Ningyin Li

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 08-03 STUDY ON THE RELATIONSHIP BETWEEN RED CELL DISTRIBUTION WIDTH AND THE INCREASE OF URIC ACID IN CHINESE HYPERTENSIVE PATIENTS

Objective: We hypothesized that red cell distribution width (RDW) would be associated with increases in serum uric acid (UA) in hypertension patients. Design and method: All subjects were participants of the China Stroke Primary Prevention Trial (CSPPT, clinicaltrials.gov identifier: NCT00794885). This study was a randomized, doubleblind clinical trial conducted from May 19, 2008, to August 24, 2013. 15486 participants provided written informed consent. Eligible participants were men and women aged 45 to 75 years old who had hypertension, defined as seated resting systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher at both the screening and recruitment visits or were taking an antihypertensive medication. Participants were scheduled for follow-up every 3 months. At each follow-up visit, vital signs, study drug adherence, concomitant medication use, adverse events, and possible endpoint events were documented by trained research staff and physicians. For testing the primary hypothesis, the efficacy analyses for the primary outcome were conducted according to the ITT principle. All analyses were performed using EmpowerStats (http://www.empowerstats.com) and the statistical package R. Data are presented as mean ± standard deviation (SD) or proportions. Results: There was a strong relationship between RDW level and UA increase. In the following cases, we can see the same relationship: UA increase value and the increase rate rised with RDW increasing in patients less than and greater than 60 years old (P < 0.05). Whether hypertensive patients taking enalapril or enalapril-folic acid tablets, the level of UA and RDW were into a significant positive correlation (P < 0.05). In patients with normal or elevated mean-SBP, UA also rised with the rising of RDW (P < 0.05). Conclusions: In hypertension patients, the UA increase with the rising of RDW. We also evaluated the relationship could not be affected by other variables including gender, age, anti-hypertensive drugs mean-SBP and mean-DBP.

PS 17-36 THE CHARACTERISTICS OF ARTERIAL STIFFNESS AND CARDIAC REMODELING IN MIDDLE-AGED FEMALE HYPERTENSIVE PATIENTS

Objective: We hypothesized that cardiac remodeling would be associated with correlation index of arteriosclerosis. And there are differences between males and females. The purpose of this study is to illustrate the characteristics of the arterial stiffness and cardiac remodeling in female hypertension patients. Design and method: One hundred and forty hypertensive patients provided written informed consent. Eligible participants were men and women aged 45 to 65 years old who had hypertension. Some indicators of the cardiac anatomy structures, the cardiac functionwere measured by M-mode echocardiography, two-dimensional echocardiography, doppler echocardiographic determination and tissue Doppler imaging. The SphygmoCor Vx Pulse Wave Velocity System was used to measure the carotid and femoral artery pulse wave velocity (cf-PWV). For testing the primary hypothesis, the efficacy analyses for the primary outcome were conducted according to the ITT principle. Results: There was a strong relationship between cardiac remodeling and correlation index of arteriosclerosis. In the following cases, we can see the same relationship: in the male and female patients, with the increase of augmentation index (AIx), ejection fraction (EF) were significantly increased (P < 0.001). in the females, AIx increase value, the decrease of ankle brachial index (ABI) and PWV rised with left ventricular end-diastolic dimension (LVDD), end-diastolic volume (EDV) and left ventricular mass index (LVMI) decreasing in patients (P < 0.05). in the male patients, the level of aortic artery systolic blood pressure (ASP) and cardio-ankle vascular index (CAVI) also raised with the rising of LVDD, LVMI and interventricular septal diastolic thickness (P < 0.05). Conclusions: In female patients with hypertension, the characteristic of cardiac remodeling is the decrease of LVDD. But in male patients, LVDD increasing is the main characteristic. It is still necessary to detect the sex hormones, in order to confirm the differences characteristic of cardiac between males and females are related to them.

MPS 15-02 GENDER BASED COMPARISON OF THE PROTECTIVE EFFECTS OF ASTRAGALUS ON CARDIOVASCULAR SYSTEM IN HYPERTENSIVE PATIENTS WITH METABOLIC SYNDROME

Objective: To investigate the influence of Astragalus in the protection of cardiovascular structure and function in essential hypertensive patients with metabolic syndrome (MetS) depending on gender. Design and Method: This is a prospective, open labeled, parallel randomized controlled trial. 206 hypertensive patients with MetS between 18 and 60 years were randomly assigned to control group, Astragalus group 1 (Astragalus 10 g/d) and Astragalus group 2 (Astragalus 5 g/d). Metabolic related indexes were measured by laboratory blood tests. Left ventricular end diastolic dimension (LVEDd), interventricular septal thickness (IVST), left ventricular diastolic posterior wall thickness (LVPWT), deceleration time (DT), early diastolic mitral annular velocity/late diastolic velocity of tricuspid annulus (E’/A’), pulmonary venous arterial reversal velocity (Ar) and mitral flow velocity (Vp) were measured by ultrasound echocardiogram. Cardio-ankle vascular index (CAVI) and ankle brachial index (ABI) were obtained by arteriosclerotic instrument. Aortic pulse wave analyzer was used to measure the carotid and femoral artery pulse wave velocity (cf-PWV) and augmentation index (AIx). All of the indicators were compared between pre-treatment and post-treatment after a 12 months follow-up. This research program is registered under the Chinese Clinical Trial Register Website (ChiCTR-TRC-11001747). Results: Triglyceride (TG), E’/A’ and Vp were significantly improved after treatment with Astragalus in females as compared to males (P = 0.026, P = 0.031, P = 0.042 respectively). CAVI and AIx were also reduced significantly in females (P = 0.036, P = 0.017 respectively). However, other indicators showed no difference after treatment (P > 0.05). In males, most indicators had no significant difference except total cholesterol (TC) and ABI which were reduced significantly after treatment (P = 0.033, P = 0.029 respectively). Conclusions: The protective effect of Astragalus on cardiovascular structure and function is better in female patients than male. The sex hormones might have a role in it. A further long term study would be helpful in confirming the efficacy of Astragalus extract.

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.

M-007 EFFECTS OF MONO-THERAPY AND COMBINATION OF CALCIUM CHANNEL BLOCKERS AND ANGIOTENSIN-CONVERTING ENZYME INHIBITORS ON THE LEFT VENTRICULAR HYPERTROPHY IN CHINESE HYPERTENSIVE PATIENTS: A META-ANALYSIS

Background A meta-analysis was carried out to compare the effect of calcium channel blockers (CCBs) and angiotensin-converting enzymeinhibitors (ACE-Is) alone and their combination onthe reversion of left ventricular hypertrophy (LVH)in Chinese hypertensive patients. Methods Retrieved relevant medical database, including Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature Database, Chinese Scientific Journals Full-text Database, and Chinese Journal Full-text Database. Selected clinical studies were according to predefined inclusion and exclusion criteria. The RevMan 5.1 software was used to analysis the data. Results Ten studies, total 859 patients were identified. There were statistically significant in SBP (95% CI: −10.55, −2.43), DBP (95% CI: −6.76, −2.21), left ventricular mass index (LVMI) (95% CI: −8.43, −2.19), interventricular septal thickness (IVST) (95% CI: −2.00, −0.66) and left ventricular posterior wall thickness(LVPWT) (95% CI: −1.41, −0.33) in CCBs and ACE-Iscombination versus CCB monotherapy (P < 0.05). In addition, compared with ACE-Is monotherapy, the combination treatment showed prior effect on the decreasing of LVMI(95% CI: −15.06, −8.01),IVST(95% CI: −1.25, −0.27), and LVPWT(95% CI: −1.01, −0.59) (P < 0.05). The left ventricular end diastolic diameter (LVDd), fraction shortening (FS)and ejection fractions (EF)were no difference in CCBs or ACE-Is mono-therapy and their combination (P > 0.05). Conclusions The combination therapy with CCBs and ACE-Is is more superior than individual agents in regression of left ventricular hypertrophy. Further large, multicenter, RCTs are required. Funding The present study is supported by the Key Project of Science and Technology of TCMin Gansu Province of China (GZK-2010-Z1) and the Key Funding of the Second Hospital of Lanzhou University (YJ2010–02).