Cardioprotection of ischemic preconditioning in rats involves upregulating adiponectin.

It has been reported that ischemic preconditioning (IPC) and adiponectin (APN) are cardioprotective in many cardiovascular disorders. However, whether APN mediates the effect of IPC on myocardial injury has not been elucidated. This study was conducted to investigate whether IPC affects myocardial ischemic injury by increasing APN expression. Male adult rats with cardiac knockdowns of APN and its receptors via intramyocardial small-interfering RNA injection were subjected to IPC and then myocardial infarction (MI) at 24 h after IPC. Globular APN (gAd) was injected at 10 min before MI. APN mRNA and protein levels in myocardium as well as the plasma APN concentration were markedly high at 6 and 12 h after IPC. IPC ameliorated myocardial injury as evidenced by improved cardiac functions and a reduced infarct size. Compared with the control MI group, rats in the IPC + MI group had elevated levels of left ventricular ejection fraction and fractional shortening and a smaller MI size (P < 0.05). However, the aforementioned protective effects were ameliorated in the absence of APN and APN receptors, followed by the inhibition of AMP-activated protein kinase (AMPK) phosphorylation, but reversed by gAd treatment in wild-type rats, and AMPK phosphorylation increased (P < 0.05). Overall, our results suggest that the cardioprotective effects of IPC are partially due to upregulation of APN and provide a further insight into IPC-mediated signaling effects.

Association of ADAMTS-7 Levels with Cardiac Function in a Rat Model of Acute Myocardial Infarction.

BACKGROUND/AIMS: High ADAMTS-7 levels are associated with acute myocardial infarction (AMI), although its involvement in ventricular remodeling is unclear. In this study, we investigated the association between ADAMTS-7 expression and cardiac function in a rat AMI model. METHODS: Sprague-Dawley rats were randomized into AMI (n = 40) and sham (n = 20) groups. The left anterior descending artery was sutured to model AMI. Before surgery and 7, 14, 28, and 42 days post-surgery, ADAMTS-7 and brain natriuretic peptide (BNP), and cartilage oligomeric matrix protein (COMP) were assessed by ELISA, western blot, real-time RT-PCR, and/or immunohistochemistry. Cardiac functional and structural parameters were assessed by M-mode echocardiography. RESULTS: After AMI, plasma ADAMTS-7 levels increased, peaking on day 28 (AMI: 13.2 ± 6.3 vs. sham: 3.4 ± 1.3 ng/ml, P < 0.05). Compared with the sham group, ADAMTS-7 expression was higher in the infarct zone at day 28. COMP present in normal myocardium was degraded by day 28 post-AMI. Plasma ADAMTS-7 correlated positively with BNP (r = 0.642, P = 0.025), left ventricular end-diastolic diameter (r = 0.695, P = 0.041), left ventricular end-systolic diameter (r = 0.710, P = 0.039), left ventricular ejection fraction (r = 0.695, P = 0.036), and left ventricular short-axis fractional shortening (r = 0.721, P = 0.024). CONCLUSIONS: ADAMTS-7 levels may reflect the degree of ventricular remodeling after AMI.

Association between plasma ADAMTS-7 levels and ventricular remodeling in patients with acute myocardial infarction.

BACKGROUND: The metalloproteinase family of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) degrades extracellular matrix. However, the relevance of the ADAMTS family to cardiovascular diseases remains largely unknown. The study aimed to examine plasma ADAMTS-7 levels in patients with acute myocardial infarction (AMI) and the relationship between plasma ADAMTS-7 levels and heart function. METHODS: This was a prospective study performed in 84 patients with ST-elevation myocardial infarction (STEMI), 70 patients with non-STEMI (NSTEMI), and 38 controls. Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma ADAMTS-7 levels. Cardiac structure and function were assessed using two-dimensional transthoracic echocardiography. Patients were stratified according to left ventricular ejection fraction (LVEF) ≤ 35% or >35%. RESULTS: Plasma ADAMTS-7 levels were higher in patients with LVEF ≤ 35% compared with those with LVEF >35% (6.73 ± 2.47 vs. 3.22 ± 2.05 ng/ml, P < 0.05). Plasma ADAMTS-7 levels were positively correlated with brain natriuretic peptide (BNP), left ventricular mass index (LVMI), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD) and negatively correlated with the 6-min walk test (P < 0.05). According to the receiver operating characteristic (ROC) curve, using a cutoff value of plasma ADAMTS-7 of 5.69 ng/ml was associated with a specificity of 61.0% and a sensitivity of 87.6% for the diagnosis of heart failure after AMI. Logistic regression analysis indicated that the association between ADAMTS-7 and heart failure after AMI was independent from traditional cardiovascular risk factors and other biomarkers (odds ratio = 1.236, 95% confidence interval: 1.023 to 1.378, P = 0.021). CONCLUSIONS: Elevated ADAMTS-7 level may be involved in ventricular remodeling after AMI.

Ambulatory arterial stiffness index correlates with ambulatory pulse pressure but not dipping status in patients with grade 1/grade 2 essential hypertension.

OBJECTIVE: To evaluate the relationship between ambulatory arterial stiffness index (AASI) and other parameters derived from ambulatory blood pressure (BP) monitoring, including dipping status, in patients with grade 1/grade 2 hypertension. METHODS: This retrospective analysis included baseline data from Chinese outpatients enrolled into a previous study, who had clinic diastolic BP of 90-109 mmHg and systolic BP <180 mmHg, had undergone 24-h ambulatory BP monitoring and routine blood chemistry investigations, and had estimated glomerular filtration rate (eGFR) data. RESULTS: Out of 120 patients screened, 87 were included. No significant difference in 24-h AASI was found between dippers and nondippers. The 24-h AASI significantly correlated with age, systolic BP and pulse pressure, and inversely correlated with 24-h diastolic BP variation and eGFR. In dippers and nondippers, AASI correlated with daytime pulse pressure, daytime diastolic BP variation and eGFR; in nondippers, AASI also correlated with 24-h systolic BP and 24-h pulse pressure. The 24-h AASI was significantly associated with 24-h pulse pressure and daytime pulse pressure. CONCLUSION: In patients with grade 1/grade 2 essential hypertension, AASI shows a significant correlation with ambulatory pulse pressure.

The preventive effect of garlicin on a porcine model of myocardial infarction reperfusion no-reflow.

OBJECTIVE: To evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI). METHODS: 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). RESULTS: 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). CONCLUSIONS: Garlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA.

[The effects of olmesartan on ambulatory blood pressures and blood pressure variability in patients with mild to moderate essential hypertension].

OBJECTIVE: To evaluate the effect of olmesartan medoxomil tablets (olmesartan) in comparison with Olmetec on 24 h ambulatory blood pressure (ABPM) and blood pressure variability (BPV) in patients with mild to moderate hypertension. METHODS: A randomized, double-blind, double-mimic controlled trial was performed.Forty-eight patients with mild to moderate essential hypertension were randomly into treatment group (olmesartan) and control group (Olmetec) for eight weeks. The ABPM was taken before and at the end of the trial. RESULTS: After eight weeks, treatment with olmesartan induced a significant reduction in ABPM in patients [(9 ± 3)/(11 ± 3) mmHg(1 mmHg = 0.133 kPa)], which is similar with the reduction by Olmetec [(9 ± 4)/(9 ± 5) mmHg], P > 0.05. This situation holds for BPV with the standard deviations of 24 h, systolic blood pressure/diastolic blood pressure of pre-treatment and pro-treatment were (10 ± 2)/(11 ± 3) mmHg vs (10 ± 3)/(12 ± 2) mmHg in olmesartan group, and (10 ± 3)/(11 ± 3) mmHg vs (12 ± 3)/(12 ± 4) mmHg in Olmetec group. (3) There is no difference in the rate of adverse event between olmesartan (10.42%) and Olmetec (8.33%) treatment (P > 0.05). CONCLUSION: Similar to Olmetec, treatment with olmesartan once daily can significantly reduce ABPM in patients with mild to moderate essential hypertension.

[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.

[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.

[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.

Alprostadil liposome microsphere preparation stabilizes vascular plaques and inhibits intra-plaque inflammation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Treatment with ALMP can stabilize vulnerable plaques by inhibiting inflammation.

Improved blood pressure control with nifedipine GITS/valsartan combination versus high-dose valsartan monotherapy in mild-to-moderate hypertensive patients from Asia: results from the ADVISE study, a randomized trial.

AIMS: ADVISE was a 12-week, multicenter, randomized, prospective, open-label, parallel-group study comparing combination therapy of nifedipine GITS 30 mg plus valsartan 80 mg (N + V) with high-dose valsartan (160 mg) monotherapy (V160) in Asian patients with hypertension. METHODS: Patients with hypertension inadequately controlled with valsartan 80 mg for at least 4 weeks were randomized. The coprimary endpoints were the mean changes in clinic systolic and diastolic blood pressures (SBP and DBP, respectively) at Week 12. Other endpoints included blood pressure (BP) control rate, response rate, and adverse events. RESULTS: The full analysis set (FAS) comprised 359 patients. Least squares (LS) mean changes in SBP were -18.3 mmHg (N + V; n = 177) and -16.5 mmHg (V160; n = 182) (difference: -1.9 mmHg; P = 0.0998). DBP LS mean changes were -9.8 mmHg (N + V) and -7.4 mmHg (V160) (difference: -2.4 mmHg; P = 0.0011). BP control rates were significantly higher in the N + V group (Week 4: 51.2% vs. 38.4%, P = 0.0138; Week 8: 68.3% vs. 50.3%, P = 0.0004; and Week 12: 71.2% vs. 55.5%, P = 0.0024). Similar findings were observed when patients were stratified according to smoking status, SBP baseline quartiles, and ESC/ESH guideline-defined added-risk category. The BP response rate was also higher in the N + V group compared with the V160 group. Rates of adverse drug reactions (all mild-to-moderate) were similar: 4.5% (N + V) and 4.4% (V160). CONCLUSIONS: Although one of the coprimary endpoints did not reach statistical significance, combination treatment with N + V provided a greater early and more consistent BP-lowering effect than monotherapy with V160, including superior reduction in DBP and BP control rates.

[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.

Long-term efficacy of olmesartan medoxomil in Chinese hypertensive patients as assessed by clinic, ambulatory and home blood pressure measurements.

BACKGROUND AND OBJECTIVES: There is limited information on the long-term efficacy and safety of olmesartan medoxomil in the management of hypertension in Chinese patients. We therefore conducted the present multicentre, single-arm, prospective, observational study to investigate the 24-week efficacy and safety of olmesartan medoxomil in patients with mild to moderate hypertension. METHODS: Eligible patients (diastolic blood pressure [BP] 90-109 mmHg and systolic BP <180 mmHg off antihypertensive medication) were started on olmesartan medoxomil 20 mg once daily, with the possible up-titration to 40 mg once daily during 24 weeks of follow-up, to control clinic BP to the target level (<140/90 and <130/80 mmHg in diabetes mellitus). In a subset of enrolled patients, 24-h ambulatory and home BP monitoring were also performed. RESULTS: In the intent-to-treat analysis (n = 348), at 24 weeks of follow-up, the mean ± SD changes from baseline in clinic systolic/diastolic BP were 21.2 ± 14.2/16.0 ± 8.8 mmHg (p < 0.001). The proportions of patients who achieved the goal BP for systolic, diastolic and both were 81, 80 and 75 %, respectively. Olmesartan medoxomil also significantly (p < 0.001) reduced systolic/diastolic BP measured at patients' homes by 17.7 ± 13.1/12.1 ± 7.9 mmHg from baseline (n = 109), and reduced mean 24-h, daytime and night-time ambulatory BP by 13.3 ± 16.3/7.6 ± 9.5 mmHg, 13.9 ± 17.4/8.0 ± 10.4 mmHg and 12.3 ± 18.1/6.8 ± 10.2 mmHg, respectively (n = 87). Seven (2.0 %) serious adverse events were reported during follow-up. CONCLUSION: In Chinese hypertensive patients, olmesartan medoxomil is efficacious in lowering BP as assessed by three different BP-measuring methods and has an acceptable long-term safety and tolerability profile.

Using different methods to evaluate the efficacy of olmesartan medoxomil in Chinese patients with mild to moderate essential hypertension according to ambulatory blood pressure monitoring.

OBJECTIVE: To evaluate the efficacy of olmesartan medoxomil in Chinese patients with mild to moderate essential hypertension using different methods according to ambulatory blood pressure monitoring. METHODS: Chinese patients 18-75 years of age with clinic diastolic blood pressure (BP) 90-109 mmHg and systolic BP less than 180 mmHg were treated with olmesartan medoxomil 20-40 mg once daily for 24 weeks to reach the goal BP (< 140/90 and < 130/80 mmHg in diabetes) in a multicenter study. The trough-to-peak ratio (T/P ratio) and the smoothness index (SI) for systolic/diastolic BP were calculated using different methods according to ambulatory blood pressure monitoring. RESULT: Olmesartan medoxomil 20-40 mg once daily reduced the systolic/diastolic ambulatory BP for 24-h, daytime, and night-time by 13.3 ± 16.3/7.6 ± 9.5, 13.9 ± 17.4/8.0 ± 10.4, and 12.3 ± 18.1/6.8 ± 10.2 mmHg in all eligible patients at week 24 from baseline (n = 87, P < 0.0001). The global and individual T/P ratios were 0.64/0.62 and 0.32/0.30 (n = 87) for systolic/diastolic BP, whereas these were 0.71/0.70 and 0.31/0.39 in fair responders (n = 71). Global and individual SI were 6.81/5.37 and 0.92/0.67 (n = 87) for systolic/diastolic BP, whereas these were 7.04/5.44 and 1.03/1.03 in fair responders (n = 71). Global and individual T/P ratios for systolic/diastolic BP were 0.75/0.82 and 0.45/0.46 in the 20 mg subgroup (n = 41), whereas these were 0.44/0.59 and 0.30/0.29 in the 40 mg subgroup (n = 30). Global and individual SI were 5.70/5.32 and 1.03/0.87 for systolic/diastolic BP in the 20 mg subgroup (n = 41), but these were 3.64/2.46 and 1.01/0.60 in the 40 mg subgroup (n = 30). CONCLUSION: The duration of the antihypertensive action of olmesartan medoxomil with 20-40 mg once daily can be assessed by the global T/P ratio and SI rather than the individual values, even in different populations and dosages.

Reduction of the morning blood pressure surge treated with olmesartan in Chinese patients with mild to moderate essential hypertension--a multicenter, open-label, single treatment group clinical study.

OBJECTIVE: To investigate the morning blood pressure surge (MBPS) in Chinese patients with mild to moderate essential hypertension treated with long-term administration of olmesartan, an angiotensin II receptor antagonist according to ambulatory blood pressure monitoring (ABPM). MATERIALS AND METHODS: In a multi-center, prospective study, we investigated the long-term efficacy of olmesartan by ABPM in 18-75 years-old Chinese patients with mild to moderate hypertension (clinic diastolic blood pressure [DBP] 90-109 mm Hg and systolic blood pressure [SBP] < 180 mmHg). After a 1 week placebo runin, 87 patients were treated with olmesartan 20 mg once daily in the morning for 24 weeks. Ambulatory blood pressure monitoring was conducted at baseline and at the end of 24 weeks. At baseline, patients with an MBPS > or = 23 mmHg were classified as the MBPS group (n = 41), and all other patients were classified as the non-MBPS group (n = 46). RESULTS: The mean systolic and diastolic blood pressures (SBP/DBP) over 24 hours were reduced from 141.78 +/- 12.8/91.17 +/- 7.34 to 128.35 +/- 15.86/83.58 +/- 9.53 mmHg (p < 0.01). The mean blood pressure in the final 6 hours of the dosing interval dropped from 135.75 +/- 5.84/87.29 +/- 4.80 mmHg to 122.98 +/- 6.46/80.49 +/- 4.31 mmHg (p < 0.01). The MBPS for SBP/ DBP were reduced from 35.68 +/- 8.85/29.77 +/- 17.19 mmHg to 28.62 +/- 15.08/19.08 +/- 11.01 mmHg in the MBPS group (p < 0.05). The reductions in MBPS after treament with olmesartan were significantly different between the two groups (p < 0.01). CONCLUSIONS: Olmesartan effectively reduces blood pressure in patients with essential hypertension, and olmesartan especially reduces the MBPS in MBPS-prone 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.

Serum uric acid in patients with acute ST-elevation myocardial infarction.

BACKGROUND: Few studies investigated serum uric acid levels in patients with acute Stelevation 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.

Cardioprotective effect of liposomal prostaglandin E1 on a porcine model of myocardial infarction reperfusion no-reflow.

OBJECTIVE: To evaluate whether liposomal prostaglandin E1 (lipo-PGE1) can decrease reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI). METHODS: Twenty-two male Chinese mini-swines were randomized into three groups: six in a sham-operation group, and eight each in the control and lipo-PGE1 groups. The distal part of the left anterior descending coronary artery (LAD) in the latter two groups was completely occluded for 2 h, and then reperfused for 3 h. Lipo-PGE1 (1 µg/kg) was injected 10 min before LAD occlusion until reperfusion for 1 h in the lipo-PGE1 group. Hemodynamic data and proinflammatory cytokines were examined before AMI, 2 h after occlusion, and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining were performed to evaluate the myocardial no-reflow area (NRA). RESULTS: Left ventricular systolic pressure and end-diastolic pressure significantly improved in the lipo-PGE1 group after reperfusion compared with the control group and also 2 h after AMI (P<0.05 for both). MCE and double staining both showed that lipo-PGE1 decreased reperfusion NRA after AMI (P<0.05, P<0.01). Lipo-PGE1 decreased serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) after myocardial infarction reperfusion (P<0.05 for both). CONCLUSIONS: Lipo-PGE1 is cardioprotective in our porcine model of myocardial infarction reperfusion no-reflow, decreasing NRA and attenuating the inflammatory response.

CXC chemokine ligand 16 as a prognostic marker in patients with intermediate coronary artery lesions: a 2-year follow-up study.

There is no reliable way to identify the high-risk patients with intermediate coronary artery lesions (diameter stenosis 20%-70%) in early stage. Soluble CXC chemokine ligand 16 (CXCL16) is a newly discovered chemokine that can mediate inflammatory responses. It is released by proteolytic cleavage of its membrane-bound form, named scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) that can promote the uptake of oxidized low-density lipoprotein cholesterol by macrophages. We have hypothesized that CXCL16 is an indicator of the prognosis of intermediate coronary artery lesions, and thus assessed the association between plasma CXCL16 concentrations and the 2-year prognosis in 616 patients with intermediate coronary artery lesions. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, revascularization and angina pectoris requiring re-hospitalization. During the median follow-up time of 24 months, 69 events occurred. The plasma concentrations of CXCL16 (median 7712.88 pg/ml vs. 6792.43 pg/ml, P = 0.014) and high-sensitivity C-reactive protein (hs-CRP) (median 2.82 mg/L vs. 1.68 mg/L, P < 0.001) were higher in patients with events than patients without events. Cox hazard proportion analysis showed patients in upper CXCL16 quartile were more likely to suffer from adverse outcome than patients in lower quartile (RR = 1.271, P = 0.029, 95% CI: 1.025-1.577) after adjusting for sex, age, smoking, hypertension, diabetes, fat, dyslipidemia, hs-CRP, and medication use. In conclusion, plasma level of CXCL16 is an independent predictor of the prognosis of the patients with intermediate coronary lesions. Elevated plasma CXCL16 is associated with higher risk for these patients.