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Contains fulltext : 48945.pdf (Publisher’s version ) (Closed access) AIMS: The efficacy and safety of rosuvastatin, atorvastatin, and placebo were compared in patients with the metabolic syndrome. METHODS AND RESULTS: Patients with the metabolic syndrome with low-density lipoprotein cholesterol (LDL-C) > or =3.36 mmol/L (130 mg/dL) and multiple risk factors conferring a 10-year coronary heart disease risk score of >10% were randomized (2:2:1) to receive rosuvastatin 10 mg, atorvastatin 10 mg, or placebo for 6 weeks. Subsequently, the rosuvastatin 10 mg and placebo groups received rosuvastatin 20 mg and the atorvastatin 10 mg group received atorvastatin 20 mg for 6 weeks. LDL-C was reduced significantly more in patients receiving rosuvastatin 10 mg when compared with those receiving atorvastatin 10 mg at 6 weeks [intention-to-treat (ITT) population by randomized treatment: 41.7 vs. 35.7%, P < 0.001; ITT population by as-allocated treatment: 42.7 vs. 36.6%, P < 0.001]. Significant LDL-C reductions were also observed in patients receiving rosuvastatin when compared with those receiving atorvastatin at 12 weeks (48.9 vs. 42.5%, P < 0.001). More patients achieved LDL-C goals with rosuvastatin when compared with atorvastatin. Rosuvastatin increased high-density lipoprotein cholesterol significantly more than atorvastatin. Treatments were well tolerated. CONCLUSION: At equivalent doses, rosuvastatin had a significantly greater effect than atorvastatin in lowering LDL-C and improving the lipid profile and was well tolerated in patients with the metabolic syndrome.

Low-density-lipoprotein (LDL) oxidation may provide the crucial link between plasma LDL and atherosclerotic-lesion formation. Oxidation can be induced in vitro by incubating LDL with cells or metal ions and can be measured by continuously monitoring conjugated-diene absorbance at 234 nm. Measurement of LDL oxidizability was improved by performing the assay with 0.05 g of LDL-protein per liter of phosphate buffer containing 1 mumol of EDTA, by initiating oxidation by adding CuCl2 (5 mumol/L) at 30 degrees C, and by using a short-run ultracentrifugation method for isolating LDL, which reduced the time needed for obtaining purified LDL and thus reduced in vitro oxidation. LDL apolipoprotein analysis and oxidizability determination showed that this method is better than the longer sequential-isolation procedure. Adding butylated hydroxytoluene (BHT) to plasma as an antioxidant unpredictably increased the LDL oxidation lag time, making BHT unsuitable as an antioxidant. Adding EDTA appeared to be sufficient to prevent in vitro oxidation. Additionally, the diene production correlated highly with the concentration of thiobarbituric acid-reactive substances (r = 0.97). No relation between the vitamin E content of LDL and the oxidation lag time was found.

We evaluated the density-gradient ultracentrifugation method in a swinging-bucket rotor (Anal Biochem 111, 149-157, 1981) in a slightly modified version for isolation and determination of high-density lipoprotein (HDL) subfractions. We prestained the serum with Coomassie Brilliant Blue R, which did not change the hydrated densities of the lipoproteins, and after only 2.2 X 10(8) gav . min obtained an equilibrium distribution of the lipoproteins along the gradient. The density distribution of the HDL of 120 sera obtained from apparently healthy persons and from patients with different types of hyperlipoproteinemia was bimodal. The HDL2 could be isolated in the density range 1.072-1.098 kg/L and the HDL3 at 1.100-1.176 kg/L, the latter fraction being more heterogeneous. At a solvent density of 1.100 we obtained similar results for HDL2-and HDL3-cholesterol by ultracentrifugation in two different fixed-angle rotors with tube angles of 15 degrees or 35 degrees. Independent of the rotor and the ultracentrifugation technique, subfractionation at d = 1.100 resulted in more distinct stained entities than ultracentrifugation at d = 1.125. In the swinging-bucket rotor procedure, interference by sinking pre-beta-lipoproteins was minimized because, having hydrated densities between 1.058 and 1.075, they could be removed without aspirating the HDL2. The method is both accurate and precise. For HDL2- and HDL3-cholesterol determined in a thawed frozen serum pool, CVs were 8.8 and 6.3%, respectively (n = 18).