Lp(a) lipoprotein is a major risk factor for cardiovascular disease: pathogenic mechanisms and clinical significance

The results of two previous and two recent studies of middle-aged males and females are presented to exemplify the clinical importance of lipoprotein (a) (Lp(a)) as a risk factor for atherosclerosis and coronary heart disease. In these studies various conventional and recently suggested risk factors were included and different methods for Lp(a) quantification were used. Lp(a) was a significant risk factor in all four studies. In the recent prospective case-control study, Lp(a) and cholesterol were found to act synergistically and predict primary acute myocardial infarction in Swedish males. A cholesterol level above 6.5 mmol/1 increased the risk of acute myocardial infarction if the Lp(a) level was above 200 mg/1. The plasma apo A-I level was a protective factor. In the other recent case-control study, an Lp(a) level above 500 mg/1 was a highly significant risk factor in Black and White US women with myocardial infarction or advanced coronary artery disease in addition to low density lipoprotein cholesterol levels above 130 mg/dl. A high apo A-I level was a protective factor. In these studies no other factors tested reached significance in multivariate logistic regression analysis. A hypothetical association between high Lp(a) levels and intracellular infection with Chlamydia pneumoniae is discussed. The results suggest that the Lp(a) level is useful in identifying high-risk individuals. Lowering low density lipoprotein cholesterol below 100 mg/dl (7lt;2.6 mmol/1) seems to be most important in both males and females with high-risk Lp(a) levels.     

Comparative long-term experience with immunoadsorption and dextran sulfate cellulose adsorption for extracorporeal elimination of low-density lipoproteins

Two low-density lipoprotein (LDL) apheresis methods allowing a specific extracorporeal removal of atherogenic lipoproteins from plasma were compared concerning their efficacy and safety in the long-term therapy of severe familial hypercholesterolemia. Five patients were treated with immunoadsorption (IMA) at weekly intervals over 3 years each, and three patients received weekly therapy with dextran sulfate cellulose adsorption (DSA) for up to 2 years. The mean plasma volume processed per session to decrease total cholesterol to a target level of 100–150 mg/dl at the end of LDL apheresis was significantly lower in DSA than in IMA: 143% vs. 180% of the individual plasma volume. Both LDL apheresis procedures achieved a mean acute reduction of plasma LDL cholesterol by more than 70%. The average interval concentrations of plasma LDL cholesterol obtained without concomitant lipid-lowering medication were 151 ± 26 mg/dl compared to 351 ± 65 mg/dl at baseline in the IMA-treated patients and 139 ± 18 mg/dl compared to 359 ± 48 mg/dl at baseline in the DSA-treated patients. Two patients from the DSA group died after 2 years of study participation due to a stroke and a sudden cardiac death several days after the last plasma therapy. Treatment-related side effects were infrequent. Long-term therapy with IMA and DSA was associated with symptomatic improvement of coronary artery disease and mobilization of tissue cholesterol deposits. Analysis of coronary angiograms after 3 years of weekly LDL apheresis with IMA revealed in five patients nearly identical atherosclerotic lesions without definite regression or progression.Abbreviations LDL low-density lipoprotein - IMA immunoadsorption - DSA dextran sulfate cellulose adsorption - apo apolipoprotein - Lp(a) lipoprotein(a) - HDL high-density lipoprotein - ACE angiotensin-converting enzyme     

The effect of oestrogen implants on high density lipoproteins and its subfractions in women in their pre-mature menopause

Oestrogen is recognized as having profound effects on lipid and lipoprotein levels. It is also considered as the agent protecting the pre-menopausal woman from arteriosclerotic cardiovascular disease. High density lipoprotein (HDL) has also been ascribed a protective role against the development of arteriosclerosis. The effect of natural oestrogen (17β-oestradiol) administered in the form of a subcutaneous pellet on concentrations of lipids and lipoproteins, particularly high density lipoproteins and its subfractions were determined in three young women with premature menopause. Plasma cholesterol, low density lipoprotein and very low density lipoprotein and very low density lipoprotein levels decreased following oestrogen implantation. High density lipoproteins and in particular subfraction 2 (density cut 1.063-1.125 gm/ml) and subfraction 3 (density cut 1.125-1.21 gm/ml) increased profoundly but there was a slight fall in the HDL 2/HDL 3 cholesterol ratio. The HDL/LDL cholesterol ratio increased from 0.21 to 0.46. A decrease in the urinary FSH levels paralleled these changes in the lipoprotein concentrations. Oestrogen administered in this form, unlike other oestrogen or mixed oestrogen-progestogen compounds is a definite modifier of arteriosclerotic risk, and as such could be given therapeutically in menopausal hypercholesterolemic females.     

内源性高甘油三酯血症患者血浆VLDL、LDL及HDL对血凝的影响

目的：研究内源性高甘油三酯血症(HTG)患血浆极低密度脂蛋白(VLDL)、低密度脂蛋白(LDL)及高密度脂蛋白(HDL)是否发生了氧化修饰及其对血凝的影响。方法：对2l例内源性高甘油三酯血症患与2l例年龄性别相近的正常人的血脂、脂质过氧化物进行了分析。用一次性密度梯度超速离心法分离血浆VLDL、LDL及HDL，测定这三种脂蛋白的234nm光吸收、相对电泳迁移率(REM)和硫代巴比妥酸反应物质(TBARS)，分别将这三种脂蛋白加入由正常人新鲜混合血浆构成的反应系统中，按试剂盒分别测定凝血酶原时间(PT)及活化部分凝血酶原时间(APIT)。结果：内源性HTG患血浆TG含量平均升高2．73倍，HDLC下降l.7l倍，同时LPO升高1．22倍;HTG组VLDL、LDL及HDL的REM、234nm光吸收值、TBARS含量均较对照组显增加(P＜0．01)，表明内源性HTG患血浆VLDL、LDL及LDL均发生了氧化修饰生成Ox—VLDL、Ox-LDL.PT及APTT在分别加入HTG组的VLDL、LDL及HDL后均比加入相应正常组脂蛋白明显缩短(P均＜0．05)。相关分析表明，HTG组血浆VLDL及HDL相对电泳迁移率(REM)与PT呈负相关(P＜0．01)。结论：HTG患血浆VLDL、LDL及HDL发生了氧化修饰，并使PT及APTT明显缩短。     

Lp(a) lipoprotein enters cultured fibroblasts independently of the plasma membrane low density lipoprotein receptor

Lp(a) lipoprotein shares the apoB antigen with low density lipoprotein (LDL). The Lp(a) antigen is unique for Lp(a) lipoprotein. Fibroblast association (i.e. plasma membrane binding plus intracellular accumulation), plasma membrane binding, intracellular accumulation and degradation of 125I-Lp(a) lipoprotein were studied in strains from subjects with or without autosomal dominant hypercholesterolemia (HC). Subjects without HC (non-HCs) have cell surface receptors for low density lipoprotein (LDL receptors). On the average, HC heterozygotes have half-normal LDL receptor activity and "receptor-negative" HC homozygous cell strains lack functional receptors. Fibroblast processing of 125I-Lp(a) lipoprotein was compared to fibroblast processing of 125I-LDL. LDL receptor-dependent processing of 125I-LDL was saturated at about 50 microgram apo 125I-LDL.ml-1 in non-HC fibroblasts. 125I-Lp(a) lipoprotein was, however, largely processed independently of receptor mechanisms by non-HC cells (highest concentration examined 150 microgram apo 125I-Lp(a) lipoprotein . ml-1). Lp(a) lipoprotein did not interfere with 125I-LDL for fibroblast association, but inhibited 125I-LDL degradation. The interference with 125I-LDL degradation was time dependent. Only slightly higher 125I-Lp(a) lipoprotein processing values were found in non-HC and HC heterozygous strains than in "receptor-negative" HC homozygous strains. However, non-HC cells had more than tenfold higher 125I-LDL processing values than "receptor-negative" HC homozygous cells.     

冠心病患者血清脂蛋白a、同型半胱氨酸及低密度脂蛋白水平与不良心脑血管事件的相关性分析

目的探究冠心病患者血清脂蛋白a[Lp(a)]、同型半胱氨酸(Hcy)及低密度脂蛋白(LDL)水平与不良心脑血管事件的相关性。方法回顾性分析2017年1月至2018年6月期间到我院就诊149例冠心病患者相关资料,分析随访期间患者不良心脑血管事件发生情况,依据随访期间是否出现不良心脑血管事件分为研究组与对照组,比较两组患者Lp(a)、Hcy以及LDL水平,三指标水平对不良心脑血管事件诊断价值,对三指标之间相关性进行分析。结果随访期间患者不良心脑血管事件发生率为10.07%(15/149);研究组患者血清中Lp(a)、Hcy以及LDL水平显著高于对照组(P<0.05);ROC曲线显示Lp(a)、Hcy以及LDL对不良心脑血管事件诊断最佳截断值分别为180mg/L、15μmol/L以及3.78mmoL/L,,其诊断灵敏度分别为73.27%、84.35%与81.29%,其诊断特异性分别为79.35%、81.34%以及80.24%;Pearson相关性分析显示Lp(a)与Hcy之间关系为正相关(r=0.371,P<0.05),Hcy与LDL之间为负相关(r=-0.513,P<0.05),Lp(a)与LDL之间没有相关性(r=0.068,P>0.05)。结论冠心病患者血清中Lp(a)、Hcy以及LDL水平异常升高状态会增加患者不良心脑血管事件发生风险。     

Apolipoprotein E phenotype and lipoprotein(a) in familial hypercholesterolaemia implication for lipoprotein(a) metabolism

The mechanisms regulating plasma levels of lipoprotein(a) [Lp(a)] are largely unknown. A two- to three-fold increase in Lp(a) levels in patients with familial hypercholesterolaemia (FH) has implied that LDL receptor activity may be an important factor in determining plasma Lp(a) levels, as it is in determining low-density lipoprotein (LDL) cholesterol concentration. Common apolipoprotein E (apoE) variants also affect plasma LDL cholesterol levels. We therefore examined the effect of the common apoE variants on plasma Lp(a) levels in 149 patients with heterozygous FH. Patients with the apoE₂ allele (n = 11) had significantly higher plasma levels of LDL cholesterol compared to those with a apoE₃E₃ phenotype, while patients with the apoE₄ isoform had similar levels. However, there was a significant effect of the apoE₂ allele in lowering Lp(a) levels, compared to the apoE₃E₃ group. The median Lp(a) concentration in patients possessing an apoE₂ isoform was 13.1 mg/dl below the median, while in those with an apoE₄ allele the median Lp(a) levels were 4.13 mg/dl higher. There was a marked inverse correlation between plasma Lp(a) and LDL cholesterol concentration in the FH patients carrying the apoE₂ allele. Our data imply that difference in Lp(a) levels observed between FH patients with different apoE isoforms does not result from altered clearance of Lp(a) via the LDL receptor pathway, and suggest that apoE mediated hepatic up-take, or conversion, of remnant particles may be determining Lp(a) production rate.Abbreviations apo apoprotein - CHD coronary heart disease - FH familial hypercholesterolaemia - HDL high-density lipoprotein - LDL low-density lipoprotein - Lp(a) lipoprotein(a)     

Cholesterol lipoproteins,triglycerides, rural-urban differences and prevalence of dyslipidaemia among males in Rajasthan

To develop profiles of serum cholesterol lipoproteins and triglycerides, influence of rural versus urban lifestyle in their levels and prevalence of dyslipidaemias, we studied cohorts of male population in Rajasthan. Fasting blood samples were obtained from 401 men (age range 20-73 years) randomly selected from a larger sample of 3397 during a comprehensive cardiovascular risk factor survey in rural (202 men) and urban (199 men) populations. Serum total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides (TG) were determined and correlated with age and anthropometric variables. The lipid levels were classified according to US National Cholesterol Education Program (NCEP) guidelines. The mean +/- SD levels in mg/dl were, total cholesterol 170.5 +/- 40, LDL cholesterol 102.1 +/- 36, HDL cholesterol 43.6 +/- 12 and TG 124.0 +/- 50. The mean levels in rural vs. urban population were total cholesterol 165 +/- 37 vs. 176 +/- 43 (p = 0.008), LDL cholesterol 97 +/- 33 vs. 108 +/- 39 (p = 0.003), HDL cholesterol 44 +/- 13 vs. 43 +/- 12 (p = 0.44) and TG 122 +/- 46 vs 126 +/- 55 (p = 0.41). There was significant positive correlation of age and body-mass index with total and LDL cholesterol and triglycerides but not with HDL cholesterol. When classified according to the NCEP guidelines high total cholesterol (> or = 240 mg/dl) and LDL cholesterol (> or = 160 mg/dl) was in 33 (8.3%). Borderline high total cholesterol (200-239) was in 64 (16%) and borderline high LDL cholesterol (130-159) in 55 (13.7%). Borderline high triglyceride (200-400 mg/dl) was in 33 (8.2%) and severe hypertriglyceridaemia in none. Low HDL cholesterol (< 35 mg/dl) was in 96 (23.9%) and protective level of HDL cholesterol (> or = 60 mg/dl) in 47 (11.7%). In urban as compared to rural men the prevalence of hypercholesterolaemia > 200 mg/dl (28% vs 22%) and hyper LDL cholesterolaemia (26% vs 18%) were significantly more.     

Lipoprotein (a), low-density,intermediate-density lipoprotein,and blood pressure in a young male population

Summary Both hypercholesterolemia and hypertension are risk factors for atherosclerotic vascular disease, and elevated cholesterol levels occur more frequently than expected in patients with hypertension. Elevated levels of intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL) were shown to be atherogenic, and LDL, comprising the major cholesterol-carrying fraction in human plasma, are structurally related to lipoprotein (a) [Lp(a)], a further risk factor for atherosclerosis. In the present study we investigated 200 male employees (mean age 26±7 years) to determine whether the relationship of IDL and Lp(a) to systemic blood pressure is similar to the reported correlations between total and LDL cholesterol and systemic blood pressure. To this end blood pressure was measured several times in each individual, and lipids, lipoprotein-cholesterol, apolipoprotein B (apo B), and Lp(a) were determined in fasting serum. IDL cholesterol and apo B, the main protein component of IDL and LDL correlated with blood pressure. However, levels of Lp(a) correlated neither with systolic or diastolic blood pressure nor with lipoprotein cholesterol, body weight, or age. Although IDL and Lp(a) are considered lipoprotein risk factors for atherosclerosis, levels of Lp(a), unlike IDL, are not related to blood pressure, body weight, or age. Our data suggest different metabolic and pathophysiological mechanisms of the risk factors, IDL, LDL, and Lp(a).Abbreviations VLDL very low density lipoprotein - IDL intermediate-density lipoprotein - LDL low-density lipoprotein - ApoB Apolipoprotein B - Lp(a) lipoprotein (a) - BMI body mass index Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

Changes in Lp(a) lipoprotein and other plasma proteins during acute myocardial infarction

The sequential changes of Lp(a) lipoprotein concentrations in patients (n=59) suffering acute myocardial infarction (AMI) were examined and compared with other plasma proteins. The temporal and quantitative characteristics of the responses in concentration of acute phase reactants (CRP, haptoglobin, α₁-antitrypsin, α-acid glycoprotein), lipids (total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol) and apolipoproteins AI and B were similar to previous reports. Lp(a) lipoprotein showed transient changes with an initial decrease of 10–25% compared to the 3-month control value, followed by rebound on day 7–11 above admission level, before again declining. We were able to demonstrate a quantitative relationship between infarct size and alterations in plasma levels of acute phase reactants. However, in addition to rather unusual significant fluctuations during AMI, Lp(a) lipoprotein changes seemed unrelated to infarct size. These findings do not support the view that Lp(a) lipoprotein acts as an acute phase reactant.     

Associations between the lipid profile and the development of hypertension in young individuals – the preliminary study

IntroductionHypertension is the leading direct cause of death in the world and one of the most important risk factors for cardiovascular disease (CVD). Elevated blood pressure (BP) often coexists with lipid disorders and is an additional factor that increases CV risk. Nowadays, we are able to distinguish low density lipoproteins (LDL) and high density lipoproteins (HDL) subfractions. Except LDL also HDL small subfractions can increase the risk of CV events. Therefore, we aimed to investigate the associations between changes of lipoprotein subfractions and the risk of hypertension development.Material and methodsIn 2-year long study 200 volunteers with normal blood pressure at the age of 19–32 years were included. Each volunteer underwent detailed medical examination, 12-lead electrocardiogram was taken at rest, echocardiogram, lipid subfraction assessment (using Lipoprint^®) and two 24-hour BP measurements.ResultsMean total cholesterol concentration was 189 mg/dl (4.89 mmol/l), with mean LDL concentration of 107 mg/dl (2.77 mmol/l), HDL of 63 mg/dl (1.63 mmo/l), very low-density lipoprotein (VLDL) of 40 mg/dl (1.04 mmol/l) and triglycerides (TG) of 89 mg/dl (1.00 mmol/l). Subfractions LDL 1–3 were most abundant, LDL 4–5 making up a marginal portion and LDL 6–7 were not observed. Whereas, subfractions HDL 4–6 were most abundant, in lower concentration was present HDL 1–3 and HDL 8–10. We showed that increased systolic blood pressure coreclated significantly with HDL cholesterol concentrations (p = 0.0078), HDL intermediate subgractions (p = 0.0451), with HDL-3 subfraction (p = 0.0229), and intermediate density lipoprotein-A (IDL-A) (p = 0.038). A significant correlation between increased diastolic blood pressure and HDL lipoprotein levels (p = 0.0454) was only observed.ConclusionsObtained results indicating correlation between total HDL levels and HDL-3 subfraction concentration (for systolic BP) and the tendency to develop hypertension.Key words: hypertension, high density lipoproteins, low density lipoproteins, lipid profile, lipoprotein subfractions     

A case of hyperalphalipoproteinemia with complete deficiency of cholesteryl ester transfer activity]

A 68-year-old male patient with benign hypertension shows high levels of high density lipoprotein cholesterol (HDL-C) of 171 mg/dl. The serum total cholesterol was 240 mg/dl. An abnormal slow alpha band and polydisperse low density lipoprotein (LDL) bands were detected by agarose gel and polyacrylamide gel electrophoresis. The slow alpha band was considered as an apo E-rich HDL. A peak of large HDL particle and a peak of abnormal high-molecular-LDL particle were observed in the patient's serum by gel permeation high performance liquid chromatography. Cholesteryl ester transfer activity (CETA) of the patient's serum was completely deficient (0.0%/10 microliters/18 hr). From these results, it is strongly suggested that patient's hyper-HDL-cholesterolemia caused by a complete deficiency of CETA.     

Comparative effects of two HMG-CoA reductase inhibitors (lovastatin and pravastatin) on serum lipids and lipoproteins

The effects of the HMG-CoA reductase inhibitors lovastatin and pravastatin were studied over 4 months on serum lipids and lipoproteins in 35 patients with severe primary hypercholesterolaemia. In 17 patients 20 mg of lovastatin/day lowered the total cholesterol level by 18% (baseline 373 mg/dl) and LDL cholesterol by 20% (baseline 300 mg/dl). The corresponding data for 40 and 80 mg of lovastatin/day were respectively -23% and -29% for total cholesterol, and -30% and -36% for LDL cholesterol. Pravastatin at 20 mg/day lowered the total cholesterol in 18 patients by 20% (baseline 373 mg/dl) and LDL cholesterol by 24% (baseline 307 mg/dl). The corresponding data for 40 mg of pravastatin per day were 24% for total cholesterol and 30% for LDL cholesterol. So the effects of both HMG-CoA reductase inhibitors on total and LDL cholesterol are comparable. HDL (high-density lipoprotein) cholesterol was increased by lovastatin, whereas pravastatin showed no influence on HDL cholesterol. The reduction of serum triglycerides, VLDL triglycerides and VLDL cholesterol was more pronounced under treatment with lovastatin than under pravastatin.     

Long-term experience with extracorporeal low-density lipoprotein cholesterol removal by dextran sulfate cellulose adsorption

Summary Patients with familial hypercholesterolemia have a high incidence of coronary heart disease due to diet- and drug-resistant, elevated low-density lipoprotein cholesterol (LDL-C). Five patients with familial hypercholesterolemia and diet- and drug-resistant LDL-C > 230 mg/dl were treated by LDL apheresis using dextran sulfate cellulose adsorption (Liposorber System LA-15, Kaneka). Plasma separation was by 0.5-m² polysulfone hollow fiber filter. Two columns containing 150 ml of dextran sulfate cellulose alternately adsorbed LDL and were regenerated by 4.1% saline. The five patients received a total of 360 treatments at 7-day intervals. The treated plasma volume per session was 4.1 ± 0.41. Postapheresis values compared with preapheresis were: total cholesterol, 40%; LDL-C, 28%; VLDL-C, 65%; HDL-C, 95%; triglycerides, 70%; white blood cells, 116%; platelets, 87%; C3 complement, 79%; fibrinogen, 64%; albumin, 94%. The decrease in HDL-C per treatment was not significant. The safety parameters showed only slight changes. The initial LDL of 436 ± 172 mg/dl decreased to mean pre-apheresis levels of between 150 and 100 mg/dl. The anti-atherogenic HDL increased in three and remained unchanged in two patients. Adverse events like hypotension, angina pectoris, and technical problems occurred in 11 of the 360 treatments. Long-term treatment of patients with diet- and drug-resistant familial hypercholesterolemia by extracorporeal dextran sulfate cellulose adsorption is effective and safe.Abbreviations LDL low-density lipoprotein - LDL-C lowdensity lipoprotein cholesterol - VLDL very low-density lipoprotein - HDL high-density lipoprotein - HDL-C high-density lipoprotein cholesterol - CHD coronary heart disease - FH familial hypercholesterolemia - HMG CoA hydroxy-3methyl-glutaryl coenzyme A - PTT partial thromboplastin time - IU international units - ANOVA analysis of variance     

Serum levels of lipoprotein (a) and other lipids in angiographically defined coronary artery disease patients and healthy blood bank donors

Lipoprotein (a) (Lp(a)) and other lipid values have been correlated with angiographically defined [table: see text] coronary artery disease. To study this relationship in Indian patients, plasma levels of Lipoprotein (a) and other lipids were assessed in 74 patients undergoing Coronary arteriography and also in 53 age and sex matched healthy male blood bank donors who served as controls. Total cholesterol (mg/dl) (211 +/- 56 vs 186 +/- 43; p < 0.001), low density lipoprotein Cholesterol (mg/dl) (117 +/- 40 vs 88 +/- 29; p > 0.001) and low density lipoprotein/high density lipoprotein cholesterol ratio (2.6 +/- 0.8 vs 2.2 +/- 0.9; p < .001) were significantly higher in patients than controls. High density lipoprotein-cholesterol (mg/dl) (43.5 +/- 6 vs 42.1 +/- 7; p-ns) very low density lipoprotein-cholesterol (mg/dl) (49.7 +/- 17 vs 56.1 +/- 25; p-ns) and triglycerides (mg/dl) (155 +/- 101 vs 167 +/- 88; p-ns) were not statistically different in two groups. Lipoprotein (a) levels showed highly skewed distribution. Patients (n = 74) showed almost five fold higher lipoprotein (a) levels (mg/dl) as compared to controls (n = 53) [105 +/- 565 vs 23 +/- 76]. Patients with very high lipoprotein (a) levels [values of more than 40 mg/dl] (n = 18) had high density lipoprotein cholesterol and total cholesterol significantly lower than rest of the patient group. [high density lipoprotein cholesterol (mg/dl) 41.00 +/- 3.7 vs 44 +/- 6.4; p < 0.01 and total cholesterol (mg/dl) 192 +/- 34 vs 217 +/- 53; p < 0.05].     

Plasma lipids and lipoproteins and essential hypertension

In recent years there have been many studies demonstrating a correlation between increased arterial blood pressure and altered lipid profiles, and there has been an especially positive correlation between high cholesterol levels and blood pressure. There are differences between the various reports that are important. In our study the lipid distribution in 105 hypertensive patients with mild or moderate arterial hypertension according to WHO criteria without clinically or ultrasonographically apparent atherosclerosis was compared to the lipid distribution in 65 age-matched healthy persons. On the epidemiological level a significant, positive association was found between LDL serum levels (P 0.001), Apo B serum levels (P 0.001), serum triglyceride levels (P 0.05) and VLDL serum levels (P 0.01) and arterial hypertension. However, in contrast to recent reports, no significant difference was found between total serum cholesterol levels in normotensives and hypertensives, and there was no difference in HDL serum levels. No evidence could be found for a significant increase in lipoprotein (a) serum levels in hypertensives.Abbreviations LDL low density lipoprotein - VLDL very low density lipoprotein - HDL high density lipoprotein - Apo B 100 apolipoprotein B 100 - Apo A I apolipoprotein A I Correspondence to: H. Vetter     

Acute effects of estradiol and progesterone on insulin, lipids and lipoproteins in postmenopausal women: a pilot study

OBJECTIVES: To examine the acute effects of estradiol-17beta (E(2)) and progesterone (P) on serum levels of insulin, lipids and lipoproteins in estrogen-deficient postmenopausal women, whereby, a direct cause-effect relationship could be established without the influence of lifestyle changes. MATERIALS AND METHODS: Nine postmenopausal women were given oral E(2) (Estrace) 2 mg/day for 28 days and oral micronized P (Prometrium) 200 mg/day in the last 14 days of E(2) treatment. Fasting blood samples were obtained before starting E(2) (day 1) and P (day 15) and on day 29. Serum levels of insulin, triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and lipoprotein (a) (Lp(a)) at the three time points were compared by Friedman analysis of variance (ANOVA). Corresponding levels of glucose, the apolipoproteins (Apo) A1 and B and serum androgen levels were also evaluated. RESULTS: E(2) decreased while P increased fasting levels of insulin (32.45+/-3.57, 26.36+/-2.90 and 37.36+/-3.67 pmol/l on day 1, 15 and 29 respectively; P<0.01). Fasting glucose to insulin ratios changed inversely (P<0.01). E(2) increased HDL from 1.07+/-0.05 mmol/l on day 1 to 1.17+/-0.07 mmol/l on day 29 but decreased corresponding levels of Lp(a) from 261+/-93 to 211+/-83 U/l (P=0.03 for both). TC and LDL levels fell significantly after 14 days of E(2) treatment with no further decrease when P was added. Androgen levels remained unchanged during hormone treatment. CONCLUSION: The sequential, acute effects of E(2) and micronized P on insulin and lipids confirm a direct cause-effect relationship. The acute effects of P on insulin in particular, highlights the importance of standardizing the medication days according to estrogen and progestin in the clinical evaluation of their true metabolic impact in longer-term studies and may influence the choice of progestin type, dose and duration in hormone replacement.     

Atherogenic lipid profiles in Filipino adolescents with low body mass index and low dietary fat intake

This study reports mean lipid levels and their association with body composition, diet, and activity level in 300 male and 308 female adolescents (14–16 years) living in Cebu City, the Philippines. Participants were selected from the Cebu Longitudinal Health and Nutrition Survey (CLHNS), a 1‐year birth cohort study begun in 1982–83. Lipid profiles suggest high cardiovascular disease (CVD) risk in this sample, despite low intake of dietary fat (22% for both sexes) and an absence of obesity (0.3% of sample). Mean lipid levels for males and females were, respectively, 153.2 mg/dl and 182.5 mg/dl for total cholesterol (TC), 91.9 mg/dl and 104.6 mg/dl for low‐density lipoprotein cholesterol (LDL‐C), 38.3 mg/dl and 41.3 mg/dl for high‐density lipoprotein cholesterol (HDL‐C, geometric mean), and 73.9 mg/dl and 79.6 mg/dl for triglycerides (TG, geometric mean). The atherogenic ratio of TC/HDL‐C was high at 4.16 and 4.55 for males and females. Adjusting for maturational changes, the body mass index (BMI) and skinfold measures were positively associated with most lipids in males. Among females, BMI and skinfolds related positively to LDL‐C and TG, and inversely to HDL‐C. Although males had a higher waist hip ratio (WHR), WHR only predicted lipid profiles in females. Activity level had a beneficial association with lipid profiles in both sexes, while dietary fat intake was positively associated with LDL‐C in males and with HDL‐C in females. In sum, diet, adiposity, and physical activity predict variability in lipid profiles in this adolescent Filipino population. However, the low fat intake and near‐absence of obesity raise questions about the causes of the high apparent risk for future CVD in this young population. Am. J. Hum. Biol. 15:688–696, 2003. © 2003 Wiley‐Liss, Inc.     

Long-term effect of intensified insulin treatment on lipid parameters in diabetes mellitus type I

Summary Premature atherosclerosis is often found in patients with diabetes mellitus (DM) type I, and alterations in lipid metabolism seem to play an important role in the development of this complication.Intensified insulin therapy improves glycemic control parameters significantly. To evaluate the effect of this optimized insulin treatment (OIT) not only on glycemic control, but also on plasma lipids, 24 patients with DM type I (19 men and 5 women, 18 to 61 years) were switched from a standard insulin therapy to a regimen of OIT which has been maintained for more than 3 years now. After 2 years on OIT a reduction of HbAlc values from 8.1% to 7.5% (p<0.0l) was accompanied by an increase in HDL cholesterol from 52 to 67 mg/dl (p<0.05) and a decrease of triglyceride levels from 319 to 67 mg/dl (p<0.001). At the end of the second year on OIT some of the patients exhibited a reversal of the favorable trend in HbAlc and lipid values. Intensified instructions regarding the implementation of OIT were therefore repeated and resulted in a renewed improvement of overall HbAlc, HDL cholesterol and triglyceride levels to 6.43%, 67 mg/dl, and 78 mg/dl, respectively. Our findings underline the value of OIT not only for glycemic control, but also for the control of plasma lipids considered to be major risk factors for coronary artery disease.Abbreviations DM diabetes mellitus - OIT optimized insulin therapy - CAD coronary artery disease - LDL low density lipoprotein - VLDL very low density lipoprotein - HDL high density lipoprotein     

Effects of estrogen on susceptibility to oxidation of low-density and high-density lipoprotein in postmenopausal women

Objective: To investigate the effects of estrogen on the susceptibility to oxidation of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in postmenopausal women. Methods: A total of 23 postmenopausal women were treated with 0.625 mg of conjugated equine estrogen daily for 3 months. Blood samples were obtained before and after therapy. Plasma levels of total cholesterol and triglyceride and the concentrations of cholesterol, triglyceride, phospholipid in LDL and HDL were determined enzymatically and the levels of apolipoprotein A-I, A-II in HDL and apolipoprotein B in LDL were measured by turbidimetric immunoassay. The isolated LDL and HDL were incubated at 37°C for 24 h with CuSO₄ 5 μmol/l and the lipid peroxide concentration of LDL and HDL was measured. Results: Estrogen significantly reduced the plasma level of total cholesterol and significantly increased the plasma level of triglyceride. The LDL concentrations of cholesterol, phospholipid and apolipoprotein B were significantly decreased following estrogen therapy. The triglyceride level of LDL did not change significantly. The HDL concentrations of cholesterol, triglyceride, phospholipid and apolipoprotein A-I and A-II were all significantly elevated after estrogen therapy. Estrogen significantly inhibited the peroxidation of LDL at 50–2000 μg of LDL protein (14.17±4.17–11.49±1.42 nmol/200 μg of LDL protein, P<0.001) and of HDL (4.49±1.74–3.37±1.24 nmol/200 μg of HDL protein, P<0.03) induced by their incubation in the presence of CuSO₄. Conclusions: Estrogen inhibited the susceptibility of LDL and HDL to oxidative modification and favorably affected lipid metabolism by reducing the number of LDL particles and increasing the number of HDL particles in plasma that were resistant to oxidation.