Lipid profiles in untreated patients with rheumatoid arthritis.

OBJECTIVE: To investigate lipid profiles in patients with untreated active rheumatoid arthritis (RA) and to assess the relationship of the inflammatory condition of RA with lipid profiles. METHODS: Forty-two patients with RA and 42 age and sex matched healthy controls were studied. Patients with RA had not been treated with corticosteroid or disease modifying antirheumatic drugs prior to the study. Total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apolipoprotein A1 (apo A1), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and C-reactive protein (CRP) were measured in both groups. RESULTS: The levels of apo A1 and HDL-cholesterol were significantly lower in patients than in controls (128.5 vs. 151.8 mg/dl, 41.2 vs. 54.9 mg/dl, respectively). The level of Lp(a) was significantly higher in patients than in controls (27.1 vs. 18.0 mg/dl). The ratios of apo B/apo A1, total cholesterol/HDL-cholesterol, and LDL-cholesterol/HDL-cholesterol were significantly higher in patients than in controls (0.82 vs. 0.67, 4.4 vs. 3.4, 2.8 vs. 1.9, respectively). CRP showed a significant correlation with apo A1 (r = -0.44, p<0.01) and HDL-cholesterol (r = -0.35, p<0.05). CONCLUSION: Our study suggests that patients with untreated active RA have altered lipoprotein and apolipoprotein patterns that may possibly expose them to higher risk of atherosclerosis. The inflammatory condition of RA may affect the metabolism of HDL-cholesterol and apo A1.     

Apolipoprotein E polymorphism affects plasma levels of lipoprotein(a)

In a group of 303 healthy Caucasian adults of both sexes we studied the influence of the apolipoprotein E (apo E) polymorphism on plasma levels of Lipoprotein(a) (Lp(a)). The APOE^*2 allele was found to decrease the mean plasma Lp(a) level by 24.8%, whereas the APOE^*4 allele increased the mean Lp(a) level by 25.7%. These effects were parallel to the effect of apo E polymorphism on plasma cholesterol and low density lipoprotein (LDL)-cholesterol. For the Lp(a) levels, the genetic variance associated with the APOE locus contributed about 4% to the total phenotypic variance. For plasma cholesterol and LDL-cholesterol this contribution was 4.5 and 6.3%, respectively. We also found a significant positive correlation between LDL-cholesterol and Lp(a) levels. Since the apo E polymorphism effects LDL-receptor activity, we conclude that, at least in healthy normolipidemic individuals, plasma levels of Lp(a) are modulated by the LDL-receptor activity.     

Association of apo A-IV 360 (Gln --> His) polymorphism with plasma lipids and lipoproteins: the Framingham Offspring Study

The effect of a common apolipoprotein (apo) A-IV polymorphism (substitution of histidine for glutamine at position 360) on plasma lipid, lipoprotein cholesterol and lipoprotein(a) (Lp(a)) levels, and on low-density lipoprotein (LDL) particle size was examined by genotyping in 2322 Caucasian men and women (mean age: 48.9+/-10.1 years) participating in the Framingham Offspring Study (FOS). The relative frequencies of the apo A-IV-Gln (apo A-IV-1) and the apo A-IV-His (apo A-IV-2) alleles were 0.932 and 0.068, respectively, and were in Hardy-Weinberg equilibrium. No effect of the apo A-IV-2 genotype was observed on plasma triglyceride, total and lipoprotein cholesterol, and LDL particle size in either men or women after adjustment for age and body mass index. To avoid a possible interaction between the apo E genotype and the apo A-IV genotype, subgroup analyses were undertaken in 1,414 male and female subjects with the apo E3/3 genotype. Among women in this group there was a significant effect of the apo A-IV-2 allele on triglyceride levels (p=0.046). This effect was no longer significant after adjustment for age and BMI (p=0.074). No significant allele effect on other lipoprotein levels, including Lp(a), was noted in apo E3/3 men or women. We have also conducted a meta-analysis of our own data and of other studies found in the literature, indicating a significant lowering effect of apo A-IV-2 on plasma triglycerides, but no effects on other parameters. In conclusion, the apo A-IV-2 allele is associated with a modest reduction in plasma triglyceride levels in the general population.     

Serum lipids,lipoproteins and apolipoproteins levels in patients with nonalcoholic steatohepatitis

GOALS/BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a form of liver disease that is histologically indistinguishable from alcoholic hepatitis but occurs in persons who do not consume alcohol in excess. The objectives of this study are to measure serum levels of lipids, lipoproteins and apolipoproteins (apo AI, apo B), lipoprotein (a) [Lp (a)] in patients with nonalcoholic steatohepatitis (NASH), and to investigate the relationship with liver histology. STUDY: The scope of this study is composed of 36 patients (27 males, 9 females) with NASH, diagnosed by biochemical liver function tests, sonographic examination of liver and liver biopsy and 32 healthy adults as a control group (22 males, 10 females). Serum lipids, lipoproteins and apo AI, apo B, and Lp (a) measurements were taken in the study group and controls, and a correlation with histopathologic findings was searched for. RESULTS: Serum mean levels (+/- SD as mg/dl) of total cholesterol (201.05 +/- 34.48), triglyceride (225.94 +/- 156.50), and LDL-cholesterol (111.77 +/- 19.85) in patients with NASH were significantly higher than those of the control group (170.68 +/- 31.06; 138.81 +/- 49.96; 100.68 +/- 17.98; respectively) and serum HDL-cholesterol level (41.22 +/- 2.47) was less than that of the control group (45.06 +/- 8.32) (P = 0.017). The serum mean level of apo AI (151.54 +/- 30.90) in the study group was lower than that of the controls (160.62 +/- 22.11), but the difference was not significant (P = 0.17). However, the serum apo AI level in patients with liver fibrosis (140.62 +/- 35.62) was significantly lower than that of patients without liver fibrosis (164.57 +/- 25.47) (P = 0.01). The serum mean level of apo B (89.80 +/- 20.62) in the patients was significantly higher than the control group (73.25 +/- 25.39) (P = 0.004), but not correlate with liver histopathology. The serum Lp (a) levels in both the patients (13.09 +/- 9.61) and the controls (12.01 +/- 7.50) were not different (P = 0.61). Hypertriglyceridemia (above 220 mg/dL) had a positive correlation with steatosis of the liver (r = 0.333, P = 0.04) and a negative correlation with liver fibrosis (r = -0.438, P = 0.008). There was a significant negative correlation between apo AI and steatosis (r = -0.360, P = 0.03), inflammation (r = -0.364, P = 0.03) and fibrosis of liver (r = -0.418, P = 0.01). A positive correlation of serum LDL-cholesterol (r = 0.507, P = 0.002) and Lp(a) (r = 0.394, P = 0.01) concentrations with liver fibrosis was also noted. CONCLUSIONS: Abnormalities of lipid metabolism such as the increase of serum triglyceride, cholesterol and LDL-cholesterol level and decrease of HDL-cholesterol may be the contributing factors in the development of NASH. The decrease in apo AI and the increase in LDL and Lp (a) in patients were correlated with liver fibrosis. Apo AI may be a serum marker for liver fibrosis in patients with NASH.     

Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study

The association of an elevated level of lipoprotein (a) (Lp(a)) with the development of coronary heart disease (CHD) remains controversial. Lp(a) was investigated as a CHD risk factor in the PRIME Study, a prospective cohort study which included 9133 French and Northern Irish men aged 50-59 at entry, without a history of CHD and not on hypolipidaemic drugs. During a follow-up of 5 years, 288 subjects experienced at least one CHD event (myocardial infarction (MI), coronary death, angina pectoris). Lp(a) was measured by immunoassay in all subjects on fresh plasma obtained at entry. Traditional cardiovascular risk factors such as low-density lipoproteins (LDL)-cholesterol, HDL-cholesterol, triglycerides, the presence of diabetes, hypertension or smoking were determined. Logistic regression analysis was used to evaluate Lp(a) level as a CHD risk factor after controlling for the other risk factors. In addition, its possible interaction with LDL- and HDL-cholesterol levels was investigated. Lp(a) appeared a significant risk factor (P<0.0006) in the whole cohort without between-population interaction, even if the association was not statistically significant in the Belfast sample. The relative risk (RR) of CHD events in subjects with Lp(a) levels in the highest quartile was 1.5 times that of subjects in the lowest quartile (RR: 1.56; 95% confidence intervals (CIs): 1.10-2.21). A high Lp(a) level was a risk for MI, coronary death and angina pectoris. A significant interaction term between Lp(a) and LDL-cholesterol levels, however, was found. The relative CHD risk associated with a Lp(a) level > or =33 mg/dl in comparison with Lp(a) <33 mg/dl increasing gradually from 0.82 (95% CI: 0.28-2.44) in men with LDL-cholesterol in the lowest quartile (<121 mg/dl) to 1.58 (95% CI: 1.06-2.40) in the highest quartile (>163 mg/dl). In conclusion, Lp(a) increased the risk for MI and angina pectoris, especially in men with a high LDL-cholesterol level. This study which analyzed Lp(a) level using a measurement independent of apolipoprotein (a) size on fresh plasma, has confirmed utility of Lp(a) as a predictor of CHD.     

Probucol promotes reverse cholesterol transport in heterozygous familial hypercholesterolemia. Effects on apolipoprotein AI-containing lipoprotein particles

In order to investigate the effect of Probucol therapy on reverse cholesterol transport, apo AI-containing lipoprotein particles were isolated and characterized, and their cholesterol effluxing capacity and LCAT activity were assayed in four familial hypercholesterolemia patients before and after 12 weeks of Probucol therapy. Four major subpopulations of apo A-containing lipoprotein particles are separated before and after drug treatment; LpAI, LpAI:AII, LpAIV, LpAI:AIV:AII. Probucol reduces both total plasma and LDL-cholesterol (-17 and -14%, respectively). Apo B decreases slightly (-7.6%). Plasma HDL-cholesterol and apo AI decrease by 36.6 and 34.7%. LpA-I showed a marked decrease (-46%). Moreover, plasma LCAT and CETP activities were markedly increased under Probucol treatment. Analysis of lipoprotein particles showed that Probucol induces a decrease of protein content and an increase of cholesterol and triglycerides contents. Interestingly, Probucol induces an enhancement of LCAT activity in LpAI (4.5-fold). This drug induces a trend toward greater cholesterol efflux from cholesterol-preloaded adipose cells promoted by Lp AI and Lp AIV but not by Lp AI:AII. This study confirms the hypothesis, in addition to the lowering LDL-cholesterol levels and antioxidant effects of Probucol, that HDL reduction was not an atherogenic change in HDL system but may cause an antiatherogenic action by accelerating cholesterol transport through HDL system, promoting reverse cholesterol transport from peripheral tissues.     

Interaction between a common variant of the cholesteryl ester transfer protein gene and the apolipoprotein E polymorphism: effects on plasma lipids and lipoproteins in a cohort of 7-year-old children

BACKGROUND AND AIM: Common variations in genes, such as apolipoprotein E (apo E) and cholesteryl ester transfer protein (CETP), are major determinants of plasma lipid and lipoprotein levels. As both apo E and CETP contribute to the reverse transport of cholesterol to the liver, the effects of variations at the CETP locus may very well interact with the apo E genotype. METHODS AND RESULTS: As part of an ongoing study, the combined effects of the apo E genotype and heterogeneity at the CETP gene locus on plasma lipids and lipoproteins were studied in a birth cohort sample of 257 Dutch prepubescent boys and girls (aged 6.7-8.1 years). The children with an apo E2E3 genotype (carrying the epsilon 2 allele; arg158-->cys) had lower concentrations of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) than those with an apo E4E3 (carrying the epsilon 4 allele; cys112-->arg) or apo E3E3 genotype (homozygous for the parent epsilon 3 allele). These associations were statistically significant in children who were homozygous (p = 0.004 for LDL; p = 0.002 for apo B) or heterozygous (p < 0.0001 for LDL and apo B) for the absence of the Taq-IB polymorphism at the CETP gene locus (B2 allele), but not in those homozygous for the presence of this variant (B1B1). The highest plasma high-density lipoprotein cholesterol (HDL-C) concentrations were observed in children with the CETP B2B2 genotype. The difference in HDL-C levels between the CETP genotype groups was statistically significant only in E2E3 carriers (p = 0.01). The LDL/HDL ratio was significantly lower in E2E3 carriers, but not when combined with a CETP B1B1 genotype. CONCLUSION: These findings indicate that the apo E genotype and heterogeneity at the CETP gene locus have an additive and interactive influence on plasma lipid and lipoprotein levels in children.     

Postprandial lipoprotein(a) response to a single meal containing either saturated or omega-3 polyunsaturated fatty acids in subjects with hypoalphalipoproteinemia.

We have recently reported that the apolipoprotein (apo) B-100-apo(a) complex, the protein moiety of lipoprotein(a) [Lp(a)], has a high affinity for triglyceride(TG)-rich particles (TRP) and that this complex can affiliate with endogenous TG-rich lipoproteins. To shed more light on the apo B-100-apo(a) complex associated with plasma TRP during postprandial lipidemia, we fed five male subjects presenting with primary hypoalphalipoproteinemia (HP) and four male controls a single fat meal (60 g/m2) containing saturated fatty acids (SFA) and, 6 weeks later, an isocaloric meal containing omega-3 polyunsaturated fatty acids. The subjects were phenotyped for plasma Lp(a) and apo C-III levels, apo(a) and apo E isoforms, and lipoprotein lipase and hepatic lipase activities. Vitamin A was included in the meal as a marker of intestinally derived TRP. Following the SFA meal, three of the HP subjects showed a decrease in plasma levels of Lp(a) that lasted 10 to 12 hours in the presence of an increased hypertriglyceridemic response. Two HP subjects who had low preprandial lipoprotein lipase activity and elevated plasma apo C-III levels showed an increase in plasma Lp(a) levels along with the hypertriglyceridemic excursion. However, in all cases, inclusive of the controls, there was an elevation in plasma levels of TRP of Sf greater than 1,000 that contained apo B-100-apo(a) 6 to 8 hours after the meal. This TRP excursion appeared not to be related to the basal levels of plasma Lp(a), high-density lipoprotein (HDL) cholesterol, TGs, or apo(a) and apo E isoforms, and it did not coincide with the retinyl ester peak.(ABSTRACT TRUNCATED AT 250 WORDS)     

HDL-cholesterol level provides additional prognosis in acute coronary syndromes

In the setting of acute coronary syndromes, plasma lipids have not been defined as prognostic variables, however little research has been dedicated to this specific issue. In order to test the independent predictive value for in-hospital events of low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides measured at hospital admission, 97 individuals with unstable angina or non-ST-elevation acute myocardial infarction were evaluated. In-hospital events, defined as death, non-fatal myocardial infarction or recurrent unstable angina, were significantly predicted by HDL-cholesterol (C-statistics=0.69; 95% CI=0.55-0.83, P=0.018), contrary to LDL-cholesterol (C-statistics=0.40; 95% CI=0.24-0.56, P=0.23) and triglycerides (C-statistics=0.48; 95% CI=0.31-0.65, P=0.83). The best HDL-cholesterol cut-off point was 32 mg/dl, with a 33% incidence of events in patients with HDL-cholesterol < or =32 mg/dl, compared with only 9% in those with HDL-cholesterol>32 mg/dl (P=0.003). Logistic regression analysis showed HDL-cholesterol< or =32 mg/dl (OR=3.6; 95% CI=1.0-14; P=0.05) and TIMI Risk Score (OR=2.3; 95% CI=1.4-2.9, P=0.001) as the independent predictors of events. Furthermore, the addition of HDL-cholesterol to TIMI Risk Score improved its C-statistic from 0.81 to 0.85. In conclusion, as opposed to LDL-cholesterol and triglycerides, HDL-cholesterol level adds prognostic value to the prediction of in-hospital recurrent events during non-ST-elevation acute coronary syndromes.     

An interaction between apo C-III variants and protease inhibitors contributes to high triglyceride/low HDL levels in treated HIV patients.

BACKGROUND: Long-term therapy with protease inhibitors (PI) is associated with hypertriglyceridaemia, low high-density lipoprotein (HDL) levels and accumulation of apolipoprotein (apo) E- and apo C-III-containing lipoproteins. OBJECTIVES: To evaluate the impact, on this dyslipaemic phenotype, of three polymorphisms of the apo C-III gene: two on an insulin response element and one in the 3'-region. Apo E genotypes were evaluated also. DESIGN: Sixty consecutive male patients attending the HIV follow-up consultation were included during a 3-month period. All patients received at least one PI. Apo C-III and apo E genotypes were determined. Besides routine bio-clinical examination, a detailed exploration of lipoproteins and of insulin secretion markers was carried out. METHODS: Plasma lipoparticles, insulin, proinsulin and C-peptide were measured by specific immuno-assays. Determination of apo C-III genotypes (-455C/T, -482C/T and SstI) and of apo E alleles (epsilon2, epsilon3 and epsilon4) were performed by amplification and endonuclease digestion and were confirmed by allele-specific oligonucleotide hybridization. RESULTS: Distribution of apo C-III alleles defined four major haplotypes. Carriers of the -455C variant had 30% lower levels of HDL-cholesterol than non-carriers. Plasma triglycerides increased according to the number of variant alleles. In multivariate analysis, a model including age, body mass index, clinical stage and treatment length, plasma insulin and apo C-III haplotypes explained around 43% of the HDL-cholesterol and triglycerides variability. Measurements of lipids before and after the use of PI demonstrated synergistic effects of the treatment and apo C-III variants on triglyceride levels. CONCLUSIONS: Apo C-III polymorphisms might identify a genetic predisposition to develop dyslipidaemia under PI therapy.     

Interactions between fibrinolysis, lipoproteins and leptin related to a first myocardial infarction.

BACKGROUND: The summarized importance of haemostatic and metabolic variables (insulin, lipids including lipoprotein (a) [Lp(a)] and leptin) in predicting first myocardial infarction, as well as possible interactions among these variables, have not been reported. DESIGN: A prospective case-control study nested within the Northern Sweden Health and Disease Cohort. METHODS: Sixty-two men diagnosed with a first myocardial infarction were sex- and age-matched with 124 controls. Conditional logistic regression was conducted including established risk factors, plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) mass concentration, von Willebrand factor, insulin, proinsulin, specific insulin, apolipoprotein A-I (apo A-I), Lp(a), and leptin. Interaction analysis was also performed for tPA, apo A-I, Lp(a), leptin and proinsulin. RESULTS: Smoking, low plasma levels of apo A-I and high plasma levels of cholesterol, Lp(a), tPA, PAI-1, proinsulin and leptin were associated with myocardial infarction in univariate conditional logistic regression analysis. High tPA [odds ratio (OR), 21.3; 95% confidence interval (CI), 2.04-222] and Lp(a) (OR, 7.21; 95% CI, 1.31-39.8) and low apo A-I (OR, 0.15; 95% CI, 0.02-0.93) remained significant risk determinants in multivariate analysis with smoking habits, body mass index, hypertension, cholesterol, and diabetes included as covariates. There were non-significant synergic interactions between high Lp(a) and leptin and tPA, respectively, and between high Lp(a) and low apo A-I. CONCLUSION: Plasma levels of tPA, Lp(a), and apo A-I are independently associated with subsequent development of a first myocardial infarction in men.     

国人健康男女及冠心病患者血浆脂蛋白(a)水平

为了了解国人人群脂蛋白(a)的分布及水平,探讨脂蛋白(a)与冠心病及其它血脂与载脂蛋白的关系,本文应用单价抗载脂蛋白(a)及抗载脂蛋白B抗体夹心酶联法测定668名健康人血浆脂蛋白(a),测得(?);122.34±141.97mg/L,M为81.07mg/L(0～1 250mg/L),呈典型的正偏态分布,无性别年龄差异,与其它脂类及载脂蛋白不相关。48例冠心病患者血浆脂蛋白(a)水平及>200mg/L的频率分布均明显高于同年龄对照组,提示高脂蛋白(a)水平是致动脉粥样硬化的一个独立危险因素。     

Apolipoproteins E and C-III in apo B- and non-apo B-containing lipoproteins in middle-aged women from the Stanislas cohort: effect of oral contraceptive use and common apolipoprotein E polymorphism

Oral contraceptive (OC) use and common apo E polymorphism are well known to modify serum lipid and lipoprotein concentrations. The combined effect of OC use and apo E genotype on the concentration of apo E or apo C-III in apo B- (apo E-LpB or apo C-III-LpB) or in non-apo B-containing lipoparticles (apo E-Lp-non-B or apo C-III-Lp-non-B) are unknown. Our study comprised 613 women, aged 30-45 years, genotyped for common apo E polymorphism and who differed in their combined low-dose OC consumption. The concentrations of apo C-III, apo C-III-LpB and apo C-III-Lp-non-B were significantly higher in OC users than in non-users by 13, 23 and 8% respectively, without significant interaction with the apo E genotype. The concentrations of apo E and apo E-Lp-non-B were significantly lower (differences being -14% and -31% respectively) in OC users than in controls whereas the apo E-LpB concentration was significantly higher (+19%), resulting in a redistribution of apo E from Lp-non-B towards LpB. Total apo E and apo E-Lp-non-B concentrations were higher in subjects carrying the epsilon2 allele and lower in those with the epsilon4 allele when compared to epsilon3/epsilon3 subjects (P < 0.001). The opposite held for the apo E- LpB concentration (P < 0.05). The main finding is the significant interaction between apo E genotype and OC use (P < 0.01) on apo E-Lp-non-B concentration, the epsilon4 carriers showing the smallest differences between OC users and non-users in comparison with the epsilon2 or epsilon3/epsilon3 carriers. These results suggest that the common apo E polymorphism can modulate the OC use effect.     

A case of symptomatic hypobetalipoproteinemia with unusual distribution of apolipoprotein E]

A case of symptomatic hypobetalipoproteinemia (hypo-beta LP) with unusual distribution of apolipoprotein E (apo E) in a 68-year-old male patient with chronic heart failure and liver cirrhosis associated with low triiodothyronine (T3) syndrome is reported. There was nothing in the family history to suggest familial hypo-beta LP. In this case, levels of apo B and low-density lipoprotein were very low, and the fraction of beta lipoprotein on polyacrylamide-gel disc electrophoresis (PAGE) was only 7%. However, the triglyceride level was normal due to the presence of chylomicron, in spite of hypocholesterolemia and hypophospholipidemia. The mid-band lipoprotein on PAGE showed that Lp (a) lipoprotein concentration was normal (18.3 mg/dl). The activities of lecithin cholesterol acyltransferase, hepatic triglyceride lipase and lipoprotein lipase (LPL) were low. The concentrations of apo C-II, apo C-III and apo E were low, while those of apo A-I and apo A-II were normal. The author recently reported that the apo C of high-density lipoprotein (HDL-apo C) was detected in alpha lipoprotein, but that HDL-apo E was detected in the near alpha 2-globulin region behind alpha lipoprotein on agarose-gel immunofixation electrophoresis. The author therefore named it alpha 2-apo E, and later found that the fraction percentage of alpha 2-apo E depends on lipolysis and is inversely correlated to the concentration of apo B.(ABSTRACT TRUNCATED AT 250 WORDS)     

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

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

Plasma lipoproteins in soy-treated postmenopausal women: a double-blind, placebo-controlled trial

BACKGROUND AND AIM: Postmenopausal modification of the lipid profile plays a major role in the risk of ischemic heart disease. Lifestyle counseling and estrogen replacement therapy have all been proposed as first-line measures, but there is no agreement on the best way to treat climacteric dyslipidemia. Soybean-based diet seems particularly attractive in this context, given its cholesterol lowering potential, its hypothetical anticancerous effects and possible modification of climacteric symptoms. METHODS AND RESULTS: We evaluated the effect of 60 g isolated soy protein (ISP) daily on the lipid profile of 104 postmenopausal women (53.3 +/- 3.3 years) in a double-blind, parallel, placebo-controlled (caseinate) trial, as part of a broader assessment of the effect of ISP on climacteric symptomatology. Serum total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apo A-I, apo B and lipoprotein (a) were determined before and after a 12-week diet modification. Seventy-seven women completed the trial. Both soy and placebo determined a significant reduction in total cholesterol (-0.42 +/- 0.79 and -0.40 +/- 0.57 mmol/L) and LDL-cholesterol (-0.35 +/- 0.72 and -0.31 +/- 0.54 mmol/L), but only soy had a significant lowering effect on apo B and the LDL-cholesterol/HDL-cholesterol ratio (-6% and -8% from baseline respectively); lipoprotein (a) plasma levels were not significantly changed by either treatment. Forty-four women were dyslipidemic at baseline; those with increased LDL concentrations showed a somewhat greater improvement in their lipoprotein profile (LDL-cholesterol and apo B reduction) with soy rather than placebo. No further information emerged when the subjects were divided into three apo E phenotypes. CONCLUSIONS: We conclude that diet supplementation with 60 g ISP is slightly better than caseinate in favorably modifying the lipoprotein metabolism of postmenopausal women; this effect is more evident in hypercholesterolemic subjects.     

Apolipoprotein E polymorphism in men and women from a Spanish population: allele frequencies and influence on plasma lipids and apolipoproteins.

The apolipoprotein (apo) E phenotype and its influence on plasma lipid and apolipoprotein levels were determined in men and women from a working population of Madrid, Spain. The relative frequencies of alleles epsilon(2), epsilon(3) and epsilon(4) for the study population (n=614) were 0.080, 0.842 and 0.078, respectively. In men, apo E polymorphism was associated with variations in plasma triglyceride and very low-density lipoprotein (VLDL) lipid levels. It was associated with the proportion of apo C-II in VLDL, and explained 5.5% of the variability in the latter parameter. In women apo E polymorphism was associated with the concentrations of plasma cholesterol and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) related variables. The allelic effects were examined taking allele epsilon(3) homozygosity as reference. In men, allele epsilon(2) significantly increased VLDL triglyceride and VLDL cholesterol concentrations, and this was accompanied by an increase of the apo C-II content in these particles. Allele epsilon(4) did not show any significant influence on men's lipoproteins. In women, allele epsilon(2) lowered LDL cholesterol and apo B levels, while allele epsilon(4) increased LDL cholesterol and decreased the concentrations of HDL cholesterol, HDL phospholipid and apo A-I. These effects were essentially maintained after excluding postmenopausal women and oral contraceptive users from the analysis. In conclusion: (1) the population of Madrid, similar to other Mediterranean populations, exhibits an underexpression of apo E4 compared to the average prevalence in Caucasians, (2) gender interacts with the effects of apo E polymorphism: in women, it influenced LDL and HDL levels, whereas in men it preferentially affected VLDL, and (3) allele epsilon(2) decreased LDL levels in women, while it increased both VLDL lipid levels and apo C-II content in men, but, in contrast to allele epsilon(4), it did not show an impact on HDL in either sex.     

Serum lipids and lipoproteins in patients with primary gout

Summary Serum lipid and lipoprotein values of 32 male patients suffering from gout were quantitated and compared with corresponding values of a random control group which did not differ significantly with regard to age, body weight index and socio-economic status. All patients were on therapy with allopurinol which lasted on average for 6 years. The most striking differences between patients and controls were the increased triglyceride and apo B values and the decreased HDL-cholesterol (HDL-C) and HDL-phospholipid (HDL-PL) values in the patient group. The values of total cholesterol, LDL-cholesterol, apo A-I and Lp (a) were not significantly different between patients and controls. The great differences in the ratios of apo B/LDL-C, apo A-I/HDL-C and apo A-I/HDL-PL values suggest that gout is connected with changes in the chemical composition of the major lipoprotein classes. In three normolipemic individuals who were treated for 3 weeks with allopurinol no changes in lipoproteins and apolipoproteins were apparent. The results are discussed in view of the atherosclerosis risk of patients suffering from gout.     

An increased number of very-low-density lipoprotein particles is strongly associated with coronary heart disease in Japanese men,independently of intermediate-density lipoprotein or low-density lipoprotein

BACKGROUND: Japanese patients with coronary heart disease (CHD) usually have slightly elevated triglyceride levels but virtually normal low-density lipoprotein (LDL)-cholesterol levels. DESIGN: Case-control study. METHODS: To explore the atherogenecity of mild hypertriglyceridemia, we measured very-low-density lipoprotein (VLDL) composition and apolipoprotein (apo) B in VLDL, intermediate-density lipoprotein (IDL), light LDL and dense LDL fractions separated by ultracentrifugation in 61 men with angiographically proven CHD and in 69 men without CHD. Apo B, E, C1 and C3 in VLDL were measured by enzyme-linked immunosorbent assay. RESULTS: Although total- and LDL-cholesterol levels were similar in CHD and control participants, triglyceride levels were significantly higher and high-density lipoprotein (HDL)-cholesterol levels were lower in CHD patients. Triglyceride, cholesterol and apo C1 and E levels in VLDL were two-fold higher and VLDL-apo B level was three-fold higher in CHD than control patients. IDL-triglyceride levels were significantly elevated in CHD, but IDL-cholesterol level was not. Apo B levels of the dense LDL fraction were significantly elevated in CHD groups, but those of the light LDL fraction were not. These differences were constant when triglyceride levels matched between both groups. Multiple logistic regression analysis revealed that the VLDL-apo B and VLDL-apo C1 levels were significantly associated with the incidence of CHD independent of the plasma triglyceride, HDL-cholesterol or apo B levels in dense LDL. CONCLUSION: These results suggest that an increased number of VLDL particles is strongly associated with CHD, independently of traditional risk factors or newly recognized atherogenic lipoproteins, such as IDL or small, dense LDL, in Japanese men.     

Risk factors that discriminate 'high- risk' from 'low-risk' Japanese patients with coronary artery disease

Although various risk factors have been implicated in the progression of coronary artery disease (CAD), coronary risk factors specifically related to the long-term prognosis for high-risk CAD have not been determined. The study enrolled 311 consecutive Japanese patients with CAD who underwent diagnostic coronary arteriography and divided them into 2 groups: (i) 135 high-risk patients with either impaired left ventricular function (ejection fraction <50%) or multivessel disease and (ii) 176 low-risk patients with normal left ventricular function and 0- or 1-vessel disease. The prevalence of risk factors including age, gender, smoking, hypertension, diabetes mellitus (DM), obesity and lipid variables were compared between the 2 groups. The prevalence of DM, a serum high-density lipoprotein (HDL)-cholesterol level below 35 mg/dl and a serum lipoprotein (Lp) (a) level above 25 mg/dl was significantly higher in the high-risk group as compared with the low-risk group. Multiple logistic regression analysis demonstrated that DM (odds ratio (OR): 1.72, 95% confidence intervals (CI): 1.02-2.92, p<0.05), a low HDL-cholesterol level (OR: 2.49, 95% CI: 1.49-4.17, p<0.001) and a high Lp(a) level (OR: 1.68, 95% CI: 1.02-2.76, p<0.05) were all independent risk factors for high-risk CAD. However, if the patients with 0-vessel disease were excluded from the low-risk group, a low HDL-cholesterol level was found to be the only independent predictor for high-risk CAD (OR: 2.07, 95% CI: 1.15-3.70, p<0.05). Among both men and smokers in this population, a higher Lp(a) level was found to be a significant predictor for high-risk CAD. A low serum level of HDL-cholesterol, a high serum level of Lp(a) and DM were significant predictors of high-risk in patients with CAD. Among patients with a significant coronary stenosis or left ventricular dysfunction, a low serum level of HDL-cholesterol was the only significant predictor for high-risk CAD.