Acute changes in lipid, lipoprotein, apolipoprotein, and low-density lipoprotein particle size after an endurance triathlon

The effect of an endurance triathlon (2.4-mile swim, 112-mile bicycle ride, 26.2-mile run, in succession) on plasma total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein (apo) A-I and B levels, and LDL particle size was determined in 34 male and six female participants 6 to 12 hours before and immediately after the completion of the triathlon. Plasma TG decreased significantly (70% decrease) in both men and women. In men the change in plasma TG was inversely associated with baseline TG values (P less than .0001). Plasma TC and LDL cholesterol did not change significantly in male athletes but decreased significantly in women. A significant increase in HDL cholesterol was observed in both men (18% increase, P less than .0001) and women (5% increase, P less than .01). In men the increase in HDL cholesterol was inversely correlated with the decrease in triglycerides (P less than .0002). Plasma apo A-I levels increased significantly only in the male group (P less than .005), whereas plasma apo B levels decreased significantly in both men and women (P less than .0005). LDL particle size increased in seven males, whereas in the remaining males and all females no change in LDL size was observed. The increase in LDL particle size in these seven subjects was associated with a greater decline in plasma TG compared with the remaining men (P less than .005) and women (P less than .03). These results indicate that prolonged strenuous physical exercise can induce acute modifications of plasma lipoproteins, which may in part be related to enhanced lipolysis.     

The NHLBI Twin Study: heritability of apolipoprotein A-I, B, and low density lipoprotein subclasses and concordance for lipoprotein(a).

Heritability of plasma apolipoprotein (apo) A-I, apo B, and low density lipoprotein (LDL) subclasses and concordance for lipoprotein(a) excess were assessed in 109 monozygotic (MZ) and 113 dizygotic (DZ) twin pairs participating in the third examination of the National Heart, Lung, and Blood Institute Twin Study. The intraclass correlation coefficient for apo A-I was significantly greater in MZ twins (0.56) than in DZ twins (0.37, P less than 0.05); however, apo A-I showed an unequal distribution in the two groups, with significantly greater total variance in DZ twins. Therefore the among-component estimate of genetic variance was applied, and the results indicated no significant heritability for apo A-I (P = 0.59). MZ and DZ twins had equal apo B variance. The intraclass correlation coefficient for apo B in MZ twins (0.71) was significantly higher than in DZ twins (0.25) (P less than 0.0001), indicating significant heritability for apo B. Plasma apo A-I levels were significantly correlated with alcohol intake (P less than 0.0001), body mass index (BMI, P less than 0.0001), and physical activity, while apo B levels were significantly correlated only with BMI (P less than 0.05). After plasma apo A-I and apo B concentrations were adjusted for all of these variables and for cigarette smoking, the analysis of variance and intraclass correlation coefficients remained virtually unchanged. The LDL type intraclass correlation coefficient was higher in MZ twins (0.58) than in DZ twins (0.32, P less than 0.005); however, greater total variance for this parameter in DZ twins was observed and after applying the among component estimate of genetic variance, no significant heritability of LDL type was observed. After adjustment for covariate effects the conclusions were not changed. Only 8.4% of MZ twin pairs, as compared with 26.7% of DZ twin pairs, were discordant for elevated lipoprotein(a) on gradient gels (P less than 0.0001). Our data indicate that there is a strong heritability for plasma apo B and lipoprotein(a), with only weak evidence for heritability of LDL type or plasma apo A-I levels within this population sample.     

Levels of serum lipids, apolipoproteins A-I and B and pseudocholinesterase activity and their discriminative values in patients with coronary by-pass operation

Serum lipids and apoproteins A-I and B were measured in 115 male patients and serum pseudocholinesterase activity (PChE) was determined in 83 patients with 3 vessel coronary artery disease (CAD). The control subjects were matched according to sex, smoking, relative weight and age and were free from heart disease. The CAD patients had significantly higher serum VLDL cholesterol and triglyceride levels and lower HDL cholesterol and apo A-I levels and lower HDL to total cholesterol ratio than the controls. The concentrations of serum total cholesterol and LDL cholesterol were only slightly (6.4% and 8.8%, on an average) higher in CAD patients than in controls. The apo B levels of CAD patients were also slightly lower in patients than in controls. The CAD patients had slightly higher PChE activities than controls. The ratios of apo A-I to PChE and HDL cholesterol to PChE were significantly (about 30%, P less than 0.001) lower in patients than in controls. In discriminant analysis between the groups HDL cholesterol and apo A-I showed the best (74% success in reclassifying the patients to correct groups), and total cholesterol, triglycerides, LDL cholesterol and apo B remarkably weak discriminating power among the single variables of serum lipids and lipoproteins. In discriminating analysis the apo A-I/PChE and HDL cholesterol/PChE ratios showed relatively high (77.1 and 71.1% success from the patients to correct groups) and serum PChE activity weak discriminating power. These results indicate that low levels of HDL cholesterol and apo A-I and the low ratio of HDL cholesterol to total cholesterol are the most potent metabolic risk factors for 3 vessel coronary artery disease in a population with relatively high serum total cholesterol level. The determinations of apo A-I/PChE and HDL cholesterol/PChE ratios may be an additional, valuable tool in discriminating the risk for CAD.     

Effects of estrogen replacement on plasma lipoproteins and apolipoproteins in postmenopausal, dyslipidemic women.

The effects of oral estrogen replacement (ethinyl estradiol 0.02 mg/d) on plasma triglyceride, total cholesterol, very-low-density lipoprotein (VLDL) cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) A-I and B levels and LDL particle size were assessed in 20 postmenopausal women with a previous hysterectomy and various forms of dyslipidemia (LDL cholesterol > or = 4.14 mmol/L [160 mg/dL] and/or HDL cholesterol < or = 1.03 mmol/L [40 mg/dL]). All subjects were studied while on a standard cholesterol-lowering diet, and were sampled in the fasting state before beginning estrogen therapy and after a mean of 13 weeks of estrogen therapy. Lipids were measured by standardized enzymatic techniques, apos were measured by enzyme-linked immunoassays, and LDL particle size was measured by gradient gel electrophoresis. Mean values for plasma lipid parameters (mmol/L) at baseline and during estrogen replacement were as follows: triglyceride, 2.11 and 2.75 (30% increase); total cholesterol, 7.45 and 6.52 (13% decrease); VLDL cholesterol, 1.09 and 1.22 (12% increase); LDL cholesterol, 5.09 and 3.70 (27% decrease); and HDL cholesterol, 1.27 and 1.58 (24% increase). Mean values for apo A-I were 163 and 254 mg/dL (56% increase), and for apo B they were 170 and 148 mg/dL (13% decrease). The LDL particle score was 4.09 and 4.52 (11% smaller). Changes in all parameters were statistically significant (P = .05) except for VLDL cholesterol. These data indicate that estrogen replacement is effective in decreasing LDL cholesterol and apo B concentrations and increasing HDL cholesterol and apo A-I concentrations in dyslipidemic postmenopausal women, but it should not be used in patients with baseline fasting triglyceride levels higher than 2.82 mmol/L (250 mg/dL) unless it is accompanied by a progestin. Our data indicate that this form of estrogen replacement could lower the risk of coronary artery disease (CAD) by more than 50% in these women, based on favorable alterations in plasma lipoproteins.     

Relationships of serum lipoproteins and apoproteins to sex hormones and to the binding capacity of sex hormone binding globulin in healthy Finnish men

We have determined the levels of serum sex hormones, the binding capacity of sex hormone binding globulin (SHBG), urinary estrogens, serum lipids, lipoproteins, and apolipoproteins A-I, A-II, and B in 30 healthy middle-aged Finnish men with similar dietary habits. Serum levels of total testosterone, free testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), and the binding capacity of SHBG were all positively correlated to high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apo A-I) (r = .43 to .80, P less than 0.05 to 0.001). Total testosterone and 5 alpha-DHT showed a positive correlation to the ratio of apo A-I to Apo A-II (r = .37, P less than 0.05 and r = .58, P less than 0.01, respectively). Serum estradiol levels were negatively correlated to serum total cholesterol, low density lipoprotein cholesterol (LDL), and Apo B (r = -.51 to -.56, P less than 0.01). Moreover, serum free estradiol was negatively correlated to HDL-C and Apo A-I (r = -.46 and r = -.50, P less than 0.01). In multiple linear regression analysis, 5 alpha-DHT was the most significant independent determinant of HDL-C and apo A-I levels when androgens, luteinizing hormone, estradiol, binding capacity of SHBG, and exogenous factors such as age, body mass index (BMI), smoking, alcohol consumption, and diet were taken into account. Multivariate analysis also demonstrated that both total and free estradiol were inversely related to serum Apo B levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lipoproteins and apolipoproteins in young male survivors of myocardial infarction

Plasma and lipoprotein cholesterol, triglycerides, apolipoproteins (apo) A-I, A-II, B and phospholipid concentrations were measured at 10 days and 4 months after myocardial infarction (MI) in 60 young Kuwaiti male MI survivors below the age of 40 years. Controls were matched for age, relative weights, smoking, dietary habits and physical activities. The young MI survivors had significantly higher levels of total and LDL-cholesterol, and ratios of LDL/HDL- and LDL/HDL2-cholesterol. Total VLDL and LDL triglycerides, and phospholipids were also elevated in MI survivors compared to controls. Similarly, plasma and LDL-apo B as well as the ratios of apo B/apo A-I were higher in the MI group. There was no significant change in the levels of VLDL and HDL3-cholesterol and of apo A-II in these patients compared to their controls. Concentrations of HDL- and HDL2-cholesterol and of plasma and HDL apo A-I were significantly lower in the young MI survivors compared to the control subjects. The better discriminating lipoproteins and apolipoproteins in MI patients in descending order were HDL2-cholesterol greater than apo B greater than apo A-I greater than VLDL-triglyceride greater than HDL-cholesterol greater than LDL/HDL2-cholesterol greater than triglycerides. The data indicate that measurement of HDL2-cholesterol, apo B and apo A-I may be useful indicators in assessing coronary artery disease risk than triglycerides (TG), total cholesterol (TC), LDL-cholesterol and HDL-cholesterol.     

Bone mineral content and levels of gonadotropins and estrogens in amenorrheic running women

Serum gonadotropin and estrogen levels and their relationship to bone mineral content in exercise-related amenorrhea were studied in 11 amenorrheic women and 24 eumenorrheic women, all of whom were runners. Serum estradiol, LH, FSH, estrone, and testosterone were measured in serial blood samples obtained at 15-min intervals for 4 h. The amenorrheic women had lower estradiol, LH, FSH; and estrone levels as well as a higher estrone-estradiol ratio than did the eumenorrheic women. There was no difference in testosterone levels. The amenorrheic women had lower LH pulse amplitudes, whereas no differences were found in FSH pulse amplitudes. LH and FSH pulse frequencies did not differ between the two groups. Bone mineral content of the lumbar spine was lower in amenorrheic women and was positively correlated with estradiol levels in all women. There was no difference in bone mineral content of the radius. These data suggest that, in exercise-related amenorrhea, low serum LH, FSH, and estrogen levels reflect an alteration in the hypothalamic control of gonadotropin release. Reduced circulating estrogen levels in amenorrheic running women may be a cause of low mineral content of the spine.     

Computed tomography-measured trunk fat and plasma lipoprotein levels in nonobese women

The associations between total adiposity, adipose tissue distribution measured by computed axial tomography (CAT), regional variation in fat cell size, and plasma lipoprotein levels were studied in a sample of 22 premenopausal healthy nonobese women aged 34.6 +/- 3.1 years (mean +/- SD) (% body fat, 27.8 +/- 5.8). In these nonobese women, no associations were found between total adiposity, adipose tissue distribution, and plasma triglyceride or very-low-density lipoprotein levels. However, total adiposity (as reflected by the body density-derived fat mass and by the adipose tissue volume measured by CAT), as well as the total trunk fat areas (measured at the abdominal and thoracic levels) were positively correlated with plasma low-density lipoprotein (LDL) cholesterol (.05 greater than P less than .01) and LDL apolipoprotein (apo) B (.05 greater than P less than .0005) levels. Because of these associations with LDL-C and LDL apo B levels, these body fatness indicators were negatively correlated with the HDL-cholesterol/LDL-cholesterol and HDL-apo A-I/LDL-apo B ratios. However, few significant associations were observed between the proportion of abdominal fat estimated by the waist/hip circumference ratio (WHR) and the lipoprotein-lipid profile (r = .45 and r = .44, P less than .05 with HDL triglyceride (TG) and LDL-apo B/LDL-cholesterol ratio, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of large-dose progesterone on plasma levels of lipids, lipoproteins and apolipoproteins in males

Eleven men with sexual deviation syndrome were hospitalized for treatment with medroxyprogesterone acetate (Depo-provera). Plasma total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, apo A-I and LDL apo B were measured before and during Depo-provera treatment. Ten normolipidemic and one mildly hypertriglyceridemic patient with 117 +/- 17% ideal body weight were maintained on a regular hospital diet before and during the study. They received an average total dose of 1273 +/- 467 mg Depo-provera by im injections over a mean period of 17 +/- 6 days. In the whole group, Depo-provera significantly reduced the plasma total cholesterol by 12% (p less than 0.0005), triglycerides by 24% (p less than 0.005), LDL cholesterol by 13% (p less than 0.01), LDL apo B by 15% (p less than 0.05), and apo A-I by 7% (p less than 0.05). Total HDL cholesterol, HDL2 cholesterol and HDL3 cholesterol did not change significantly. Excluding from the data analysis a normolipidemic patient who had a significant weight loss during the study and the hypertriglyceridemic patient, the fall in apo A-I during Depo-provera treatment was no longer statistically significant. We conclude that short-term, pharmacological doses of progesterone significantly reduce plasma concentrations of cholesterol, triglycerides, LDL cholesterol, and LDL apo B in men.     

Influence of triglyceride concentration on the relationship between lipoprotein cholesterol and apolipoprotein B and A-I levels

A sample of 2,103 men aged 47 to 76 years from the Québec Cardiovascular Study cohort was examined to quantify the influence of plasma triglyceride (TG) levels on the relationship between plasma lipoprotein cholesterol and either apolipoprotein A-I (apo A-I) or apo B concentrations. Regression analyses between high-density lipoprotein cholesterol (HDL-C) and apo A-I through TG tertiles showed highly significant correlations (.62 < or = r < or = .75, P < .0001) in all TG tertiles between these 2 variables. The associations for plasma apo B versus low-density lipoprotein cholesterol (LDL-C) and non-HDL-C levels were also studied on the basis of TG concentrations, and correlation coefficients between either LDL-C or non-HDL-C and apo B were essentially similar among TG tertiles (.78 < or = r < or = .85 and .83 < or = r < or = .86 for LDL-C and non-HDL-C, respectively, P < .0001). Regression analyses also showed that lower HDL-C levels were found for any given apo A-I concentration among men in the 2 upper TG tertiles, whereas lower LDL-C concentrations were observed at any given apo B level among subjects in the upper TG tertile. We further investigated whether there were synergistic alterations in the HDL-C/apo A-I and LDL-C/apo B ratios as a function of increasing plasma TG. A significant association was noted between these 2 ratios (r = .37; P < .0001). Mean HDL-C/apo A-I and LDL-C/apo B ratios were then calculated across quintiles of plasma TG concentrations. Increased TG concentrations were first associated with a reduced HDL-C/apo A-I ratio, followed by a decreased LDL-C/apo B ratio. These results suggest that a relatively modest increase in TG may rapidly alter the relative cholesterol content of HDL particles. Finally, the cholesterol content of the non-HDL fraction appears to be influenced less by TG levels than HDL-C and LDL-C fractions. Thus, the plasma apo B-containing lipoprotein cholesterol level may provide a better index of number of atherogenic particles than the LDL-C concentration, particularly in the presence of hypertriglyceridemia (HTG).     

Apolipoprotein B in human aortic biopsies in relation to serum lipids and lipoproteins

A total of 46 patients, aged 39-71 years (mean 57.7), were studied. Forty-eight percent of the patients were hyperlipidemic and 63% had earlier suffered a myocardial infarction. Biopsies from aorta were obtained during coronary bypass surgery. Apo B was extracted from the intima by incubation of the tissue in buffer, followed by collagenase digestion. Intimal apo B was quantified in an immunoradiometric assay. There were significant correlations between total or collagenase-extractable apo B and serum cholesterol (rs = 0.39, P less than 0.01), serum triglycerides (rs = 0.33, P less than 0.05), LDL cholesterol (rs = 0.33, P less than 0.05) and serum apo B (rs = 0.37, P less than 0.05). The correlations were strongest for the collagenase-extractable apo B, while no correlations were observed for the buffer-extractable intimal apo B. No significant correlations were found between intimal apo B and serum HDL, apo A-I, smoking habits, history of hypertension or sustained myocardial infarction. Follow-up data were available for 42 of the patients, with a mean follow-up period of 35.1 months. The patients were classified according to symptoms of angina pectoris at the time of follow-up. There were significantly lower levels of serum apo A-I in the patients with poorer clinical prognosis. In a linear multiple stepwise regression analysis, apo A-I and serum LDL were significantly and independently related to clinical prognosis (R2 = 0.31).     

Long-term exercise training with constant energy intake. 3: Effects on plasma lipoprotein levels

The composition and concentration of plasma lipoproteins were studied in five young men (mean BMI = 27.5 +/- 2.9 (s.d.] before, during (after 25 and 50 days of training), and after the completion of a 100 day exercise training program that induced daily 4.2 MJ calorie deficit. Along with reductions in body weight (from 86.7 +/- 20.0 to 78.7 +/- 17.1 kg, P less than 0.01) and in fat mass (from 17.0 +/- 9.7 to 10.4 +/- 7.4 kg, P less than 0.01), the exercise training program induced numerous changes in plasma lipoprotein levels. Plasma total cholesterol level fell significantly after 25 days of training (P less than 0.05) and remained significantly reduced at the end of the training experiment (P less than 0.05). This reduction in total plasma cholesterol was accompanied by reductions in plasma apoprotein (apo) B, LDL-cholesterol and LDL-apo B levels (P less than 0.05). There were trends for reductions in plasma triglyceride and VLDL components that were significant only for VLDL-triglycerides (P less than 0.05). Plasma HDL-cholesterol levels increased significantly only at the end of the training program (P less than 0.01). This increase in plasma HDL-cholesterol was not accompanied by an increase in plasma apo A-I levels suggesting that exercise training produced an increase in HDL cholesterol content rather than an increase in HDL particle number. Ratios of HDL-cholesterol/cholesterol (P less than 0.01) and apo A-I/apo B (P less than 0.05) were significantly increased by exercise training, suggesting a decreased risk of cardiovascular disease. These results indicate that a reduction in fat mass solely induced by aerobic exercise training has substantial beneficial effects on plasma lipoprotein levels.     

Estradiol, testosterone, apolipoproteins, lipoprotein cholesterol, and lipolytic enzymes in men with premature myocardial infarction and angiographically assessed coronary occlusion

A series of thirty-three Venezuelan men with premature myocardial infarction (mean age (M +/- SEM) 45 +/- 1.5 yrs) and with greater than 50% occlusion of at least 2 coronary arteries, and 19 weight matched control men (age 44 +/- 2 yrs) with normal coronary arteries on coronary angiography were studied. The percentages of significantly abnormal (greater than +/- 2 S.D. of controls) serum or plasma concentrations of various measurements (in decreasing order) were: estradiol (33%), total apolipoprotein (apo)B (24%), estradiol/testosterone ratio (21%), low density lipoprotein (LDL) apo B (19%), apo AI (17%), apo AI/total plasma apo B ratio (17%), total cholesterol (17%), and LDL-cholesterol (LDL-C) (11%). In addition, a multivariate discriminant function analysis showed that only estradiol, apo AI, LDL-C, estradiol/testosterone ratio and total cholesterol were statistically significant independent markers of myocardial infarction with occlusive coronary disease in these patients. Both serum estradiol and estradiol/testosterone ratio correlated positively with plasma apo B and LDL apo B, and inversely with apo AI; serum testosterone correlated inversely with plasma apo B (p less than 0.05). The data suggest that circulating sex hormones (estrogens, testosterone) are not only independent markers of coronary disease but may be pathogenetically linked to apo B and apo AI metabolism.     

Effect of alcohol intake and exercise on plasma high-density lipoprotein cholesterol subfractions and apolipoprotein A-I in women

Abstinence from alcohol consumption for 3 weeks was followed by 3 weeks of wine intake in 18 inactive and 18 physically active premenopausal women (runners). The runners weighed less and had higher plasma high-density lipoprotein (HDL) cholesterol and lower low-density lipoprotein cholesterol levels than the inactive women. There were no differences between groups in plasma total cholesterol, triglyceride and apolipoprotein A-I concentrations. Runners had higher plasma HDL2 cholesterol concentrations than inactive women (34 +/- 17 vs 19 +/- 12 mg/dl), but HDL3 cholesterol concentration did not differ between the groups (41 +/- 10 vs 39 +/- 9 mg/dl). Addition of 35 g/day of ethanol for 3 weeks did not result in a significant change in either group for any of the variables measured. The amount of exercise appears to be a more important determinant of plasma lipoproteins and apolipoprotein A-I than alcohol intake in premenopausal women.     

Effects of prolactin and estrogen deficiency in amenorrheic bone loss

To determine whether hyperprolactinemic women with menses are at risk for the development of osteopenia and to define the effects of PRL excess and estrogen deficiency on bone mass in amenorrheic women, spinal and radial bone densities were measured in 25 hyperprolactinemic women (13 with amenorrhea and 12 with regular menstrual periods) and 11 women with hypothalamic amenorrhea. The degree of hyperprolactinemia was comparable in the hyperprolactinemic women with and without menstrual periods [mean, 55 +/- 18 (+/- SD) and 57 +/- 16 micrograms/L, respectively]. The mean spinal bone density in the hyperprolactinemic amenorrheic women (148 +/- 26 mg/K2HPO4.cm3) was significantly lower (P less than 0.01) than that in 19 normal women (178 +/- 21 mg/K2HPO4.cm3), and 6 of the former group had values greater than 2 SD below normal. However, the mean spinal bone density in the eumenorrheic hyperprolactinemic women (171 +/- 22 mg/K2HPO4.cm3) was similar to that in the normal women and was significantly greater (P less than 0.05) than that in the hyperprolactinemic amenorrheic women. The mean spinal bone density in the women with hypothalamic amenorrhea (128 +/- 24 mg/K2HPO4.cm3) and normal PRL levels was also significantly (P less than 0.001) lower than that in normal women or hyperprolactinemic euenorrheic women. Six of the women with hypothalamic amenorrhea had bone density measurements greater than 2 SD below normal. The spinal bone density values were similar in the amenorrheic women with or without hyperprolactinemia. The mean radial bone density in the hyperprolactinemic women with amenorrhea (0.69 +/- 0.03 g/cm2) was comparable to that in the women with hypothalamic amenorrhea (0.69 +/- 0.05 g/cm2), and both groups had significantly (P less than 0.05) lower values than normal women (0.72 +/- 0.03 g/cm2). Radial bone density was normal in the hyperprolactinemic eumenorrheic women. The mean serum estradiol level in the hyperprolactinemic amenorrheic women (120 +/- 90 pmol/L) was significantly (P less than 0.05) lower than that in the hyperprolactinemic eumenorrheic women measured during the follicular phase of their cycles (240 +/- 180 pmol/L) and was comparable to that in the women with hypothalamic amenorrhea (80 +/- 40 pmol/L). Multiple comparisons of clinical variables, serum hormone concentrations, and bone mass demonstrated a significant correlation (P = 0.0125) between bone density and serum dehydroepiandrosterone sulfate levels, which suggests a role for endogenous androgens in the maintenance of premenopausal bone mass.(ABSTRACT TRUNCATED AT 400 WORDS)     

Differences in apolipoproteins and low-density lipoprotein subfractions in postmenopausal women on and off estrogen therapy: results from the Framingham Offspring Study

The use of estrogens by postmenopausal women has been associated with reduced risk of coronary artery disease (CAD) in some studies, possibly due to favorable effects of estrogens on plasma lipoproteins. In order to examine such effects, we studied 180 postmenopausal women from the Framingham Offspring Study, selected by type of menopause (natural or oophorectopic) and estrogen use. We determined fasting plasma total cholesterol, triglyceride, very-low-density lipoprotein (VLDL) cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) A-l and B concentrations, as well as LDL particle size (LDL 1 to LDL 6). Apo A-l levels were significantly (P less than .005) higher, and diastolic blood pressure and glucose levels were significantly (P less than .05) lower in postmenopausal women taking estrogen regardless of type of menopause. HDL cholesterol levels were also higher in women taking oral estrogens, but differences were significant only for the oophorectomized group (P less than .02). Total cholesterol, VLDL cholesterol, and LDL cholesterol levels were significantly lower (P less than .01) in women with natural menopause who were taking estrogens than in women with natural menopause not taking this medication. No significant differences between estrogen users and nonusers were found with regard to triglyceride levels or LDL particle score, in either the natural menopause or oophorectomy groups. These data indicate that estrogen use in postmenopausal women is associated with significantly elevated plasma apo A-l levels and decreased LDL cholesterol concentrations.     

Differential effects of continuous versus intermittent administration of growth hormone to hypophysectomized female rats on serum lipoproteins and their apoproteins

The effects of the plasma pattern of GH on serum and lipoprotein levels of total cholesterol, triglycerides, apolipoprotein A-I (apo A-I), apolipoprotein B 48/100 (apo B), and apolipoprotein E (apo E) were studied in hypophysectomized female Sprague-Dawley rats, which had been given replacement therapy with L-T4 and hydrocortisone. Bovine GH (1 mg/kg.day) was administered sc either continuously by means of osmotic minipumps or by two daily injections. Serum lipoproteins were separated by sequential ultracentrifugation into very low density lipoproteins [density (d) less than 1.006 g/ml], low density lipoproteins (LDL; d 1.006-1.063 g/ml) and high density lipoproteins (HDL; d 1.063-1.21 g/ml). The content of total cholesterol and triglycerides were then determined. Apo A-I, apo B, and apo E were isolated from rat serum and antibodies raised in rabbits. In serum and in lipoprotein fractions, the content of apo A-I, apo-B, and apo E were determined by electroimmunoassay. After hypophysectomy, there occurred a decrease in serum cholesterol and serum levels of apo A-I and apo E, in spite of replacement therapy with T4 and cortisone. Similar changes were also observed in HDL. In contrast, apo B, cholesterol, and triglycerides were increased in LDL. Estradiol treatment had no effect on these changes. Continuous infusion of GH resulted in an increase in cholesterol and apo E in serum and HDL to the levels of intact females. In contrast, GH given twice daily had no effect. Therefore, the sexually dimorphic secretion of GH may be important for the regulation of sex differences in apo E and HDL cholesterol levels. There were no consistent effects of GH treatment on the levels of apo A-I in serum or HDL, but GH treatment resulted in a decrease in apo B and triglycerides in both serum and LDL, regardless of the mode of administration. This suggests that GH regulates the serum and LDL levels of apo B and triglycerides independently of the secretory pattern.     

The effect of lovastatin treatment on low-density lipoprotein hydrated density distribution and composition in patients with intermittent claudication and primary hypercholesterolemia.

The effects of lovastatin treatment on density distribution and composition of low-density lipoproteins (LDL) were studied using a density gradient ultracentrifugation method in 35 hypercholesterolemic patients with severe peripheral vascular disease. Lovastatin caused a 32% mean reduction in LDL particle mass and a 36% reduction in LDL cholesterol. The cholesteryl ester to apolipoprotein (apo) B, free cholesterol to apo B, and phospholipid to apo B weight ratios in LDL decreased significantly during treatment (P less than .01, P less than .01, and P less than .001, respectively). The effect on plasma triglycerides (Tg) was not uniform. Plasma Tg levels decreased in 25 patients, but increased in 10 patients. Since plasma Tg level influences the LDL density distribution and composition, the patients were also subgrouped and analyzed according to change in plasma Tg. In those with increased plasma Tg, the light LDL particles were reduced more and the dense particles less compared with patients with decreased Tg. The mean Tg content of LDL increased (from 7.7% to 9.3%; P less than .05) and the weight ratio of core lipids (cholesteryl ester/Tg) in LDL decreased (from 4.57 to 3.44; P less than .01) in patients with increased plasma Tg during treatment. The results indicate that the change in plasma Tg (decrease or increase) determined the qualitative changes in LDL observed during lovastatin treatment.     

Effects of fenofibrate on high and low density lipoprotein metabolism in heterozygous familial hypercholesterolemia

This study investigates the influence of pharmacological doses of fenofibrate on HDL and LDL metabolism in 5 familial hypercholesterolemia heterozygotes. Fenofibrate lowered plasma low density lipoprotein cholesterol (20%, P less than 0.025), triglycerides (37%: P less than 0.005) and apolipoprotein B (14%: P less than 0.05) but increased apo A-I (20%; P = 0.01). Kinetic studies showed that the drug markedly increased the fractional catabolic rate of LDL-apo B by 59% and its synthetic rate by 36%. Fractional catabolic rate of apo A-I was also increased by 26% but accompanied by a much greater increase of its synthetic rate (49%). Thus the change in balance between catabolism and synthesis of both apoproteins affected by fenofibrate accounts for the observed plasma concentration changes, which may be considered as favourable with regard to the management of atherosclerosis.     

Changes in the composition of plasma lipoproteins in the chronic uremic rat

The effect of chronic renal failure on the lipid and apolipoprotein concentrations of plasma, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) was studied in an experimental uremic rat model. Control rats were sham-operated and were divided into adlibitum-fed and pair-fed groups. The rats were studied (after an overnight fast) 32 days after the onset of uremia. The uremic rats had a 4-fold increase in plasma urea nitrogen and creatinine. The pair-fed and ad-lib-fed controls had similar levels of plasma urea nitrogen and lipid profiles. In the uremic rats, plasma triglyceride (TG) levels were increased 3.8-fold due to increased TG in the VLDL, IDL and HDL fractions. Their 2-3-fold increase in plasma free cholesterol (FC), esterified cholesterol (EC) and phospholipids (PL) were due to FC, EC and PL increases in VLDL, IDL, LDL and HDL. Their increase in plasma apo B (x 2.4) and apo E (x 1.5) were due to increases in VLDL, IDL and LDL. Their plasma apo A-I increased 2.4 fold due to increases in the LDL and HDL fractions. Uremic rats also had increases in the FC/PL molar ratio in VLDL, IDL and LDL. In their LDL, the apo B/total cholesterol (TC), apo B/PL and apo B/apo E molar ratios were decreased. In their HDL, the apo E/TC and apo E/PL molar ratios were decreased and the apo A-I/apo E molar ratio was increased. In conclusion, chronic uremia causes both quantitative changes in the levels and qualitative changes in the composition of the plasma lipoprotein particles. These results are compatible with the decreased hepatic lipase activities and impairment of remnant clearance observed in human chronic renal failure.