Atorvastatin protects endothelium by decreasing asymmetric dimethylarginine in dyslipidemia rats.

BACKGROUND: Asymmetric Dimethylarginine (ADMA) is an inhibitor of endogenous nitric oxide synthase, which is the key synthase for nitric oxide (NO) production. Whether statins could protect endothelium by reducing ADMA concentration is unclear, and whether this effect is associated with the dose of statins usage is also needed further studied. METHODS: Dyslipidemia rat model was produced by giving high-fat and high-cholesterol diet for 8 weeks. Thereafter, low-dose (5 mg/kg body weight/day) and high-dose (20 mg/kg body weight/day) atorvastatin were orally prescribed for 4 weeks. Parameters of interest including lipid profiles, inflammatory and oxidative markers, NO production and plasma levels of ADMA and ADMA concentration of myocardium were evaluated. Liver enzymes and creatinine kinase (CK) were also detected for safety concern. RESULTS: At baseline, all parameters were comparable between the sham and the dyslipidemia groups. At 8 weeks of dyslipidemia establishment, as compared to the sham group, body weight and lipid profiles were significantly elevated, and plasma levels of C-reactive protein (CRP), malondialdehyde (MDA) and ADMA were concomitantly increased in accompanying with NO reduction in the dyslipidemia groups. With 4 weeks of atorvastatin therapy, as compared to the control group, lipid disorders and NO production were improved, and plasma levels of CRP, MDA and ADMA were significantly decreased in the high-dose atorvastatin group. ADMA concentration of cardiac tissues was also significantly reduced in the high-dose atorvastatin group. Notably, there was a trend to similar effects which did not reach statistical significance in the low-dose atorvastatin group when compared to the control group. Liver enzyme and CK were comparable after 4 weeks of atorvastatin therapy between groups. CONCLUSION: In rats with dyslipidemia, atorvastatin therapy could reduce plasma level of ADMA and ADMA concentration in cardiac tissues, and these effects are associated with the dose of atorvastatin therapy.

Meta-Analysis Evaluating the Efficacy and Safety of Low-Intensity Warfarin for Patients >65 Years of Age With Non-Valvular Atrial Fibrillation.

Nonvalvular atrial fibrillation (NVAF) is the most common arrhythmia. It is of a high disability and death rate, and seriously affects quality of life. Although New oral anticoagulants (NOACs) are recommended for anticoagulation therapy of atrial fibrillation, they are not widely used for the high cost and limited availability. Warfarin is effective and economical. The risk of thromboembolism and anticoagulant hemorrhage is higher in patients >65 years with NVAF. So, it is of great clinical significance to explore the optimal anticoagulation intensity of warfarin in patients >65 years of China, and other ethnicities. Some studies suggested that low-intensity international normalized ratio (INR) has similar antithrombotic efficacy comparing to standard-intensity INR, whereas bleeding risk was significantly reduced. But others showed conflicting results. We pooled the efficacy and safety data of low- and standard-intensity warfarin therapy for patients over 65 years with NVAF by meta-analysis, as to evaluate optimal INR intensity of warfarin therapy in patients over 65 years. We identified 18 studies providing data of 2105 patients receiving anticoagulation therapy with warfarin. On meta-analysis (odds ratio [OR] [95% confidence interval {CI}]), low-intensity INR conferred similar efficacy to standard intensity INR on all thrombosis (1.28 [0.90 to 1.81]), stroke (1.09 [0.67 to 1.77]), other thromboembolism ([peripheral and pulmonary embolism] 2.26 [0.89 to 5.79]), and all cause death (1.38 [0.94 to 2.02]). Low-intensity INR conferred better safety profile than standard intensity INR in major bleeding (intracranial and gastrointestinal hemorrhage) (0.32 [0.19 to 0.52]), minor bleeding (gum, nasal cavity and conjunctival hemorrhage, skin ecchymosis, hematuria, hemoptysis) (0.30 [0.20 to 0.45]), and all bleeding (0.30 [0.22 to 0.40]). In conclusion, low-intensity INR (1.5 to 2.0) of warfarin therapy is as effective as standard intensity INR (2.0 to 3.0) therapy in reducing thromboembolic risk in patients>65 years with NVAF, and has a safer profile of bleeding.

Effects and potential mechanism of atorvastatin treatment on Lp-PLA2 in rats with dyslipidemia.

INTRODUCTION: The effects of statins on lipoprotein-associated phospholipase A2 (Lp-PLA2) are controversial, and the present study aimed to investigate whether atorvastatin could reduce Lp-PLA2 in rats with dyslipidemia. MATERIAL AND METHODS: A high-fat and high-cholesterol diet was prescribed to produce a dyslipidemia model. Thereafter, low-dose atorvastatin (5 mg/kg/day), high-dose atorvastatin (20 mg/kg/day) or saline (without-treatment group) was prescribed for 14 days. At 6 weeks after dyslipidemia model establishment and 14 days of atorvastatin treatment, fasting venous blood was drawn for biochemical analysis. Between-group differences and Pearson correlation analysis were conducted. RESULTS: Compared to the normal-control group, fasting plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly increased in dyslipidemia groups, while plasma nitric oxide (NO) levels were significantly decreased with attendant elevation of plasma C-reactive protein (CRP) and rho-associated kinase 1 (ROCK1) levels (p < 0.05). At 14 days of atorvastatin treatment, compared to the without-treatment group, plasma levels of TC and LDL-C in the high-dose group were significantly reduced (p < 0.05); and compared to low-dose and without-treatment groups, NO up-regulation (1.8 ±1.1 µmol/l), and CRP (-0.8 ±0.4 ng/ml), ROCK1 (-124 ±65 mmol/l) and Lp-PLA2 (-3.8 ±1.2 ng/ml) reduction were more significant in the high-dose group (p < 0.05). Pearson correlation analysis showed that TC (r = 0.365), LDL-C (r = 0.472), CRP (r = 0.501) and ROCK1 (r = 0.675) were positively correlated with Lp-PLA2, while NO (r = -0.378) and atorvastatin (r = -0.511) were negatively correlated with Lp-PLA2. CONCLUSIONS: Atorvastatin treatment is beneficial for reducing the Lp-PLA2 level in rats with dyslipidemia, which may be related to reduced ROCK1 expression in a dose-dependent manner.