irb+Ben rats, Irb rats and Ben rats compared with untreated SHR (P = 0.007, P = 0.020, P = 0.039, separately). E’/A’ increased in Irb+Ben rats, Irb rats and Ben rats compared with untreated SHR (P = 0.019, P = 0.032, P = 0.041, separately). Irb+Ben combination resulted in better outcomes of IVSd, E/E’ and E’/A’ than irbesartan or benazepril alone (P < 0.05 for all). Conclusions: Hypertension associated with diastolic dysfunction. Irbesartan, benazepril and dual therapy provide therapeutic benefit in the blood pressure control, as well as improvement of left ventricular hypertrophy and diastolic dysfunction. The combination of these two RAS antagonists significantly attenuating development of hypertension and reducing left ventricular hypertrophy than monotherapy, however, this result could be related to the better antihypertensive effect of combination treatment. There was no evidence of differential effects of irbesartan and benazepril on the outcomes of left ventricular structure and function.

524 ACHIEVING THE BETTER BLOOD PRESSURE CONTROL TROUGH THE HOME BLOOD PRESSURE MEASUREMENT OF NURSE MONITORING

Objective: To assess whether home blood pressure measurement which conducted by nurses can improve the hypertension control rates. Methods: Hypertensive patients from the out-patient section were evaluated initially byphysicians and conducted home blood pressure measurement by nurses. A treatment plan was designed and monitored by nurses. Patients were trained to use automated digital home BP monitor and requested to provide 42 BP readingsduring 12-month period. These values were reviewed by the physician-nurse team, and the treatment regimen was adjusted to achieve a goal BP of less than 135/85 mm Hg. Results: One hundred and six consecutively referred patients were enrolled in the study (mean ± SD age, 64 ± 14 years; 58% female; baseline BP, 156 ± 16/85 ± 11 mm Hg). Ninety-four patientssubmitted BP data after 1 month, and 78 patients completed the entire 12-month study period. Overall, mean BP decreased to 138 ± 17/78 ± 8 mm Hg at 1 month and 131 ± 9/75 ± 7 mm Hg at 12 months (P < .01 vs baseline). The percentage of patients who achieved BP control to less than 135/85 mm Hg increased from 0% at baseline to 63% at 12 months. Intensification of antihypertensive drug therapy was required, on average, in 24% of patients at each study interval. Conclusion: Home BP measurement managed by a physician-nurse team has the potential to improve long-term hypertension control rates in a geographically dispersed population. It could reduce both cost and inconvenience associated with the treatment of hypertension. Funding: The present study is supported by the Key Project of Science and Technology of TCM in Gansu Province, China(GZK-2010-Z1).

1073 CHANGES IN FEMALE HORMONE LEVELS UNDER DIFFERENT ANTIYPERTENSIVE COMBINATION THERAPY: ROLE OF OXIDATIVE STRESS

Background: Oxidative stress is involved in the pathogenesis of essential hypertension. Estrogen has long been recognized to offer cardiac benefit and vascular protection against atherosclerosis. Thus, this randomized controlled study aimed to test the hypothesis that antihypertensive treatment could attenuate sex hormone levels by modulating oxidative stress in hypertensive women. Methods: One hundred and fifty one women (23-60 years) with mild or moderate hypertension, randomized to a once daily treatment with felodipine combined with irbesartan or metoprolol for 48 weeks. Levels of serum estradiol, testosterone, 8-Hydroxy-2’-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) were measured at baseline and after 24-weeks and 48-weeks of therapy. Results: The two combination regimens were similarly effective in lowering blood pressure. After 48 weeks, in felodipine-irbesartan group, levels of estradiol increased under treatment (P = 0.003) and decreased under felodipine-metoprolol treatment (P < 0.001). As shown in Table 1. the concentration of testosterone declined after felodipine-irbesartan therapy (P < 0.001) and increased under felodipine-metoprolol treatment (P < 0.001). In the felodipine-irbesartan group, decreases of 8-OHdG, 4-HNE (P < 0.001) and MDA (P < 0.001) were observed. The felodipine-irbesartan combination resulted in less oxidative stress. The differences in changes in 8-OHdG, 4-HNE and MDA between the two groups were significant (P < 0.05). Correlation was found between changes in levels of 8-OHdG, 4-HNE and MDA with estradiol (P < 0.05 for all). TABLE 1 Serum estradiol and testosterone at baseline, 24 weeks and 48 weeks in two groups Data are shown as mean ± SD. F+I, Felodipine 5-10 mg + irbesartan 150 mg. F+M, Felodipine Conclusions: The data suggest that the felodipine-irbesartan combination regimen help maintain estradiol in hypertensive women, whereas felodipine-metoprolol regimen did not. Oxidative stress reduction may be one mechanism.

E-011 THE RELATIONSHIP BETWEEN OXIDATIVE STRESS AND SEXUAL DYSFUNCTION IN FEMALE PATIENTS WITH HYPERTENSION

Backround Evidencessuggest that female sexual dysfunction(FSD) is more prevalent in hypertensive women than in normotensive women. One possible explanation might be the impacts of hypertension oxidative stress. The aim of this study was to evaluate the relationship between oxidative stress and FSD in hypertensive women. Methods Total of 160 hypertensive (1 or 2 degree) women and 50 normotensive women, aged 18–60 years, were investigated. Hypertensive patients were newly diagnosed, previously untreated no less than one month. Female sexual function was evaluated using a female sexual function index (FSFI) questionnaire. Levels of serum 8-Hydroxy-2’-deoxyguanosine (8-OHdG), 4-hydroxynonenal (HNE) and malondialdehyde (MDA) were measured. Linear regression analysis was used to identify predictors of an abnormal FSFI score with variables associated with it during univariate analysis. Funding from: The Specific Project of Technological Research and Development in Gansu Province of China(0709TCYA068). Results Sexual dysfunction was found in 60.4% of hypertensive women compared with 26.0% of normotensive women (P = 0.000). FSD rates gradually increased in older compared with younger hypertensive women. The mean score of FSFI at baseline decreased with age,and the between-age-groupdifference was statistically significant (P = 0.000). Levels of8-OHdG,HNE and MDA werelower in hypertensive patients compared with normotensive women (P = 0.003,P = 0.001,P = 0.000, respectively). In hypertensive women, levels of 8-OHdG,HNE and MDA did not statistically differ between women with FSD and normal sexual function (P = 0.375, P = 0.452, P = 0.378, respectively). No statistically significant correlation was found between FSFI score and concentration of8-OHdG,HNE and MDA(P = 0.231, P = 0.142, P = 0.104, respectively). Serum 8-OHdG,HNE and MDA were not predictors of FSFI score. Conclusions These results suggest that FSD is more prevalent in women withessential hypertension compared with women with normalblood pressure. Status of oxidative stress is enhanced in hypertensive women. However, no relationship shows between FSD and oxidative stress. This topic need to be explored in the future study.