Effect of Tongguan Capsules () on Restenosis after Coronary Stent Implantation: Study Protocol for A Randomized Controlled Trial.

BACKGROUND: Although percutaneous coronary intervention (PCI) had become widely employed therapeutic procedure for coronary artery disease, stent restenosis limited the benefits of this revascularization and the question how to prevent such events remained unresolved. While numerous empirical observations suggested Tongguan Capsules (), a patented Chinese Medicine, could decrease frequency and duration of angina pectoris attacks, evidence supporting its efficacy on restenosis remained inadequate. OBJECTIVE: This trial was designed to determine whether Tongguan Capsules would reduce restenosis rate in patients after successful stent implantation. METHODS: Approximately 400 patients undergoing percutaneous coronary stent deployment were enrolled and randomized to control group or Tongguan Capsules (4.5 g/d) for 3 months. All patients received standard anti-platelet, anti-coagulation and lipid-decreasing treatments, concurrently. The primary clinical endpoint was the 12-month incidence of the major adverse cardiovascular events (defined as cardiac death, myocardial infarction, and recurrence of symptoms requiring additional revascularization). The angiographic end point was restenosis rate at 6 months. CONCLUSION: This study would provide important evidence for the use of Tongguan Capsules in patients after stent implantation in combination with routine therapies, which may significantly reduce incidence of the restenosis so as to potentially improve the clinical outcomes. (registration number: ChiCTR-TRC- ChiCTR-IIR-17011407).

Cardiac CaMKIIδ and Wenxin Keli Prevents Ang II-Induced Cardiomyocyte Hypertrophy by Modulating CnA-NFATc4 and Inflammatory Signaling Pathways in H9c2 Cells.

Previous studies have demonstrated that calcium-/calmodulin-dependent protein kinase II (CaMKII) and calcineurin A-nuclear factor of activated T-cell (CnA-NFAT) signaling pathways play key roles in cardiac hypertrophy (CH). However, the interaction between CaMKII and CnA-NFAT signaling remains unclear. H9c2 cells were cultured and treated with angiotensin II (Ang II) with or without silenced CaMKIIδ (siCaMKII) and cyclosporine A (CsA, a calcineurin inhibitor) and subsequently treated with Wenxin Keli (WXKL). Patch clamp recording was conducted to assess L-type Ca2+ current (ICa-L), and the expression of proteins involved in signaling pathways was measured by western blotting. Myocardial cytoskeletal protein and nuclear translocation of target proteins were assessed by immunofluorescence. The results indicated that siCaMKII suppressed Ang II-induced CH, as evidenced by reduced cell surface area and ICa-L. Notably, siCaMKII inhibited Ang II-induced activation of CnA and NFATc4 nuclear transfer. Inflammatory signaling was inhibited by siCaMKII and WXKL. Interestingly, CsA inhibited CnA-NFAT pathway expression but activated CaMKII signaling. In conclusion, siCaMKII may improve CH, possibly by blocking CnA-NFAT and MyD88 signaling, and WXKL has a similar effect. These data suggest that inhibiting CaMKII, but not CnA, may be a promising approach to attenuate CH and arrhythmia progression.

Familial hypercholesterolemia in very young myocardial infarction.

Familial hypercholesterolemia (FH) is one of the most common causes of premature myocardial infarction (MI). However, The patterns of FH remained unrecognized in clinical care, especially in very young patients (VYPs, ≤35 years) with MI. The present study enrolled a total of 1,093 VYPs (≤35 years) presenting a first MI. Clinical diagnosis of FH was made using Dutch Lipid Clinic Network criteria. Coronary severity was assessed by Gensini score (GS). Patients were followed for a median of 40-months with cardiac death, stroke, MI, post-discharge revascularization or unstable angina as primary endpoints. The detected rates of definite/probable FH were 6.5%. The prevalence reached up to 10.3% in patients ≤25 years. The FH had similar levels of comorbidities but was younger, more likely to be very high risk (VHR) and had higher GS (p < 0.05) than unlikely FH. Notably, the FH on prior lipid-lowering medication presented a lower GS compared to those untreated. Differences in event rates were similar in FH as unlikely FH (11.8% vs. 8.1%, adjusted hazard ratio 1.35 [0.64-2.86], p = 0.434) but patients on treatment improved outcome (6.5% vs. 10.5%, adjusted hazard ratio 0.35[0.13-0.95], p = 0.039). The early identification and treatment might be critical to reduce cardiovascular risk in VYPs with MI.

Predictive value of big endothelin-1 on outcomes in patients with myocardial infarction younger than 35 years old.

AIM: The predictive value of big endothelin-1 (ET-1) for cardiovascular outcomes in myocardial infarction (MI) patients younger than 35 years old has not been characterized. METHODS: A total of 565 consecutive MI patients younger than 35 years old were studied and followed up for 37.78 ± 24.9 months. RESULTS: Multivariable Cox regression analysis showed that big ET-1 was positively correlated with major adverse cardiovascular events [MACEs] (odds ratio: 3; 95% CI: 1.92-4.68; p < 0.001). The area under receiver operating characteristics curve showing the predictive value of big ET-1 on MACEs was 0.67. CONCLUSION: The study first demonstrated that big ET-1 was an independent predictor for MACEs in MI patients younger than 35 years old.

Association between fibrinogen level and the severity of coronary stenosis in 418 male patients with myocardial infarction younger than 35 years old.

Fibrinogen (Fib) is a useful marker for predicting the severity of coronary artery disease (CAD) in adult population. However, whether Fib can be a predictor for the presence and severity of CAD in very young MI patients (≤35 years old) remains to be determined. A total of 418 males from 61,863 patients with MI who were under 35 years old were sequentially recruited in our study. The patients were divided into two main groups and three subgroups according to coronary angiograph and Gensini score (GS) system: no coronary artery stenosis (group A), the results of the coronary artery stenosis (group B); low GS, intermediate GS and high GS. Data indicated that Fib, body mass index, current smoking, white blood cell count (WBCC) and GS were significantly higher in group B than those in group A (all P < 0.01). Moreover, there were significant differences in Fib, mean age, diabetes mellitus, family history of CAD, WBCC, left ventricular ejection fraction, and GS between high GS and low GS subgroups (all P < 0.01). A positive correlation between Fib levels and GS was found (r = 0.242, p < 0.001). Receiver operating characteristics curve analysis demonstrated that the best cut-off level of Fib predicting the severity of coronary stenosis was 3.475g/L (sensitivity 64%; specificity 70%) and the area under the curve was 0.656. Fib was also independently associated with high GS (OR=2.173, 95%CI 1.011-4.670, P = 0.047) after adjusting for potential confounders. In conclusion, Fib is significantly related to the presence and severity of coronary stenosis in male patients with MI under 35 years old.

Relation of N-terminal pro-brain natriuretic peptide and new-onset atrial fibrillation in patients with acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: Several observational studies evaluated the associations of baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) and new-onset atrial fibrillation (AF) in patients with acute coronary syndrome (ACS), but the results were contradictory. METHODS: Electronic bibliographic databases were searched from inception to May 2015, and the results reviewed by two independent reviewers. Pooled standardized mean difference (SMD) and 95% confidence interval (CI) were calculated to assess associations between NT-proBNP levels and new-onset AF in patients with ACS. We performed sensitivity analyses to explore the potential sources of heterogeneity and estimated publication biases. RESULTS: Six papers, including 5861 patients (438 with AF and 5423 without AF) with ACS were analyzed. Overall, the NT-proBNP levels were higher in patients with new-onset AF than controls without AF. The SMD of the NT-proBNP levels between the patients with and those without AF was 0.53 units (95% CI 0.37-0.70), test for overall effect z-score =6.30 (p < 0.00001). The heterogeneity test showed that there were moderate differences between individual studies (p = 0.02; I(2) =( )62%). Further analysis revealed that differences of ethnic groups and the sample size of studies possibly account for this heterogeneity. CONCLUSIONS: In spite of moderate heterogeneity across the enrolled studies, our meta-analysis suggests that increased NT-proBNP levels are associated with greater risk of new-onset AF with ACS, which indicates that NT-proBNP levels may be a useful biomarker in predicting new-onset AF in patients with ACS.