Objective: Cardiovascular disease is the leading cause of mortality in women in the United States. Aggressive treatment of modifiable risk factors (e.g., hypercholesterolemia) is essential in reducing disease burden. Despite guidelines recommending the use of statin treatment in hypercholesterolemic women, this patient group is often undertreated. This subgroup analysis of the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial examines the effects of statin therapy in hypercholesterolemic women. Methods: As part of the STELLAR trial, 1,146 women with elevated low-density lipoprotein cholesterol (LDL-C 160 and <250mg/dL) and triglycerides <400mg/dL were randomized to rosuvastatin 10-40mg, atorvastatin 10-80mg, simvastatin 10-80mg, or pravastatin 10-40mg for 6 weeks. Results: LDL-C reduction with rosuvastatin 10mg, atorvastatin 10mg, simvastatin 20mg, and pravastatin 40mg was 49%, 39%, 37%, and 30%, respectively, after 6 weeks. High-intensity statins (rosuvastatin 20-40mg and atorvastatin 40-80mg) reduced LDL-C to the greatest extent: 53% with rosuvastatin 20mg, 57% with rosuvastatin 40mg, 47% with atorvastatin 40mg, and 51% with atorvastatin 80mg. Similar results were observed for non-high-density lipoprotein cholesterol (non-HDL-C). Increases in HDL-C were greater with rosuvastatin across doses than with other statins. All treatments were well tolerated, with similar safety profiles across dose ranges. Conclusions: Statin therapies in the STELLAR trial led to reductions in LDL-C, non-HDL-C, and triglycerides and increases in HDL-C among hypercholesterolemic women, with rosuvastatin providing the greatest reductions in LDL-C and non-HDL-C.

Individuals with abnormal blood lipids and lipoproteins are at increased risk for cardiovascular disease. With the development of effective dietary, behavioral, and pharmaceutical treatments to optimize blood lipoproteins, accurate clinical assessment of blood lipids and lipoproteins are essential for patient management and research. This article discusses the use of a variety of lipid analyses currently available. The use of traditional lipoprotein measurements, including Friedewald calculation of low-density lipoprotein (LDL) cholesterol and ultracentrifugation methods to measure blood lipoproteins, are discussed. Newer analytic techniques, including the vertical analytic profile, nuclear magnetic resonance, direct LDL measurement, LDL size determination, and triglyceride-rich lipoprotein remnants, are also described. Despite the development of a number of lipid and lipoprotein assays, lipoprotein analysis with a Friedewald- calculated LDL measurement remains the lipoprotein analysis performed in approximately 93% of clinical laboratories. It remains to be determined if the alternative lipid and lipoprotein assays currently available will become more widely utilized in the future.

The objective of this study was to determine the metabolic effects of estrogen replacement therapy in postmenopausal women with type 2 diabetes. Twenty-five postmenopausal, type 2 diabetic women completed a randomized, blinded, cross-over trial of conjugated equine estrogen, 0.625 mg/day, vs. placebo for 8 weeks, separated by a 4-week washout period. When compared with 8 weeks of placebo, estrogen reduced fasting serum glucose (7.2 ± 0.3 vs. 8.4 ± 0.4 mmol/L, P = 0.0003), glycated hemoglobin (8.7 ± 0.4% vs. 9.3 ± 0.4%, P = 0.04), total cholesterol (5.27 ± 0.20 vs. 5.50 ± 0.21 mmol/L, P = 0.04), low-density lipoprotein cholesterol (2.47 ± 0.13 vs. 2.69 ± 0.14 mmol/L, P = 0.02), serum apolipoprotein B (114± 6 vs. 121 ± 5 mg/dL, P = 0.03), and postprandial glucose area under the curve (by 12%, P = 0.015). Estrogen replacement therapy also increased high-density lipoprotein (HDL) cholesterol (1.27 ± 0.08 vs. 1.1 ± 0.07 mmol/L, P = 0.0002), high-density lipoprotein2 cholesterol (0.41± 0.04 vs. 0.30 ± 0.03 mmol/L, P = 0.0001), and fasting triglyceride (2.17 ± 0.21 vs. 1.94 ± 0.16 mg/dL , P= 0.02) concentrations but not postprandial triglyceride area under the curve (P = not significant). We conclude that estrogen replacement therapy improves glycemic control, blood lipoproteins, and apolipoprotein B concentrations while modestly increasing triglyceride levels in postmenopausal, type 2 diabetic women.

Information on genetic susceptibility to Graves' disease in African Americans is limited. We studied DRB1, DQB1, DRB3 subtypes, DQA1*0501, DQA1*0201, and CTLA-4 polymorphisms in 49 African American patients with adult onset Graves' disease and 47 racially-matched controls using PCR-based sequence-specific priming methods. There were no significant differences in DRB1 or DQB1 allelic frequencies or CTLA-4 polymorphisms between patients and controls. However, we found that the frequency of DRB3 was significantly increased in the patients (75.5% vs. 57.4%, P = 0.006, X2 = 3.52), especially for the DRB3*0202 subtype (53.1% vs. 23.4, P = 0.003, X2 = 8.91). In this one respect, the finding was in concordance with our previous observations in Caucasian patients with adult-onset Graves' disease. In addition, whereas the frequency of DQA1*0501 was increased (P = 0.018, X2 = 5.63) in our patients, the haplotype of DRB3/DQA1*0501, or DRB3*0202/DQA1*0501 was found to be more strongly associated (P = 0.008, X2 = 7.0; P = 0.0008, X2 = 11.34, respectively). These data suggest that DRB3*0202, particularly when found with DQA1*0501 in a haplotype is a susceptible gene(s) for Graves' disease in adult African Americans. Considering these data with those in Caucasian patients, our results would suggest that the primary Graves susceptible locus is likely DRB3 and not DRB1.

New Zealand White rabbits were made hypercholesterolemic by feeding a high cholesterol diet (10 g/kg diet) with or without added antioxidants. The antioxidants used were either probucol (10 g/kg) or vitamin E (10 g/kg) plus vitamin C (0.6 g/kg). Serum cholesterol concentrations were monitored as a function of time. At the end of 10 wk, serum and lipoprotein vitamin E concentrations, the extent of oxidation of lipoprotein fractions (thiobarbituric acid reacting sub stances), the susceptibility of lipoprotein to oxidation in vitro (conjugated diene formation) and the extent of atherosclerosis (aortic area stained by Sudan IV and plaque thickness) were measured. Rabbits fed diets sup plemented with vitamins E and C had markedly higher serum vitamin E concentrations, marked vitamin E en richment in all lipoprotein fractions, less oxidation in VLDL and LDL and enhanced resistance of LDL to further in vitro oxidation, but did not have significantly less aortic atherosclerosis. Rabbits given supplemental probucol likewise exhibited reduced oxidation of lipoproteins. However, aortic atherosclerosis in these animals was significantly lower, as were serum cholesterol concentrations. Inhibition of lipoprotein oxi dation itself was not sufficient to reduce atherosclerosis in cholesterol-fed New Zealand White rabbits. J. Nutr. 124: 2123-2130, 1994.