The preventive effect of garlicin on a porcine model of myocardial infarction reperfusion no-reflow / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI).</p><p><b>METHODS</b>Twenty-two male Chinese mini swines were randomized into 3 groups: sham-operation group (n=6), control group (n=8), and garlicin group (n=8). The distal part of left anterior descending coronary artery (LAD) in swines of the latter two groups was completely occluded by dilated balloon for 2 h and a successful AMI model was confirmed by coronary angiography (CAG) and electrocardiograph (ECG), which was then reperfused for 3 h. In the sham-operation group, balloon was placed in LAD without dilatation. Garlicin at a dosage of 1.88 mg/kg was injected 10 min before LAD occlusion until reperfusion for 1 h in the garlicin group. To assess serial cardiac function, hemodynamic data were examined by catheter method before AMI, 2 h after occlusion and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining with Evans blue and thioflavin-S were performed to evaluate myocardial no-reflow area (NRA) and risk area (RA).</p><p><b>RESULTS</b>Left ventricular systolic pressure and left ventricular end-diastolic pressure significantly improved in the garlicin group after reperfusion compared with the control group P<0.05) and 2 h after AMI (P<0.05). MCE showed garlicin decreased reperfusion NRA after AMI compared with the control group (P <0.05). In double staining, NRA/RA in the garlicin group was 18.78%, significantly lower than that of the control group (49.84%, P<0.01).</p><p><b>CONCLUSIONS</b>Garlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA.</p>

Association between left ventricular diastolic function and blood pressure variability in essential hypertensive patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between blood pressure variability (BPV) and left ventricular diastolic function in patients with essential hypertension.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>High variability of SBP is correlated with left ventricular diastolic dysfunction in hypertensive patients.</p>

Serum uric acid in patients with acute ST-elevation myocardial infarction / 世界急诊医学杂志（英文）

BACKGROUND: Few studies investigated serum uric acid levels in patients with acute ST-elevation myocardial infarction (STEMI). The study was to assess the clinical value of serum uric acid levels in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: Totally 502 consecutive patients with STEMI were retrospectively studied from January 2005 to December 2010. The level of serum lipid, echocardiographic data and in-hospital major adverse cardiovascular events (MACE) in patients with hyperuricemia (n=119) were compared with those in patients without hyperuricemia (n=383). The relationship between the level of serum uric acid and the degree of diseased coronary artery was analyzed. All data were analyzed with SPSS version 17.0 software for Student's t test, the Chi-square test and Pearson's correlation coefficient analysis. RESULTS: Serum uric acid level was positively correlated with serum triglyceride level. Hyperlipidemia was more common in hyperuricemia patients than in non-hyperuricemia patients (43.7％ vs. 33.7％, P=0.047), and serum triglyceride level was significantly higher in hyperuricemia patients (2.11±1.24 vs. 1.78±1.38, P=0.014). But no significant association was observed between serum uric acid level and one or more diseased vessels (P>0.05). Left ventricular end-diastolic diameter (LVEDd) was larger in hyperuricemia patients than in non-hyperuricemia patients (53.52±6.19 vs. 52.18±4.89, P=0.041). The higher rate of left systolic dysfunction and diastolic dysfunction was discovered in hyperuricemia patients (36.4％ vs. 15.1％, P<0.001; 68.2％ vs. 55.8％, P=0.023). Also, hyperuricemia patients were more likely to have in-hospital MACE (P<0.05). CONCLUSIONS: Serum uric acid level is positively correlated with serum triglyceride level, but not with the severity of coronary artery disease. Hyperuricemia patients with STEMI tend to have a higher rate of left systolic dysfunction and diastolic dysfunction and more likely to have more in-hospital MACE.

Short-term impact of modified blood-lipid reports on physicians' lipid lowering drug prescribing behavior and knowledge improvement on dyslipidemia / 中华心血管病杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Alprostadil liposome microsphere preparation stabilizes vascular plaques and inhibits intra-plaque inflammation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Vulnerable plaques play an important role in the onset of sudden cardiac events and strokes. How to stabilize vulnerable plaques is still a challenge to medical science. Alprostadil is a biologically active substance with strong activity on vessel. Our study assessed the stabilizing effects of an alprostadil liposome microsphere preparation (ALMP) on vulnerable plaques in the brachiocephalic artery of apolipoprotein E (Apo E) knockout mice.</p><p><b>METHODS</b>Seventy-two male Apo E-knockout mice were fed a high-fat diet beginning at eight weeks of age. At week 17, they were divided randomly into groups for treatment with a high dose (3.6 µg×kg(-1)×d(-1)) or low dose (1.8 µg×kg(-1)×d(-1)) of an ALMP, or 0.2 ml/d normal saline (control group). The drug was administered using a micro-capsule pump. Twenty weeks after drug administration, pathological changes in the vulnerable plaques within the brachiocephalic artery were assessed, and levels of anti-mouse monocyte/macrophage monoclonal antibody (MOMA-2) and superoxide anions in the plaques were detected using immunofluorescence. The soluble intercellular adhesion molecule-1 (ICAM-1) expression was measured by ELISA, and the expression of matrix metalloproteinase-9 (MMP-9) and CD40 mRNA was measured using RT-PCR. Thrombospindin-1 (TSP-1) expression was detected using Western blotting.</p><p><b>RESULTS</b>Compared with the control group, ALMP treatment significantly reduced the plaque area in the brachiocephalic artery (P < 0.01), significantly lowered the contents of the lipid core (P < 0.01), significantly reduced the number of ruptured fibrous caps (P < 0.05), and increased the thickness of the fibrous cap and significantly reduced the incidence of intra-plaque hemorrhage (P < 0.05). ALMP treatment significantly reduced the expression of MOMA-2, superoxide anion, MMP-9, ICAM-1 and CD40 in the plaques (P < 0.01), decreased plasma ICAM-1 expression (P < 0.01), and increased the expression of TSP-1.</p><p><b>CONCLUSIONS</b>Treatment with ALMP can stabilize vulnerable plaques by inhibiting inflammation.</p>

Aortic artery elastic lamina degradation, collagen remodeling, oxides stress and inflammation in the apolipoprotein E deficient mice with or without aortic banding / 中华心血管病杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>

ADAMTS-1 expression in rat myocardium after ischemic preconditioning: age-associated differences / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been found that cardiac protection afforded by ischemic preconditioning (IPC) is significantly reduced in the senescent myocardium. ADAMTS-1 (a disintesrin and metalloprotease with thrombospondin type 1 motifs) has been shown to inhibit angiogenesis in a variety of in vitro and in vivo assays. The aim of this study was to investigate the age-associated differences in ADAMTS-1 protein expression in rat myocardium after ischemic preconditioning.</p><p><b>METHODS</b>Sixty-four young (4 months) and old (24 months) male Sprague-Dawley rats were randomly assigned to an IPC group (40 rats) or a sham group (rats). A model of delayed IPC was induced and rats were sacrificed and myocardial samples were harvested from the ischemic-reperfused region for immunohistochemical detection of ADAMTS-1 at serial time points after IPC. A model of myocardial infarction was produced by ligation of the left anterior descending coronary artery in additional sets of young and old rats after sham or IPC procedures, then age-associated myocardial infarction survival after IPC was calculated.</p><p><b>RESULTS</b>ADAMTS-1 expression increased significantly in old rats compared to young rats (P < 0.05). The mean densities of ADAMTS-1 protein at 0, 6, 12, and 24 hours in young-IPC group after IPC were 0.05 ± 0.01, 0.13 ± 0.03, 0.16 ± 0.04, and 0.12 ± 0.03 vs. 0.07 ± 0.03, 0.20 ± 0.03, 0.24 ± 0.05, and 0.21 ± 0.04 in old-IPC group. IPC resulted in diminished survival rates (5/35 vs. 6/14, old-IPC group vs. old-sham group, P < 0.05), reduced left ventricular fractional shortening ((13.9 ± 2.8)% vs. (18.3 ± 2.3)%, P < 0.05) and increased the myocardial infarction size ((37.9 ± 3.2)% vs. (32.8 ± 5.1)%, P < 0.05) in the older rats.</p><p><b>CONCLUSIONS</b>Cardioprotection with IPC is attenuated in the older heart. ADAMTS-1 expression induced by IPC is greater in old rats. Over-expression of anti-angiogenic factors might be a potential mechanism behind reduced protection after IPC associated with aging.</p>

Effect of ischemia preconditioning on pro- and anti- angiogenic molecule expression and functional arteries formation / 中华心血管病杂志

<p><b>OBJECTIVE</b>to observe the effect of ischemia preconditioning (IPC) on the expression of pro-angiogenic VEGF, PDGF and anti-angiogenic ADAMTS-1, and arteriogenesis.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>IPC promoted the formation of mature new arteries which may be modulated by upregulating VEGF, PDGF-B, and ADAMTS-1 expressions.</p>

Ischemia preconditioning attenuated myocardial ischemia via upregulating the expression of adiponectin in rat / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate whether adiponectin plays a role in the protection of myocardium in the rat myocardial ischemia preconditioning (IPC) model.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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).</p><p><b>CONCLUSION</b>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.</p>

Effect of Qingre Quyu Granule (清热祛瘀颗粒) on stabilizing plaques in the brachiocephalic artery of apolipoprotein E deficient mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Qingre Quyu Granule (清热祛瘀颗粒, QRQYG) on stabilizing vulnerable plaques in apolipoprotein E (ApoE) deficient mice.</p><p><b>METHODS</b>Seventy-two male ApoE deficient mice were given a high-fat diet from 6 weeks of age. At the 16th week, all the mice were randomized into 3 groups: the QRQYG group, the simvastatin group, and the control group. Sixteen weeks after administration of 0.9 g/kg QRQYG, 3 mg/kg simvastatin or 10 mg/kg sodium chloride per day to the respective groups, the animals were euthanized. The pathological morphologic changes in the vulnerable plaques were evaluated, the matrix metalloprotease-9 (MMP-9) expression was measured by immunohistofluorescence, the soluble intercellular adhesion molecule 1 (ICAM-1) was determined by ELISA, the nuclear factor kappaB (NF-κB) subunit p65 was measured by quantitative RT-PCR, and, finally, thrombospondin-1 (TSP-1) was determined by the immunohistochemical method.</p><p><b>RESULTS</b>The plaque cross-sectional area in the brachiocephalic artery (23.7%, P<0.01), the lipid core of the plaque (43.1%±3.1%), and the number of buried fibrotic caps of the plaque were significantly decreased in the QRQYG group compared to the control group (both P<0.01); furthermore, the thickness of the fibrotic cap of the plaque increased and the intra-plaque hemorrhage of the plaque decreased. The serum soluble ICAM-1 (27.1±5.1 μg/mL), the protein expression of MMP-9 and TSP-1 and the p65 mRNA expression increased in the QRQYG group in comparison with the control group (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>QRQYG could stabilize the vulnerable plaque through inhibition of the inflammatory response.</p>

Using the combination of traditional risk factors and quantitative coronary angiography (QCA )in predicting the risk of individuals with subclinical artherosclerosis / 中华流行病学杂志

Objective To determine whether the combination of traditional risk factors and quantitative coronary angiography (QCA) assessment could provide accurate prognostic information on a population-based study including 1137 adults with subclinical artherosclerosis and with coronary risk factors. Methods Participants underwent coronary angiography examination before the minimal stenotic diameters, segment diameters, percent stenosis, plaque areas. Other parameters were analyzed by the computer-assisted Coronary Angiography Analysis System. The Framingham Risk Score for each participant was assessed. During the 1 year follow-up period, all kinds of endpoint cardiovascular events were screened. Endpoint events were defined as death from coronary heart disease, nonfatal myocardial infarction (MI) or unstable angina pectoris. Results During the 1 year of follow-up period, a total of 124 participants developed an endpoint event, which was significantly associated with the Framingham Risk Score, calcium of plaques and the plaque areas (all Ps＜0.05).The QCA score incorporated with the QCA parameters was related to the endpoint events. The Framingham Risk Score was combined with QCA score through logistic regression for prediction of end-point events. Data from the ROC analysis showed the accuracy of this prediction algorithm was superior to the accuracy when variables themselves were used. The event-free survival rate was inferior to the control group in participates under high risk, when being screened with this prediction algorithm (P＜0.05). Conclusion The risk of cardiovascular attack in subclinical artherosclerosis individual seemed to be associated with the Framingham Risk Score, calcium of plaques and the plaque areas. When the traditional risk factors (the Framingham Risk Score) were combined with QCA, the new method could provide more prognostic information on those adults with subclinical artherosclerosis.

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 / 中华心血管病杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Echocardiographic evaluation of left ventricular geometry and function in maintenance hemodialysis uremic patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To assess left ventricular (LV) geometry, LV diastolic and systolic function in maintenance hemodialysis uremic patients.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>LV hypertrophy, LV mass increase and LV diastolic dysfunction were the major characteristic of myocardial injury in uremia patients.</p>

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 / 中华心血管病杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>TH was more effective than T in patients not responded adequately to T in Chinese hypertensive patients.</p>

Effects of perindopril and enalapril on atherosclerosis development of apolipoprotein E knockout mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the effects of perindopril and enalapril on the development of atherosclerotic lesions in ApoE knockout mice.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

The effects of various beta-blockers on myocardial gap junction structure in rat with myocardial ischemia-reperfusion injury / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the effects of carvedilol, metoprolol and propranolol on myocardial gap junction (GJ) structure in rat with myocardial ischemia and reperfusion injury.</p><p><b>METHODS</b>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.</p><p><b>RESULT</b>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).</p><p><b>CONCLUSION</b>These results suggest that beta-blockers, especially, carvedilol, could significantly attenuate IR induced CX43-GJ impairment.</p>

The clinical efficiency and safety of bisoprolol hydrochlorothiazide in patients with mild to moderate essential hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of bisoprolol/hydrochlorothiazide (Lodoz) in patients with mild and moderate essential hypertension.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Efficacy and safety of olmesartan medoxomil versus losartan potassium in Chinese patients with mild to moderate essential hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of olmesartan medoxomil compared with losartan potassium in patients with mild to moderate essential hypertension.</p><p><b>METHOD</b>This is a randomized, double-blind, double-dummy, active-controlled, parallel, multi-center study. After a 2-week placebo run-in period, a total of 287 eligible subjects were randomized at 1:1 ratio to receive olmesartan medoxomil 20 mg or losartan potassium 50 mg, once daily for 8 weeks. The blood pressure was assessed after 4 weeks treatment. If the subject's seating diastolic blood pressure (SeDBP) was still >or=90 mm Hg, the dosage was doubled for another 4 weeks; for those subjects whose SeDBP was <90 mm Hg after 4-week treatment, the initial dosage remained unchanged and the treatment continued until completion of the study.</p><p><b>RESULTS</b>(1) The mean trough reduction in SeDBP from baseline in olmesartan group was significantly greater than that in losartan group after 4 weeks (11.72 mm Hg vs 9.23 mm Hg, P=0.004) and 8 weeks treatment (12.94 mm Hg vs 11.01 mm Hg, P=0.035). (2) The number and percentage of responders in olmesartan group (81, 65.3%) were statistically higher than those (68, 52.7%) in losartan group (P=0.028) after 4 weeks treatment and were similar between the two groups after 8 weeks treatment (P>0.05). (3) Individual and overall trough/peak ratios of DBP and SBP in 24-hour ambulatory blood pressure monitoring were higher in olmesartan group than losartan group. The hypotensive effect of olmesartan was more durable than losartan at 24 hour interval. (4) The incidence of study drug-related adverse events (AEs) in olmesartan group (10.5%) was similar as that in losartan group (13.9%, P>0.05). Most of these AEs were mild and transient.</p><p><b>CONCLUSION</b>This study shows that olmesartan medoxomil, at oral dose of 20 mg-40 mg once daily was effective and safe for hypertension treatment and the hypotensive effect was superior to losartan potassium (50 mg-100 mg once daily).</p>

Effects of valsartan and captopril on expressions and activities of tissue factor and tissue factor pathway inhibitor / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of ox-LDL, ACEI and ARB on expressions and activities of TF and TFPI in VSMC.</p><p><b>METHODS</b>(1) Rabbit VSMC was cultured by explant-attached method in vitro. (2) The effects of ox-LDL and valsartan on TF and TFPI expressions were analyzed by immunohistochemistry and immunofluorescence. Laser scanning confocal microscopy were applied to analyze the effects of ox-LDL and valsartan on TF expression. The effects of ox-LDL, valsartan and captopril on TF and TFPI antigen expressions were analyzed by ELISA. Chromogenic substrate method was used to determine the effects of ox-LDL, valsartan and captopril on TF activity. The effects of ox-LDL and valsartan on TF mRNA expression were analyzed by RT-PCR.</p><p><b>RESULTS</b>(1) ox-LDL could upregulate TF antigen, activity and TF expression at mRNA level and downregulate TFPI antigen. (2) Valsartan and captopril could reduce TF antigen and activity in VSMC treated by ox-LDL, and valsartan reduce it in a dose-dependent manner. Valsartan could also attenuate TF expression at mRNA level in VSMC treated by ox-LDL. (3) Using ELISA, valsartan and captopril could also enhance TFPI antigen in VSMC treated by ox-LDL.</p><p><b>CONCLUSION</b>Our study showed upregulated TF and downregulated TFPI expression and activity by ox-LDL and these effects could be reversed by ACEI and ARB indicating a new insight on the antiatherosclerotic effects of ACEI and ARB.</p>

Fosinopril but not metoprolol attenuated the increased matrix metallo-proteinases 9 expression at mRNA and protein levels of human umbilical vein endothelial cells exposed to oscillatory flow / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of fosinopril and metoprolol on metalloproteinases 9 (MMP9) expression of human umbilical vein endothelial cells (HUVECs) stimulated by oscillatory flow.</p><p><b>METHODS</b>HUVECs were exposed to steady laminar flow or oscillatory flow, laminar flow or oscillatory flow plus various concentrations (1 x 10(-7) mol/L, 1 x 10(-5) mol/L) of fosinopril and metoprolol for 4 and 24 hours. MMP9 mRNA and protein expressions of HUVECs were determined by RT-PCR and Western blot, respectively.</p><p><b>RESULTS</b>MMP9 expression at mRNA and protein levels were significantly increased in HUVECs exposed to oscillatory flow than that to laminar flow and these could be down-regulated by coincubation with fosinopril (1 x 10(-7) mol/L, 1 x 10(-5) mol/L, P < 0.01, P < 0.05, respectively) but not by co-incubation with metoprolol.</p><p><b>CONCLUSION</b>Fosinopril can attenuate the increased MMP9 expression at mRNA and protein levels of HUVECs exposed to oscillatory flow.</p>