OBJECTIVES: The DIrect Statin COmparison of LDL-C Values: an Evaluation of Rosuvastatin therapY (DISCOVERY)-Asia study is one of nine independently powered studies assessing the efficacy of starting doses of statins in achieving target lipid levels in different countries worldwide. DISCOVERY-Asia was a 12-week, randomised, open-label, parallel-group study conducted in China, Hong Kong, Korea, Malaysia, Taiwan, and Thailand.
RESULTS: A total of 1482 adults with primary hypercholesterolaemia and high cardiovascular risk (> 20%/10 years, type 2 diabetes, or a history of coronary heart disease) were randomised in a 2 : 1 ratio to receive rosuvastatin 10 mg once daily (o.d.) or atorvastatin 10 mg o.d. The percentage of patients achieving the 1998 European Joint Task Force low-density lipoprotein cholesterol (LDL-C) goal of < 3.0 mmol/L at 12 weeks was significantly higher in the rosuvastatin group (n = 950) compared with the atorvastatin group (n = 471) (79.5 vs. 69.4%, respectively; p < 0.0001). Similar results were observed for 1998 European goals for total cholesterol (TC), and the 2003 European goals for LDL-C and TC. LDL-C and TC levels were reduced significantly more with rosuvastatin compared with atorvastatin. Both drugs were well-tolerated and the incidence and type of adverse events were similar in each group.
TRIALS REGISTRATION: The trial registry summary is available at http://www.clinicaltrials.gov/; ClinicalTrials.gov Identifier: NCT00241488
CONCLUSIONS: This 12-week study showed that the starting dose of rosuvastatin 10 mg o.d. was significantly more effective than the starting dose of natorvastatin 10 mg o.d. at enabling patients with primary hypercholesterolaemia to achieve European goals for LDL-C and TC in a largely Asian population in real-life clinical practice. The safety profile of rosuvastatin 10 mg is similar to that of atorvastatin 10 mg in the Asian population studied here, and is consistent with the known safety profile of rosuvastatin in the white population.
METHODS: cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles were synthesized by a chemical method. Dynamic light scattering (DLS) was utilized to detect the size distribution and polydispersity index (PDI) of the nanoparticles. The safety of the nanoparticles was detected by CCK8 in vitro and HE staining and kidney function in vivo. Cell apoptosis was detected by flow cytometry detection and TUNEL staining. Oxidative stress responses (ROS, SOD, MDA, and NOX levels) were tested via a DCFH-DA assay and commercial kits. Immunofluorescence and phagocytosis experiments were used to detect the targeting of nanoparticles. Magnetic resonance imaging (MRI) was used to detect the imaging performance of cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles. Using western blotting, the expression changes in LXRα and ABCA1 were identified.
RESULTS: cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles were successfully established, with a particle size of approximately 150 nm and PDI less than 0.3, and showed high safety both in vitro and in vivo. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles showed good targeting properties and better MRI imaging performance in AS. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles showed better antioxidative capacities, MRI imaging performance, and diagnostic and therapeutic effects on AS by regulating the expression of LXRα and ABCA1.
CONCLUSION: In the present study, cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles with high safety and the capacity to target vulnerable plaques of AS were successfully established. They showed better performance on MRI images and treatment effects on AS by promoting cholesterol efflux through the regulation of ABCA1. These findings might address the problems of off-target effects and side effects of nanoparticle-mediated drug delivery, which will enhance the efficiency of AS treatment and provide new ideas for the clinical treatment of AS.
Methods: Mice (n = 48) were fed high-fat diet (HFD) for 25 weeks to induce obesity, after which half were maintained on HFD and half switched to low-fat diet (LFD)while they were given normal water (H2O) or 0.1% (w/v) SCE in water at week 0-4 which was increased to 1% (w/v) at week 5-9. Effects of treatment with SCE were compared between HFDH2O, HFDSCE, LFDH2O and LFDSCE groups. Respiratory exchange ratios (RER) were measured at weeks 0, 5 and 10. Food, water intake and body weight were measured weekly. Plasma lipid profile and organ weights were determined at week 10.
Results: SCE had significantly reduced RER at week 9 (P = 0.011). Food intake, body weight, and abdominal adipose tissue weight were not altered by SCE at weeks 5 and 10. However, significant increase in plasma and liver cholesterol (P < 0.050) was observed.
Conclusion: Our findings suggest that SCE induced lipolysis and body fat oxidation and increased energy expenditure. Further studies in other animal models should be done to confirm the consistency of these results.
MATERIALS AND METHODS: This was an investigator-initiated, single-center, randomized, controlled, clinical trial in patients with T2DM and DKD, comparing 12-weeks of low carbohydrate diet (<20g daily intake) versus standard low protein (0.8g/kg/day) and low salt diet. Patients in the VLCBD group underwent 2-weekly monitoring including their 3-day food diaries. In addition, Dual-energy x-ray absorptiometry (DEXA) was performed to estimate body fat percentages.
RESULTS: The study population (n = 30) had a median age of 57 years old and a BMI of 30.68kg/m2. Both groups showed similar total calorie intake, i.e. 739.33 (IQR288.48) vs 789.92 (IQR522.4) kcal, by the end of the study. The VLCBD group showed significantly lower daily carbohydrate intake 27 (IQR25) g vs 89.33 (IQR77.4) g, p<0.001, significantly higher protein intake per day 44.08 (IQR21.98) g vs 29.63 (IQR16.35) g, p<0.05 and no difference in in daily fat intake. Both groups showed no worsening of serum creatinine at study end, with consistent declines in HbA1c (1.3(1.1) vs 0.7(1.25) %) and fasting blood glucose (1.5(3.37) vs 1.3(5.7) mmol/L). The VLCBD group showed significant reductions in total daily insulin dose (39(22) vs 0 IU, p<0.001), increased LDL-C and HDL-C, decline in IL-6 levels; with contrasting results in the control group. This was associated with significant weight reduction (-4.0(3.9) vs 0.2(4.2) kg, p = <0.001) and improvements in body fat percentages. WC was significantly reduced in the VLCBD group, even after adjustments to age, HbA1c, weight and creatinine changes. Both dietary interventions were well received with no reported adverse events.
CONCLUSION: This study demonstrated that dietary intervention of very low carbohydrate diet in patients with underlying diabetic kidney disease was safe and associated with significant improvements in glycemic control, anthropometric measurements including weight, abdominal adiposity and IL-6. Renal outcomes remained unchanged. These findings would strengthen the importance of this dietary intervention as part of the management of patients with diabetic kidney disease.
METHODS: Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed.
RESULTS: A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the double-placebo group (hazard ratio, 0.69; 95% CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups.
CONCLUSIONS: Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk. (Funded by the Wellcome Trust and others; TIPS-3 ClinicalTrials.gov number, NCT01646437.).