Richard A. Muesing

Dietary cis and trans monounsaturated and saturated FA and plasma lipids and lipoproteins in men.

Trans monounsaturated fatty acids (TFA) are hypercholesterolemic compared to oleic acid to a degree approaching or equivalent to saturated FA. However, it is unknown to what extent these effects may be due to cholesterol lowering by oleic acid rather than elevation by saturated FA and TFA. In order to better understand the impact of replacing TFA in foods, it is first necessary to know the relative lipid-modifying effects of the major FA that change as TFA are lowered or removed. For 5 wk, 50 normocholesterolemic men were fed controlled diets providing approximately 15% of energy from protein, 39% from fat, and 46% from carbohydrate in a randomized, 6×6, crossover design. Eight percent of energy was replaced across diets with the following: carbohydrate (CHO) (1∶1 simple to complex); oleic acid (OL); TFA; stearic acid (STE); TFA/STE (4% of energy from each); carbon 12∶0 16∶0 saturated FA (LMP). LDL cholesterol concentrations (mmol/l) were as follows (different superscripts indicate significance at P≤0.01): OL 2.95a; CHO 3.05a,b; STE 3.10b,c; LMP 3.21c,d; TFA+STE 3.32d,e; and TFA 3.36e. HDL cholesterol concentrations (mmol/L) were as allows: STE 1.16a; IFA 1.16a,b; TFA/STE 1.17a,b; CHO 1.19b; OL 1.24c; and LMP 1.30d. Triacylglycerides were highest after STE (1.13) and lowest after OL (0.88) (P<0.001). Thus, compared to the carbohydrate control diet, TFA raised LDL cholesterol at least equivalent to LMP but had no effect on HDI cholesterol; STE had no effect on LDL cholesterol but lowered HDL cholesterol; LMP raised both LDL cholesterol and HDL cholesterol; and oleic acid raised HDL cholesterol but had no effect on LDL cholesterol.

Effects of Conjugated Equine Estrogen With and Without Three Different Progestogens on Lipoproteins, High-density Lipoprotein Subfractions, and Apolipoprotein A-i

The effects of conjugated equine estrogen and subsequent cyclical progestogen supplementation on lipoprotein and apolipoprotein A-I levels were investigated in three groups of postmenopausal women. Unopposed conjugated equine estrogen (0.625 mg) lowered total cholesterol 4-8% and low-density lipoprotein (LDL) cholesterol 12-19% below pre-treatment levels in all three groups. Levels of highdensity lipoprotein (HDL) cholesterol and apolipoprotein A-I were increased 9-13 and 9-18%, respectively, with unopposed estrogen. The increase in HDL cholesterol was mainly due to increases in the high-density lipoprotein2 (HDL2) subfraction. Addition of medroxyprogesterone acetate, norethindrone acetate, or d,l-norgestrel at doses shown previously to provide protection against endometrial hyperplasia reversed some of the beneficial estrogen effects, reducing levels of HDL cholesterol 14-17%, HDL2 cholesterol 22-37%, and apolipoprotein A-I 11-15% from those obtained cholesterol 22-37%, and apolipoprotein A-I 11-15% from those obtained with unopposed estrogen. The LDL cholesterol levels fell 12-19% with unopposed estrogen but remained 7-12% below baseline when progestogens were added. These observations demonstrate that after 3 months of treatment, all three progestogens reversed some of the favorable effects of unopposed estrogen on lipoproteins but permitted a continued modest reduction in LDL cholesterol.

Lipoprotein and apolipoprotein levels in angiographically defined coronary atherosclerosis

Recent studies suggest that apolipoproteins and subfractions of high-density lipoprotein (HDL) cholesterol may be better predictors of atherosclerotic coronary artery disease (CAD) than are plasma cholesterol and total HDL cholesterol. To examine this hypothesis, plasma cholesterol and triglyceride, cholesterol of low-density lipoprotein, HDL and its subfractions 2 and 3, apolipoprotein A-I, the apolipoprotein B of low-density lipoprotein, the ratio of apolipoprotein EII to EIII, and ratios of several of these variables were measured in a selected series of 126 patients (83 men and 43 women) who underwent coronary angiography for suspected CAD. Mean values of many of these variables differed significantly between the men with CAD and the men without significant CAD, when controlled for age, use of beta blockers and diuretic drugs. Using multivariate logistic regression analysis, the only variable that made a significant independent contribution in predicting CAD in men was the ratio of HDL cholesterol to total plasma cholesterol (p less than 0.0001). The mean of this ratio was 0.17 +/- 0.01 mg/dl in the men with CAD and 0.23 +/- 0.02 mg/dl in the male controls. All men with ratios of less than 0.15 mg/dl had significant CAD, defined as 50% or greater luminal diameter narrowing of 1 or more of the major coronary arteries. No measurement was a significant univariate or multivariate predictor of CAD in the women, but the power to detect such predictors was reduced because of small group sizes. In conclusion, the ratio of HDL cholesterol to plasma cholesterol may be superior to many of the more recently described lipoprotein and apolipoprotein-derived predictors of CAD.

Plasma Lipoprotein (a) Levels in Men and Women Consuming Diets Enriched in Saturated, Cis -, or Trans -Monounsaturated Fatty Acids

Studies that have shown adverse effects of trans-unsaturated fatty acids on plasma lipoprotein (a) [Lp(a)] levels have used levels of trans-fatty acid that are higher than those in the average U.S. diet. This study was conducted to clarify the effects on Lp(a) of trans-fatty acids levels commonly found in U.S. diets. Lp(a) levels were measured in a double-blind study of 29 men and 29 women who ate 4 controlled diets in random order for 6 weeks each. Fatty acids represented 39% to 40% of energy. The diets were: (1) Oleic (16.7% of energy as oleic acid); (2) Moderate trans (3.8% of energy as trans-monoenes, approximately the trans content of the U.S. diet); (3) High trans (6.6% of energy as trans-monoenes); (4) Saturated (16.2% of energy as lauric plus myristic plus palmitic acids). The Saturated diet lowered Lp(a) levels significantly (by 8% to 11%). Compared to the Oleic diet, the trans diets had no adverse effect on Lp(a) levels when all subjects were considered collectively. A subset with initially high levels of Lp(a) (> or = 30 mg/dL), however, responded to the High trans diet with a slight (5%) increase in Lp(a) levels relative to the Oleic and Moderate trans diets. Thus, in amounts commonly found in the typical U.S. diet, saturated fatty acids consistently decrease Lp(a) concentrations. The adverse effects of replacing cis- with trans-fatty acids are only suggestive and are restricted to high trans intakes in subjects with high Lp(a) levels.

Effects of Alcohol Consumption on Lipoproteins of Premenopausal Women A Controlled Diet Study

A substantial portion of American women consume alcohol, but controlled studies of alcohol-induced changes in lipoproteins of women are rare. In this study, the effects of alcohol consumption (equivalent to two drinks per day) on the lipoprotein profiles of 34 premenopausal women were measured while controlling subjects diet and various other potentially confounding variables including phase of the menstrual cycle. Alcohol and no-alcohol treatments were administered in a crossover design, and blood samples were obtained during the early follicular phase of the third month of treatment. With alcohol, HDL cholesterol levels increased 10%, LDL levels decreased 8%, and levels of lipoprotein(a) were unchanged. The increase in HDL cholesterol was due to an increase in both HDL2 and HDL3, and the overall size of HDL particles was increased. HDL particles containing apolipoprotein (apo) A-I and apoA-II as well as those containing apoA-I but no apoA-II were elevated in response to alcohol. Although these observations are limited to a single phase of the menstrual cycle, the alcohol-induced changes in lipoproteins are consistent with changes that are thought to confer protection against coronary heart disease.

Progestins and oral contraceptive-induced lipoprotein changes: A prospective study

In order to determine the effects on plasma lipoproteins of oral contraceptives containing progestins with varying androgenic potency, 136 healthy women were randomized into 3 groups and followed prospectively for one year while receiving either 50 mcg ethinyl estradiol and 1.0 mg ethynodiol diacetate (EED), 50 mcg ethinyl estradiol and 1.0 mg norethindrone acetate (ENA), or 50 mcg ethinyl estradiol and 0.5 mg d-1 norgestrel (ENG). Comparison was made to a self-selected group of 50 women using alternative means of contraception. Plasma cholesterol increased by 7-9% and triglycerides by 32-57% in all 3 groups (p less than 0.05). ENG use resulted in other significant lipoprotein changes including an 18% increase in low density lipoprotein cholesterol (LDL-C), a 13% fall in high density lipoprotein cholesterol (HDL-C) and a 27% decline in HDL2 cholesterol (HDL2-C) (p less than 0.05). Apoprotein A-I (Apo A-I) increased by 9% with ENA and by 11% with EED (p less than 0.05), but did not change significantly with ENG. This prospective study demonstrates that in oral contraceptive agents with identical estrogen, progestins with different androgenic potency produce major and different changes in plasma lipoproteins.

Alterations in Serum Levels of Lipids and Lipoproteins with Indinavir Therapy for Human Immunodeficiency Virus—Infected Patients

Alterations in lipid metabolism have been associated with the use of protease inhibitors. Sequential lipid analyses were performed on serum samples from human immunodeficiency virus-infected antiretroviral-naive patients who received indinavir in combination with two nucleoside reverse transcriptase inhibitors. Serum levels of cholesterol, triglycerides, high-density lipoproteins (HDLs), and low-density lipoproteins (LDLs) were measured at baseline and at periodic intervals. After 48 weeks of indinavir therapy, mean serum levels +/- SD rose as follows: cholesterol, from 167.2 +/- 36.0 to 206.3 +/- 32.4 mg/dL (P < .0005); triglycerides, from 110.4 +/- 47.5 to 158.4 +/- 72.5 mg/dL (P < .0101); and LDLs, from 106.6 +/- 35.1 to 136.1 +/- 31.6 mg/dL (P = .0029). There was no significant change in the serum HDL fraction. Mean serum lipoprotein (a) levels +/- SD rose from 6.5 +/- 1.4 to 9.6 +/- 2.0 mg/dL after 30 weeks (P = .0695). Potential mechanisms for the noted increases include alterations in serum lipoprotein lipase activity or changes in hepatic lipid metabolism. The clinical significance of these changes remains to be determined.

Estrogen Replacement Therapy and Coagulation: Relationship to Lipid and Lipoprotein Changes

Objective To examine the relationship of estrogen-induced changes in lipids and lipoproteins with alterations in the coagulation system. Methods Coagulation and lipid indices were measured in 31 postmenopausal women, ages 40–60 years, after a 3-month course of 0.625-mg conjugated equine estrogen. We analyzed changes in variables from baseline to 3 months using t tests for paired samples or the Wilcoxon matched-pairs signed-rank test. Results Unopposed estrogen replacement therapy produced statistically significant decreases in antithrombin-III antigen (P = .006) and activity (P = .001) and total protein S (P = .003) and a significant increase in protein C antigen (P = .017). C4b-binding protein also decreased significantly from baseline to 3 months (P < .001). Mean fibrinogen level decreased by 18.2 mg/dL, not a statistically significant change (P = .213). Estrogen produced the expected statistically significant changes in lipids and lipoproteins. Several correlations between changes in lipids and lipoproteins and coagulation indices were statistically significant. Protein C antigen and activity changes correlated directly with high-density lipoprotein cholesterol changes (r = .52, P ≤ .005; r = .38, P ≤ .05; respectively), and protein C antigen also correlated directly with increases in apoprotein A-I (r = .54, P ≤ .005). Triglyceride changes correlated directly with changes in protein C antigen (r = .36, P ≤ .05) and activity (r = .49, P ≤ .005) and inversely with C4b-binding protein (r = − .58, P ≤ .01). Apoprotein B was correlated with free protein S (r = .48, P ≤ .01). Conclusions Although several estrogen-induced changes may decrease atherosclerotic potential and hypercoagulability, others may promote coagulability. These divergent effects may be manipulated pharmacologically by other estrogen compounds or by the addition of various progestins.

Estrogen replacement therapy and coagulation: Relationship to lipid and lipoprotein changes

Objective: To examine the relationship of estrogen-induced changes in lipids and lipoproteins with alterations in the coagulation system. Methods: Coagulation and lipid indices were measured in 31 postmenopausal women, ages 40–60 years, after a 3-month course of 0.625-mg conjugated equine estrogen. We analyzed changes in variables from baseline to 3 months using t tests for paired samples or the Wilcoxon matched-pairs signed-rank test. Results: Unopposed estrogen replacement therapy produced statistically significant decreases in antithrombin-III antigen (P = .006) and activity (P = .001) and total protein S (P = .003) and a significant increase in protein C antigen (P = .017). C4b-binding protein also decreased significantly from baseline to 3 months (P Conclusions: Although several estrogen-induced changes may decrease atherosclerotic potential and hypercoagulability, others may promote coagulability. These divergent effects may be manipulated pharmacologically by other estrogen compounds or by the addition of various progestins.

Glucose and lipid metabolism during acebutolol and propranolol therapy of angina in nondiabetic patients.

The metabolic effects of acebutolol, a cardioselective beta‐adrenergic blocker, and of propranolol, a nonselective beta blocker, were evaluated. Our subjects were 20 men with chronic stable angina; none had diabetes. An initial 4‐wk, single‐blind control phase was followed by two drug treatment periods, each a 3‐wk double‐blind titration phase (using increasing doses of acebutolol or propranolol), followed by a 5‐wk double‐blind maintenance phase. Metabolic studies were performed at the end of the control and maintenance phases. Propranolol induced elevation in basal serum glucose concentrations and both propranolol and acebutolol decreased glucose tolerance at 2.5 and 3 hr. There was no noticeable effect on insulin secretion by either drug. Neither propranolol nor acebutolol induced hyperlipidemia. There was a small decrease in total serum cholesterol after propranolol. Both drugs decreased low‐density lipoprotein cholesterol. No effects were noted on the levels of serum triglycerides, high‐density lipoprotein cholesterol, or free fatty acids.