Effects of tamoxifen on lipid profile and coagulation parameters in male patients with pubertal gynecomastia

BACKGROUND/AIM: The estrogenic actions of tamoxifen on lipid profiles and hemostasis have been extensively demonstrated in women. Due to limited experience with this drug in males, it is uncertain whether these effects are also present in men. The aim of our study was to assess the response of blood lipids, lipoproteins, and coagulation parameters in a group of men taking tamoxifen. METHODS: We studied 15 healthy boys with pubertal gynecomastia who were given 10 mg tamoxifen per day. Total testosterone, sex-hormone-binding globulin, estradiol, serum lipids, apolipoprotein B, apolipoprotein A-I, lipoprotein(a), fibrinogen, antithrombin III, von Willebrand factor, and markers of activated coagulation and fibrinolysis were determined at baseline and 1 and 3 months after beginning of the tamoxifen treatment. RESULTS: Total cholesterol and lipoprotein(a) showed moderate but significant decreases from baseline. Low-density lipoprotein and high-density lipoprotein cholesterol concentrations as well as triglyceride and apolipoprotein B levels became lower, but these changes were not statistically significant. Among clotting parameters, antithrombin III was reduced, and von Willebrand factor increased significantly. Markers of activated coagulation and fibrinolysis remained unchanged throughout the period of therapy. CONCLUSIONS: The effects of tamoxifen on blood lipids and hemostasis we found in this group of healthy young men were qualitatively similar, but lesser than those previously described in women.     

Effects of transdermal application of 7-oxo-DHEA on the levels of steroid hormones, gonadotropins and lipids in healthy men

The aim of this study was to investigate the effect of 7-oxo-DHEA (dehydroepiandrosterone) on the serum levels of steroid sexual hormones, gonadotropins, lipids and lipoproteins in men. 7-oxo-DHEA was applied onto the skin as a gel to 10 volunteers aged 27 to 72 years for 5 consecutive days. The single dose contained 25 mg 7-oxo-DHEA. Serum concentrations of testosterone, estradiol, cortisol, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), total cholesterol, HDL- and LDL-cholesterol, triglycerides, apolipoprotein A-I and B and lipoprotein(a) were measured before the beginning and shortly after the end of the steroid application. After the treatment, we noted the following significant changes: a decline of testosterone and estradiol levels, increase of LH, HDL-cholesterol and apolipoprotein A-I levels. The decrease of total cholesterol levels was of the borderline significance. A slight but significant increase was found in apolipoprotein B and lipoprotein(a). The most expressive was the fall of the atherogenic index. We suggest that the gel containing 7-oxo-DHEA might be a suitable drug for improving the composition of the steroid and lipid parameters in elderly men.     

Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease.

OBJECTIVE--To examine whether method of infant feeding is associated with adult serum lipid concentrations and mortality from ischaemic heart disease. DESIGN--Follow up study of men born during 1911-30. SETTING--Hertfordshire, England. SUBJECTS--5718 men, for 5471 of whom information on infant feeding had been recorded by health visitors and 1314 of whom had died. 485 of the men born during 1920-30 and still living in Hertfordshire who had blood lipid measurements. MAIN OUTCOME MEASURES--Death from ischaemic heart disease; serum cholesterol and apolipoprotein concentrations. RESULTS--474 men had died from ischaemic heart disease. Standardised mortality ratios were 97 (95% confidence interval 81 to 115) in men who had been breast fed and had not been weaned at 1 year, 79 (69 to 90) in breast fed men who had been weaned at 1 year, and 73 (59 to 89) in men who had been breast and bottle fed. Compared with men weaned before one year men not weaned had higher mean serum concentrations of total cholesterol (6.9 (not weaned) v 6.6 (weaned) mmol/l), low density lipoprotein cholesterol (5.0 v 4.6 mmol/l) and apolipoprotein B (1.14 v 1.08 g/l). Men who had been bottle fed also had a high standardised mortality ratio for ischaemic heart disease (95; 68 to 130) and high mean serum concentrations of total cholesterol (7.0 mmol/l), low density lipoprotein cholesterol (5.1 mmol/l), and apolipoprotein B (1.14 g/l). In all feeding groups serum apolipoprotein B concentrations were lower in men with higher birth weight and weight at 1 year. CONCLUSIONS--Age of weaning and method of infant feeding may influence adult serum low density lipoprotein cholesterol concentrations and mortality from ischaemic heart disease. Adult serum apolipoprotein B concentrations are related to growth in fetal life and infancy.     

Sialic acid and oxidizability of lipid and proteins and antioxidant status in patients with coronary artery disease

The aim of this study was to investigate the possible relationship between serum total sialic acid (TSA) concentration, recently shown to be a cardiovascular risk factor, and lipid and protein oxidation and antioxidant status and the severity of coronary artery disease (CAD) according to the obstructive vessel number in patients. The study was carried out on a total of 200 patients (142 men and 58 women) who were hospitalized for elective coronary angiographic evaluation with complaint of typical angina pectoris. According to the results of angiography, 150 patients had angiographically proven CAD (CAD group) and 50 patients had a history suggestive of angina pectoris but normal coronary angiograms (control group). The CAD group was further divided into single-, double- and triple-vessel disease groups according to the number of vessels involved. Lipid parameters were determined by routine laboratory methods. Plasma malondialdehyde (MDA) and vitamin E concentrations were determined by high-performance liquid chromatography. TSA and other oxidant and antioxidant parameters were studied spectrophotometrically. Our results demonstrated significant increases both in TSA levels and in indicators of oxidative stress in the patients with CAD compared with the controls. However, antioxidant parameters were decreased in the patients with CAD. We found strong positive correlations between TSA and plasma MDA, Delta-MDA which represents the degree of oxidative modification of apolipoprotein B-containing lipoproteins, serum protein carbonyls and apolipoprotein B and weak correlations between TSA and low density lipoprotein cholesterol, triacylglycerol, paraoxonase, glutathione peroxidase (GPx), vitamin C and vitamin E. In conclusion, TSA is related to markers of lipid and protein oxidation, paraoxonase and GPx activities, vitamin C and E levels and the severity of CAD.     

Growth in utero and serum cholesterol concentrations in adult life.

OBJECTIVE--To see whether reduced rates of fetal growth are related to raised serum cholesterol concentrations in adult life. DESIGN--Follow up study of men and women whose size at birth had been recorded. SETTING--Jessop and Northern General Hospitals, Sheffield. SUBJECTS--219 men and women born in the Jessop Hospital during 1939-40. MAIN OUTCOME MEASURES--Serum concentrations of total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B. RESULTS--Men and women who had had a small abdominal circumference at birth had raised serum concentrations of total and low density lipoprotein cholesterol and apolipoprotein B. This was independent of the duration of gestation. Serum concentrations of total cholesterol fell by 0.25 mmol/l (95% confidence interval 0.09 to 0.42) with each 1 in (2.54 cm) increase in abdominal circumference. The corresponding figure for serum low density lipoprotein cholesterol was 0.26 mmol/l (0.11 to 0.42) and for serum apolipoprotein B 0.04 g/l (0.02 to 0.07). Small head and chest circumferences at birth and short length were each associated with raised serum low density lipoprotein cholesterol concentrations but the trends disappeared in a simultaneous regression with abdominal circumference at birth. The association between abdominal circumference at birth and low density lipoprotein cholesterol concentration was independent of social class, current body weight, cigarette smoking, and alcohol consumption. CONCLUSION--Raised serum cholesterol concentrations in adult life are associated with impaired growth during late gestation, when fetal undernutrition has a disproportionate effect on liver growth. Impaired liver growth may permanently alter low density lipoprotein cholesterol metabolism.     

外源性睾酮对去睾丸家兔性激素以及血脂和载脂蛋白水平的影响

目的 :探讨不同剂量的外源性睾酮对去势 (双侧睾丸切除 )雄性家兔性激素以及血脂和载脂蛋白水平的影响。方法 :成熟雄性新西兰白兔 40只 ,随机分成 5组 (n =8) :对照组、单纯去势组、低睾酮血症组 [去势后肌注十一酸睾酮 (TU) ,3mg/kg ,每 2周一次 ]、生理水平组 (去势后肌注TU ,6mg/kg ,每 2周一次 )及高睾酮血症组 (去势后肌注TU ,1 2mg/kg ,每 2周一次 )。 8周后测量血清总睾酮 (TT)、雌二醇 (E2 )、脱氢表雄酮 (DHEA)及总胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL C) ,低密度脂蛋白胆固醇 (LDL C) ,甘油三酯 (TG) ,载脂蛋白A1 (ApoA1 ) ,载脂蛋白B(ApoB)。结果 :雄兔血清TT水平在去势后明显下降至极低水平 ,明显低于对照组 (P <0 .0 1 ) ,3mg/kgTU补充后轻度升高 ,仍明显低于对照组 (P <0 .0 1 ) ,形成低睾酮血症 ,6mg/kgTU补充后与对照组相比无显著差异 (P >0 .0 5) ,接近生理水平 ,1 2mg/kgTU补充后明显高于对照组和低睾酮血症组 (P均 <0 .0 1 ) ,形成高睾酮血症。血清E2 水平在对照组和生理水平组相近并且最低 ,单纯去势组和低睾血症组相近 ,高睾酮血症组最高。E2 /TT比值在对照组和生理水平组相近并且最小 ,在单纯去势组最大 ,低睾酮血症组大于高睾酮血症组。单纯去势组、低睾酮血症组和高睾酮血症     

Association of Endogenous Testosterone with Lipid and Blood Glucose Profiles in Elderly Men with Angiographically Proven Cardiovascular Disease of Nadia and Murshidabad District,West Bengal

Testosterone is commonly known for its role in the regulation of reproductive physiology in men. Epidemiologic studies suggest that endogenous testosterone levels may be implicated in cardiovascular diseases (CVDs). Our study aimed to investigate the relationship between serum total testosterone (TT) levels and lipid profile as well as fasting blood glucose (FBG) levels in male patients ranging from 40 to 70 years old with angiographically proven CVDs from Nadia and Murshidabad district of West Bengal, India. These data were compared with the normal men with no CVD history. We observed a significantly low serum TT levels in CVD patient group compared to the normal group. Among CVD patients, a significant (p < 0.05) negative association was found between serum TT and total cholesterol, triglyceride, low density lipoprotein and very low density lipoprotein, whereas a significant positive correlation (p < 0.05) was found between serum TT and high density lipoprotein. We also observed a highly significant negative correlation between TT and FBG levels in CVD patient group. Thus, in these two densely populated district of West Bengal with poor socio-economic condition, low levels of serum TT in elderly men is associated with CVD that appear together with an atherogenic lipid milieu that may be involved in the pathogenesis of CVD. Results further indicate that low serum TT might have a role in the development of hyperglycemia as evidenced from high FBG level in elderly men.     

Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data.

To examine the association between cigarette smoking in adults and serum lipid and lipoprotein concentrations the results of 54 published studies were analysed. Overall, smokers had significantly higher serum concentrations of cholesterol (3.0%), triglycerides (9.1%), very low density lipoprotein cholesterol (10.4%), and low density lipoprotein cholesterol (1.7%) and lower serum concentrations of high density lipoprotein cholesterol (-5.7%) and apolipoprotein AI (-4.2%) compared with nonsmokers. Among non-smokers and light, moderate, and heavy smokers a significant dose response effect was present for cholesterol (0, 1.8, 4.3, and 4.5% respectively), triglycerides (0, 10.7, 11.5, and 18.0%), very low density lipoprotein cholesterol (0, 7.2, 44.4, and 39.0%), low density lipoprotein cholesterol (0, -1.1, 1.4, and 11.0%), high density lipoprotein cholesterol (0, -4.6, -6.3, and -8.9%), and apolipoprotein AI (0, -3.7 and -5.7% in non-smokers and light and heavy smokers). These dose response effects may provide new evidence for a causal relation between exposure to cigarette smoke and changes in serum lipid and lipoprotein concentrations whether as a direct result of physiological changes or of dietary changes induced by smoking. Adequate prospective data to estimate the excess risk of coronary artery disease existed only for cholesterol concentration. When that information was combined with data from the present study, and given that smokers as a group face an average overall excess risk of coronary artery disease of 70%, it was estimated that the observed increased serum cholesterol concentration in smokers may account for at least 9% of that excess risk. Furthermore, the dose response effect of smoking on serum cholesterol concentration suggests a gradient of increased absolute risk of coronary artery disease between light and heavy smokers.     

C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study.

OBJECTIVE--To test the hypothesis that minor chronic insults such as smoking, chronic bronchitis, and two persistent bacterial infections may be associated with increases in C reactive protein concentration within the normal range and that variations in the C reactive protein concentration in turn may be associated with levels of cardiovascular risk factors and chronic coronary heart disease. DESIGN--Population based cross sectional study. SETTING--General practices in Merton, Sutton, and Wandsworth. SUBJECTS--A random sample of 388 men aged 50-69 years from general practice registers. 612 men were invited to attend and 413 attended, of whom 25 non-white men were excluded. The first 303 of the remaining 388 men had full risk factor profiles determined. INTERVENTIONS--Measurements of serum C reactive protein concentrations by in house enzyme linked immunosorbent assay (ELISA); other determinations by standard methods. Coronary heart disease was sought by the Rose angina questionnaire and Minnesota coded electrocardiograms. MAIN OUTCOME MEASURES--Serum C reactive protein concentrations, cardiovascular risk factor levels, and the presence of coronary heart disease. RESULTS--Increasing age, smoking, symptoms of chronic bronchitis, Helicobacter pylori and Chlamydia pneumoniae infections, and body mass index were all associated with raised concentrations of C reactive protein. C Reactive protein concentration was associated with raised serum fibrinogen, sialic acid, total cholesterol, triglyceride, glucose, and apolipoprotein B values. C Reactive protein concentration was negatively associated with high density lipoprotein cholesterol concentration. There was a weaker positive relation with low density lipoprotein cholesterol concentration and no relation with apolipoprotein A I value. C Reactive protein concentration was also strongly associated with coronary heart disease. CONCLUSION--The body''s response to inflammation may play an important part in influencing the progression of atherosclerosis. The association of C reactive protein concentration with coronary heart disease needs testing in prospective studies.     

Variation and significance of serum leptin,blood lipid level,adiponectin, NO and TNF-α for patients with non-traumatic ischemic necrosis of the femoral head

ObjectiveTo investigate the changes of serum leptin, lipid levels, adiponectin, NO and TNF-α in patients withnon-traumatic ischemic necrosis of the femoral head of the femoral head and its meanings.MethodsA total of 80 patients with ischemic necrosis of the femoral head were selected from January 2015 to January 2016. And 30 healthy volunteers who took the same time were selected as the control group. Both subjects were given venous blood in the morning fasting. Serum leptin levels were measured by radioimmunoassay. Serum lipids, high and low density lipoprotein, cholesterol, triglyceride and apolipoprotein A1 were detected by automatic biochemical analyzer. Apolipoprotein B was measured by radioimmunoassay. The levels of serum adiponectin were measured by radioimmunoassay. The levels of NO and TNF-α in serum were measured by enzyme-linked immunosorbent assay (ELISA).ResultsCompared with the control group, the levels of cholesterol, triglyceride level, middle and low density lipoprotein and apolipoprotein B were significantly increased in INFH serum; the levels of high density lipoprotein and apolipoprotein A1 were significantly decreased The contents of NO and TNF-α were significantly increased, the content of adiponectin was significantly decreased. There was significant difference between the two groups (P < .05).ConclusionThe levels of serum cholesterol, triglyceride level, low density lipoprotein level, apolipoprotein B level, leptin, NO and TNF-α levels in serum of INHF patients were positively correlated with the condition of INHF patients, and high density lipoprotein levels, Apolipoprotein A1 levels and adiponectin levels were negatively correlated with INHF patients.     

An olive oil-rich diet results in higher concentrations of LDL cholesterol and a higher number of LDL subfraction particles than rapeseed oil and sunflower oil diets

We investigated the effect of olive oil, rapeseed oil, and sunflower oil on blood lipids and lipoproteins including number and lipid composition of lipoprotein subclasses. Eighteen young, healthy men participated in a double-blinded randomized cross-over study (3-week intervention period) with 50 g of oil per 10 MJ incorporated into a constant diet. Plasma cholesterol, triacylglycerol, apolipoprotein B, and very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) cholesterol concentrations were 10;-20% higher after consumption of the olive oil diet compared with the rapeseed oil and sunflower oil diets [analysis of variance (ANOVA), P < 0.05]. The size of IDL, VLDL, and LDL subfractions did not differ between the diets, whereas a significantly higher number (apolipoprotein B concentration) and lipid content of the larger and medium-sized LDL subfractions were observed after the olive oil diet compared with the rapeseed oil and sunflower oil diets (ANOVA, P < 0.05). Total HDL cholesterol concentration did not differ significantly, but HDL(2a) cholesterol was higher after olive oil and rapeseed oil compared with sunflower oil (ANOVA, P < 0.05).In conclusion, rapeseed oil and sunflower oil had more favorable effects on blood lipids and plasma apolipoproteins as well as on the number and lipid content of LDL subfractions compared with olive oil. Some of the differences may be attributed to differences in the squalene and phytosterol contents of the oils.     

Impact on lipoprotein profile after long-term testosterone replacement in hypogonadal men.

Testosterone serum levels may influence the lipoprotein metabolism and possibly atherogenic risk. Our aim was to investigate the effects of long-term testosterone supplementation in hypogonadal men on multiple lipoprotein markers. 18 Hypogonadal men were studied before and after 3, 6, and 18 (n = 7) months of treatment with testosterone enanthate. During treatment, serum testosterone and estradiol increased, reaching normal levels (p < 0.0001 and 0.003, respectively). This was associated with a decrease in HDL cholesterol (from 1.40 +/- 0.10 mmol/l to 1.22 +/- 0.08 mmol/l, p < 0.001) after six months at the expense of HDL2 cholesterol (p < 0.01), as well as apoprotein A1 (from 139 +/- 3.4 mg/dl to 126 +/- 3.0 mg/dl, p < 0.005). Hepatic lipase activity increased (p < 0.05) and correlated positively with testosterone (r = 0.56, p < 0.02) and negatively with HDL cholesterol (r = - 0.58, p < 0.02). Total and LDL cholesterol, triglycerides, and apoprotein B did not increase. Among the seven patients who completed 18 months of treatment, triglycerides, total cholesterol, LDL and HDL cholesterol, as well as total cholesterol/HDL cholesterol ratio values did not differ from baseline while apoprotein A1 (p < 0.03) and HDL cholesterol (p < 0.015) remained decreased and hepatic lipase unchanged. Restoration of testosterone levels in hypogonadal men in this study did not reveal unfavorable changes based on total cholesterol/HDL cholesterol and LDL cholesterol/apoprotein B ratios, which are both atherogenic risk markers. Whether the changes in light of lipoprotein metabolism will adversely influence cardiovascular risk over time remains to be determined.     

Effects of probucol on plasma lipids, lipoproteins and parameters of high density lipoprotein metabolism.

Eight patients with primary hypercholesterolemia were treated with probucol for 17 weeks. Plasma total cholesterol, low density lipoprotein (LDL)-cholesterol, and high density lipoprotein (HDL)-cholesterol decreased by 16.6, 15.0 and 25.7%, respectively, in response to probucol treatment. Plasma levels of apolipoprotein B and apolipoprotein A-I also decreased, while apolipoprotein A-II concentrations were unchanged. The decrease in HDL-cholesterol levels was associated with a reduction in HDL particle size. No changes in the plasma lecithin:cholesterol acyltransferase activity or mass occurred in response to probucol treatment. In contrast, a significant 25% increase in plasma cholesteryl ester and triglyceride transfer activity occurred following probucol treatment. There was a positive correlation (R = 0.94) between cholesterol ester and triglyceride transfer. We propose that the increase in lipid transfer activity may in part explain the changes in HDL concentration and size, as well as the previously reported effect probucol has on reducing atherosclerosis in animal models.     

Testosterone replacement in hypogonadal men alters the HDL proteome but not HDL cholesterol efflux capacity

The effects of androgens on cardiovascular disease (CVD) risk in men remain unclear. To better characterize the relationship between androgens and HDL, we investigated the effects of testosterone replacement on HDL protein composition and serum HDL-mediated cholesterol efflux in hypogonadal men. Twenty-three older hypogonadal men (ages 51-83, baseline testosterone < 280 ng/dl) were administered replacement testosterone therapy (1% transdermal gel) with or without the 5α-reductase inhibitor dutasteride. At baseline and after three months of treatment, we determined fasting lipid concentrations, HDL protein composition, and the cholesterol efflux capacity of serum HDL. Testosterone replacement did not affect HDL cholesterol (HDL-C) concentrations but conferred significant increases in HDL-associated paraoxonase 1 (PON1) and fibrinogen α chain (FGA) (P = 0.022 and P = 0.023, respectively) and a decrease in apolipoprotein A-IV (apoA-IV) (P = 0.016). Exogenous testosterone did not affect the cholesterol efflux capacity of serum HDL. No differences were observed between men who received testosterone alone and those who also received dutasteride. Testosterone replacement in older hypogonadal men alters the protein composition of HDL but does not significantly change serum HDL-mediated cholesterol efflux. These effects appear independent of testosterone conversion to dihydrotestosterone. Further research is needed to determine how changes in HDL protein content affect CVD risk in men.     

Apolipoprotein E polymorphism alters the association between body fatness and plasma lipoproteins in women

The aim of the present study was to investigate the associations between total adiposity, body fat distribution, and plasma lipoprotein levels within groups of women defined on the basis of apolipoprotein E phenotypes, in order to verify whether apoE polymorphism could modify these associations. In women having only apolipoprotein E3 isoforms (n = 24), body fat mass, the waist: hip circumference ratio, and computed tomography-derived total and intra-abdominal fat areas were all positively correlated with very low density lipoprotein (VLDL) and low density lipoprotein (LDL) lipids and apolipoprotein B concentrations. These body fatness variables were also negatively correlated with plasma high density lipoprotein (HDL) cholesterol concentration. These associations were, however, altered in the groups of women carrying either apoE2 or E4 isoforms. Indeed, in women carrying the apoE2 isoform (n = 22), body fatness variables were predominantly associated with VLDL components concentration (0.05 greater than P less than 0.01) and with LDL triglyceride content. No association was found between adiposity and LDL cholesterol or apolipoprotein B levels in these women. In contrast, no relationship was found between total adiposity, regional fat accumulation, and VLDL fraction in women carrying the apolipoprotein E4 isoform (n = 17). In this latter group, computed tomography-measured total abdominal fat accumulation was positively correlated with LDL apolipoprotein B (r = 0.58, P less than 0.05) concentration, whereas intra-abdominal fat accumulation was positively correlated with both LDL cholesterol and apolipoprotein B concentrations (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect on lipoprotein profile of replacing butter with margarine in a low fat diet: randomised crossover study with hypercholesterolaemic subjects.

OBJECTIVE--To examine the effect on lipid and lipoprotein concentrations when butter or an unsaturated margarine is used for cooking or spreading in a reduced fat diet. DESIGN--Randomised crossover study with two intervention periods of six weeks'' duration separated by a five week washout. SETTING--Community setting in New Zealand. SUBJECTS--49 volunteers with polygenic hypercholesterolaemia and baseline total cholesterol concentration in the range 5.5-7.9 mmol/l. MAIN OUTCOME MEASURES--Concentrations of total and low density lipoprotein, Lp(a) lipoprotein, high density lipoprotein, apolipoprotein B 100, and apolipoprotein A I. RESULTS--Concentrations of low density lipoprotein cholesterol and apolipoprotein B were about 10% lower with margarine than with butter. Lp(a) lipoprotein and high density lipoprotein cholesterol concentrations were similar with the two diets. CONCLUSION--Despite concerns about adverse effects on lipoproteins of trans fatty acids in margarines, the use of unsaturated margarine rather than butter by hypercholesterolaemic people is associated with a lipoprotein profile that would be expected to reduce cardiovascular risk.     

Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6-year follow-up study

Apolipoprotein E (apoE) polymorphism is a genetic determinant of plasma lipid levels and of coronary heart disease (CHD) risk. We determined the apoE phenotypes and plasma lipid levels in 1577 youths aged 3 to 18 years in 1980. The subjects were randomly selected from five areas of Finland. ApoE phenotyping was performed directly from plasma by isoelectric focusing and immunoblotting. The apoE allele frequencies in the population sample were epsilon 2 = 0.039, epsilon 3 = 0.767, and epsilon 4 = 0.194. There were no differences in the apoE phenotype distribution between East and West Finland or between sexes. The concentrations of serum total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B increased with apoE phenotype in the order of E2/2, E3/2, E4/2, E3/3, E4/3, and E4/4. This increase was already seen in 3-year-old children; it was observed in both sexes, but was clearer in males than in females. The mean levels of high density lipoprotein (HDL) cholesterol, apolipoprotein A-I, triglyceride, Lp[a] lipoprotein, and the activity of lecithin:cholesterol acyltransferase did not differ between the apoE phenotypes. The observed differences in serum cholesterol remained fairly stable during the 6-year follow-up from 1980 to 1986, while the mean serum cholesterol concentration in the whole study population decreased by 6.3%. This study confirms the reported higher frequency of the epsilon 4 allele in Finns as compared to most other populations; this may contribute to the high rates of CHD in Finland as compared to most other populations. The results do not, however, explain the higher rate of CHD in East Finland in comparison to the western part of the country.     

Testosterone up-regulates scavenger receptor BI and stimulates cholesterol efflux from macrophages

By lowering high density lipoprotein (HDL) cholesterol, testosterone contributes to the gender difference in HDL cholesterol and has been accused to be pro-atherogenic. The mechanism by which testosterone influences HDL cholesterol is little understood. We therefore investigated the effect of testosterone on the gene expression of apolipoprotein A-I (apoA-I), hepatic lipase (HL), scavenger receptor B1 (SR-BI), and the ATP binding cassette transporter A1 (ABCA1), all of which are important regulators of HDL metabolism. In both cultivated HepG2 hepatocytes and primary human monocyte-derived macrophages, testosterone led to a dose-dependent up-regulation of SR-BI, which was assessed on both the mRNA and the protein levels. As a functional consequence, we observed an increased HDL(3)-induced cholesterol efflux from macrophages. At supraphysiological dosages, testosterone also increased the expression of HL in HepG2 cells. Testosterone had no effect on the expression of apoA-I in HepG2 cells and ABCA1 in either HepG2 cells or macrophages. These data suggest that testosterone, despite lowering HDL cholesterol, intensifies reverse cholesterol transport and thereby exerts an anti-atherogenic rather than a pro-atherogenic effect.     

Prolonged infection with hepatitis B virus and association between low blood cholesterol concentration and liver cancer.

OBJECTIVE--To determine whether prolonged infection with hepatitis B virus is associated with a lower blood cholesterol concentration. DESIGN--Cross sectional study. SETTING--81 villages in rural China with a high prevalence of chronic infection with hepatitis B virus. SUBJECTS--1556 apparently healthy men aged 35-64 years, randomly selected. MAIN OUTCOME MEASURES--Hepatitis B virus carrier state; plasma concentrations of cholesterol, apolipoprotein B, and apolipoprotein A I. RESULTS--238 (15%) of the men were positive for hepatitis B surface antigen, indicating that they were chronic carriers. Plasma concentration of cholesterol was 4.2% (0.11 mmol/l) lower among carriers (that is, positive for hepatitis B surface antigen) than among non-carriers (95% confidence interval 0.6% to 8.0% (0.01 to 0.21 mmol/l), p < 0.05), and apolipoprotein B concentration was 7.0% (0.036 g/l) lower (2.8% to 11.2% (0.014 to 0.058 g/l), p < 0.001). In contrast, no association was observed between plasma concentrations of cholesterol or apolipoprotein and hepatitis B that had been eradicated (that is, patient positive for hepatitis B core antibody but negative for hepatitis B surface antigen). CONCLUSIONS--Chronic hepatitis B virus infection, which usually starts in early childhood in China, seems to lead not only to a greatly increased risk of death from liver disease but also to a somewhat lower cholesterol concentration in adulthood. This common cause produces an inverse association between cholesterol concentration and risk of death from liver cancer or from other chronic liver diseases.     

Effects of mild physical exercise on serum lipoproteins and metabolites of arachidonic acid: a controlled randomised trial in middle aged men.

To study the effects of physical exercise on biochemical risk factors for ischaemic heart disease 31 healthy middle aged men undertook regular physical exercise for two months and 29 served as controls in a randomised trial. In the men taking regular exercise serum cholesterol concentrations increased 26% more in the high density lipoprotein subfraction two (HDL2) and decreased 31% more in the subfraction three (HDL3) and 9% more in the low density lipoprotein fraction than in the control group. A tendency towards increased plasma 6-keto-prostaglandin F1 alpha concentration and decreased serum thromboxane B2 concentration was found during the period of regular exercise, but prostaglandin E2 concentrations remained unchanged. The increase in plasma 6-keto-prostaglandin F1 alpha concentration was associated with an increase in serum HDL2 cholesterol concentration in the group taking regular exercise. Our data suggest that mild regular physical exercise favourably influences cholesterol distribution in serum lipoproteins in healthy middle aged men and may have beneficial effects on circulating metabolites of arachidonic acid.