Oral contraceptive and postmenopausal estrogen effects on lipoprotein triglyceride and cholesterol in an adult female population: relationships to estrogen and progestin potency.

PIP: A study of the prevalence of hyperlipidemia has been conducted among female telephone company employees using oral contraceptives (OCs) or estrogenic hormones. This paper relates hormone formulation and estrogen/progestin potency to striglyceride and cholesterol concentrations in total plasma and lipoprotein fractions and relative lipid composition. Changes in these lipid parameters are of interest because they may predict atherosclerosis risk. Results in 148 hormone users are compared with those in 306 nonhormone users. All data are adjusted for the effects of age, relative body weight, cigarette smoking, and alcohol intake. Triglyceride concentrations in whole plasma, very low density lipoprotein (VLDL), and high density lipoprotein (HDL) are elevated 1.5-2.5 fold with increasing estrogen potency. Low density lipoprotein (LDL) triglyceride concentration is elevated to a similar degree among OC users regardless of estrogen potency, but there is no significant effect of postmenopausal estrogen use on LDL triglyceride concentrations. The LDL cholesterol concentration shows an increasing trend with increasing estrogen potency in a random sample of OC-treated women, but is slightly lower than control in postmenopausal women treated with estrogen alone. The HDL cholesterol concentration in plasma is highest with hormones having the greatest estrogen potency and lowest with those having the greatest progestin potency. The VLDL cholesterol to triglyceride ratio adjusted for triglyceride concentration is significantly increased with the use of Ovral, a progestin-predominant contraceptive preparation. The LDL cholesterol to triglyceride ratio is reduced with the use of all OCs examined, except for Ovral, where the ratio is above average. The HDL cholesterol to triglyceride ratio is reduced for all combination OCs examined. The use of a sequential OC or postmenopausal estrogens is not associated with a significant alteration in the cholesterol to triglyceride ratio in any lipoprotein fraction. Knowledge of estrogen and progestin potency and kind of progestin are important in predicting the effect of OCs on plasma and lipoprotein lipids. On the basis of observed differences in lipoprotein lipid concentrations and relationships, the potential arteriosclerotic risk from sex hormones may vary among OC formulations.^ieng

How blind was the patient blind in AMIS?

The Aspirin Myocardial Infarction Study (AMIS) was a double-blind placebo-controlled trial to test the effect of aspirin on the survival of 4524 people who had experienced a prior heart attack. Shortly before their closeout visits, 400 of the participants were randomly selected to be interviewed concerning their perceptions of their treatment assignments; 380 were actually interviewed. A bare majority (52)% correctly identified their study therapy, 28% mistakenly named the alternative treatment, 13% declined to guess, and 7% specified extraneous substances. According to the proposed formula for evaluating the patient blind, only 24% of the sample made "informed" guesses regarding their therapy, while the remainder guessed in an uninformed way or not at all. Those who tested their capsules (usually be taste) showed proportionately more correct responses than the nontesters. Correctness also varied with the reasons for the subjects' guesses (e.g., side effects). Among the sample as a whole, most people were only moderately or less than moderately certain their guess was correct. Even among those who were in fact correct, only 18% were absolutely certain of their choice.

Distribution of lipoproteins triglyceride and lipoprotein cholesterol in an adult population by age, sex, and hormone use- The Pacific Northwest Bell Telephone Company health survey.

This report describes the distribution of lipoprotein triglyceride and lipoprotein cholesterol in employees of the Pacific Northwest Bell Telephone Company. Means, medians, and selected percentiles are presented for very low, low, and high density lipoproteins (VLDL, LDL, and HDL, respectively) in 606 randomly selected white subjects aged 20-59. Results are specific for age decade, sex, and female sex hormone usage. Women who use sex hormones have significantly higher concentrations of triglycerides in all of the fractions across all age decades from 20 to 59 than do women not taking hormones. The average VLDL, LDL, and HDL triglyceride levels in women taking hormones are 69, 25 and 18 mg/dl which are considerably higher than the corresponding averages of 44, 17 and 12 mg/dl noted in women not taking hormones. Men have the highest average VLDL triglyceride value (85 mg/dl) but their average triglyceride concentrations in the LDL and HDL fractions (18 and 12 mg/dl) approximate those of women not taking hormones. This study in a well-defined population provides references standards for lipoprotein triglyceride concentrations. These results can be used to evaluate the effect of sex hormone treatment on the lipoprotein triglyceride content in VLDL, LDL and HDL, and to assess triglyceride content as a potential risk factor in men and older women.

PIP: A study of lipoprotein triglyceride and lipoprotein cholesterol distribution was done between 1973-76 on a randomly selected group of 606 white male and female employees, aged 20-59, of the Pacific Northwest Bell Telephone Company. Data obtained were used to ascertain whether triglyceride content of lipoprotein differs in men and women by observing mean, standard and percentile distribution of VLDL, LDL, and HDL (very low, low, and high density lipoprotein). A high proportion of women, i.e. 50% in the age group 20-29, and 50-59, reported current use of some form of exogenous sex hormone preparation. The average VLDL, LDL, and HDL triglyceride level in women taking hormones were 69, 25, and 18 mg/dl, considerably higher than the corresponding averages of 44, 17, and 12 mg/dl observed in women not taking hormones. For VLDL triglyceride, the youngest and oldest male groups had lower average levels than females in the same age taking hormones; in the middle-age group the levels were the same among men and women. For VLDL cholesterol, the 20-29 year old male and female hormone users had similar concentration levels, but male values were higher in each of the remaining age strata. These data confirm the fact that lipoprotein triglyceride rise is associated with the type of oral contraceptives used in the U.S., and with postmenopausal treatment as well.

Relationships of gender, sex hormone use, and age with lipoprotein cholesterol/triglyceride ratios in an adult population. The Pacific Northwest Bell Telephone Company health survey.

UNLABELLED: Effects of gender, sex hormone use, and age on lipoproteins composition have been evaluated in 603 Caucasian subjects, ages 20-59, randomly selected from employees participating in the Pacific Northwest Bell Telephone Company Health Survey. Lipoprotein composition in this analysis is defined as the cholesterol to triglyceride (C/TG) ratio in each lipoprotein fraction. The lipoprotein C/TG ratio is inversely related to the lipoprotein triglyceride concentrations in VLDL, LDL and HDL; the ratio falling in each instance as lipoprotein triglyceride concentration increases. Plots of this relationship are virtually superimposable among women hormone users and nonusers and men in VLDL and HDL and between men and nonhormone taking women in LDL. A consistently lower C/TG ratio is observed in LDL for hormone-treated women compared to the other 2 groups. Age in these analysis is without effect. CONCLUSIONS: We hypothesize that a lower LDL (C/TG) ratio is hormone-treated women may render the lipoprotein less crystalline or smectic and potentially less atherogenic. No such difference exists in the lipoprotein C/TG ratio between men and nonhormone-treated women and therefore cannot explain the observed difference in atherosclerosis sick. Nonetheless, the C/TG ratios may predict atherosclerosis if the ratio is high in VLDL or in LDL. However, the significance of the HLD (C/TG) ratio remains to be established.

Quantitation of apolipoprotein A-I of human plasma high density lipoprotein.

High density lipoproteins (HDL) may be controlled via their major apolipoprotein, A-I. To study this apolipoprotein, a simple, precise, and accurate immunodiffusion assay for A-I was developed and applied in a sample of Bell Telephone Company employees. A-I showed a slight increase with age in men (r=0.11, n=263) and women (r=0.15, n=257). A-I correlated closely with HDL cholesterol (r=0.72). It was weakly related to total triglyceride in women (r=0.24) but was inversely related in men (r=-0.17). Women on estrogen had the highest A-I levels (149 mg/dl +/- 26, x +/- S.D., n=29, p is less than 0.05), followed by women on combination oral contraceptives (141 +/- 26, n=80) whereas women on no medication had lower levels (129 +/- 25, n=99, p is less than 0.01) but men had the lowest levels (120 +/- 20, p is less than 0.01) In a separate group of 14 women given estrogen for 2 wks (1 mug/kg/day), A-I increased by 24%. Thus A-I is increased by exogenous and, most likely, endogenous estrogen, Among hyperlipidemic referral subjects, those with hypercholesterolemia (n=43) and hypertriglyceridemic women (n=33) had normal A-I levels. Among hypertriglyceridemic men both A-I and HDL cholesterol values were decreased (115 +/- 20, p is less than 0.01 and 37 +/- 3, p is less than 0.01, respectively, n=68) but were significantly lower among a group of myocardial infarction survivors (107 +/- 16, p is less than 0.01, and 27 +/- 6, p is less than 0.01, respectively, n=24). High density lipoprotein levels and the content of cholesterol in HDL associated with A-I appear to be decreased in coronary heart disease.

Lipid and lipoprotein triglyceride and cholesterol interrelationships: effects of sex, hormone use, and hyperlipidemia.

The interrelationships of lipid and lipoprotein cholesterol and triglyceride concentrations in normolipidemic and hyperlipidemic employees of the Pacific Northwest Bell Telephone Company were examined bivariately using correlation analysis and multivariately by factor analysis. Application of the latter resulted in the identification of three distinct lipoprotein lipid clusters, which succinctly describes their metabolic relationships. Among normolipidemic subjects, the interrelationships were found to be similar in male and female subjects, but hormone use by women considerably altered interrelationships that involved high-density lipoprotein cholesterol (HDL-C) and triglyceride. Among hyperlipidemic subjects, we found that elevation in cholesterol level alone rarely altered relationships, but elevation in triglyceride level either alone or in conjunction with an elevation in cholesterol concentration was associated with substantial changes in relationships involving the low-density lipoprotein (LDL) fraction. In many instances, positive relationships between LDL cholesterol (LDL-C) and other lipoprotein lipids became inverse in the presence of triglyceride elevation. We conclude that hormone use by women and hypertriglyceridemia with or without an elevation in cholesterol level clearly alter lipoprotein relationships, whereas pure hypercholesterolemia does not. These alterations provide a basis for investigating pathophysiologic mechanisms in hypertriglyceridemia.

PIP: The interrelationships between lipid and lipoprotein cholesterol and triglyceride concentrations in normolipidemic and hyperlipidemic employees of the Pacific Northwest Bell Telephone Company were examined bivariately using correlation analysis and multivariately by factor analysis. Factor analysis resulted in the identification of 3 distinct lipoprotein lipid clusters, which succinctly describes their metabolic relationships. Among normolipidemic subjects, the interrelationships were found to be similar in males and females, but hormone use by women considerably altered interrelationships that involved high-density lipoprotein cholesterol (HDL-C) and triglyceride. Among hyperlipidemic subjects, elevation in cholesterol level alone rarely altered relationships, but elevation in triglyceride level either alone or in conjunction with an elevation in cholesterol concentration was associated with substantial changes in relationships involving the low-density lipoprotein (LDL) fraction. In many instances, positive relationships between LDL-C and other lipoprotein lipids became inverse in the presence of triglyceride elevation. It is concluded that hormone use by women and hypertriglyceridemia with or without an elevation in cholesterol level clearly alter lipoprotein relationships, whereas pure hypercholesterolemia does not. These alterations provide a basis for investigating pathophysiologic mechanisms in hypertriglyceridemia.

Study skills and the education of students with learning disabilities.

This article discusses an area of education for students with learning disabilities that is often neglected. The topic of study skills education, although not new to education in general, has only recently been emphasized in the literature for students with handicaps. An overview of the study skill proficiency (or lack of it) of students with learning disabilities is provided, followed by the presentation of 15 student study skill strategies designed to assist students in their use of various study skills. These strategies may be employed appropriately and effectively with many students with learning disabilities provided that individual needs and abilities are considered. The article concludes with a discussion about the implementation of a study skills program, including guidelines to follow in this process.

Type III hyperlipoproteinemia: diagnosis in whole plasma by apolipoprotein-E immunoassay.

Because the cholesterol-rich very low density (VLD) lipoproteins of subjects with type III hyperlipoproteinemia are distinctively enriched in apolipoprotein E, a radial immunodiffusion assay for apolipoprotein E in whole plasma was developed. Its diagnostic usefulness was tested in randomly selected (n = 174) and hyperlipidemic (n = 61) subsets of an adult employee population and a hyperlipidemia clinic referral group (n = 63), which included 18 patients with well-documented type III hyperlipoproteinemia. Apolipoprotein-E levels were normally distributed among the random population subset, were equal between the two sexes, and increased little with age. The mean and 99th percentile values were 24.6 and 40.1 mg/dl, respectively. All subjects with type III patterns as assigned by standard criteria from both population (n = 4) and referral sources exceeded this 99th percentile (chi +/- SD = 54.7 +/- 9.7 mg/dl). Hence a plasma apolipoprotein-E concentration exceeding 40 mg/dl appears diagnostic of type III hyperlipoproteinemia, representing the first application of an apolipoprotein immunoassay to improved diagnosis of the hyperlipoproteinemias.

Effects of oral contraceptives on lipoprotein triglyceride and cholesterol: relationships to estrogen and progestin potency.

Hormone formulation and estrogen/progestin potency were evaluated in relation to triglyceride and cholesterol concentrations in total plasma and lipoprotein fractions and in relation to lipid composition among a random sample of female telephone company personnel. Triglyceride concentrations in whole plasma, very low-density lipoprotein, and high-density lipoprotein (HDL) were elevated in response to increasing estrogen potency as were triglyceride concentrations in low-density lipoprotein (LDL). LDL cholesterol rose with increasing estrogen potency in contraceptive users but was slightly lower in postmenopausal estrogen-treated women. Plasma HDL cholesterol varied according to estrogen and progestin levels. The LDL cholesterol/triglyceride ratio was reduced for all combination oral contraceptives examined. Sequential oral contraceptives of postmenopausal estrogens did not significantly alter the cholesterol/triglyceride ratio in any lipoprotein fraction. Potential arteriosclerotic risk from sex hormone use may vary among oral contraceptive formulations.

Effect of estrogen/progestin potency on clinical chemistry measures. The Lipid Research Clinics Program Prevalence Study.

The effects of oral contraceptives of varied estrogen/progestin composition on clinical measurements of hepatic, thyroid, and renal function and carbohydrate metabolism were examined in 1,355 women in the Lipid Research Clinics Program Prevalence Study. In general, bilirubin and alkaline phosphatase levels are lower with both oral contraceptives and postmenopausal estrogen use, suggesting an estrogen effect. The least bilirubin reduction is seen with a progestin dominant oral contraceptive. A significant decrement in aspartate aminotransferase is observed in users of one high estrogen dose oral contraceptive and in postmenopausal Premarin users, while aspartate aminotransferase is higher in postmenopausal users of higher dose ethinyl estradiol. Globulins are slightly higher in all hormone use categories, suggesting an estrogen effect on hepatic secretion of this protein class into the circulation. Fasting glucose concentrations are generally slightly lower even in the progestin dominant oral contraceptives, where glucose intolerance has been described. Thyroxine concentrations are generally elevated in all women using oral contraceptives. A relationship to estrogen dose is seen in women with thyroxine concentrations greater than the 99th percentile and in postmenopausal estrogen users. Creatinine concentration is greater with the use of Ovral, a progestin dominant oral contraceptive, and lower with two estrogen dominant oral contraceptives and Premarin, suggesting a competitive effect of estrogen and progestin. Among the clinical laboratory tests considered here, oral contraceptive effects seem to be largely estrogen mediated with a suggestion of competitive effect of estrogen versus progestin only on bilirubin and creatinine levels. These observations differ from lipoproteins where opposing hormonal effects are more clearly reflected in changing lipoprotein concentrations.

Epidemiological correlates of high density lipoprotein subfractions, apolipoproteins A-I, A-II, and D, and lecithin cholesterol acyltransferase. Effects of smoking, alcohol, and adiposity.

Recent data suggest that the protection against ischemic heart disease afforded by high density lipoprotein (HDL) cholesterol (C) may be concentrated in the HDL2 subfraction. To examine the behavioral correlates of the HDL subfractions, we recalled 33 men and 17 women of a random sample from the Pacific Northwest Bell Telephone Company Health Survey. Adiposity and very low density lipoprotein (VLDL) triglyceride were negatively correlated with HDL2C. Smoking was not correlated with HDL2C, but was negatively correlated with HDL3C (men, rs = -0.635, p = 0.001; women, rs = -0.534, p = 0.014); this relationship was independent of alcohol consumption, adiposity, and VLDL triglyceride. Alcohol consumption was also more strongly related to HDL3C (men, rs = 0.248, p = 0.082; women, rs = 0.586, p = 0.007). Lecithin cholesterol acyltransferase (LCAT) mass was negatively related with HDL2C, but was positively correlated with HDL3C and apolipoprotein A-II. Smoking was negatively correlated with LCAT mass. Since it is believed that HDL3C is not associated with the risk of ischemic heart disease and since both smoking and alcohol consumption may mainly affect HDL3C, the current study suggests that the increase in risk of ischemic heart disease with smoking and the possible decrease with alcohol consumption may be mediated through mechanisms other than their effects on HDLC.

Postheparin plasma triglyceride lipases. Relationships with very low density lipoprotein triglyceride and high density lipoprotein2 cholesterol.

Hepatic triglyceride (HTGL) and lipoprotein lipase (LPL) probably have major roles in the removal of triglyceride from triglyceride-rich lipoprotein and in the formation of high density lipoprotein (HDL). However, no population-based study of their activity and relationship to lipoprotein lipid levels has been reported. To determine these relationships, we recalled 33 men and 17 women of a randomly selected sample of the Lipid Research Clinics Pacific Northwest Bell Telephone Company Health Survey. The subjects were 53 +/- 7 years old (mean +/- SD) with total triglyceride levels of 120 +/- 57 mg/dl and total cholesterol levels of 224 +/- 35 mg/dl. Postheparin plasma LPL activity (127 +/- 61 nmol/min/ml) was not significantly correlated with either age, sex, or adiposity. In contrast, HTGL activity was significantly higher in men (235 +/- 84 nmol/min/ml) than women (170 +/- 91 nmol/min/ml, p less than 0.02), and was correlated with age in men and with adiposity in women. In both men and women, HTGL activity was related positively with VLDL triglyceride and inversely with HDL2 cholesterol. When the association between HTGL activity and VLDL triglyceride was examined with values from men and women pooled, the relationship was not weakened after adjustment for the linear effect of sex, adiposity, LPL, or HDL2 cholesterol.

Hyperlipidemia in the Pacific Northwest Bell Telephone Company Health Survey. Part 1. Lipoprotein cholesterol and triglyceride concentrations.

Lipoprotein triglyceride and cholesterol concentrations and characteristics are described in normolipidemic and in three categories of hyperlipidemic subjects participating in the Pacific Northwest Bell Telephone Company Health Survey. For this study, 350 white participants 20 to 59 years of age with cholesterol or triglyceride values exceeding the age, sex, and hormone-use specific, population-based 90th percentile values were defined as having hypercholesterolemia, hypertriglyceridemia, or combined hyperlipidemia; 722 participants were classified as normolipidemic. In hypercholesterolemia, very low density lipoprotein cholesterol and triglyceride and high density lipoprotein cholesterol concentrations were higher than in normolipidemia. In hypertriglyceridemia, high density lipoprotein cholesterol was significantly lower in men and women not using sex hormones and low density lipoprotein triglyceride was significantly higher in men and women using hormones compared to normolipidemia. In combined hyperlipidemia, high density lipoprotein cholesterol concentrations were lower than in normolipidemia, but higher than in pure hypertriglyceridemia. The presence of beta migrating very low density lipoprotein and chylomicrons was seen primarily in hypertriglyceridemic or combined hyperlipidemic men. Sinking prebeta lipoprotein was equally common (20%) among all normolipidemic and hypercholesterolemic subjects, but was less common (5% to 10%) in hypertriglyceridemic and combined hyperlipidemic men and female hormone users. Quantitative and qualitative lipoprotein abnormalities associated with hyperlipidemia were found to vary by gender and by sex hormone use in women and were often, but not always, more marked in men.

Hyperlipidemia in the Pacific Northwest Bell Telephone Company Health Survey. Part 2. Lipoprotein lipid interrelationships.

The relationships of lipoprotein cholesterol and triglyceride among lipoprotein fractions have potential significance for understanding atherogenesis and distinguishing among different classes of hyperlipidemia. We have compared these relationships in normolipidemic, hypercholesterolemic, hypertriglyceridemic, and combined hyperlipidemic participants in the Pacific Northwest Bell Telephone Company Health Survey. The cholesterol/triglyceride ratio in each lipoprotein fraction was moderately higher (1% to 26%) in hypercholesterolemia but significantly lower (20% to 50%) in hypertriglyceridemia, compared to normolipidemia. In combined hyperlipidemia, the very low density lipoprotein ratios were lower than in normolipidemia, but larger than in hypertriglyceridemia. These changes were directionally the same, but differed quantitatively, in both men and women. Correlation coefficients between cholesterol and triglyceride within each fraction varied by gender and sex hormone use. The largest correlations were seen in combined hyperlipidemic men for very low density lipoproteins, normolipidemic men for low density lipoproteins, and combined hyperlipidemic women taking hormones for high density lipoproteins. The correlation of very low and low density lipoprotein cholesterol was generally negative and was strongest for hormone users (r = -0.81) and weakest for nonusers (r = -0.06). Very low density lipoprotein triglyceride and high density lipoprotein cholesterol correlations were generally negative and were strongest in hypertriglyceridemic women not taking hormones (r = -0.55) and weakest in normolipidemic hormone users (r = -0.10). This correlation was positive for hypertriglyceridemic and combined hyperlipidemic hormone users.