Ronald M. Krauss

Lipoprotein Subclasses in the Monitored Atherosclerosis Regression Study (MARS) Treatment Effects and Relation to Coronary Angiographic Progression

Accumulating evidence suggests that triglyceride-rich lipoproteins contribute to coronary artery disease. Using data from the Monitored Atherosclerosis Regression Study, an angiographic trial of middle-aged men and women randomized to lovastatin or placebo, we investigated relationships between lipoprotein subclasses and progression of coronary artery atherosclerosis. Coronary artery lesion progression was determined by quantitative coronary angiography in low-grade ( < 50% diameter stenosis), high-grade ( > or = 50% diameter stenosis), and all coronary artery lesions in 220 baseline/2-year angiogram pairs. Analytical ultracentrifugation was used to measure lipoprotein masses that were statistically evaluated for treatment group differences and relationships to progression of coronary artery atherosclerosis. All low density lipoprotein (LDL), intermediate density lipoprotein (IDL), and very low density lipoprotein (VLDL) masses were significantly lowered and all high density lipoprotein (HDL) masses were significantly raised with lovastatin therapy. The mass of smallest LDL (Svedberg flotation rate [Sf] 0 to 3), IDL (Sf 12 to 20), all VLDL subclasses (Sf 20 to 60, Sf 60 to 100, and Sf 100 to 400), and peak LDL flotation rate were significantly related to the progression of coronary artery lesions, specifically low-grade lesions. Greater baseline levels of HDL3, were related to a lower likelihood of coronary artery lesion progression. In multivariate analyses, small VLDL (Sf 20 to 60) and HDL3 mass were the most important correlates of coronary artery lesion progression. These results provide further evidence for the importance of triglyceride-rich lipoproteins in the progression of coronary artery disease. In addition, these results present new evidence for the possible protective role of HDL3 in the progression of coronary artery lesions. More specific information on coronary artery lesion progression may be obtained through the study of specific apolipoprotein B-containing lipoproteins.

Alterations in low-density lipoprotein and high-density lipoprotein subclasses among Hispanic women with polycystic ovary syndrome: influence of insulin and genetic factors

OBJECTIVEnTo examine the influence of hyperandrogenism on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclass levels as well as lipoprotein (a) levels in hyperandrogenic women compared with a control group.nnnDESIGNnCase-control study.nnnSETTINGnUniversity-based outpatient clinic.nnnPATIENT(S)nSixteen Hispanic women with polycystic ovary syndrome were compared with 21 controls matched for age, weight, and ethnicity.nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nFasting serum levels of testosterone, insulin, and lipoproteins.nnnRESULT(S)nCompared with controls, women with polycystic ovary syndrome had significantly lower levels of apolipoprotein A-I (95+/-28 mg/dL versus 144+/-42 mg/dL) and HDL2a (30.9%+/-4.4% versus 36.6%+/-5.4%) but significantly higher levels of HDL3c (5.1%+/-2.2% versus 2.4%+/-1.5%). There were no statistically significant differences in LDL subclasses between groups, but there was a high incidence (54%) of the atherogenic lipoprotein phenotype B in this Hispanic population. As a group, Hispanic women with the abnormal B phenotype had significantly higher levels of insulin, HDL, HDL2b, and triglycerides.nnnCONCLUSION(S)nHyperandrogenemia may have an adverse effect on serum lipoproteins through effects on HDL subclasses. Hispanic women may have a higher incidence of the atherogenic lipoprotein phenotype B, which may increase their risk for atherosclerosis.

Subdermal estradiol pellets following hysterectomy and oophorectomy: Effect upon serum estrone, estradiol, luteinizing hormone, follicle-stimulating hormone, corticosteroid binding globulin-binding capacity, testosterone-estradiol binding globulin-binding capacity, lipids, and hot flushes

Subderman estradiol (E2) pellets (25 mg) were inserted immediately after hysterectomy and oophorectomy in 22 menstruating women, ages 29 to 50 years. Serum samples were obtained daily for 7 days, weekly for 4 weeks, and at monthly intervals for 6 months. Although there was significant variation between patients, E2 levels remained within the follicular phase range, averaging 50 to 70 pg/ml for 3 months, and then slowly declining to a mean of 37 pg/ml at 6 months, when new pellets were inserted. Over the entire study period, the E2:estrone (E1) ratio was greater than unity. Subdermal E2 pellets limited the rise in luteinzing hormone (LH) and follicle-stimulating hormone (FSH) after gonadectomy and the levels of LH and FSH 6 months after the insertion of E2 pellets were significantly lower (p < 0.01) than in 20 postmenopausal women who had undergone oophorectomy and whose serum E2 levels were less than 20 pg/ml. Serum corticosteroid binding globulin-binding capacity (CBG-BC) and serum testosterone-estradiol binding globulin-binding capacity (TeBG-BC) remained unchanged with E2 pellets. Although high-density lipoprotein-cholesterol increased significantly (p < 0.05), low-density lipoprotein-cholesterol, total cholesterol, and triglycerides were unaffected, except for a rise in triglycerides in three older women with diabetes mellitus and hypertension. There were no complaints of severe hot flushes. Women who had vasomotor symptaoms had mild or moderate flushes that occurred at 5 or 6 months after replacements of the pellets. Thus, E2 pellets are an effective form of parenteral estrogen replacement therapy and offer both practical and theorteical advantages over other forms of estrogen.

Long-term reversible contraception with levonorgestrel-releasing Silastic rods.

Subcutaneously placed Silastic capsules containing levonorgestrel are effective for 5 years and have a higher continuation rate than other methods of reversible contraception. Six 3 cm capsules are required to achieve satisfactory circulating levels of levonorgestrel. Two 4 cm covered Silastic rods containing levonorgestrel, which are easier to manufacture, insert, and remove than the capsules, produce similar in vitro release rates. This study compared clinical and metabolic effects as well as bleeding patterns in 23 women using either six capsules (n = 11) or two covered rods (n = 12). Serum levels of levonorgestrel, lipids, and lipoproteins as well as frequency of elevated progesterone levels were compared in serum samples obtained before treatment and 1, 6, 12, 18, and 24 months after insertion with the two systems. While bleeding patterns were similar for users of the two systems, rod users had slightly higher serum levels of levonorgestrel and a lower incidence of cycles with elevated progesterone levels. Therefore, rods could replace capsules as a long-term, reversible contraceptive method.

Effects of two low-dose oral contraceptives on serum lipids and lipoproteins: Differential changes in high-density lipoprotein subclasses

Oral contraceptives containing DL-norgestrel or norethindrone with ethinyl estradiol were administered by random assignment to 21 menstruating women, matched for anthropometric measurements, age, diet, alcohol consumption, smoking, and exercise habits. Pretreatment and 7-week treatment blood samples were obtained and assayed for serum cholesterol, triglyceride high-density lipoprotein cholesterol (HDL-C), and total high-density lipoprotein (HDL), HDL2a, HDL2b, and HDL3 subclasses by analytic ultracentrifugation. Subjects using the norethindrone oral contraceptive had a significant increase in HDL-C: baseline, 46 mg/dl; 7 weeks, 51 mg/dl. Values for the subjects using the norgestrel oral contraceptive were not significantly changed: 46 and 44 mg/dl, respectively. Users of the norethindrone oral contraceptive had significant elevations of total HDL and HDL3, while norgestrel oral contraceptive users demonstrated no significant changes. HDL2b increased with the norethindrone oral contraceptive and declined with the norgestrel oral contraceptive. The changes in HDL2b from baseline to treatment were not significant (p greater than 0.05), but the change with the norethindrone oral contraceptive did differ significantly from that with the norgestrel oral contraceptive (p less than 0.02). These changes may indicate oral contraceptive-induced alterations in HDL structure and metabolism that could be related to the risk of development of atherosclerosis.