Cold Pressor Test in Primary Hypertension: A Cross-Sectional Study.

Objectives: To investigate the characteristics of patients with primary hypertension who had positive responses to the cold pressor test (CPT). Methods: This cross-sectional study was conducted between November 2018 to November 2019, and the CPT was performed in patients with primary hypertension in 48 hospitals. The demographic characteristics and complications were collected through a questionnaire and physical examinations. A 12-month follow-up was conducted to identify the occurrence of the following events: a) all-cause mortality; b) myocardial infarction; c) stroke; d) hospitalized for heart failure. Results: The CPT was positive in 30.7% of the patients. Compared with the negative CPT group, the positive CPT group was associated with a lower rate of blood pressure control, and was more likely to have a high salt diet, diabetes, hyperuricemia, left ventricular wall thickening, carotid plaques, coronary heart disease and heart failure. A high-salt diet (OR = 1.228, 95%CI: 1.037-1.456) was found to be correlated with the positive result of CPT. Among patients in the positive CPT group, those using diuretics had a significantly higher rate of blood pressure control than those not using diuretics (54.6 vs.42.6%, x2 = 6.756, P = 0.009). After a 12-month follow-up, the incidence of heart failure in the positive CPT group was significantly higher than that in the negative CPT group (7.35 vs.5.01%, x2 = 3.945, P = 0.047). Conclusions: Patients with positive responses to the CPT had lower rates of BP control and a high risk of heart failure, which may be related to their preference for a high-salt diet. The use of diuretics helps to better control blood pressure in those patients.

Heparin-induced thrombocytopenia in renal insufficiency undergoing dialysis and percutaneous coronary intervention after acute myocardial infarction: A case report.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin therapy, and is characterized by arteriovenous thrombosis and bleeding events. The incidence of HIT after percutaneous coronary intervention (PCI) in patients with myocardial infarction complicated with renal failure is rarely reported. CASE SUMMARY: We report a 73-year-old man with acute myocardial infarction and renal failure who underwent hemodialysis and PCI, and developed a progressive decline in platelets and subcutaneous hemorrhage of both upper limbs after heparin treatment. In addition to a gradual decrease in platelets, the patient's 4T's score was 7, and HIT antibody was positive, confirming the diagnosis of HIT. CONCLUSION: Patients receiving heparin combined with antiplatelet therapy should be monitored closely, especially for their platelet count. In the case of thrombo-cytopenia, HIT should be highly suspected. When the diagnosis of HIT is confirmed, timely individualized treatment should be delivered.

A randomized, controlled comparison of different intensive lipid-lowering therapies in Chinese patients with non-ST-elevation acute coronary syndrome (NSTE-ACS): Ezetimibe and rosuvastatin versus high-dose rosuvastatin.

BACKGROUND: Statin combined with ezetimibe demonstrates significant benefit in lowering low density lipid cholesterol (LDL-C) and cardiovascular events abroad, but whether intermediate intensity statins combined with ezetimibe is superior to high-intensity statin monotherapy in Chinese people is unknown. METHODS: A total of 125 patients were randomly assigned to a intermediate intensity rosuvastatin group (rosuvastatin 10mg/d, n=42), high-dose rosuvastatin group (rosuvastatin 20mg/d, n=41) or combination therapy group (ezetimibe 10mg/d and rosuvastatin 10mg/d, n=42) with a 12-week follow-up. The primary end point was the proportion of patients who achieved the 2011 ESC/EAS LDL-C goal <70mg/dL (1.8mmol/L) at week 12. Secondary end points included changes from baseline in lipids, the occurrence of all cardiovascular events, high-sensitivity C-reactive protein and safety markers. RESULTS: The combination therapy group in the primary end point was significantly higher than rosuvastatin (20mg) and rosuvastatin (10mg) at week 12 (81.0% vs 68.3% vs 33.3%, P<0.001). And the similar change was observed in reducing LDL-C levels at week 12 (67.28% vs 52.80% vs 43.89%, P<0.001). The incidence of drug-related adverse events was much higher in the rosuvastatin 20mg group than the rosuvastatin 10mg group and the combination therapy group (17.0% vs 2.4% vs 4.8%, P<0.05). CONCLUSIONS: The combination of rosuvastatin 10mg/ezetimibe 10mg was an effectively alternative therapy superior to rosuvastatin 20mg or 10mg with a greater effect on lowering LDL-C and a lower incidence of drug-related adverse events in Chinese patients.

Triiodothyronine promotes the proliferation of epicardial progenitor cells through the MAPK/ERK pathway.

Thyroid hormone has important functions in the development and physiological function of the heart. The aim of this study was to determine whether 3,5,3'-Triiodothyronine (T3) can promote the proliferation of epicardial progenitor cells (EPCs) and to investigate the potential underlying mechanism. Our results showed that T3 significantly promoted the proliferation of EPCs in a concentration- and time-dependent manner. The thyroid hormone nuclear receptor inhibitor bisphenol A (100 µmol/L) did not affect T3's ability to induce proliferation. Further studies showed that the mRNA expression levels of mitogen-activated protein kinase 1 (MAPK1), MAPK3, and Ki67 in EPCs in the T3 group (10 nmol/L) increased 2.9-, 3-, and 4.1-fold, respectively, compared with those in the control group (P < 0.05). In addition, the mRNA expression of the cell cycle protein cyclin D1 in the T3 group increased approximately 2-fold compared with the control group (P < 0.05), and there were more EPCs in the S phase of the cell cycle (20.6% vs. 12.0%, P < 0.05). The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway inhibitor U0126 (10 µmol/L) significantly inhibited the ability of T3 to promote the proliferation of EPCs and to alter cell cycle progression. This study suggested that T3 significantly promotes the proliferation of EPCs, and this effect may be achieved through activation of the MAPK/ERK signaling pathway.

Efficacy of Clopidogrel and Clinical Outcome When Clopidogrel Is Coadministered With Atorvastatin and Lansoprazole: A Prospective, Randomized, Controlled Trial.

This prospective, randomized, nonblind, controlled trial evaluated the effects of clopidogrel on platelet function upon coadministration with atorvastatin and lansoprazole. One hundred four adult patients with non-ST-segment elevated acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI) with drug-eluting stent implantation were included. All patients were treated with standard dual antiplatelet therapy (DAPT) plus rosuvastatin 10  mg daily after the operation. On the sixth day after PCI, patients were randomly divided into 4 groups, Group A: DAPT + atorvastatin 20  mg daily (a change from rosuvastatin to atorvastatin) + lansoprazole 30  mg daily, Group B: DAPT + atorvastatin 20  mg daily (a change from rosuvastatin to atorvastatin), Group C: DAPT + lansoprazole 30  mg daily (continuing to take rosuvastatin), Group D is the control group. Additional drugs were used according to the situation of patients. Platelet function and concentrations of platelet activation markers (granular membrane protein 140 (P-selectin), thromboxane B2 (TXB2), and human soluble cluster of differentiation 40 ligand (sCD40L)) were assessed before randomization and at 15- and 30-day follow-up visits. All patients were maintained on treatment for 6 months and observed for bleeding and ischemic events. A total of 104 patients were enrolled, 27 patients in group A, 26 patients in Group B/C, 25 patients in Group D separately, and all the patients were analyzed. There were no differences in platelet function and the levels of platelet activation markers (P-selectin, TXB2, and sCD40L) among or within the 4 groups at the 3 time points of interest (P > 0.05). In the subsequent 6 months, no significant bleeding events occurred, and 12 patients experienced ischemic events, these results were also not significantly different among the groups (P > 0.05). In patients diagnosed with NSTE-ACS who have had drug-eluting stent implantation, simultaneously administering clopidogrel, atorvastatin, and lansoprazole did not decrease the antiplatelet efficacy of clopidogrel or increase adverse event frequency over 6 months.

Traditional Chinese medicine Qili qiangxin inhibits cardiomyocyte apoptosis in rats following myocardial infarction.

The aim of the present study was to examine the effect of the traditional Chinese medicine Qili qiangxin on cardiomyocyte apoptosis following myocardial infarction (MI) in a rat model. MI was induced in rats by ligation of the anterior descending coronary artery. Survivors were randomly divided into the sham operation, MI, and Qili qiangxin groups (4 g/kg per day). After 28 days, infarction size was measured. In the non-infarcted zones (NIZ), the apoptotic index (AI) was measured by terminal deoxynucleotidyl transferase (TdT)-mediated digoxigenin-conjugated dUTP nick-end labeling (TUNEL). Expression of Fas was detected by immunohistochemistry, and the expression of xanthine oxidase (XO) and caspase-3 by western blot analysis. In addition, the XO and ·O2-, ·OH-scavenging activity of myocardial tissue in NIZ was measured by colorimetry. Compared to the MI group, AI and the expression of Fas and caspase-3 were significantly decreased in NIZ. The activity of XO was also considerably reduced while ·O2- and ·OH-scavenging activity was significantly increased in the Qili qiangxin group. Ventricular remodeling was attenuated but there were no significant differences in infarct size (IS) or XO expression levels between the Qili qiangxin and MI groups. In conclusion, the results suggest that Qili qiangxin may inhibit cardiomyocyte apoptosis in NIZ in rats. The potential mechanism involved may be associated with its ability to reduce reactive oxygen species (ROS) and to depress the expression of Fas and caspase-3.

Spironolactone Regulates HCN Protein Expression Through Micro-RNA-1 in Rats With Myocardial Infarction.

Emerging evidence has shown that aldosterone blockers reduced the incidence of ventricular arrhythmias in patients with myocardial infarction (MI). However, the mechanism remains unknown. In this study, we investigated the mechanism by which spironolactone, a classic aldosterone blocker, regulates hyperpolarization-activated cyclic nucleotide-gated channel (HCN) protein expression in ischemic rat myocardium after MI. Eighteen rats surviving 24 hours after MI were randomly assigned into 3 groups: MI, spironolactone, and spironolactone + antagomir-1. Six sham-operated rats had a suture loosely tied around the left coronary artery, without ligation. The border zone of the myocardial infarct was collected from each rat at 1 week after MI. HCN2 and HCN4 protein and messenger RNA (mRNA) level were measured in addition to miRNA-1 levels. Spironolactone significantly increased miRNA-1 levels and downregulated HCN2 and HCN4 protein and mRNA levels. miRNA-1 suppression with antagomir-1 increased HCN2 and HCN4 protein levels; however, HCN2 and HCN4 mRNA levels were not affected. These results suggested that spironolactone could increase miRNA-1 expression in ischemic rat myocardium after MI and that the upregulation of miRNA-1 expression partially contributed to the posttranscriptional repression of HCN protein expression, which may contribute to the effect of spironolactone to reduce the incidence of MI-associated ventricular arrhythmias.

The effects of a low-salt diet on the efficacy of different antihypertensive drug regimens.

The objective of this study was to compare the antihypertensive effects of 3 types of antihypertensive drug regimens between different salt intake levels. The 180 patients with mild to moderate primary hypertension participating in this randomized, controlled clinical trial were randomly allocated to a low-salt diet (LSD) group or a non-low-salt diet (NLSD) group. Each group included 3 subgroups: a losartan 100 mg subgroup, a losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg subgroup, and an irbesartan 150 mg/HCTZ 12.5 mg subgroup. The LSD group received a diet in which the sodium content was strictly controlled (2.3 g/day). After 2 months, the office blood pressure (BP), the 24-hour mean BP, and the morning BP were significantly reduced (P ≤ .01) in each group. No significant differences were observed between the 3 LSD subgroups (P > .05). In the NLSD group, the losartan 50 mg/HCTZ 12.5 mg subgroup, and the irbesartan 150 mg/HCTZ 12.5 mg subgroup exhibited identical antihypertensive efficacy (P > .05), and these groups were significantly different from the losartan 100 mg subgroup(P ≤ .05). The BP of the patients who received the LSD was further decreased compared with those who received the NLSD (P ≤ .05). Therefore, we concluded that this LSD exerts synergistic BP-reducing effects.

The relationship between the high-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P) and coronary in-stent restenosis.

BACKGROUND: High-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P) contributed to several beneficial effects in the cardiovascular system. We explored the relationship between the HDL-S1P concentrations and coronary in-stent restenosis (ISR). METHODS: Fifty consecutive patients with ISR and 50 normal control subjects were included. The serum S1P, HDL-S1P and clinical data were collected to explore the relationships between these parameters and ISR. RESULTS: The patients with ISR had significantly lower concentrations of serum S1P (96.10 ± 26.33 vs. 113.40 ± 32.72; P = 0.004) and HDL-S1P (32.81 ± 10.02 vs. 42.72 ± 11.75; P < 0.001). All included patients were divided into four quartiles based on their concentrations of HDL-S1P: Quartile 1 (18.63-28.51 ng/ml), Quartile 2 (28.62-37.28 ng/ml), Quartile 3 (37.35-45.27 ng/ml), and Quartile 4 (45.59-79.36 ng/ml). The rates of ISR were 84%, 48%, 40% and 28%, respectively. The patients in Quartile 1 exhibited significantly higher rates of ISR compared with the other groups (P = 0.001). A multivariate stepwise logistic regression analysis indicated that HDL-S1P (OR = 0.846, 95% CI = 0.767-0.932, P = 0.001) was an independent predictor of ISR. An ROC analysis indicated that HDL-S1P = 30.37 ng/ml and had a 90% sensitivity and a 52% specificity in predicting ISR. CONCLUSIONS: HDL-S1P is an independent predictor of ISR, and patients with higher concentrations of HDL-S1P have a low risk of ISR.

High-intensity statin therapy in patients with chronic kidney disease: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of high-intensity statin therapy in patients with chronic kidney disease (CKD). DESIGN: A systematic review and meta-analysis. DATA SOURCES: Randomised controlled trials (RCTs) comparing high-intensity statin therapy (atorvastatin 80 mg or rosuvastatin 20/40 mg) with moderate/mild statin treatment or placebo were derived from the databases (PubMed, Embase, Ovid, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, and ISI Web of Knowledge). OUTCOME MEASURE: Primary end points: clinical events (all-cause mortality, stroke, myocardial infarction and heart failure); secondary end points: serum lipid, renal function changes and adverse events. RESULTS: A total of six RCTs with 10,993 adult patients with CKD were included. A significant decrease in stroke was observed in the high-intensity statin therapy group (RR 0.69, 95% CI 0.56 to 0.85). However, the roles of high-intensity statin in decreasing all-cause mortality (RR 0.85, 95% CI 0.67 to 1.09), myocardial infarction (RR 0.69, 95% CI 0.40 to 1.18) and heart failure (RR 0.73, 95% CI 0.48 to 1.13) remain unclear with low evidence. High-intensity statin also had obvious effects on lowering the LDL-C level but no clear effects on renal protection. Although pooled results showed no significant difference between the intervention and control groups in adverse event occurrences, it was still insufficient to put off the doubts that high-intensity statin might increase adverse events because of limited data sources and low quality evidences. CONCLUSIONS: High-intensity statin therapy could effectively reduce the risk of stroke in patients with CKD. However, its effects on all-cause mortality, myocardial infarction, heart failure and renal protection remain unclear. Moreover, it is hard to draw conclusions on the safety assessment of intensive statin treatment in this particular population. More studies are needed to credibly evaluate the effects of high-intensity statin therapy in patients with CKD.

Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in coronary artery disease: A systematic review and meta-analysis.

BACKGROUND: The study performed a meta-analysis of the diagnostic performance of fractional flow reserve (FFR) derived from coronary computed tomography angiography (FFRCT) to assess the functional significance of coronary stenosis using FFR as the reference standard. METHODS: We searched the electronic databases of PubMed, EMBASE, The Chorance Library, Medion and Web of Science for relevant articles published until August 2014. Pooled estimates of sensitivity, specificity, positive (LR+) and negative likelihood ratios (LR-) with the corresponding 95% confidence intervals (CIs) and the summary receiver operating characteristic curve (SROC) were determined. RESULTS: Five studies, 706 patients and 1165 vessels or lesions were included in the meta-analysis. The pooled sensitivity and specificity for FFRCT at the per-patient level were 90% (95% CI, 85%-93%) and 72% (95% CI, 67%-76%), respectively. The corresponding pooled LR+ and LR- were 3.70 (95% CI, 2.11-6.49) and 0.15 (95% CI, 0.11-0.22), respectively. The pooled sensitivity and specificity for FFRCT on the per-vessel or per-lesion basis were 83% (95% CI, 79%-87%) and 78% (95% CI, 75%-81%), respectively. Corresponding pooled LR+ and LR- were 3.75 (95% CI, 2.09-6.74) and 0.22 (95% CI, 0.18-0.29), respectively. The area under the SROC (AUC) was 0.94 at the per-patient level and 0. 91 at the per-vessel or per-lesion level. CONCLUSIONS: The existing evidence suggests that noninvasive FFRCT has high diagnostic performance compared with invasively measured FFR for the detection of ischemia-causing stenosis in stable patients with suspected or known coronary artery disease (CAD).

Adjunctive manual thrombus aspiration during ST-segment elevation myocardial infarction: a meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this study was to synthesize evidence by examining the effects of manual thrombus aspiration on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: A total of 26 randomized controlled trials (RCTs), enrolling 11,780 patients, with 5,869 patients randomized to manual thrombus aspiration and 5,911 patients randomized to conventional percutaneous coronary intervention (PCI), were included in the meta-analysis. Separate clinical outcome analyses were based on different follow-up periods. There were no statistically reductions in the incidences of mortality (risk ratio [RR], 0.86 [95% confidence interval [CI]: 0.73 to 1.02]), reinfarction (RR, 0.62 [CI, 0.31 to 1.32]) or target vessel revascularization (RR, 0.89 [CI, 0.75 to 1.05]) in the manual thrombus aspiration arm at 12 to 24 months of follow-up. The composite major adverse cardiac events (MACEs) outcomes were significantly lower in the manual thrombus aspiration arm over the long-term follow-up (RR, 0.76 [CI, 0.63 to 0.91]). A lower incidence of reinfarction was observed in the hospital to 30 days (RR, 0.59 [CI, 0.37 to 0.92]). CONCLUSION: The present meta-analysis suggested that there was no evidence that using manual thrombus aspiration in patients with STEMI could provide distinct benefits in long-term clinical outcomes.

Calcium channel blocker compared with angiotensin receptor blocker for patients with hypertension: a meta-analysis of randomized controlled trials.

To explore the clinical effects of a calcium channel blocker compared with an angiotensin II receptor blocker in hypertensive patients, the authors collected data from randomized controlled trials. The pooled outcomes were all-cause mortality, stroke, myocardial infarction, and heart failure. Eight head-to-head trials enrolling 25,084 patients were included. There was no significant mortality difference in the two arms (relative risk, 0.99; 95% confidence interval, 0.91-1.07). However, calcium channel blockers were more effective in reducing stroke (relative risk, 0.87; 95% confidence interval, 0.76-0.99) and myocardial infarction incidence (relative risk, 0.86; 95% confidence interval, 0.76-0.98). There was no significant difference with heart failure incidence between the two arms but a lower trend in patients with angiotensin II receptor blockers was noted (relative risk, 1.4; 95% confidence interval, 0.99-1.98). The meta-analysis suggested that initially use of a calcium channel blocker might be superior to an angiotensin II receptor blocker for prevention of stroke and myocardial infarction.

Blood pressure control rate and associated risk factors in hospitals of different grades in Chongqing, China.

OBJECTIVE: The present article aimed to provide accurate estimate of the control rate of hypertension and the influencing factors in hospitals of different grades in Chongqing. METHODS: In this survey, hypertensive outpatients were recruited from 5 tertiary hospitals, 6 secondary hospitals and 5 primary hospitals in 9 districts of Chongqing from November 2011 to May 2012. Outpatients were investigated by clinical interview with BP measurement and questionnaire. Univariate analyses and logistic regression analysis was used to assess the effect of variables on control of hypertension. RESULT: A total of 2742 hypertensives were studied, of which 820 were from primary hospitals, 901 from secondary hospitals and 1021 from tertiary hospitals. The total control rate for hypertensive outpatients in Chongqing was 46.0%. The control rate of the primary,secondary and tertiary hospitals were 38.7%、46.7%、51.1%. Multinomial Logistic Regression showed that the control rate was positively correlated with mastery of knowledge of hypertension, normal BMI;whereas it was positively correlated with peasantry,the dissatisfactory with doctor's manner and the distrust to doctor. CONCLUSION: Blood pressure control rate of hypertensive outpatients in Chongqing was low.High BMI, peasantry, lack of knowledge of hypertension, doctors' manners, distrust to doctor were the key reasons for low BP control rate.

Estudio clínico del impacto de la utilización intensiva de estatinas sobre los niveles de inflamación y activación plaquetaria en la angina estable después de intervención coronaria percutánea / Impact of intensive statin use on the level of inflammation and platelet activation in stable angina after percutaneous coronary intervention: A clinical study

Fundamento y objetivo: El objetivo de este estudio fue diseñado para investigar si dosis altas de atorvastatina antes de la intervención coronaria percutánea (PCI) pueden reducir la inflamación, la activación plaquetaria y episodios cardíacos adversos mayores (MACE) en pacientes con angina estable que se someten a terapia con estatinas a largo plazo. Métodos: En total, 215 pacientes con angina estable crónica fueron asignados aleatoriamente a un tratamiento previo con 80mg de atorvastatina (12h antes de la PCI, n=106) o con 20mg de atorvastatina (12h antes de la PCI, n=109). Todos los pacientes fueron sometidos a PCI. Los niveles séricos de interleucina-6, proteína C reactiva de alta sensibilidad y factor de necrosis tumoral alfa, GMP-140 y P-selectina se midieron 24h antes y después de la PCI. Se determinó la incidencia a 30 días de MACE. Resultados: No se observaron diferencias en las características basales entre los grupos. Los niveles de inflamación y activación de las plaquetas fueron significativamente menores a las 24h en el grupo que recibió terapia intensiva con estatinas (p<0,05). Los niveles de inflamación y activación de las plaquetas aumentaron considerablemente 24h después de la PCI en el grupo que recibió la dosis más baja de atorvastatina (p>0,05). En otras palabras, el tratamiento previo con una dosis alta de atorvastatina disminuyó notablemente la incidencia de MACE durante 30 días (p<0,05). Conclusiones: El tratamiento previo con una dosis alta de atorvastatina redujo significativamente la inflamación, la activación de las plaquetas y la incidencia de ECV en pacientes con angina estable (AU)

Background and objective: This study was designed to investigate whether high-dose atorvastatin before percutaneous coronary intervention (PCI) can reduce inflammation, platelet activation, and major adverse cardiac events (MACE) in patients with stable angina who are undergoing long-term statin therapy. Methods: In total, 215 patients with chronic stable angina were randomized to pretreatment with 80mg of atorvastatin (12h before PCI; n=106) or with 20mg of atorvastatin (12h before PCI; n=109). All patients underwent PCI. Serum levels of interleukin-6, high-sensitivity C-reactive protein, tumor necrosis factor-Alpha, GMP-140, and p-selectin were measured 24h before and after PCI. The 30-day incidence of MACE was determined. Results: No differences in baseline characteristics were observed between the groups. The levels of inflammation and platelet activation were significantly lower after 24h in the group that received intensive statin therapy (P<0.05). The levels of inflammation and platelet activation increased sharply 24h after PCI in the group that received the lower dose of atorvastatin (P>0.05). In other words, pretreatment with a high dose of atorvastatin decreased the incidence of MACE sharply within 30 days (P<0.05). Conclusions: Pretreatment with a high dose of atorvastatin significantly reduced inflammation, platelet activation, and the incidence of MACE in patients with stable angina (AU)

Additional use of an aldosterone antagonist in patients with mild to moderate chronic heart failure: a systematic review and meta-analysis.

AIMS: Aldosterone antagonists (AldoAs) have been used to treat severe chronic heart failure (CHF). There is uncertainty regarding the efficacy of using AldoAs in mild to moderate CHF with New York Heart Association (NYHA) classifications of I to II. This study summarizes the evidence for the efficacy of spironolactone (SP), eplerenone (EP) and canrenone in mild to moderate CHF patients. METHODS: PubMed, MEDLINE, EMBASE and OVID databases were searched before June 2012 for randomized and quasi-randomized controlled trials assessing AldoA treatment in CHF patients with NYHA classes I to II. Data concerning the study's design, patients' characteristics and outcomes were extracted. Risk ratio (RR) and weighted mean differences (WMD) or standardized mean difference were calculated using either fixed or random effects models. RESULTS: Eight trials involving 3929 CHF patients were included. AldoAs were superior to the control in all cause mortality (RR 0.79, 95% CI 0.66, 0.95) and in re-hospitalization for cardiac causes (RR 0.62, 95% CI 0.52, 0.74), the left ventricular ejection fraction was improved by AldoA treatment (WMD 2.94%, P = 0.52). Moreover, AldoA therapy decreased the left ventricular end-diastolic volume (WMD -14.04 ml, P < 0.00001), the left ventricular end-systolic volume (WMD -14.09 ml, P < 0.00001). A stratified analysis showed a statistical superiority in the benefits of SP over EP in reducing LVEDV and LVESV. AldoAs reduced B-type natriuretic peptide concentrations (WMD -37.76 pg ml(-1), P < 0.00001), increased serum creatinine (WMD 8.69 µmol l(-1), P = 0.0003) and occurrence of hyperkalaemia (RR 1.78, 95% CI 1.43, 2.23). CONCLUSIONS: Additional use of AldoAs in CHF patients may decrease mortality and re-hospitalization for cardiac reasons, improve cardiac function and simultaneously ameliorate LV reverse remodelling.

Impact of intensive statin use on the level of inflammation and platelet activation in stable angina after percutaneous coronary intervention: a clinical study.

BACKGROUND AND OBJECTIVE: This study was designed to investigate whether high-dose atorvastatin before percutaneous coronary intervention (PCI) can reduce inflammation, platelet activation, and major adverse cardiac events (MACE) in patients with stable angina who are undergoing long-term statin therapy. METHODS: In total, 215 patients with chronic stable angina were randomized to pretreatment with 80 mg of atorvastatin (12 h before PCI; n = 106) or with 20 mg of atorvastatin (12 h before PCI; n = 109). All patients underwent PCI. Serum levels of interleukin-6, high-sensitivity C-reactive protein, tumor necrosis factor-α, GMP-140, and p-selectin were measured 24 h before and after PCI. The 30-day incidence of MACE was determined. RESULTS: No differences in baseline characteristics were observed between the groups. The levels of inflammation and platelet activation were significantly lower after 24 h in the group that received intensive statin therapy (P < 0.05). The levels of inflammation and platelet activation increased sharply 24 h after PCI in the group that received the lower dose of atorvastatin (P > 0.05). In other words, pretreatment with a high dose of atorvastatin decreased the incidence of MACE sharply within 30 days (P < 0.05). CONCLUSIONS: Pretreatment with a high dose of atorvastatin significantly reduced inflammation, platelet activation, and the incidence of MACE in patients with stable angina.

Angiogenesis in a rat model following myocardial infarction induced by hypoxic regulation of VEGF165 gene-transfected EPCs.

Hypoxia-response elements (HREs) regulate the expression of the vascular endothelial growth factor 165 (VEGF165) gene and enhance the safety and efficacy of therapeutic angiogenesis. However, the role of hypoxic regulation of VEGF165 gene-modified stem cells in promoting angiogenesis in the ischemic myocardium remains unclear. In this study, the effects of the hypoxic regulation of genetically modified endothelial progenitor cells (EPCs) on angiogenesis in the ischemic myocardium and on changes in cardiac function following acute myocardial infarction (AMI) were investigated through the transplantation of hypoxia-regulated VEGF165 gene-modified EPCs into the ischemic myocardium. Rat bone marrow-derived EPCs transfected with plasmid p6HRE-CMV­VEGF165 (6HRE-VEGF165-E), and plasmid pCMV-VEGF165 (VEGF165-E) were injected into rats with a successfully established model of AMI. The levels of VEGF165 mRNA and protein expression in the EPCs and ischemic myocardium were determined using reverse transcription-polymerase chain reaction and western blot assay, respectively, and the capillary density in the ischemic myocardium and the cardiac function of the rats were detected using immunohistochemistry and echocardiography, respectively. We found that the hypoxia promoter 6HRE-CMV effectively regulated the expression of the VEGF165 gene in the EPCs and the ischemic myocardium. In rats of the 6HRE-VEGF165-E-transplanted group, the levels of VEGF165 gene expression and capillary density in the ischemic myocardium were significantly higher than those in the other experimental groups. Moreover, cardiac function was also improved compared with that in other groups. VEGF165 gene-modified EPCs are able to significantly promote angiogenesis in the ischemic myocardium and markedly ameliorate the cardiac function of rats following AMI, especially under 6HRE regulation.

Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus

Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (Ito) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM + TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg-1·day-1). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of Ito was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated Ito reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced Ito of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.

Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus.

Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (Ito) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM + TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg-1·day-1). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of Ito was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated Ito reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced Ito of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.