[Status of glucose metabolism in Chinese essential hypertensive patients].

OBJECTIVE: To investigate glucose metabolism status and its relationship with blood pressure, obesity, renal function and cardio-cerebral vascular events in Chinese essential hypertensive patients. METHODS: Essential hypertensive patients without diabetic history were enrolled in this cross-sectional survey. All patients filled in questionnaires and received physical examination and laboratory tests. Oral glucose tolerance test (OGTT, fasting and 2 hours glucose level after drinking the 75 g glucose solution) was performed in patients who signed the informed consent. RESULTS: (1) The control rate of systolic BP was lower in patients with dysglycemia than in patients without dysglycemia (41.0% vs. 46.4%, P = 0.000). (2) The albuminuria detection rate and the abnormal rate of estimated glumerular filtration rate (eGFR) increased significantly with the deterioration of glucose metabolism. (3) Multifactor-analysis showed that abnormal waist circumference, decreased eGFR and presence of albuminuria were independent risk factors for abnormal glucose metabolism. Cardiovascular events was significantly higher in patients with abnormal glucose metabolism than patients with normal glucose metabolism. CONCLUSION: Abnormal glucose metabolism is common in Chinese essential hypertensive patients. When complicated with abnormal glucose metabolism, essential hypertensive patients had poor blood pressure control rate and were related to higher cardiovascular risk.

Efficacy and tolerability of a single-pill combination of amlodipine/valsartan in Asian hypertensive patients not adequately controlled with valsartan monotherapy.

This randomized, double-blind study evaluated efficacy of a single-pill combination of amlodipine/valsartan (Aml/Val) in Asian patients with hypertension not responding to Val 80 mg. Patients with mean sitting diastolic blood pressure (DBP) ≥90-≤110 mmHg were randomized to Aml/Val 5/80, Val 80, or Val 160 mg for 8 weeks. At week-8 endpoint, significantly greater reductions in BP were seen with Aml/Val 5/80 mg than valsartan monotherapies (p < 0.0001). The BP control was greater with Aml/Val 5/80 (70.5%) than Val (44.1-58.6%) monotherapies. The combination was well tolerated. In conclusion, single-pill combination with Aml/Val provided significant additional BP reduction and control in hypertensive patients not responding to Val 80 mg.

[Efficacy and safety of intravenous levosimendan compared with dobutamine in decompensated heart failure].

OBJECTIVE: To compare the efficacy and safety of intravenous levosimendan and dobutamine in patients with decompensated heart failure refractory to conventional medications. METHODS: Patients were recruited into this multicentre, randomised, positive-controlled and parallel-group study to receive either levosimendan or dobutamine therapy. In the levosimendan group, an initial loading dose of levosimendan of 12 microg x kg was infused over 10 min, followed by a continuous infusion of 0.1 microg x kg(-1) x min(-1) for 1 h and then 0.2 microg x kg(-1) x min(-1) for 23 h. In the control group, dobutamine was infused for 1 h at an initial dose of 2 microg x kg(-1) x min(-1) without a loading dose, followed by a continuous infusion of 4 microg x kg(-1) x min(-1) for 23 h. Hemodynamic responses at 24 h were evaluated by echocardiography (in both groups) and Swan-Gans catheter (in the levosimendan group). Clinical assessment was performed to evaluate efficacy and safety of the medications. RESULTS: A total of 225 patients from 12 medical centers were evaluated; 119 assigned to levosimendan and 106 assigned to dobutamine group. The effectiveness rate was 31.9% (38 patients) in the levosimendan group and 17.9% (19 patients) in the dobutamine group (P < 0.01). At 24 h, left ventricular ejection fraction (LVEF) was improved by 6. 4% in the levosimendan group, compared with 4.6% in the dobutamine group (P > 0.05). Stroke volume (SV) was increased by 11.1 ml in the levosimendan group and 2.8 ml in the dobutamine group respectively (P < 0.05). Dyspnea and clinical manifestations improvements were more significant in levosimendan therapy group compared to dobutamine group. There were less adverse effects including hypokalemia, hypotension and ventricular premature beats in the levosimendan group than in the dobutamine group (P < 0.05). CONCLUSION: Levosimendan was well tolerated and superior to dobutamine for patients with decompensated heart failure refractory to conventional medications.

Crosstalk between ERK1/2 and STAT3 in the modulation of cardiomyocyte hypertrophy induced by cardiotrophin-1.

BACKGROUND: The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway and the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway are the two major independent signal transduction pathways. However, it has recently been found that STAT3 may be negatively regulated by ERK1/2 in gp130-dependent signaling. Cardiotrophin-1 (CT-1), a potent novel hypertrophic cytokine, depends on gp130 to induce signaling and depends on STAT3 to exert hypertrophic effect. In this study, we examined whether STAT3 activity was negatively regulated by ERK1/2 during CT-1-induced signaling in rat cardiomyocytes and, if so, whether such crosstalk interfered with the hypertrophic effect of CT-1 and, furthermore, whether the mechanism underlying the crosstalk involved phosphorylation of serine 727 (S727) in STAT3. METHODS: The activities of ERK1/2 and STAT3 were assessed by in-gel kinase assay and Western blot analysis, respectively. The role of S727 phosphorylation in the crosstalk between ERK1/2 and STAT3 was determined by a transient transfection study using a STAT3S727A mutant. Cardiomyocyte hypertrophy was evaluated by the cellular protein-to-DNA ratio and [(3)H]-leucine incorporation. RESULTS: CT-1 simultaneously activated both ERK1/2 and STAT3 in rat cardiomyocytes. Inhibition of ERK1/2 by U0126 resulted in an increase of CT-1-induced tyrosine phosphorylation of STAT3 and, consequently, the protein-to-DNA ratio and [(3)H]-leucine incorporation. Transient transfection of the cells with STAT3S727A had no significant effect on CT-1-induced tyrosine phosphorylation of STAT3. CONCLUSIONS: STAT3 is activated by CT-1 in rat cardiomyocytes, but full activation is mitigated by the simultaneous activation of ERK1/2. The inhibition of ERK1/2 increases the activity of STAT3, which, in turn, enhances the hypertrophic effect of CT-1. The crosstalk between ERK1/2 and STAT3 is independent of the phosphorylation of the S727 in STAT3. Such crosstalk may contribute to the development of adequate cardiac hypertrophy.

[Myocardial protection and mechanism of Puerarin Injection on patients of coronary heart disease with ischemia/reperfusion].

OBJECTIVE: To explore the protective effect and the mechanism of Puerarin Injection (PI) on myocardial ischemia reperfusion in patients with coronary heart disease (CHD) and angina pectoris (AP). METHODS: Seventy-eight patients with AP planned to receive the PTCA and stenting treatment were randomly divided and single-blindedly into the conventional group and the PI group. Based on the conventional treatment and pre-operational preparation, the PI group was given 200 ml of PI by intravenous dripping once a day, beginning from one week before operation, but to the conventional group, normal saline was given for instead. The condition of AP attack in balloon dilatatory stage of PTCA was observed and change of ST segment of ECG detected by a 12-lead ECG monitor. The blood levels of von Willebrand factor (vWF:Ag), nitric oxide (NO) and endothelin-1 (ET-1) were also observed before and after treatment. RESULTS: As compared with those in the conventional group, number of patients having AP attack and ST segment change in PTCA process was lessened in the PI group, with blood levels of vWF:Ag and ET-1 obviously lower, and NO content obviously higher than those in the conventional group, CONCLUSIONS: PI could protect the myocardium in 2-3 days after ischemia reperfusion, one of the possible reasons is that PI can simulate the late phase of ischemic preconditioning, which may be related to its effect in lowering plasma vWF:Ag and ET-1, and increasing the serum NO content.

Brain natriuretic peptide for prevention of contrast-induced nephropathy after percutaneous coronary intervention or coronary angiography.

BACKGROUND: Many methods reportedly prevent contrast-induced nephropathy (CIN), but the effect of brain natriuretic peptide (BNP) on CIN is unknown. In this study we investigated recombinant BNP use before coronary angiography (CA) or nonemergent percutaneous coronary intervention (PCI) in patients with unstable angina. METHODS: One thousand patients with unstable angina were prospectively evaluated. The patients were randomly assigned to: group A, isotonic normal saline (NaCl 0.9%, 1 mL/kg/h) for 24 hours before CA or PCI; and group B, human recombinant BNP (rhBNP; 0.005 µg/kg/min). Serum creatinine (Scr) levels and estimated glomerular filtration rate were measured before and 24, 48, and 72 hours, and 7 days after the procedure. The primary outcome was CIN incidence defined according to a relative (≥ 25%) or absolute (≥ 0.5 mg/dL and 44 µmol/L, respectively) increase in Scr from baseline within 48 hours. The secondary end points were the changes in the Scr and estimated glomerular filtration rate, before and after the procedure. RESULTS: Contrast volume, a history of diabetes mellitus, and BNP administration independently predicted CIN. The incidence of CIN was significantly greater in group A than in group B (14.8% vs 5.6%; P < 0.01). Renal function was less compromised in patients who received rhBNP. The Scr of all patients with CIN remained increased for 24 hours, but it was lower and recovered faster in patients who received rhBNP. CONCLUSIONS: rhBNP administration before CA or PCI protects renal function and can significantly decrease CIN incidence.

[Clinical predictability of the waist-to-hip ratio in assessing the risk factors of cardiovascular disease among public servants in Shijiazhuang city].

OBJECTIVE: To assess the clinical predictability of waist-to-hip ratio (WHR) among female civil servants who had experienced risk factors of cardiovascular disease. METHODS: Data was gathered from 4153 female civil servants aged 21-91 y working at universities who were enrolled in health screening centre at the Second Hospital Attached to Hebei Medical University, in 2006. WHR quartiles were determined., as: < 0.80, 0.80- < 0.84, 0.84- < 0.90 and > or = 0.90. Subjects were placed into high-risk categories for cardiovascular disease on the basis of national health reference on range norms of protocol including hypertension, diabetes mellitus and dyslipidemia. RESULTS: Participants had an increased likelihood of hypertension (systolic blood pressure), dyslipidemia (elevated triacylglycerol and descending HDL-C) and diabetes mellitus at WHR > or = 0.84. All aforementioned variables had a significant odds ratio at WHR > or = 0.84. This trend was further persisted after adjustment had been made on smoking, age, and BMI. Descended HDL-C was observed at the 0.80 < or = WHR < 0.84 when compared with WHR < 0.80. CONCLUSION: These data indicated an upward shift in the critical threshold for WHR to > or = 0.84. Above which point, there was an elevation of risk factors on cardiovascular diseases among all the female civil servants. The trend persisted regardless of smoking, BMI < or > or = 28 and at what age group, among the civil servants population.

[Effects of remote preconditioning induced by skeletal muscle ischemia on myocardial cells apoptosis and roles of opioid receptors in pigs].

AIM: To investigate the effect on myocardial apoptosis and Bcl-2/Bax induced by remote preconditioning (RP) and to discuss the hypothesis from opioid receptors in pigs. METHODS: Skeletal muscle ischemia was performed in pigs by occlusion of the femoral artery (FAO) for 15 min followed by a 10 min of reperfusion. Infarction of the heart was induced by 40 min of left anterior descending coronary artery (LAD) occlusion followed by 120 min reperfusion. In the RP model induced by FAO, the role of opioid receptors was investigated by using antagonist of the opioid receptors (naloxone). The signal transduction pathway of RP was investigated by using hexamethonium. Apoptosis of left ventricular samples from nonischemic and ischemic areas was detected in situ with end-labeling (TUNEL) method and measured by flow cytometry. Bcl-2 and Bax was also measured by flow cytometry. RESULTS: (1) The apoptosis rate in ischemic myocardium in RP group measured by flow cytometry was lower (4.43% +/- 0.74%) compared with that in CONT group (15.4% +/- 1.15%), but Bcl-2/Bax was higher (1.36 +/- 0.09, CONT group: 0.56 +/- 0.08). (2) The protective effect could be prevented by naloxone used before RP protocol (apoptosis rate: 13.0% +/- 0.56% and Bcl-2/Bax: 0.69 +/- 0.18, P < 0.05). (3) Naloxone had no effect on apoptosis rate in CONT group. (4) Hexamethonium used before RP protocol had no effect on apoptosis rate and bcl-2/bax. Apoptotic cardiomyocytes detected in TUNEL correspond to the above. CONCLUSION: RP induced by skeletal muscle ischemia could prevent myocardium from apoptosis, in which Bcl-2 and Bax might take part in regulation and control. Furthermore opioid receptors could take part in triggering the course and a neuronal signal transmission from the remote area to heart could be excluded.

Different contributions of STAT3, ERK1/2, and PI3-K signaling to cardiomyocyte hypertrophy by cardiotrophin-1.

AIM: To assess the contribution of signal transducer and activator of transcription 3 (JAK-STAT3) pathway, extracellular signal-regulated kinases1/2 (ERK1/2) pathway, and phosphatidylinositol 3-kinase (PI3-K) pathway to cardiomyocytes hypertrophy induced by cardiotrophin-1 (CT-1), a new member of interleukin-6 (IL-6) family of cytokines. METHODS: STAT3, ERK1/2, and PI3-K were assessed by Western blot analysis. Activity of ERK1/2 was also confirmed by in-gel kinase assay. Hypertrophy of cardiomyocyte was evaluated by [3H]leucine incorporation and cellular protein-to-DNA ratio. RESULTS: CT-1 simultaneously activated phosphorylation of STAT3, ERK1/2, and PI3-K in rat cardiomyocytes. Parthenolide, an inhibitor of STAT, suppressed CT-1-induced [3H]leucine incorporation by 88.3 % and protein-to-DNA ratio by 75.0 %. U0126, an MEK1/2 inhibitor, increased CT-1-induced the phosphorylation of STAT3 in a dose-dependent manner and, consistently, augmented CT-1-induced increase in [3H]leucine incorporation and cellular protein-to-DNA ratio by 17.6 % and 16.3 %, respectively. Wortmannin, a PI3-K inhibitor, did not influence CT-1-induced [3H]leucine incorporation and cellular protein-to-DNA ratio. CONCLUSION: The hypertrophic effect of CT-1 was essentially mediated by STAT3, independent of PI3-K, and negatively regulated by ERK1/2 via inhibiting the phosphorylation of STAT3. The interaction between STAT3 and ERK1/2 in CT-1-induced signaling contributes to development of cardiac hypertrophy.