Long-term benefits of high-intensity atorvastatin therapy in Chinese acute coronary syndrome patients undergoing percutaneous coronary intervention: A retrospective study.

There is lack of long-term data on high-intensity statin therapy of Chinese acute coronary syndrome (ACS) patients scheduled to undergo percutaneous coronary intervention (PCI). In this retrospective study, we compared the long-term efficacy and safety of high-intensity and conventional atorvastatin therapy in reducing low-density lipoprotein cholesterol (LDL-C) and plaque size, and improving cardiac function of ACS patients who underwent PCI.We retrospectively analyzed the clinical records of 120 consecutive ACS patients who underwent PCI at our hospital. Group I received a loading dose of atorvastatin (80 mg/day) prior to PCI, followed by a maintenance dose of 40 mg/day for 3 months post-PCI. Group II received a regular dose of atorvastatin (20 mg/day) from the date of admission until 1 year post-PCI. The composite primary efficacy end point was the mean percent change in calculated LDL-C from baseline to week 48 in both groups and percentage of patients achieving the LDL-C target of ≤1.81 mmol/L.Group I had significantly higher mean baseline LDL-C than group II. Moreover, 8.3% of group I patients had an LDL-C ≤1.81 mmol/L versus 43.3% for group II. At week 24, 75.0% and 90.0% of group I and II patients, respectively, achieved the LDL-C target. At week 48, 85.0% and 96.7% of group I and II patients, respectively, achieved the LDL-C target. Additionally, the mean percent changes at week 4 from baseline in LDL-C were -33.6% ±â€Š20.0% for group I versus -12.8% ±â€Š19.6% for group II, and -47.0% ±â€Š25.5% at week 48 for group I versus -36.4% ±â€Š20.2% for group II. Meanwhile, significant reduction in plaque size and marked improvement in cardiac function were seen in patients receiving high-intensity atorvastatin therapy.Compared to conventional therapy, high-intensity statin therapy is more effective in reducing LDL-C and improving cardiac function of ACS patients, with a general benign safety profile over a period of 48 weeks. Our findings support the use of high-intensity statin therapy for Chinese ACS patients to improve the proportion of patients attaining the LDL-C target and reduction in plaque size and improvement cardiac function.

Overexpression of TIMP3 Protects Against Cardiac Ischemia/Reperfusion Injury by Inhibiting Myocardial Apoptosis Through ROS/Mapks Pathway.

BACKGROUND/AIMS: Myocardial ischemia/reperfusion (I/R) injury remains a great challenge in clinical therapy. Tissue inhibitor of metalloproteinases 3 (TIMP3) plays a crucial role in heart physiological and pathophysiological processes. However, the effects of TIMP3 on I/R injury remain unknown. METHODS: C57BL/6 mice were infected with TIMP3 adenovirus by local delivery in myocardium followed by I/R operation or doxorubicin treatment. Neonatal rat cardiomyocytes were pretreated with TIMP3 adenovirus prior to anoxia/reoxygenation (A/R) treatment in vitro. Histology, echocardiography, in vivo phenotypical analysis, flow cytometry and western blotting were used to investigate the altered cardiac function and underlying mechanisms. RESULTS: The results showed that upregulation of TIMP3 in myocardium markedly inhibited myocardial infarct areas and the cardiac dysfunction induced by I/R or by doxorubicin treatment. TUNEL staining revealed that TIMP3 overexpression attenuated I/R-induced myocardial apoptosis, accompanied by decreased Bax/Bcl-2 ratio, Cleaved Caspase-3 and Cleaved Caspase-9 expression. In vitro, A/R-induced cardiomyocyte apoptosis was abrogated by pharmacological inhibition of reactive oxygen species (ROS) production or MAPKs signaling. Attenuation of ROS production reversed A/R-induced MAPKs activation, whereas MAPKs inhibitors showed on effect on ROS production. Furthermore, in vivo or in vitro overexpression of TIMP3 significantly inhibited I/R- or A/R-induced ROS production and MAPKs activation. CONCLUSION: Our findings demonstrate that TIMP3 upregulation protects against cardiac I/R injury through inhibiting myocardial apoptosis. The mechanism may be related to inhibition of ROS-initiated MAPKs pathway. This study suggests that TIMP3 may be a potential therapeutic target for the treatment of I/R injury.