No abstract

Previously traditional dietary patterns in Japan are no longer typical. The current changing conditions provide an opportunity to examine more closely some important health conditions associated with the changed lifestyle and concentrations of dietary total fat and saturated fatty acid, and the ratio of n-3 to n-6 polyunsaturated fatty acids in the diet.

No abstract

Previous studies have shown that simvastatin, a hydroxymethyl glutaryl coenzyme A reductase inhibitor, reduces plasma cholesterol levels when administered once a day. In the present study, the efficacy and tolerability of a morning and an evening dose were compared. The dosages employed were 2.5 and 5 mg for 12 weeks. This investigation was a double-blind, placebocontrolled study involving 172 hyperlipidemic subjects whose plasma cholesterol levels were higher than 220 mg/dl. During the study period, mean changes in plasma cholesterol level (from baseline) were -11% with the 2.5-mg q.a.m. regimen, -15% with the 2.5-mg q.p.m. regimen, -14% with the 5-mg q.a.m. regimen, and -21% with the 5-mg q.p.m. regimen. Each of these changes was statistically significant when compared with that in the placebo group (/><0.001). In addition, the reduction in cholesterol level was significantly greater with the evening regimen than with the morning regimen for both the 2.5-mg (p<0.05) and the 5-mg (p<0.05) dosages. The changes in triglyceride and high density lipoprotein cholesterol levels in each group were not significantly different from those in the placebo group. There were no differences in the incidence of clinical adverse reactions among the various treatment groups. In conclusion, when simvastatin was administered orally once per day in the evening, it reduced cholesterol levels to a significantly greater degree than when it was given in the morning. (Arteriosclerosis and Thrombosis 1991;ll:816-826)

Rosuvastatin is a novel statin that has been shown to produce large dose-dependent reductions in low-density lipoprotein cholesterol (LDL-C) in Western hypercholesterolemic patients. Rosuvastatin dose response was assessed in a randomized, double-blind phase II trial in which 112 Japanese patients with fasting LDL-C > 160 and < 220 mg/dl and triglycerides < 300 mg/dl received placebo or rosuvastatin 1, 2.5, 5, 10, 20, or 40 mg once daily for 6 weeks. LDL-C change from baseline showed a linear dose response (p < 0.0001 for slope of regression line) over the rosuvastatin dose range, with each doubling of dose producing an additional 5.12% reduction. Mean reductions (least-squares mean percentage change from baseline from ANOVA) in LDL-C were 35.8% to 66.0% and significantly different from placebo at all doses (p < 0.0001). Linear dose response was also observed for total cholesterol (TC) and apolipoprotein (apo) B, but not for triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), or apo A-I or A-II. Mean changes at 6 weeks were - 25.5 to - 45.1% for TC, - 16.0 to - 26.2% for TG, + 7.5 to + 12.8% for HDL-C, - 31.9 to - 57.8% for apo B, + 5.5 to + 10.0% for apo A-I, and + 0.4 to + 8.1% for apo A-II. Rosuvastatin was well tolerated. Although there was some suggestion of increased frequency of treatment-related adverse events at higher doses, there were no clear dose relationships in safety parameters. Only one patient withdrew from the study because of a treatment-related adverse event. No patients had clinically significant elevations in liver transaminases or creatine kinase. Rosuvastatin produces good dose-related reductions in LDL-C and beneficial changes in other lipid fractions in Japanese hypercholesterolemic patients and is well tolerated.