Estrogen replacement therapy decreases platelet-activating factor-acetylhydrolase activity in post-menopausal women

Objective: To examine the effects of estrogen replacement therapy on plasma platelet-activating factor-acetylhydrolase (PAF-AH) activity and the lipoprotein profile in post-menopausal women. Method: Eight post-menopausal women received conjugated equine estrogen (0.625 mg/day) orally for a period of 10 weeks. PAF-AH activity and lipid levels were measured in plasma samples obtained from each subject prior to treatment and after 2, 6, and 10 weeks of estrogen therapy. Results: Within 2 weeks of initiating estrogen treatment, a significant reduction in PAF-AH activity (−26%) was observed. Estrogen also caused significant decreases in total cholesterol (−8%), low-density lipoprotein-cholesterol (−24%), and the ratio of apolipoprotein B to A-II (-19%). On the other hand, levels of both high-density lipoprotein-cholesterol (18%) and triglyceride (31%) were elevated. Conclusion: Estrogen exerts a favorable effect on the lipoprotein profile, but decreased plasma PAF-AH activity may facilitate platelet aggregation thereby opposing protective effect of estrogen-replacement therapy with respect to thrombotic complications.     

Phenotype of apolipoprotein E influences the lipid metabolic response of postmenopausal women to hormone replacement therapy

Objectives: We investigated whether the phenotype of apolipoprotein E (apo E) would influence the response of postmenopausal Japanese women to hormone replacement therapy (HRT). Methods: We measured the plasma levels of lipoprotein and apolipoprotein in 242 postmenopausal women at baseline and again after 12 months of HRT. Patients were divided into three groups according to apo E phenotype: E2+ (E2/2 and E2/3, n=21), E3/3 (n=176), E4+ (E3/4 and E4/4, n=45). Results: We found that the E4+ group had the highest levels of total and low density lipoprotein (LDL) cholesterol and apolipoprotein B, being significantly higher than in the E2+ group at baseline. The plasma levels of total and LDL cholesterol showed a significant decrease only in the E2+ and E3/3 groups after 12 months of HRT (E2+ group, total cholesterol −8.9% and LDL cholesterol −21.5%; E3/3 group, total cholesterol −2.9% and LDL cholesterol −9.5%). No significant difference in the reduction of total and LDL cholesterol was found in the E4+ group. Other lipid parameters did not differ in the three groups. Conclusions: These data show that the apo E phenotype influenced the response of lipid metabolism in postmenopausal women to HRT, especially in the reduction of LDL cholesterol. Therefore, apo E phenotyping may be important in predicting the cholesterol-lowering effect of HRT.     

Comparison of the long-term effects of oral estriol with the effects of conjugated estrogen on serum lipid profile in early menopausal women

Objective: We investigated the long-term effects of oral estriol (E₃) on serum levels of total cholesterol (t-Cho), high-density lipoprotein cholesterol (HDL-Cho), low-density lipoprotein cholesterol (LDL-Cho), and triglycerides in early menopausal women. Methods: We studied 67 healthy early menopausal women who were treated for 48 months with 2.0 mg of E₃ plus 2.5 mg of medroxyprogesterone acetate daily (E₃ group, n=21), 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate daily (CE group, n=19), or 1.0 μg of 1-hydroxyvitamin D₃ daily or 1.8 g of calcium lactate containing 250 mg of elemental calcium daily (control group, n=27). The serum levels of t-Cho, HDL-Cho, LDL-Cho, and triglycerides were evaluated at baseline and every 6 months. Results: After 48 months of treatment, the t-Cho decreased significantly by 4.3±2.1% (mean±SE) from baseline in the E₃ group, did not change in the CE group (−1.9±2.1%), and significantly increased (5.4±3.4%) in the control group. The HDL-Cho significantly increased in the CE group (10.7±2.4%), but not in the E₃ group (3.8±3.3%) or in the control group (−3.6±3.0%). The LDL-Cho significantly decreased in the CE group (−11.4±4.0%), did not change in the E₃ group (−5.2±3.6%), and significantly increased in the control group (11.8±6.3%). The triglyceride level decreased significantly in the E₃ group (−6.7±4.9%), whereas it significantly increased in the CE group (17.6±11.4%), and did not change in the control group (6.1±6.4%). Conclusions: Oral E₃ prevented a postmenopausal rise in the t-Cho. Oral estriol did not induce the hypertriglyceridemia that was seen after treatment with conjugated estrogen. Oral E₃ may be a useful alternative therapy in women with hypertriglyceridemia and in women who are reluctant to continue conventional hormone replacement therapy because of uterine bleeding.     

Long-term effects of transdermal and oral estrogens on serum lipids and lipoproteins in postmenopausal women

The transdermal and oral administration of estrogens for one year were compared with respect to the effects on lipid metabolism. Eighty-one postmenopausal women (1.5-3 years after menopause) were randomly divided into three groups. The first two groups received sequential estrogen treatment with either transdermal estradiol (Estraderm TTS, Ciba Geigy; 50 μg/day; 24 women) or 0.625 mg/day conjugated estrogens (Premarin, Wyeth; 20 subjects), respectively. In both groups medroxyprogesterone (10 mg/day per os) was added for 12 days of each cycle. Thirty-five subjects served as control group without therapy. No significant changes in the lipid profile was observed in control subjects after 1 year of follow-up. Serum triglycerides decreased significantly (-10.9 ± 26% S.D.; P < 0.05) in transdermal treated women, whereas it slightly rose in oral estrogen group. Comparable significant decreases in total and low density lipoprotein (LDL) cholesterol (mean range -6.5/-18.0%) were observed in women on estrogen replacement therapy. High density lipoprotein (HDL) cholesterol significantly diminished in transdermal estradiol group, but it rose slightly in the oral estrogen group. Thus the fraction of HDL cholesterol over LDL cholesterol did not change in the transdermal group whereas it significantly rose in subjects treated with oral estrogens. It remains to be established to what extent these differences on lipid metabolism are relevant for the prevention of cardiovascular diseases.     

Transdermal estrogen replacement therapy and plasma lipids in 693 French women

Objectives: The cardiovascular effects of transdermal estrogen are not so well established than those induced by oral estrogen. In a representative sample of French postmenopausal women, we assessed plasma lipid changes induced by transdermal 17β-estradiol. Methods: This cross-sectional study was carried out among the population sample of the third MONICA survey on cardiovascular risk factors. We selected 693 postmenopausal women according to the followed criteria; women with intact uterus and no menstruation for more than 12 months, women with bilateral oophorectomy, hysterectomized women older than 55 years and hysterectomized women who had followed hormone replacement therapy. We used multivariate linear regression models, taking into account confounding variables, to assess lipid changes induced by estrogen. Results: We compared 192 women currently taking transdermal 17β-estradiol (27 unopposed estrogen and 165 estrogen plus progestin) with 501 women without any hormonal treatment. After adjustment for living area, education level, income tax, smoking, alcohol consumption, physical activity, age and body mass index, transdermal estrogen replacement therapy (ERT) was significantly associated with lower levels of serum total cholesterol [6.10 (S.E., 0.11) vs 6.35 (0.09) mmol/l, P<0.01], triglycerides [1.06 (0.06) vs 1.23 (0.05) mmol/l, P<0.001], LDL-cholesterol [3.93 (0.11) vs 4.13 (0.09) mmol/l, P<0.05], VLDL-cholesterol [0.48 (0.03) vs 0.56 (0.02) mmol/l, P<0.001] and apolipoprotein B [1.20 (0.03) vs 1.26 (0.02) g/l, P<0.01]. Levels did not differ significantly for HDL-cholesterol [1.68 (0.05) vs 1.66 (0.04) mmol/l] and apolipoprotein A1 [1.79 (0.03) vs 1.81 (0.02) g/l]. Conclusion: Transdermal ERT may confer a cardiovascular protection by lowering atherogenic lipoproteins.     

Acquisition of lipoproteins in the procyclic form of Trypanosoma brucei

The procyclic form of Trypanosoma brucei binds and internalizes bovine high density lipoprotein (HDL) particles in a saturable process; the binding and uptake of ¹²⁵I-labeled HDL are inhibited by excess unlabeled HDL. We calculated that each procyclic trypanosome exposes ≈1.0×10⁶ binding sites for bovine HDL, with an equilibrium dissociation constant (K_d) of ≈1.26×10⁻⁷ M. Uptake of HDL particles does not occur at 4°C. At 28°C, a significant amount of the internalized HDL particles were efficiently degraded through a process that is sensitive to the presence of 50 μM chloroquine. These results suggested that the uptake of HDL particles in procyclic T. brucei may occur via receptor mediated endocytosis, leading to proteolytic degradation of the particles in an acidic and endocytic compartment.     

Metabolic effects of tibolone in postmenopausal women with non-insulin dependent diabetes mellitus

Objective: Postmenopausal women with non-insulin dependent diabetes (NIDDM) are frequently obese, hypertensive and hyperlipidaemic and hence at particular risk of coronary heart disease (CHD). They might therefore benefit from menopausal therapy. In view of the improvement in insulin sensitivity and the reduction in triglyceride levels induced by tibolone in healthy postmenopausal women we evaluated the effects of 12 months of tibolone on glycaemic control, serum insulin and lipid levels in postmenopausal women with NIDDM. Design: A prospective 12 months before/after intervention study. Patients: Fourteen postmenopausal women (mean age 58.14±1.25 years; mean duration of menopause 121.21±13.42 months; mean BMI: 26.55±0.97) with NIDDM (mean duration of diabetes 113.79±13.89 months). Measurements: Fasting and postprandial blood glucose levels were assessed monthly, serum fructosamine, fasting and postprandial insulin every 3 months and serum lipids (total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol) every 6 months. Results: Changes in blood glucose, both fasting and postprandial, were not statistically significant during the treatment period. Serum fructosamine concentration increased significantly after 9 months. A significant decrease in fasting and postprandial insulin concentrations was observed after 9 months. A non-significant decrease was observed in total cholesterol, LDL cholesterol and triglyceride but no change in HDL cholesterol. Body weight did not change during the period of observation. Conclusion: A slight deterioration in glycaemic control, a fall in insulin concentration and no change in serum lipids were observed in women with NIDDM during 12 months treatment with tibolone.     

Intrauterine administration of levonorgestrel in two low doses in HRT. A randomized clinical trial during one year: effects on lipid and lipoprotein metabolism

Objective: To investigate the effects on lipid and lipoprotein metabolism of two doses (5- or 10 μg/24 h) of levonorgestrel released from an intrauterine device (IUD) in combination with orally administered estradiol (2 mg estradiol valerate) in perimenopausal women. Design: A 1-year prospective randomized single blind clinical trial. setting: Department of Obstetrics and Gynaecology, Östra Hospital, Göteborg, Sweden. Subjects: Fifty-one perimenopausal women with climacteric symptoms. Outcome measures: Cholesterol in serum and in lipoprotein fractions; high-density lipoprotein 9HDL), low-density lipoprotein (LDL). Triglycerides in serum and in very low-density lipoprotein. Results: In both treatment groups significant elevations in HDL-cholesterol of similar magnitude were observed after 1 month and these changes were maintained during the 12 month observation period. In both treatment groups an initial significant decrease of LDL-cholesterol was observed and the decrement was maintained after 12 months. Serum levels of cholesterol decreased significantly in both groups after 1 month and were maintained after 12 months in the levonorgestrel-IUD (LNG-IUD) 5 μg group. However, the initial reduction of serum cholesterol in the LNG-IUD 10 μg group did not differ from baseline after 12 months. Serum triglyceride levels fluctuated during the observation period. No significant changes occurred. Conclusion: continuous combined HRT with intrauterine administration of levonorgestrel, 5- or 10 μg/24 h, in perimenopausal women was observed to increase HDL-cholesterol and to decrease LDL-cholesterol compared with pretreatment values. the low doses of levonorgestrel did not reverse the beneficial effects on lipid metabolism usually seen after estradiol administration.     

Effect of menopause on low-density lipoprotein oxidation: is oestrogen an important determinant?

Objectives: Significantly increased risk for developing cardiovascular disease in post-menopausal women is linked with the fall of oestrogen. Although supraphysiological levels of oestrogen may inhibit oxygen free radical mediated low-density lipoprotein (LDL) oxidation, the effect of physiological level of oestrogen on LDL oxidation is unknown. Methods: The present study compared oxidizability of LDL in healthy pre- and post-menopausal women by using a commonly employed copper ion-dependent method. Results: Pre-menopausal women (n=20, mean age 27) had significantly higher serum oestradiol level (576±109 pmol/l) in comparison to post-menopausal women (n=23, mean age 51, oestradiol 64±18 pmol/l, P<0.001). The oxidation of LDL in two groups was not different by measuring either the lag phase of conjugated dienes formation (54±12 vs. 55±14 min, P>0.05) or the generation of thiobarbituric acid reactive substances over 4 h of oxidation. The major lipid soluble antioxidant in LDL, vitamin E (determined as -tocopherol) is similar in two groups (2.34±0.48 vs. 2.40±0.56 nmol/mg LDL, pre- and post-menopausal subjects, respectively, P>0.05). Linear regression analysis found a weak but significant correlation between LDL vitamin E level and oxidizability of LDL in both groups but did not show effect of serum oestradiol levels. Conclusion: The results suggest that physiological levels of oestrogen may not be able to affect in vitro LDL oxidation.     

The effects of hormone replacement therapy on plasma lipids in type II diabetes

Objectives: The effects of hormone replacement therapy on cardiovascular risk factors in postmenopausal women with non-insulin dependent diabetes mellitus (type II diabetes) is uncertain. Methods: The effects of estrogen replacement therapy (ERT, conjugated equine estrogen 0.625 mg orally daily), combined estrogen and continuous progestogen therapy (HRT, 0.625 mg of conjugated equine estrogens plus medroxyprogesterone acetate 5 mg daily) or placebo was compared in 20 postmenopausal type II diabetic women and 20 normal postmenopausal women in a double blind, randomised, crossover study. Patients receiving insulin were excluded from the study and all lipid modifying drugs were ceased at least 4 weeks prior to randomisation. Other medication including oral hypoglycaemics was kept constant for the duration of the study. Results: Women with type II diabetes were a similar age (58.7±1.3 years) to the non-diabetic women (59.6±1.6 years) but they had a significantly greater body mass index, a higher incidence of treated hypertension, higher fasting plasma glucose levels, higher triglycerides and lower HDL cholesterol levels than non-diabetic women. ERT reduced total cholesterol and LDL cholesterol by a similar extent (8.9–12.3%) in normal and type II diabetic women and increased HDL cholesterol to a similar extent in both groups (11.0 and 8.9% respectively). ERT did not significantly alter fasting triglyceride levels in either group. The addition of medroxyprogesterone acetate 5 mg daily abolished the increase in HDL cholesterol associated with ERT in both groups but did not significantly affect any of the other lipid measurements. ERT and HRT did not significantly alter fasting insulin levels nor alter fasting glucose levels in either non-diabetic women or women with type II diabetes. Conclusions: ERT and HRT have similar effects on lipids in women with type II diabetes and non-diabetic women after 1 month of therapy.     

Effects of short-term melatonin administration on lipoprotein metabolism in normolipidemic postmenopausal women

OBJECTIVE: To investigate the effects of short-term administration of melatonin on lipoprotein metabolism in normolipidemic postmenopausal women. METHODS: Fifteen such women received 6.0 mg melatonin daily for 2 weeks. Blood was sampled before and after treatment. We measured concentrations of total cholesterol and total triglyceride in the plasma, as well as the levels of cholesterol, triglyceride, and protein in the very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Plasma apolipoprotein levels were determined by immunoturbidimetric assay. Activities of lipoprotein lipase, hepatic triglyceride lipase, and lecithin cholesterol acyltransferase were also determined by enzymatic analysis. RESULTS: Melatonin administration significantly increased the plasma levels of triglyceride by 27.2% (P < 0.05), of VLDL-cholesterol by 37.2% (P < 0.01), of VLDL-triglyceride by 62.2% (P < 0.001), and of VLDL-protein by 30.0% (P < 0.05). However, the plasma total cholesterol level and the concentration of lipid and protein in LDL and HDL were not significantly affected. Melatonin significantly increased the plasma levels of apolipoprotein C-II by 29.5% (P < 0.005), of C-III by 17.1% (P < 0.001), and of E by 7.6% (P < 0.05). The plasma levels of apolipoprotein A-I, A-II, and B were not altered. Melatonin significantly inhibited the activity of lipoprotein lipase by -14.1% (P < 0.05), but did not significantly affect the activities of hepatic triglyceride lipase or of lecithin cholesterol acyltransferase. CONCLUSIONS: Findings indicate that melatonin increases the plasma level of VLDL particles by inhibiting the activity of lipoprotein lipase, but may not affect the plasma levels of LDL and HDL particles in postmenopausal women with normolipidemia.     

Die Wirkungen gleicher Mengen Linolsäure in oral zugeführten,mehrfach ungesättigten Phospholipiden oder in Safloröl auf die Lipoproteine des Plasmas

Summary The effects of polyenylphosphatidylcholine in a dosage of 10 g per day were compared with an equimolar amount of linoleic acid in 7 g safloroil per day in 8 healthy subjects for 3 weeks. The concentrations of cholesterol, triglycerides, phospholipids, apolipoproteins A-I, A-II and B were measured in serum, as well in VLDL, LDL, HDL, HDL₂, HDL₃ on the day before, after 2 and 3 weeks of application and 6 months after the experiment. The diet was controlled 10 days before and during the experiment using the dietary recall method. According to the dietary records there was an increase of fat supply during application of polyenylphosphatidylcholine inhibiting decrease of LDL cholesterol, which was observed with safloroil. Phospholipid concentrations increased significantly with polyenylphosphatidylcholine in VLDL. Apolipoprotein B in LDL was significantly decreased by both substances. Apolipoprotein A-I and A-II in HDL increased significantly with polyenylphosphatidylcholine. With safloroil this effect was limited to apolipoprotein A-I, but less impressive. The effects of both substances are comparable in the decrease of apolipoprotein B and probably cholesterol. A special effect of polyenylphosphatidylcholine was observed on phospholipids in VLDL and on apolipoprotein A-I and A-II in HDL.

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Abkürzungen PPC Polyenylphosphatidylcholin - VLDL Very low density lipoproteins - LDL Low density lipoproteins - HDL High density lipoproteins - LCAT Lecithin-Cholesterin-Acyl-Transferase     

Effects of continuous medroxyprogesterone acetate on lipoprotein metabolism in postmenopausal women receiving estrogen

Objective: To investigate the effects of medroxyprogesterone acetate (MPA) on the beneficial effects of estrogen therapy on lipid metabolism in postmenopausal women. Methods: Postmenopausal women were administered either conjugated equine estrogen (CEE) 0.625 mg daily for 3 months (Group 1) or CEE 0.625 mg in conjunction with MPA 2.5 mg (Group 2) or MPA 5.0 mg (Group 3) daily for 3 months. Plasma levels of cholesterol, triglyceride, lipoprotein lipids, apolipoproteins, sex steroid hormones and lecithin cholesterol acyltransferase activity (LCAT) were determined. Lipoprotein lipase (LPL) and hepatic triglyceride lipase (H-TGL) activities were measured in postheparin plasma. Changes in the lipid concentrations and enzymatic activities were evaluated in each group. Results: Total, low-density lipoprotein (LDL) cholesterol, apolipoprotein B concentrations and LCAT activity were all significantly reduced by treatment in the three groups. The levels of high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol as well as the levels of apolipoprotein AI and AII were significantly elevated in groups 1 and 2. The mean decrease in these parameters was related to the dose of MPA. Levels of triglyceride in the HDL and HDL2 were significantly increased in group 1. The levels of triglyceride in plasma, very low density lipoprotein (VLDL), LDL, HDL3 and VLDL cholesterol and LPL activity were unaffected. H-TGL activity was significantly inhibited only in groups 1 and 2. MPA produced a dose-dependent increase in H-TGL activity. A significant negative correlation was observed between the HDL cholesterol concentration and H-TGL activity (r = 0.58 P < 0.001). Conclusions: The administration of MPA 2.5 mg and 5.0 mg did not adversely affect the changes in VLDL-LDL metabolism produced by estrogen. However, MPA has dose-dependent negative effects on HDL metabolism by increasing H-TGL activity and the 5.0 mg MPA interferes with the favorable effects on lipids of estrogen in postmenopausal women.     

National differences in lipid response to postmenopausal hormone replacement therapy

Objective: To compare the response of serum lipids and lipoproteins to the transdermal hormone replacement therapy (HRT) in five European countries. Methods: Five-hundred and sixty-seven healthy postmenopausal women from Belgium, Finland, the Netherlands, Sweden, and the UK received transdermal estradiol 50 μg daily for 12 months. In addition, two groups received transdermally norethisterone acetate (NETA) continuously, two groups sequentially (170 or 350 μg/day); one group received sequentially oral NETA (1 mg/day), and one group dydrogestrone (20 mg/day). Serum total cholesterol, HDL-, HDL2-, LDL-cholesterol, lipoprotein(a) (Lp(a)), and triglycerides were assessed before and at the end of treatment. Results: No significant national differences existed in the pretreatment levels of lipids and lipoproteins. Mean cholesterol, LDL, Lp(a), and triglycerides decreased during HRT, and HDL and HDL2 increased. Individual changes in responses to HRT were strongly dependent on pretreatment values. In this regard, British women differed from the others: their cholesterol, HDL, HDL2, and Lp(a) responses, when related to the pretreatment levels, were smaller than those of the others. Conclusion: A national difference discovered in response of serum lipids to HRT calls for caution in generalization of lipid data from one nation to another during HRT.     

Imaging of the super high affinity binding sites for [H]Ro15–4513 in rat hippocampus: comparison between in vitro and in vivo binding

The super high affinity binding sites for [³H]Ro15–4513, a partial inverse agonist of central benzodiazepine receptors, were analyzed in rat hippocampus both in vivo and in vitro. An ultra high sensitive method of autoradiography with an imaging plate system was employed for quantitative analysis of [³H]Ro15–4513 binding. In in vitro binding, the super high affinity binding sites in the hippocampus were observed when the [³H]Ro15–4513 concentration was below 0.5 nM. In vivo, the super high affinity binding sites were only found when the injected dose of Ro15–4513 was below 3.6 μg/kg and almost disappeared when the dose was increased to 10 μg/kg. These results both in vivo and in vitro indicate that there is a significant discrepancy between actual free ligand concentration in vivo and in vitro, and that concentrations in intact brain may be much lower than previously thought.     

Subfornical organ efferents enhance extracellular noradrenaline concentrations in the median preoptic area in rats

The present study was carried out to examine whether angiotensinergic pathways from the subfornical organ (SFO) regulate the noradrenergic system in the median preoptic nucleus (MnPO). Intracerebral microdialysis techniques were used to quantify the extracellular concentration of noradrenaline (NA) in the MnPO area. In urethane-anesthetized male rats, electrical stimulation (5–20 Hz, 0.6 mA) of the SFO significantly increased the NA concentration in the MnPO area, and the increase was significantly diminished by pretreatment with the angiotensin II (ANG II) antagonist saralasin (Sar; 5 μg), into the third ventricle (3V). Injections of ANG II (5 μg) into the 3V significantly enhanced NA release in the MnPO area. The data imply that the angiotensinergic pathways from the SFO to the MnPO may act to enhance NA release in the MnPO area.     

Determination of Atrazine in Soil Samples by ELISA Using Polyclonal and Monoclonal Antibodies

Atrazine concentrations were measured by polyclonal antibody (PAb) and monoclonal antibody (MAb) ELISAs in methanolic extracts of both laboratory-fortified and field samples collected from 12 maize fields. Analysis of 91 soil samples collected in the Southern Moravian region demonstrated that the ELISAs were a reliable screening tool for the determination of atrazine in soil matrices. A good correlation of results obtained by ELISAs and gas chromatography within the concentration range of 0-380 μg kg^-1 was found in the samples collected from two maize fields (r PAb ELISA-GC) = 0.97, n = 21; r (MAb ELISAGC) = 0.94, n = 21]. A somewhat lower correlation was found for the samples collected from ten additional fields within the concentration range of 0-390 μg kg^-1 [r(PAb ELISAGC) = 0.91, n = 15; r(MAb ELISA-GC) = 0.87, n = 15)]. The results obtained by PAb and MAb ELISAs showed no significant difference although the sensitivity of the PAb method was by one order of magnitude higher than that based on MAb.     

Effects of fish oil concentrate on lipoproteins and apolipoproteins in familial combined hyperlipidemia

Summary The effects of two moderate doses of long-chain n-3 fatty acids (3.0 and 4.5 g EPA + DHA per day for 4 weeks each) on serum lipids and lipoproteins of patients with familial combined hyperlipidemia (FCH) were studied in a double-blind, placebo-controlled clinical trial. In nine patients with FCH n-3 fatty acids led to a statistically significant, dose-dependent fall in very low density lipoprotein (VLDL) triglycerides (3 g/day: –42%, 4.5 g/day: –55%) VLDL cholesterol (3 g/day: –41%, 4.5 g/day: –47%), and VLDL apolipoprotein (apo) B-100 (3 g/day: –40%, 4.5 g/day: –56%). No overall change in low-density lipoprotein (LDL) cholesterol was found, as confirmed statistically. However, when analyzing the data of single patients LDL cholesterol and LDL apo B did not change in five patients but increased dose dependently (from pretreatment 4.80±0.93 mmol/l to 5.70+0.93 mmol/l LDL cholesterol after 4.5 g/day) in four. LDL and VLDL composition as indicated by cholesterol/apo B-100 and triglyceride/apo B-100 ratios did not change significantly. High-density lipoprotein (HDL) cholesterol was unchanged; the HDL cholesterol/apo A-I+apo A-II ratio increased by 19% (P<0.05) during fish oil treatment. We conclude that in FCH moderate doses of long-chain n-3 fatty acids are highly effective in lowering pathological VLDL triglycerides, VLDL cholesterol, and VLDL apo B. LDL cholesterol must, however, be monitored during treatment as it may rise substantially in some although not in all patients with this disease.Abbreviations EPA eicosapentaenoic acid - DHA docosahexaenoic acid - FCH familial combined hyperlipidemia - VLDL very low density lipoprotein - LDL low-density lipoprotein - HDL high-density lipoprotein - apo apolipoprotein Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

Effects of tibolone on lipoprotein(a) and HDL subfractions

Objective: To determine the effects of tibolone, a synthetic steroid used to alleviate climacteric symptoms and prevent osteoporosis, on lipoprotein metabolism, with particular reference to lipoprotein(a) levels and HDL subfraction profiles.Design: Thirty nine postmenopausal women were treated with tibolone (Livial) 2.5 mg/day for 6 months and fasting serum lipoprotein levels were estimated at 0, 2, 4 and 6 months. Results: Lipoprotein(a) levels were reduced significantly over the 6 months from a median level of 245 (range <60–780) mg/I to 152 (range <60–530) mg/l, a reduction of 39% in the median level. A decrease was observed in approximately two thirds of the women. Reductions were noted in all 6 subjects whose pretreatment levels were high, although concentrations remained at a level associated with increased risk in all but one. There were significant decreases in triglycerides and VLDL cholesterol and no significant change in LDL cholesterol. There was a significant reduction of 18% in HDL cholesterol and a 26% reduction in the HDL₂:HDL₃ ratio. Conclusion: The reduction in lipoprotein(a) levels may have a beneficial effect on cardiovascular risk, which could go some way towards balancing the potentially adverse effect on the cardiovascular system caused by the reduction in HDL cholesterol.     

Receptors and molecular heterogeneity of lipoprotein particles containing apolipoprotein A-I

High density lipoproteins (HDL) are heterogeneous, with respect to their hydrated density (HDL2, HDL3), and to their apolipoprotein composition (Lp A-I : A-II contains both apolipoprotein A-I and A-II, Lp A-I contains apolipoprotein A-I but not apolipoprotein A-II). Lp A-I and Lp A-I and Lp A-I : A-II particles have different metabolic functions. Only Lp A-I particles seem to be involved in the antiatherogenic role of HDL. Alcohol consumption raises Lp A-I : A-II level but not Lp A-I. Different tissue possess specific binding sites for HDL: steroidogenic tissue, hepatocytes peripheral cells. Apolipoprotein A-I and/or A-II are possible ligands. HLD, after binding to the receptor, can provide the cells with cholesterol, or promote an efflux of cholesterol from the cells and the "reverse cholesterol transport" from the peripheral cells to the liver. The HDL subfractions possess different metabolic roles: binding of Lp A-I to mouse adipose cell receptors promotes cholesterol efflux. Apo A-II are antagonists for this effect.