[The effects of aranidipine on ambulatory blood pressures in patients with mild to moderate essential hypertension].

OBJECTIVE: To evaluate the effect of aranidipine enteric-coated capsules on 24 h blood pressure and blood pressure variability (BPV) in patients with mild to moderate essential hypertension. METHODS: This was an open clinical trial with 2 weeks of placebo run-in period. A total of 74 patients with blood pressure (140-180/95-110 mm Hg (1 mm Hg = 0.133 kPa) were treated by aranidipine (5 mg/d) for 4 weeks.If clinical sitting blood pressure < 140/90 mm Hg at 4th week, aranidipine at 5 mg/d would be continued for another 8 weeks.If not, the dosage would be increased to 10 mg/d.If blood pressure <140/90 mm Hg at 8th week, aranidipine at 5 mg/d or 10 mg/d would be given constantly.If not, the dosage would be increased to 20 mg/d and given for another 4 weeks. All patients performed 24 h ambulatory blood pressure monitoring (ABPM) before and after the treatment with BPV evaluated by the average 24 h per unit time blood pressure standard deviation and morning blood pressure surge (MBPS). RESULTS: (1) After 12 weeks' treatment with aranidipine, the mean 24 h blood pressure was reduced significantly compared with the baseline [(14 ± 13)/(11 ± 9) mm Hg, both P < 0.05] with trough/peak (T/P) ratio of SBP and DBP in responders of 75.31% and 78.15%, respectively.(2) After 12 weeks' treatment, standard deviations of 24 h, daytime SBP/DBP and nighttime SBP/DBP were reduced significantly[(25 ± 3)/(14 ± 4) mm Hg vs (11 ± 3)/(8 ± 2) mm Hg, (24 ± 5)/(14 ± 4) mm Hg vs (11 ± 3)/(8 ± 2) mm Hg, (10 ± 3)/(8 ± 4) mm Hg vs (8 ± 3)/(6 ± 3) mm Hg], respectively with all P < 0.05.Significant decrease was shown in MBPS compared to the baseline [(27 ± 11) mm Hg vs (19 ± 9) mm Hg, P < 0.05]. (3) The incidence of adverse events was 13.4%, including mild dizziness, flushing and palpitation. CONCLUSION: Administration of aranidipine enteric-coated capsules can control 24 h blood pressure effectively and reduce BPV significantly in patients with mild to moderate essential hypertension with good safety profile.

[Efficacy and safety of aranidipine in Chinese patients with mild-to-moderate essential hypertension].

OBJECTIVE: To assess the efficacy and safety of aranidipine versus retard-released felodipine in Chinese patients with mild-to-moderate essential hypertension. METHODS: This was a multicenter, randomized, double-blind, placebo and active antihypertensive drug parallel-controlled study. After 2 weeks of placebo run-in period, 315 patients at 6 centers with diastolic blood pressure (DBP) between 95 to 109 mm Hg (1 mm Hg = 0.133 kPa) while systolic blood pressure (SBP) below 180 mm Hg were randomized to receive aranidipine 5-20 mg/d (n = 126) or retard-released felodipine 5-10 mg/d (n = 126) for 12 weeks. Others (n = 63) received placebo for 4 weeks. Their blood pressures were evaluated at baseline and the end of Weeks 4, 8 and 12. RESULTS: After a 12-week treatment, SBP decreased from 148.8 ± 10.7 mm Hg to (132.8 ± 11.2) mm Hg while DBP dropped from ( 98.4 ± 2.8) mm Hg to (83.9 ± 7.5) mm Hg. There were significant differences with the baseline values (P < 0.0001). After a 4-week treatment, the reductions of SBP in aranidipine and retard-released felodipine groups were (12.1 ± 11.0) mm Hg and (12.2 ± 11.2) mm Hg while the reductions of DBP in two groups (11.8 ± 6.9) mm Hg and (12.1 ± 7.9) mm Hg respectively. The reductions of SBP and DBP in two groups were (2.3 ± 8.4) mm Hg and (4.0 ± 5.1) mm Hg and they were significantly superior to that in placebo group (P < 0.0001). But no significant difference existed between aranidipine and retard-released felodipine groups. Also no significant differences were found between these two antihypertensive therapy groups at the end of Weeks 4, 8 and 12 in the reduction of blood pressure, total response rate and blood pressure control rate. But 20 mg daily aranidipine was significantly superior to 10 mg daily retard-released felodipine in the control rates of SBP and DBP. Adverse events occurred at 24.22% and 29.92% in aranidipine and retard-released felodipine groups respectively (P = 0.305). CONCLUSION: Administration of aranidipine 5-20 mg/d can effectively control blood pressure and is not inferior to retard-released felodipine 5-10 mg/d. The efficacy of 20 mg/d aranidipine is superior to that of retard-released felodipine 5-10 mg/d. And the effectiveness and safety of aranidipine are similar to those of retard-released felodipine.

[Association between left ventricular diastolic function and blood pressure variability in essential hypertensive patients].

OBJECTIVE: To investigate the relationship between blood pressure variability (BPV) and left ventricular diastolic function in patients with essential hypertension. METHODS: Left ventricular diastolic function of 252 hypertensive patients were assessed by early (E) diastolic transmitral flows to early diastolic mitral annular velocity (Ea) (E/Ea) ratio derived from Doppler echocardiography. Patients were divided into two groups according to normal left ventricular diastolic function group (E/Ea<15, n = 168) and left ventricular diastolic dysfunction group (E/Ea ≥ 15, n = 84). All patients were monitored by ambulatory blood pressure. Standard deviation (SD) and coefficient of variation (CV) of blood pressure were calculated as the BPV. Relationship between BPV and left ventricular diastolic function were analyzed by multivariate logistic regression analysis. RESULTS: All-day average diastolic blood pressure(DBP), the day systolic blood pressure (SBP), night SBP, night DBP, SBPSD, DBPSD and DBPCV in the left ventricular diastolic dysfunction group were significantly higher than in the normal diastolic function group (all P < 0.05). Multivariate logistic regression analysis showed that left ventricular diastolic dysfunction was associated with SBPSD (OR:1.126, 95%CI:1.054-1.203, P < 0.01), SBPCV (OR:1.127, 95%CI:1.036-1.225, P < 0.01) in this patient cohort. CONCLUSION: High variability of SBP is correlated with left ventricular diastolic dysfunction in hypertensive patients.

[Short-term impact of modified blood-lipid reports on physicians' lipid lowering drug prescribing behavior and knowledge improvement on dyslipidemia].

OBJECTIVE: To compare the physicians' lipid lowering drug prescribing behavior and knowledge on dyslipidemia before and at 8 months after new-issued blood-lipid reports in our hospital. METHOD: Blood-lipid reports in our hospital is newly modified in that the classification of dyslipidemia and lipid-lowering guideline and target lipid level are listed on the back of lipid report besides the normal lipid value listed immediately after the measured lipid levels. Physicians' lipid lowering drug prescribing behavior and knowledge on dyslipidemia before and at 8 months after new-issued blood-lipid reports were examined in 143 doctors from various departments before and at 8 months after new-issued lipid reports. RESULTS: At 8 months after the new issued lipid reports, doctors' cognition rate about the guideline was significantly increased [83.9% (120/143) vs. 67.1% (96/143), P < 0.001] and the guideline was considered more helpful on daily practice [75.3% (58/77) vs. 55.8% (43/77), P = 0.005] compared to baseline. However, the prescription rate of dyslipidemia therapy did not change significantly (69.2% vs. 63.2%, P = 0.117) at 8 months after the new issued lipid reports. CONCLUSIONS: The modification of the blood-lipid reports improved doctors' knowledge on dyslipidemia and on the "Chinese guidelines on prevention and treatment of dyslipidemia in adults". However, the lipid lowering drug prescribing behavior remained unchanged at 8 months after the modification of the lipid reports. Further investigation is warranted to see if the lipid lowering drug prescribing behavior could be changed in the long-term.

[Aortic artery elastic lamina degradation, collagen remodeling, oxides stress and inflammation in the apolipoprotein E deficient mice with or without aortic banding].

OBJECTIVE: To explore the elastic lamina degradation and the collagen remodeling of aortic artery as well as oxides stress and inflammation of the apolipoprotein (Apo E) deficient mice with or without experimental hypertension. METHODS: Eighty male Apo E deficient mice were fed with high-fat diet beginning at six weeks of age. At 8-week old, they were randomly divided into hypertension group and control group (n=40 each), the mice in hypertension group were subjected the suprarenal aortic constriction operation and then randomly divided into two subgroups: 15 weeks age and 30 weeks age groups. At the end of experiment, the vascular elastic lamina degradation and the content of collagen were determined by morphological method, plasma ICAM-1 level was measured by ELISA, and the rennin activity measured by radioimmunoassay, the superoxide anion detected by fluorescence, the MOMA-2 observed by immunofluorescence in all animals. mRNA expression of NF-κB P65 and MMP9 was detected by real-time PCR. RESULT: In 15-week old group, the elastic lamina degradation Grade II and the intima-media thickness in the hypertension group were significantly higher than in the control group [(5.4±3.3)% vs. (8.9±2.5)%, P<0.05; (98.66±18.90) µm vs. (70.08±11.71) µm, P<0.05]. In 30-week old group, the elastic lamina degradation Grade III, the III type of collagen and the intima-media thickness were also significantly higher than in the control group [(15.2±3.7)% vs. (8.1±3.3)%, P<0.01; (23.00±7.73)% vs. (11.00±3.82)%, P<0.05; (147.31±22.60) µm vs. (103.98±17.21) µm, P<0.01]. The level of ICAM-1 in hypertension group was significantly higher than that of control group in both 15-week old and in 30-week old mice [(46.3±3.7) µg/ml vs. (40.6±5.7) µg/ml, P<0.05; (56.0±3.1) µg/ml vs. (45.2±2.8) µg/ml, P<0.05]. The superoxide anion, the MOMA-2, mRNA expression of NF-κB P65 and MMP9 in the hypertension group were significantly higher than in the control group in both 15-week old and in the 30-week old mice. The increase in hypertension group was more pronounced in the 30-week old mice than in the 15-week old mice. CONCLUSION: The elastic lamina degradation and the collagen remodeling of aortic artery as well as oxides stress and inflammation are more significant in the Apo E deficient mice with hypertension than in control Apo E deficient mice.

Effects of exogenous urotensin II on vascular remodelling after balloon injury.

1. Urotensin II (U-II) is a powerful vasoconstrictor peptide that stimulates cell proliferation. However, the systemic effects of U-II on cellular and extracellular matrix responses of vessel walls have not been investigated. The aim of the present study was to determine the effect of exogenous U-II on arterial neointimal hyperplasia after balloon injury. 2. A stenosis model of the thoracic aorta after balloon injury was established in male Wistar rats. Rats were divided into three groups (n = 5 in each): (i) uninjured; (ii) injured for 21 days; and (iii) injured and then treated with U-II (1 nmol/kg per h) via an osmotic minipump for 21 days. Another group of rats were killed on Days 7 and 14 after balloon injury for the analysis of in vitro collagen synthesis and secretion with U-II treated by [(3)H]-proline incorporation and determination of [(3)H]-hydroxyproline radioactivity, respectively. 3. Urotensin II immunoreactivity was 1.74-fold higher in vessels injured for 21 days than in uninjured vessels and mRNA levels of the urotensin UT receptor were upregulated by 55% following injury. After U-II treatment, the mRNA levels of the UT receptor were further upregulated (by 40%). In addition, U-II treatment increased the intimal area of injured aortas (13 +/- 5 vs 7 +/- 2% in group iii and ii, respectively), as well as increasing collagen content and cell proliferation. Protein levels of matrix metalloproteinase 1 were decreased in U-II-treated rats. In vitro, U-II treatment increased collagen synthesis and secretion in uninjured vessels in a concentration-dependent manner (10(-10), 10(-9) and 10(-8) mol/L U-II), especially in injured aortas on Day 7 after injury. 4. In conclusion, exogenous U-II may upregulate mRNA levels of the UT receptor, as well as increase collagen and cell proliferation, all of which would contribute to intimal hyperplasia after angioplasty.

[Usability of the laboratory report and knowledge of lipid-lowering in out-patients from dyslipidemia-related departments].

OBJECTIVE: To investigate the usability of laboratory test report from the angle of patients and understand to what degree the patients master the knowledge of lipid-lowering. METHODS: A total of 508 outpatients, selected from a Grade III-A general hospital, were queried by a questionnaire, their medical records and test reports were reviewed and their heights and weights were measured. In the study, 431 of them fulfilled the inclusion criteria and their information about lipid lowering treatment and treatment compliance were collected. RESULTS: Of the 508 subjects, 90.2% (458/508) read the report seriously; however, only 47.4% (240/508) took drugs according to the doctor's prescription even if the tests were "normal". Of the 431 lipid-lowering therapy related patients, only 26.4% (112/431) chose right in their cardiovascular risk classification, and less than 37.1% (160/431) agreed that "different people had different lipid lowering target". Of the 381 patients who needed the lipid-lowering treatment, 71.7% (273/381) recognized the need for treatment, but 98.7% (376/381) answered a wrong target for treatment; 60.9% (232/381) recognized that the reference values given in the laboratory test reports should be the target for treatment. Of the 246 patients under the lipid-lowering treatment, 35.4% (87/246)had reached their treatment goals, and only 52.0% (128/246) had a good compliance. CONCLUSION: Most patients read and trusted the laboratory test reports. However, dyslipidemia patients scarcely knew their lipid lowering treatment goals and their cardiovascular risk levels. The compliance of patients was poor, and the goal attainment was low. The laboratory medicine department should find out a simple and intuitional way to change the current situation.

[Effect of ischemia preconditioning on pro- and anti- angiogenic molecule expression and functional arteries formation].

OBJECTIVE: to observe the effect of ischemia preconditioning (IPC) on the expression of pro-angiogenic VEGF, PDGF and anti-angiogenic ADAMTS-1, and arteriogenesis. METHODS: rat heart IPC model was made by 4 circles of occluding the LAD for 6 min followed by 6 min of reperfusion. The expression of VEGF, PDGF-B and ADAMTS-1 in the ischemic area was examined with immunohistochemistry at 6, 12 and 24 h after IPC. IPC plus myocardial infarction model was induced by LAD ligation 24 h after IPC, 14 days later, the anti-SM-α-actin antibody was used to detect the mature neovascularization in the border of the infracted area. RESULTS: VEGF, PDGF-B and ADAMTS-1 were significantly upregulated in the ischemic area in IPC group compared with the control group (P < 0.05). Density of mature arteries was also significantly increased in IPC plus MI group than that in MI group (P < 0.05). CONCLUSION: IPC promoted the formation of mature new arteries which may be modulated by upregulating VEGF, PDGF-B, and ADAMTS-1 expressions.

[Ischemia preconditioning attenuated myocardial ischemia via upregulating the expression of adiponectin in rat].

OBJECTIVE: To investigate whether adiponectin plays a role in the protection of myocardium in the rat myocardial ischemia preconditioning (IPC) model. METHOD: Infarct size was measured by Masson's Trichrome staining, the expression of protein and mRNA of adiponectin at 0, 6, 12 and 24 h after IPC was examined by immunohistochemistry and quantitative real time RT-PCR, plasma levels of adiponectin at above mentioned four time points after IPC were detected by ELISA in IPC and MI rats. RESULT: Infarct size was smaller in IPC than in MI rats (20% ± 2% vs. 31% ± 3%, P < 0.05). The expression of adiponectin mRNA at 6 h and 12 h after IPC was 2.2 and 2.1 times higher than in Sham rats at respective time points (P < 0.05). Immunohistochemistry staining evidenced increased adiponectin expression in the ischemic area and weak expression of adiponectin in non-ischemic area (P < 0.05). Compared to the sham group, the plasma level of adiponectin increased significantly at 0, 6 and 12 h after IPC (0 h: 7.40 ± 0.47 vs. 10.90 ± 1.74; 6 h: 8.18 ± 1.41 vs. 10.98 ± 1.74; 12 h: 6.97 ± 1.02 vs. 9.31 ± 0.96, P < 0.05). CONCLUSION: IPC reduced infarction size, upregulated the myocardial expression of adiponectin at mRNA and protein levels, and increased plasma adiponectin concentration, suggesting that the adiponectin may play a critical role in the protective effect of IPC.

Novel mitochondrial DNA mutations associated with Chinese familial hypertrophic cardiomyopathy.

1. Hypertrophic cardiomyopathy (HCM) is a genetic disorder that has a complex set of symptoms and potentially devastating consequences. Increasing evidence indicates that mitochondrial DNA (mtDNA) mutations are responsible for the development of HCM, but the mtDNA mutations appear to differ considerably among different populations and regions. 2. In the present study, three families with HCM were found and investigated: one in Shandong province and two in the Chongqing region of China. The entire mtDNA genome from the 18 affected and 66 unaffected family members was sequenced directly and the mtDNA mutations were determined. 3. The frequency of haplogroup M10 was significantly higher in family members with HCM (HCM group) than in unaffected family members (normal group). Three mtDNA mutations were found with a significantly higher frequency in affected individuals than in unaffected family individuals, namely G7697A in the cytochrome c oxidase subunit II gene (P < 0.0001; odds ratio (OR) 227.5; 95% confidence interval (CI) 23.6­2194.8) and T12477C (P = 0.0037; OR 5.6; 95% CI 1.8­17.6) and G13135A in the NADH dehydrogenase 5 gene (P < 0.0001; OR 26.0; 95% CI 6.9­98.3), suggesting that these mutations are probably associated with susceptibility to HCM. In addition, mitochondrial Complex I activity was markedly decreased in the HCM group, suggesting that these mutations most likely affect mitochondrial respiratory function. 4. In conclusion, the results of the present study imply that mtDNA mutations G7697A, T12477C and G13135A are genetic factors that indicate a susceptibility to HCM and that could be used for the large-scale screening of genetic markers as well as the early diagnosis of HCM.

[Efficacy and safety of the single pill combination of valsartan 80 mg plus amlodipine 5 mg in mild to moderate essential hypertensive patients without adequate blood pressure control by monotherapy].

OBJECTIVE: To evaluate the efficacy and safety of a once daily valsartan/amlodipine 80/5 mg combination tablet in Chinese mild to moderate hypertensive patients without adequate blood pressure control by monotherapy. METHODS: Two multicenter, randomized, double-blind, double dummy, active-controlled, parallel group trials were conducted. After a washout period (no medication) of 1-4 weeks, patients with Mean Sitting Diastolic Blood Pressure (MSDBP) > or = 95 mm Hg (1 mm Hg = 0.133 kPa) and < 110 mm Hg received a monotherapy of either Amlodipine 5 mg (in study 1) or valsartan 80 mg (in study 2) for 4 weeks. Patients with MSDBP > or = 90 mm Hg and < 110 mm Hg at the end of the monotherapy period were randomized to receive valsartan/amlodipine 80/5 mg treatment, or continue with the monotherapy. RESULTS: In study 1, compared with amlodipine 5 mg, valsartan/amlodipine 80/5 mg once daily further reduced mean sitting systolic blood pressure (MSSBP)/MSDBP 4.4/3 mm Hg (P < 0.0001). In study 2, compared with valsartan 80 mg, valsartan/amlodipine 80/5 mg once daily further reduced MSSBP/MSDBP 6.4/4.2 mm Hg (P < 0.0001). The blood pressure (BP) control rates (BP < 140/90 mm Hg) of combination treatment group were 71.0% and 71.2% respectively, and significantly higher than the monotherapy groups in both trials. Incidence of adverse events was comparable in monotherapy and combination therapy groups. CONCLUSION: Our results showed that valsartan/amlodipine 80/5 mg was superior to amlodipine 5 mg or valsartan 80 mg alone in lowering blood pressure and BP control in patients with mild to moderate hypertension not adequately controlled with amlodipine 5 mg or valsartan 80 mg monotherapy. No new or unexpected safety issues were identified with valsartan/amlodipine combination therapy compared with monotherapy.

[Echocardiographic evaluation of left ventricular geometry and function in maintenance hemodialysis uremic patients].

OBJECTIVE: To assess left ventricular (LV) geometry, LV diastolic and systolic function in maintenance hemodialysis uremic patients. METHODS: Forty uremic patients and forty-five normal subjects were included in this study. LV volume, LV mass index (LVMI), relative wall thickness (RWT), LV mass and diastolic volume ratio (LVM/EDV) were measured. Mitral flow E velocity and A velocity ratio, deceleration time, mitral flow E velocity and mitral annulus Ea velocity ratio (E/Ea), pulmonary vein flow S velocity and D velocity ratio, atrial flow reversal velocity of pulmonary vein flow, mitral inflow propagation velocity, left atrium volume (LAV) and pulmonary artery systolic pressure (PASP) were determined for diastolic function evaluation. LV ejection fraction (LVEF) and single volume (SV) were derived from 3D echocardiography, systolic velocity of mitral valve annulus (Sa) by pulse tissue Doppler imaging (TDI) were used to evaluate systolic function. The time to peak systolic velocity (Ts) and early diastole velocity (Td) of LV 12 segments were measured using TDI. The maximal difference of Ts and Td (Ts-Dif and Td-Dif) were calculated to assess LV systolic and diastolic asynchrony. RESULTS: RWT, LVMI and LVM/EDV were significantly increased in uremic patients. There were 50% concentric, 17.5% eccentric hypertrophy and 17.5%concentric remodeling, respectively in uremic patients. The indices for LV diastolic function (E/Ea, LAV and PASP) were significantly higher in uremic patients than those in control subjects (P < 0.01). About 85% of the diastolic dysfunction in uremic patients presented as impaired relaxation pattern and 32.5% as increased filling pressure. LVEF and SV were similar between uremic patients and control subjects. Sa was significantly lower in uremic group than that in controls (P < 0.05). Ts-Dif was similar between the 2 groups while Td-Dif was significantly higher in uremic patients than control subjects (P < 0.05). CONCLUSION: LV hypertrophy, LV mass increase and LV diastolic dysfunction were the major characteristic of myocardial injury in uremia patients.

[Effects of perindopril and enalapril on atherosclerosis development of apolipoprotein E knockout mice].

OBJECTIVE: To compare the effects of perindopril and enalapril on the development of atherosclerotic lesions in ApoE knockout mice. METHODS: ApoE knockout mice were treated with perindoprilor (1.5 mg.kg(-1).d(-1), n = 20), enalapril (7.5 mg.kg(-1).d(-1), n = 20) or saline (0.2 ml saline/d, n = 20) per gavage for 20 weeks. Blood pressure and lipids were measured at the study end. Aortic root atherosclerotic plaque was then quantified and the content of collagen and the size of lipid core in the plaque assessed. Cryostat sections were used to quantify the expressions of monocyte/macrophage-2 (MOMA-2), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and matrix metalloproteinases-9 (MMP-9) in the plaque by immunofluorescence method. RESULTS: Blood pressure and lipid profiles were similar among different groups. Compared with control group, the plaque areas of perindopril group and enalapril group displayed significantly decrease (25.33% and 22.86%, respectively, both P < 0.01). However, no significant different were observed in the plaque size between the different ACE inhibitors groups. Perindopril group and enalapril group also significantly decreased the size of lipid core (52.98% and 38.98%, respectively, both P < 0.01) and the expression of MOMA-2 (88.38% and 52.16%, respectively, both P < 0.01), ICAM-1 (80.87% and 49.59%, respectively, both P < 0.01), VCAM-1 (77.56% and 56.44%, respectively, both P < 0.01) and MMP-9 (86.93% and 55.56%, respectively, both P < 0.01), and increased the plaque collagen content (298.36% and 168.14%, respectively, both P < 0.01) and the effects of perindopril was superior to those of enalapril (all P < 0.05). CONCLUSIONS: ACE inhibitors significantly suppressed tissue inflammation and attenuated the development of atherosclerosis in ApoE knockout mice independent of their effects on the lipid and blood pressure. Perindopril is superior to enalapril in stabilizing the plaques and has similar effect on reducing the plaque size as that of enalapril.

[A randomized, double-blind, double-dummy study comparing a fixed dose combination of telmisartan 80 mg plus hydrochlorothiazide 12.5 mg to telmisartan 80 mg in Chinese hypertensive patients who failed to respond adequately to telmisartan 80 mg].

OBJECTIVE: To evaluate the efficacy and safety of a fixed dose combination of telmisartan 80 mg plus hydrochlorothiazide (HCTZ) 12.5 mg (TH) to telmisartan 80 mg (T) in Chinese patients who failed to respond adequately to treatment with T. METHOD: This is a multi-center, randomized, double-blind, double-dummy clinical study. A total of 699 eligible hypertensive patients entered a one-week screening phase prior to the eight-week open-label T period. At the end of eight weeks, 345 patients who failed to respond to T (DBP > or = 90 mm Hg, 1 mm Hg = 0.133 kPa) were randomized to receive either TH (175 patients) or T (170 patients) for another eight weeks. Sitting and standing BP were taken 24 hours post-dose and adverse events were documented at visit with 4 weeks interval. Laboratory, ECG and physical examination were performed at screening, at baseline and at the final visit. RESULTS: After 8 weeks treatment, (1) The mean trough reduction in sitting diastolic blood pressure (SiDBP) from baseline in TH group was greater than that in T group (10.1 mm Hg vs 7.7 mm Hg, P = 0.0017). The mean trough reduction in sitting systolic blood pressure (SiSBP) from baseline was 14.2 mm Hg in TH group and 7.4 mm Hg in T group (P < 0.0001). (2) The mean trough reduction in standing DBP and standing SBP from baseline were significantly greater in TH group (8.7 mm Hg and 12.9 mm Hg) compared those in T group (7.3 mm Hg and 7.0 mmHg, P = 0.0350, P < 0.0001). (3) The number and percentage of responders in TH group (129, 74.6%) were significantly higher than in T group (100, 59.2%, P = 0.0016). (4) The incidence of the study drug-related adverse events was similar between TH and T group (3.5% vs. 3.6%, P > 0.05). CONCLUSION: TH was more effective than T in patients not responded adequately to T in Chinese hypertensive patients.

[The effects of various beta-blockers on myocardial gap junction structure in rat with myocardial ischemia-reperfusion injury].

OBJECTIVE: To compare the effects of carvedilol, metoprolol and propranolol on myocardial gap junction (GJ) structure in rat with myocardial ischemia and reperfusion injury. METHODS: Rats were divided randomly into five groups: sham operation group (SO), myocardial ischemia and reperfusion group (IR), IR + carvedilol group (CV), IR + metoprolol group (MT), and IR + propranolol group (PP). The left anterior descending branch was ligated for 30 minutes and reperfused for 4 hours (IR). After 4 h reperfusion, the distribution and composition of gap junctional connexin 43 (CX43) were observed by immunofluorescence and laser scanning confocal microscopy (LSCM), and the quantification of CX43 was measured by LSCM. RESULT: Compared with SO group, IR resulted in abnormal distribution and composition of CX43-GJ and the impairment of CX43-GJ was significantly attenuated by CV, MT and PP treatments with the best effect observed in CV group (P<0.05 vs. MT and PP). CONCLUSION: These results suggest that beta-blockers, especially, carvedilol, could significantly attenuate IR induced CX43-GJ impairment.

XS0601 reduces the incidence of restenosis: a prospective study of 335 patients undergoing percutaneous coronary intervention in China.

BACKGROUND: XS0601, consisting of active ingredients (Chuangxiongol and paeoniflorin), has been shown to inhibit arterial neointimal hyperplasia in animal models and in preliminary human studies. The objective of this study was to evaluate the safety and efficacy of XS0601 in preventing restenosis following percutaneous coronary intervention (PCI). METHODS: A multi-center, randomized, double-blind, placebo-controlled trial was conducted. A total of 335 patients were randomized into treatment with the oral administration of XS0601, or a placebo for 6 months after successful PCI. Angiographic follow-up was scheduled at 6 months, and clinical follow-ups performed at 1, 3 and 6 months after PCI. The primary end point was angiographic restenosis. The secondary end points were the combined incidence of death, target lesion nonfatal myocardial infarction, repeat angioplasty, and coronary artery bypass graft surgery. RESULTS: A total of 308 patients (91.9%) completed the study and 145 cases (47.1%) received angiographic follow-up. The restenosis rates were significantly reduced in the XS0601 group as compared with the placebo group (26.0% vs. 47.2%, P < 0.05), and the minimum lumen diameter (MLD) was greater [(2.08 +/- 0.89) mm for XS0601 vs. (1.73 +/- 0.94) mm for placebo, P < 0.05]. XS0601 also significantly reduced the combined incidence of major adverse cardiac event (10.4% in the XS0601 group vs. 22.7% in the placebo group, P < 0.05). The incidence of recurrent angina at 3 and 6 months after PCI was also significantly reduced in XS0601 group (7.1% and 11.0%) as compared with those in placebo group (19.5% and 42.9%) (P < 0.05). No significant side effects occurred within the 6-month follow-up period in the XS0601 group. CONCLUSION: Administration of XS0601 for 6 months is demonstrated to be safe and effective in reducing restenosis in post-PCI patients.

Clinical study on effect of Garlicin in stabilizing the carotid artery atherosclerotic plaque in patients with primary hypertension and coronary artery disease.

OBJECTIVE: To investigate the effect of garlicin in treating carotid artery atherosclerotic plaque (CAAP) in patients with primary hypertension and coronary heart disease (PHT-CHD). METHODS: Seventy-nine patients with PHT-CHD were randomly divided into the treated group (39 patients) treated with garlicin and fosinopril and the control group (40 patients) treated with fosinopril alone. The change of CAAP was evaluated by high frequency ultrasonic examination every six months, and the changes of intercellular adhesion molecule-1 (ICAM-1) and high sensitive C-reactive protein (hs-CRP) were measured by ELISA, with the observation proceeding for 52 weeks totally. RESULTS: By the end of the experiment, the number of complex plaques, Crouse integrals, intima-media thickness, serum ICAM-1 and hs-CRP were significantly lower in the treated group than those in the control group with significant difference (P < 0.05). CONCLUSION: Garlicin could stabilize CAAP to a certain extent and shows a definite vascular protective effect in patients with PHT-CHD.

[The clinical efficiency and safety of bisoprolol hydrochlorothiazide in patients with mild to moderate essential hypertension].

OBJECTIVE: To investigate the efficacy and safety of bisoprolol/hydrochlorothiazide (Lodoz) in patients with mild and moderate essential hypertension. METHODS: After 2 weeks of placebo run-in period, 90 hypertensive patients with sitting diastolic blood pressure (DBP) between 95 and 109 mm Hg (1 mm Hg = 0.133 kPa) and systolic blood pressure (SBP) below 180 mm Hg were treated by Lodoz (2.5 mg/6.25 mg/day) for 4 weeks. If DBP > 90 mm Hg at 4 weeks, Lodoz (5 mg/6.25 mg/day) was given for another 8 weeks. Clinic systolic and diastolic blood pressure measurements and ambulatory blood pressure monitoring (ABPM) were performed at the end of placebo run-in period and at 4 and 8 weeks. RESULTS: After 4 or 8 weeks treatment with Lodoz, clinic systolic and diastolic blood pressure, the 24-hour mean, daytime and nocturnal blood pressures reduced significantly compared to placebo run-in period [SBP and DBP reduced (14.89 +/- 10.99)/(10.37 +/- 7.35) mm Hg (4 weeks) and (19.40 +/- 10.55)/(13.31 +/- 7.77) mm Hg (8 weeks)] respectively (P < 0.05). The total efficacy rate is 59.3% for Lodoz 2.5 mg/6.25 mg and 69.8% for Lodoz 5 mg/6.25 mg. The trough: peak ratio for SBP and DBP were 91.5% and 94.4% with Lodoz 2.5 mg/6.25 mg, and 79.9% and 80.5% with Lodoz 5 mg/6.25 mg. The smoothness index (SI) for SBP and DBP were 9.07 and 6.48 with Lodoz 2.5 mg/6.25 mg, and 4.17 and 4.47 with Lodoz 5 mg/6.25 mg, respectively. Few side effects were observed during treatment including mild headache and dizziness and slightly increased serum urea acid. CONCLUSION: Lodoz (2.5 mg/6.25 mg and 5 mg/6.25 mg) can effectively reduce the 24 hours blood pressure in patients with mild to moderate essential hypertension.

[Effects of midazolam and estazolam as hypnotics in hypertensive patients with chronic insomnia: a multicentre, open labeled, randomized clinical trial].

OBJECTIVE: To compare the safety and efficacy of midazolam and estazolam in hypertensive patients with chronic insomnia. METHODS: In this multicentre, open labeled, randomized clinical trial, 217 adult (18 - 75 years) hypertensive patients (BP range 140 mm Hg or= 3 times/week for more than 1 month) were randomly divided into midazolam (7.5 - 15 mg before sleep, n = 113) or estazolam group (1 - 2 mg before sleep, n = 104). Patients took medication according to own need. Sleep diary should be completed within 15 minutes after getting up next morning. Follow-up analysis was performed in patients completed 8 sleep diaries or received midazolam or estazolam for 1 month. Patients' sleep diaries were evaluated, blood pressure and heart rate before and after therapy were measured and adverse events were recorded. RESULTS: (1) Blood pressure was equipotent reduced after both treatments (-11.8/7.3 mm Hg for midazolam group, and -9.1/5.6 mm Hg for estazolam group, all P < 0.05 vs. before treatment). (2) The total sleep score was also significantly decreased in both groups after medication (P < 0.01) and midazolam was significantly superior to estazolam in shortening sleep latency, reducing awakening frequency, improving objective sleep evaluation and decreasing daytime sleepiness, but there were no differences in dream frequency and total sleep time. (3) The adverse reactions such as dizziness, headache and nausea was similar in midazolam (3%) and estazolam group (7%, P > 0.05). CONCLUSIONS: It is safe to take midazolam or estazolam for hypertensive patients with chronic insomnia and both drugs reduced blood pressure. Midazolam is superior to estazolam in shortening sleep latency, reducing awakening frequency, improving objective sleep evaluation and decreasing daytime sleepiness.