Subclinical hypothyroidism and lipid abnormalities in older women attending a vascular disease prevention clinic: effect of thyroid replacement therapy

The authors evaluated the frequency and type of lipid disorders associated with subclinical hypothyroidism (SH) in older women referred to their university vascular disease prevention clinic. They also assessed the results of thyroid replacement therapy. Fasting serum lipid profiles and thyroid function tests were measured in 333 apparently healthy women (mean age: 71.8 +/- 7 years). These women were divided into 3 groups: group I: 60-69 years old (n = 132); group II: 70-79 years old (n = 153); group III: 80-89 years old (n = 48). SH was defined as a serum thyrotropin concentration higher than 3.20 mlU/mL with a normal free thyroxine concentration. The prevalence of SH was 7.5%. Thyrotropin was higher than 3.20 mU/mL in 25 women; 7 (5.3%), 14 (9.2%), and 4 (8.3%) in groups I, II, and III, respectively. Low-density lipoprotein cholesterol (LDL-C) concentrations were higher in the women with SH (p = 0.037). The mean values of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio, lipoprotein (a) (Lp[a]), apolipoprotein A-I (apo AI) apolipoprotein B100 (apo B) and apo B/apo A ratio were higher and triglycerides (TG) were lower, compared with those with normal levels of thyrotropin. However, none of these differences reached significance. Restoration of euthyroid status (thyroxine: 50-100 microg/day) in 17 SH women significantly improved TC (p = 0.017), LDL-C (p = 0.014), TC/HDL-C (p = 0.05), LDL-C/HDL-C (p = 0.03), apo B (p = 0.013), and Lp(a) (p = 0.0005) values. SH is relatively common in older women attending a vascular disease prevention clinic. Thyroid hormone replacement therapy significantly improved serum lipids. In particular, the reduction in LDL-C and Lp(a) concentrations may be of clinical benefit.     

Elevated serum lipoprotein(a) in subclinical hypothyroidism

OBJECTIVES Asymptomatic lymphocytic thyroiditis and subclinical hypothyroidism are associated with increased risk for coronary artery disease. The present study aimed at evaluating serum lipoprotein(a)(Lp(a), measured as apo(a), and other lipid parameters In 32 subjects with asymptomatic subclinical hypothyroidism. SUBJECTS Thirty-two Chinese subjects with asymptomatic subclinical hypothyroidism were compared to 96 age and sex-matched healthy controls. RESULTS Subclinical hypothyroid patients had higher (P < 0.005) apo(a), total triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) but lower (P < 0.05) high density lipoprotein cholesterol (HDL-C) levels compared with sex and age-matched controls (apo(a) 296 (48–1650) vs 182 (19–1952 U/I), geometric mean (range); TG 1.86 ± 0.94 vs 1.33±0.74mmol/l (mean ± SD); TC 6.10 ±1.17 vs 5.42 ±1.13 mmol/l; LDL-C 410 ± 1.00 vs 3.49 ± 0.96 mmol/l; HDL-C 1.15 ± 0.40 vs 1.34 ± 0.40 mmol/l, respectlvely). Apo A-I and apo B were also higher than controls (1.96 ± 048 vs 1.48 ± 029 g/l and 1.44 ± 042 vs 1.05±029 g/l, respectively). Total cholesterol/HDL ratio and LDL/HDL ratio were also elevated in these subjects (577 ± 1.96 vs 428 ±1.19 and 389 ± 1.41 vs 2.79 ± 0.97, respectively, both P < 0.0005). Individual analysis revealed that 16 (50%) subjects had hyperlipoprotelnaemia (TC > 5.2 mmol/l in 10;TC > 52 mmol/l and TG > 2.3mmol in six) as compared to 21(208%) in the control group (P < 0.005). Subjects with TSH ± 11.0mlU/l had significantly higher TC/HDL and LDL/HDL ratios. A significant correlation was observed between TSH levels and TC/HDL ratios (r = 0.455, P < 001). CONCLUSIONS Subclinical hypothyroidism Is associated not only with elevated LDL-cholesterol levels and low HDL-cholesterol levels but also with elevated lipoprotein (a). This may further Increase the risk development of atheroscierosis.     

Postprandial changes in the distribution of apolipoprotein AIV between apolipoprotein B- and non apolipoprotein B-containing lipoproteins in obese women

Plasma apolipoprotein AIV (apo AIV) level has been shown to be a good marker of triglyceride changes after a high-fat diet. However, the distribution of apo AIV between apo B- and non-apo B-containing lipoproteins (Lp) during the postprandial state has not been described as well as the influence of obesity on this distribution. Our aim was to study the influence of parameters related to obesity and insulin resistance on the postprandial changes in apo AIV-containing Lp after a high-fat meal in obese women. Twenty-three overweight or obese women (body mass index [BMI] ranging from 29.1 and 64.0 kg.1 m(-2)), for whom blood samples were taken after fasting overnight, participated in the study. Thirteen of these obese women were given a fatty meal and, in this case, blood samples were taken at fast and 30 minutes, 1, 2, 4, and 6 hours after ingestion of the fat meal. Apo AIV-containing particle families, Lp B:AIVf (family [f] of particles containing at least apo B and apo AIV) and Lp AIV non-Bf (family [f] of particles containing apo AIV, but free of apo B) were quantified by sandwich enzyme-linked immunosorbent assay (ELISA). When fasting, Lp B:AIVf and Lp AIV non-Bf did not correlate with any of the parameters related to obesity and insulin resistance, if one excepts a positive correlation between HDL-cholesterol (HDL-C) and Lp AIV non-Bf. Postprandial lipemia was associated with a trend towards an increase in the plasma levels of apo AIV-containing Lp 6 hours after fat ingestion. The postprandial peak of Lp B:AIVf and Lp AIV non-Bf occurred 2 hours after the triglyceride peak. The distribution between apo B- and non-apo B-containing Lp did not change after ingestion of the fat meal, if one excepts a tendancy towards a lower ratio of bound and nonbound forms at 8 hours. Fasting plasma Lp B:AIVf concentration correlated with the area under the curve (AUC) of plasma triglycerides (beta = 0.11, P <.02). In a multivariate analysis, BMI (beta = 51.85, P <.001), fasting triglycerides (beta = 431.08, P <.01), and low-density lipoprotein-cholesterol (LDL-C) (beta = 2638.57, P <.005) were independent and positive determinants of the AUC of Lp AIV non-Bf, while waist circumference (beta = -23.94, P <.001), cholesterol (beta = -1655.02, P <.01), and systolic blood pressure (beta = -6.34, P <.05) were negative and independent determinants of this AUC. Fasting Lp B:AIVf may represent a good marker of the postprandial triglyceride increase in obese women. Changes in apo AIV concentrations in apo B- and non-apo B-containing Lp after a fat meal depend mainly on the degree of obesity rather than on insulin resistance. This effect is more obvious for Lp AIV non-Bf than for Lp B:AIVf.     

Serum lipoprotein(a) concentrations and apolipoprotein(a) phenotypes in the families of NIDDM patients

Summary We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotype in 87 members (42 males, 45 females) of 20 diabetic families, 26 of whom were diagnosed with non-insulin-dependent diabetes mellitus (NIDDM) with moderate glycaemic control (HbA_1c7.1±1.2%). Apo(a) phenotyping was performed by a sensitive, high-resolution technique using SDS-agarose/gradient PAGE (3–6%). To date, 26 different apo(a) phenotypes, including a null type, have been identified. Serum Lp(a) levels of NIDDM patients and non-diabetic members of the same family who had the same apo(a) phenotypes were compared, while case control subjects were chosen from high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups with the same apo(a) phenotypes in the same family. Serum Lp(a) levels were significantly higher in NIDDM patients than in non-diabetic subjects (39.8±33.3 vs 22.3±19.5 mg/dl, p<0.05). The difference in the mean Lp(a) level between the diabetic and non-diabetic groups was significantly (p<0.05) greater than that between the high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups. An analysis of covariance and a least square means comparison indicated that the regression line between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in the diabetic patient group was significantly (p<0.01) elevated for each apo(a) phenotype, compared to the regression line of the control group. These data, together with our previous findings that serum Lp(a) levels are genetically controlled by apo(a) phenotypes, suggest that Lp(a) levels in diabetic patients are not regulated by smaller apo(a) isoforms, and that serum Lp(a) levels are greater in diabetic patients than in non-diabetic family members, even when they share the same apo(a) phenotypes.Abbreviations Lp(a) Lipoprotein(a) - apo(a) apolipoprotein(a) - NIDDM non-insulin-dependent diabetes mellitus - TC total cholesterol - LDL low density lipoprotein - TG triglycerides - HDL-C high density lipoprotein-cholesterol - LDL-C low density lipoprotein-cholesterol - PBS phosphate buffered saline The first two authors contributed equally to this work     

Plasma lipoprotein (a) concentrations in hypothyroid, euthyroid and hyperthyroid subjects.

OBJECTIVE: Alterations of the lipid profile are a well known phenomenon in thyroid dysfunction. Thyroid hormones regulate lipid metabolism through various mechanisms, but a key role is played by the LDL receptor pathway. Thyroid hormone influence on lipoprotein (a) [Lp(a)] metabolism is known. METHODS AND RESULTS: Therefore we studied Lp(a) concentrations in a group of 16 hypothyroid patients and in a group of 22 hyperthyroid patients. Twenty-six euthyroid subjects were used as a control group. Plasma Lp(a) concentrations in hyperthyroid patients (23.2 +/- 28.1 mg/dl) were significantly lower than those of the hypothyroid patients (27.1 +/- 19.2, p < 0.05). There were negative correlations between plasma Lp(a) concentrations and total T4 levels in patients with hyperthyroidism and hypothyroidism (r: -0.49, p < 0.05; r: -0.40, p < 0.05, respectively). Also, decreased HDL-C levels, increased LDL-C, total cholesterol and apo B levels in the hypothyroid patients according to euthyroid subjects were observed (p < 0.05). Decreased LDL-C levels, increased HDL-C and apo Al levels in the hyperthyroid patients according to euthyroid subjects were determined (p < 0.05). CONCLUSIONS: It was concluded that plasma Lp(a) concentrations increase in hypothyroid patients and the observed relationships between thyroid status and Lp(a) levels can be explained by impaired catabolism of apo B and Lp(a) in hypothyroidism.     

Associations among serum lipoprotein(a) levels, apolipoprotein(a) phenotypes, and myocardial infarction in patients with extremely low and high levels of serum lipoprotein(a).

A high serum lipoprotein(a) [Lp(a)] level, which is genetically determined by apolipoprotein(a) [apo(a)] size polymorphism, is an independent risk factor for coronary atherosclerosis. However, the associations among Lp(a) levels, apo(a) phenotypes, and myocardial infarction (MI) have not been studied. Patients with MI (cases, n = 101, M/F: 86/15, age: 62+/-10y) and control subjects (n = 92, M/F: 53/39, age: 58+/-14y) were classified into quintile groups (Groups I to V) according to Lp(a) levels. Apo(a) isoform phenotyping was performed by a sensitive, high-resolution technique using sodium dodecyl sulfate-agarose/gradient polyacrylamide gel electrophoresis (3-6%), which identified 26 different apo(a) phenotypes, including a null type. Groups with higher Lp(a) levels (Groups II, III, and V) had higher percentages of MI patients than that with the lowest Lp(a) levels (Group I) (54%, 56%, or 75% vs. 32%, p<0.05). Groups with different Lp(a) levels had different frequency distributions of apo(a) isoprotein phenotypes: Groups II, III, IV, and V, which had increasing Lp(a) levels, had increasingly higher percentages of smaller isoforms (A1-A4, A5-A9) and decreasingly lower percentages of large isoforms (A10-A20, A21-A25) compared to Group I. An apparent inverse relationship existed between Lp(a) and the apo(a) phenotype. Subjects with the highest Lp(a) levels (Group V) had significantly (p<0.05) higher serum levels of total cholesterol, apo B, and Lp(a). Patients with MI and the controls had different distributions of apo(a) phenotypes: i.e., more small isoforms and more large size isoforms, respectively (A1-A4/A5-A9/A10-A20/A21-A25: 35.7%/27.7%/20.8%/15.8% and 22.8%/23.9%/29.4%/23.9%, respectively). Lp(a) (parameter estimate +/- standard error: 0.70+/-0.20, Wald chi2 = 12.4, p = 0.0004), apo(a) phenotype (-0.43+/-0.15, Wald chi2 = 8.17, p = 0.004), High-density lipoprotein-cholesterol, apo A-I, and apo B were significantly associated with MI after adjusting for age, gender, and conventional risk factors, as assessed by a univariate logistic regression analysis. The association between Lp(a) and MI was independent of the apo(a) phenotype, but the association between the apo(a) phenotype and MI was not independent of Lp(a), as assessed by a multivariate logistic regression analysis. This association was not influenced by other MI- or Lp(a)-related lipid variables. These results suggest that apo(a) phenotype contributes to, but does not completely explain, the increased Lp(a) levels in MI. A stepwise logistic regression analysis with and without Lp(a) in the model identified Lp(a) and the apo(a) phenotype as significant predictors for MI, respectively.     

Postprandial hyperlipidemia: another correlate of the "hypertriglyceridemic waist" phenotype in men

Fasting hypertriglyceridemia has been reported to be predictive of an exaggerated triglyceride (TG) response to an oral fat load. Abdominal obesity has also been associated with postprandial hyperlipidemia. The objective of the present study was to quantify the contribution of abdominal obesity and fasting hypertriglyceridemia to the magnitude of postprandial lipemia. For that purpose, potential differences in postprandial TG-rich lipoprotein (TRL) levels were examined among men characterized by the absence/presence of the "hypertriglyceridemic waist" phenotype following a standardized breakfast with a high fat content (64% calories as fat). Sixty-nine men (mean age +/- S.D.: 45.1 +/- 10.5 years) were classified according to waist girth (< 90 or >/ or = 90 cm) and fasting TG concentrations (< 2.0 or > or = 2.0 mmol/l). Subjects characterized by "hypertriglyceridemic waist" (waist > or = 90 cm and fasting TG > or = 2.0 mmol/l) showed the highest TRL-TG concentrations (P < 0.0001) throughout the entire postprandial period (8 h) as well as elevated concentrations of apolipoprotein (apo) B-48 and apo B-100 in all TRL fractions (large, medium and small) compared to subjects with low fasting TG levels who had waist girth values either above or below 90 cm. These higher postprandial TRL-TG levels among carriers of the "hypertriglyceridemic waist" phenotype also led to significantly greater postprandial TG-total area under the curve (AUC) in total TRLs resulting mainly from the increased concentrations of large- and medium-sized TRLs. Furthermore, subjects characterized by the "hypertriglyceridemic waist" phenotype displayed higher fasting insulin concentrations and postprandial insulin AUC compared to men with low fasting plasma TG levels and low waist girth values. In conclusion, results of the present study indicate that postprandial hyperlipidemia is associated with the simultaneous presence of abdominal obesity and elevated fasting TG concentrations: a condition that we have described as the "hypertriglyceridemic waist" phenotype.     

The lipoprotein fraction between VLDL and LDL detected by biphasic agarose gel electrophoresis reflects serum remnant lipoprotein and Lp(a) concentrations

We analyzed lipoprotein profiles in 616 Japanese by biphasic agarose gel electrophoresis using Chol/Trig Combo(TM) to yield HDL, VLDL, LDL and CM fractions which were stained with cholesterol and triglyceride reagents, respectively. To further evalute the pattern of electrophoresis, we analyzed the fraction between VLDL and LDL to confirm the possibility of a MidBand by using an automatic-five-fraction function. The cholesterol concentrations in MidBand (MidBand-C) showed a good correlation to remnant-like particle-cholesterol (RLP-C) (r = 0.95) in 23 consecutive samples (TC < 220 mg/dl, Lp(a) < 30 mg/dl). However, MidBand-C concentrations of subjects with high Lp(a) levels (Lp(a) > 30 mg/dl) were also high compared to RLP-C concentrations. The average MidBand-C levels in elderly normolipidemic control subjects (TC < 220, TG < 150) were 5.2 +/- 2.4 mg/dl in 30 males (mean age, 70 +/- 10 years) and 5.4 +/- 2.0 mg/dl in 40 females (64 +/- 11 years). The average MidBand-C levels of normolipidemic patients with coronary artery diseases (CAD; TC < 220, TG < 150) were 9.4 +/- 4.1 mg/dl in 126 males (mean age, 66 +/- 10 years) and 9.1 +/- 4.0 mg/dl in 44 females (67 +/- 10 years). These levels were significantly higher than control values (p < 0.0001). Areas under ROC curves were greater for MidBand-C than for TC, LDL-C and TG when used to discriminate between the patients with CAD and normolipidemic control subjects for each sex. There results suggest that the MidBand-C level may be useful as an indicator of risk for CAD.     

女性原发性高血压患者绝经前后脂蛋白(a)及血脂水平变化的研究

目的　观察女性原发性高血压患者绝经前后脂蛋白 (a) [L p(a) ]及血脂水平的变化 ,探讨其对女性冠心病发病情况可能存在的影响。方法　女性原发性高血压患者 12 1例 ,测定 L p(a)、总胆固醇 (TC)、三酰甘油 (TG)、低密度脂蛋白胆固醇 (L DL- C)和高密度脂蛋白胆固醇 (HDL- C)。对比绝经前后 L p(a)及血脂水平的变化 ,并与女性健康体检者 (对照组 )进行对比。结果　高血压组 L p(a)、TC、TG、L DL - C均显著高于对照组 ,而 HDL - C及 HDL - C/TC则明显低于对照组 ,在所有原发性高血压患者中 ,绝经后的患者 L p(a)、TC、TG、L DL - C显著高于绝经前患者 ,而 HDL - C/ TC则前者低于后者。结论　绝经后原发性高血压患者 L p(a)、TC、L DL - C均明显高于绝经前患者 ,而HDL- C/ TC则低于绝经前患者 ,提示绝经后女性原发性高血压患者 L p(a)及血脂水平增高与内源性雌激素水平下降有关 ,是绝经后冠心病发病率明显上升的重要原因。     

High lipoprotein(a) levels and small apolipoprotein(a) sizes are associated with endothelial dysfunction in a multiethnic cohort

OBJECTIVES: This study sought to determine the effect of lipoprotein(a), or Lp(a), levels and apolipoprotein(a), or apo(a), sizes on endothelial function and to explore ethnic differences in their effects. BACKGROUND: Although high levels of Lp(a) have been shown to confer increased cardiovascular risk in Caucasians, its significance in non-Caucasian populations is uncertain. The pathogenic role of the apo(a) component of Lp(a) is also unclear. METHODS: The relationship of Lp(a) levels and apo(a) sizes to endothelial function was examined in a multiethnic cohort of 89 healthy subjects (age 42 +/- 9 years; 50 men, 39 women) free of other cardiac risk factors. Endothelium-dependent, flow-mediated dilation (FMD) and endothelium-independent, nitrate-induced dilation (NTG) were assessed by ultrasound imaging of the brachial artery. RESULTS: Plasma Lp(a) levels were lowest in Caucasians (18.3 +/- 21.1 mg/dl, n = 40); intermediate in Hispanics (30.2 +/- 30.5 mg/dl, n = 21); and highest in African Americans (68.8 +/- 46.0 mg/dl, n = 28). Lipoprotein(a) levels were found to correlate inversely to FMD (r = -0.33, p < 0.005) but not to NTG (r = 0.06, p = 0.60). This association remained significant after adjusting for gender (p = 0.002). In addition, subjects with small apo(a) size of 相似文献   

Insulin resistance and adiposity influence lipoprotein size and subclass concentrations. Results from the Insulin Resistance Atherosclerosis Study

BACKGROUND: Insulin resistance and obesity are associated with a dyslipidemia composed of high levels of triglycerides (TG), low levels of high-density lipoprotein cholesterol (HDL-C), and no change in level of low-density lipoprotein cholesterol (LDL-C). We examined the association of insulin resistance and adiposity with lipoprotein particle size, concentration, and subclass concentrations. METHODS: The Insulin Resistance Atherosclerosis Study is a multicenter cohort study of middle-aged men and women. Lipoprotein lipid concentrations were determined using standard methods. Lipoprotein size, particle concentration, and subclass concentrations were determined using nuclear magnetic resonance technology. Insulin resistance (SI) was determined based on the frequently sampled intravenous glucose tolerance test and the MINMOD program. A higher SI represents less insulin resistance. Fasting insulin, body mass index, waist circumference, and waist/hip ratio were assessed. RESULTS: Among the 1371 participants were 754 women and 617 men; 459 Hispanics, 383 African Americans, and 529 non-Hispanic whites; 437 with type 2 diabetes, 301 with impaired glucose tolerance, and 633 with normal glucose tolerance. The mean (SD) age was 55.5 (8.5) years, body mass index was 29.3 (5.8) kg/m2 , and SI was 1.6 (1.8) units. Adjusted for age, sex, and ethnicity, SI was not associated with LDL-C (r = 0.01); however, S I was associated with LDL size (r = 0.34, P < .001), LDL particle concentration (r = -0.28, P < .001), small LDL (r = -0.34, P < .001), intermediate LDL (r = -0.37, P < .001), and large LDL (r = 0.21, P < .001). In addition, S I was associated with TG (r = -0.36, P < .001), VLDL particles (r = -0.08, P < .01), large VLDL (r = -0.32, P < .001), VLDL size (r = -0.38, P < .001), HDL-C (r = 0.37, P < .001), HDL particles (r = 0.09, P < .001), large HDL (r = 0.31, P < .001), and HDL size (r = 0.33, P < .001). A factor analysis revealed a factor that accounted for 41.4% of the variance across the lipoprotein measures and that was correlated with SI (r = -0.33, P < .001). Similar results of opposing direction were observed for analyses of lipoprotein measures with fasting insulin and adiposity. CONCLUSIONS: The dyslipidemia associated with insulin resistance and obesity includes effects on lipoprotein metabolism that are missed when traditional lipoprotein cholesterol and total TG are examined. Lipoprotein size and subclasses should be examined in studies investigating the roles of insulin resistance and obesity in the pathogenesis and prevention of atherosclerosis.     

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

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

Subcutaneous central fat is associated with cardiovascular risk factors in men independently of total fatness and fitness

The purpose of this study was to analyze the single and independent associations of whole body composition and fat distribution with cardiovascular disease (CVD) risk factors and fitness in middle-aged men. Sixty-two healthy Caucasian men (37.6 +/- 2.9 yr, 81.8 +/- 11.3 kg, 171.5 +/- 4.9 cm) participated in the study. Dual-energy x-ray absorptiometry (DXA) was used to assess total and regional body composition. The triceps, biceps, midthigh, calf, subscapular, chest, abdominal and suprailiac skinfolds, and the waist, hip and midthigh circumferences, and sagittal diameter were estimated. Cardiovascular fitness was estimated with a submaximal test. Bivariate and partial correlation analysis were used to study the association of total body percent fat (%fat), DXA trunk fat and trunk skinfolds (sum of subscapular, chest, abdominal, and suprailiac) and fitness with insulin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein AI (apo AI), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and diastolic and systolic blood pressure. All anthropometric and DXA body composition variables were significantly correlated with TC/HDL-C (from .26 to .50, P < .05). Similar relationships were found for insulin, HDL-C, and systolic blood pressure (r from .26 to .47, P < .05). Cardiovascular fitness was significantly (P < .05) associated with insulin (r = -.36), HDL-C (r = .27), TC/HDL (r = -.27), and with systolic blood pressure (r = -.37). After controlling for trunk skinfolds, none of the anthropometric and DXA body composition variables were correlated with any of the CVD risk factors. Similarly, when controlling for trunk skinfolds, cardiovascular fitness was not related to any of the metabolic variables. After adjusting for %fat, DXA trunk fat, and cardiovascular fitness, trunk skinfolds remained significantly (P < .05) related to insulin (r = .35), HDL-C (r = -.40), TC/HDL-C (r = .43), and apo AI (r = -.39). In conclusion, this study suggests that subcutaneous truncal fat, as estimated by skinfolds, is an independent predictor of CVD risk factors, and that the association between cardiovascular fitness and these risk factors may be mediated by the levels of abdominal subcutaneous fat in Caucasian middle-aged men.     

The rebound of lipoproteins after LDL-apheresis. Kinetics and estimation of mean lipoprotein levels

We studied the rebound of lipoproteins in 20 hypercholesterolemic men [mean total cholesterol (TC) levels 9.6+/-1.8 mmol/l] after LDL-apheresis (LA) to determine the rate of recovery and the change in cholesterol synthesis, and to find a uniform estimation for time-averaged levels. After 10-20 months on biweekly LA using dextran sulfate cellulose columns and concomitant simvastatin administration, time-averaged levels (+/-SD) measured by integration of the area under the curve were as follows: TC 4.4+/-1.0 mmol/l, LDL cholesterol (LDL-C) 2.5+/-1.0 mmol/l, apolipoprotein B (apo B) 1. 3+/-0.3 g/l, triglycerides (TG) 1.7+/-0.7 mmol/l, HDL-C 1.1+/-0.2 mmol/l, and lipoprotein(a) [Lp(a)] 53.7+/-49.4 mg/dl. Mean acute reductions in TC, LDL-C, apo B, Lp(a), and TG were 61, 77, 75, 76, and 62%, respectively. HDL-C levels were not influenced. Median recovery half times for TC, LDL-C, apo B, and Lp(a) were 3.0, 4.0, 2. 3, and 3.5 days, respectively. The rebound of Lp(a) was identical to LDL-C, in 12 and 13 days post-treatment, respectively, whereas apo B and TC returned to pre-treatment levels in 7.5 and 10 days, respectively, due to the fast rebound of VLDL particles. Notwithstanding these differences, time-averaged levels (C(AVG)) could be estimated uniformly for the four latter parameters with the formula: C(AVG)=C(MIN)+0.73(C(MAX)-C(MIN)), where C(MAX) and C(MIN) are the immediate pre- and post-treatment levels. During long-term treatment the whole-body cholesterol synthesis was increased as measured by the ratio lathosterol to cholesterol of 3.24+/-1.49 mmol/mmol, whereas no further transient increase in the recovery period after LA was found. In conclusion, long-term LA and simvastatin therapy induced acute and chronic changes in lipids and lipoproteins showing the feasibility of biweekly treatment. It was shown that time-averaged levels, as a measure for the effective plasma levels, can be accurately estimated from pre- and post-treatment levels only.     

Adiponectin is independently associated with apolipoprotein B to A-1 ratio in Koreans

Apolipoprotein B to A-1 (apo B/A-1) ratio is reportedly a better predictor of atherosclerotic vascular disease than low-density lipoprotein cholesterol (LDL-C). The aim of this study was to assess the association of serum apo B/A-1 ratio with insulin resistance and adiponectin in patients with different grades of glucose intolerance. Patients were divided according to glucose tolerance into 3 groups: normal glucose tolerance without metabolic syndrome (n = 229), impaired fasting glucose (subjects with fasting plasma glucose level between 100 and 125 mg/dL, n = 658), and type 2 diabetes mellitus (n = 381). Serum concentrations of apo B, apo A-1, glucose, total cholesterol (TC), triglycerides, and high-density lipoprotein cholesterol (HDL-C) and adiponectin were measured. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance index (HOMA-IR). There were significant differences in metabolic parameters among the groups, including waist circumference, insulin, HOMA-IR, and apo B/A-1 ratio, which increased sequentially with glucose intolerance, whereas adiponectin level decreased with increasing severity of glucose intolerance. The apo B/A-1 ratio was significantly correlated with TC, triglycerides, LDL-C, HDL-C, adiponectin, and HOMA-IR in normal glucose tolerance, impaired fasting glucose, and type 2 diabetes mellitus. Multiple regression analysis showed that apo B/A-1 ratio was significantly associated with TC, LDL-C, HDL-C, and adiponectin. In conclusion, apo B/A-1 ratio was significantly associated with insulin resistance according to glucose intolerance; and serum adiponectin was an important independent factor associated with apo B/A-1 ratio in Koreans.     

检测视黄醇结合蛋白4在非酒精性脂肪性肝病中的意义

目的探讨非酒精性脂肪性肝病(NAFLD)患者血清视黄醇结合蛋白4(RBP4)的临床意义。方法选择NAFLD肝患者62例,正常对照60例,采用ELISA方法测定空腹血清RBP4,同时检测其血糖、血脂、肝功能及胰岛素水平,并计算胰岛素抵抗指数(HOMA-IR)。结果与正常对照组比较,NAFLD患者的空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、低密度酯蛋白(LDL-C)、血清胰岛素(FINS)、HOMA-IR、ALT、AST和RBP4显著增高(P<0.01),而且NAFLD患者治疗后血清RBP4水平显著降低。相关分析显示,血清RBP4与FBG、TC、TG、FINS、HOMA-IR呈正相关。结论在NAFLD的发病过程中,RBP4可能参与其发病,在其早期诊断和评判肝脏损害程度中有一定的临床意义。     

Metabolic and anthropometric determinants of serum Lp(a) concentrations and Apo(a) polymorphism in a healthy Arab population.

BACKGROUND: Blood lipoprotein(a) Lp(a) concentrations are an important risk factor for atherosclerosis. The basis for this atherogenic property of Lp(a) and the factors that influence its cross-population levels, however, remain poorly understood. OBJECTIVES: To investigate the relationship between serum Lp(a) and metabolic and anthropometric parameters in a healthy Kuwaiti population. DESIGN: Cross-sectional study. SUBJECTS: 177 (72 male, 105 female) randomly recruited healthy Kuwait Arabs aged 17-60 y MEASUREMENTS: Metabolic parameters in serum: Lp(a), apo(a) phenotypes, lipids and lipoproteins, glucose and urate. Anthropometric parameters: body mass index (BMI) and waist:hip-ratio (WHR). RESULTS: The distribution of Lp(a) concentrations was positively skewed (median 153 mg/l, range 0-1086). Women had higher concentrations-(194, 0-1086) than men (117, 0-779), P = 0.069. Lp(a) and insulin concentrations were significantly higher when the men and women were obese. In all subjects, there were significant correlations between Lp(a) and BMI (r = 0.23), total cholesterol (TC) (r = 0.17) and LDL (r = 0.20). Lp(a) correlated only with glucose in men (r = 0.28). In women it correlated with age (r = 0.20), BMI (r = 0.30), BP (r = 0.20), TC (r = 0.20) and LDL (r = 0.26). Multivariate analyses confirmed BMI and low-density lipoprotein (LDL) as the significant determinants of serum Lp(a). On apo (a) phenotyping, 114 (67%), 51 (30%) and 6 (4%) had single, double and null phenotypes respectively. The isoforms and their corresponding kringle IV repeat numbers were: F (14 repeats in 3%, mean Lp(a) 497 mg/l); S1 (19 repeats in 14%, mean 245 mg/l); S2 (23 repeats in 16%, mean 264 mg/l); S3 (27 repeats in 35%, mean 236 mg/l); and S4 (35 repeats in 28%, mean 235 mg/l). DISCUSSION AND CONCLUSION: The results from the Kuwaiti population studied suggest that: (1) serum Lp(a) concentrations and distribution are similar to the pattern in Caucasians and Asians but not African-Americans or Africans; (2) serum Lp(a) is variably influenced by BMI and LDL--the impact of either factor differs between the sexes; (3) there is a high frequency of the single-banded phenotype; (4) contrary to reports in some Caucasian and Asian populations, there is no simple relationship between kringle IV repeat numbers and plasma Lp(a) concentrations.     

Association of serum apolipoprotein C III levels and apolipoprotein C III gene Sst I polymorphism with carotid intima-media thickness in Chinese type 2 diabetic patients

Apolipoprotein C III (apo C III) plays a central role in regulating plasma metabolism of triglyceride-rich lipoprotein (TRL). The G3238C allele (Sst I) in the 3'-untranslated region has been found to be associated with raised apo C III levels and hypertriglyceridemia (HTG). Some studies suggest that apo C III and the S(2) allele of apo C III gene are independent risk factors for atherosclerotic diseases. To study the potential association between these factors we analyzed the clinical data and their correlations with serum apo C III levels, apo C III gene Sst I polymorphism, and carotid intima-media thickness (IMT) in 78 unrelated Chinese patients with type 2 diabetes. Apo C III gene Sst I polymorphism was examined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Carotid IMT was measured by color doppler ultrasound examination. Serum apo C III levels were found to be positively associated with plasma TG ( r = 0.527, P < 0.001), TC (r = 0.424, P < 0.001), LDL-C (r = 0.308, P < 0.01) concentrations, and carotid IMT (r =0.359, P < 0.01 ). Multivariate analysis (backward) showed that diastolic blood pressure, apo C III, and fasting insulin levels were independent risk factors of carotid IMT. However, the results did not show the association between S(2) allele and carotid IMT in our diabetic patients. Thus, our study suggested that apo C III is an independent risk factor for atherosclerotic diseases in Chinese type 2 diabetes.     

Lipoprotein (a) levels and apolipoprotein (a) isoform size in patients with subclinical hypothyroidism: effect of treatment with levothyroxine.

The increased risk for ischemic heart disease (IHD) associated with subclinical hypothyroidism (SH) has been partly attributed to dyslipidemia. There is limited information on the effect of SH on lipoprotein (a) [Lp(a)], which is considered a significant predictor of IHD. Serum Lp(a) levels are predominantly regulated by apolipoprotein [apo(a)] gene polymorphisms. The aim of our study was to evaluate the Lp(a) levels and apo(a) phenotypes in patients with SH compared to healthy controls as well as the influence of levothyroxine substitution therapy on Lp(a) values in relation to the apo(a) isoform size. Lp(a) levels were measured in 69 patients with SH before and after restoration of a euthyroid state and in 83 age- and gender-matched healthy controls. Apo(a) isoform size was determined by sodium dodecyl sulfate (SDS) agarose gel electrophoresis followed by immunoblotting and development via chemiluminescence. Patients with SH exhibited increased Lp(a) levels compared to controls (median value 10.6 mg/dL vs. 6.0 mg/dL, p = 0.003]), but this was not because of differences in the frequencies of apo(a) phenotypes. There was no association between thyrotropin (TSH) and Lp(a) levels in patients with SH. In subjects with either low (LMW; 25 patients and 28 controls) or high (HMW; 44 patients and 55 controls) molecular weight apo(a) isoforms, Lp(a) concentrations were higher in patients than in the control group (median values 26.9 mg/dL vs. 21.8 mg/dL, p = 0.02 for LMW, and 6.0 mg/dL versus 3.3 mg/dL, p < 0.001 for HMW). Levothyroxine treatment resulted in an overall reduction of Lp(a) levels (10.6 mg/dL baseline vs. 8.9 mg/dL posttreatment, p = 0.008]). This effect was mainly evident in patients with LMW apo(a) isoforms associated with high baseline Lp(a) concentrations (median values 26.9 mg/dL vs. 23.2 mg/dL pretreatment and posttreatment, respectively; p = 0.03). In conclusion, even though a causal effect of thyroid dysfunction on Lp(a) was not clearly demonstrated in patients with SH, levothyroxine treatment is beneficial, especially in patients with increased baseline Lp(a) levels and LMW apo(a) isoforms.     

Lp(a) lipoprotein and lipids in patients with rheumatoid arthritis: serum levels and relationship to inflammation

Objectives Changes in lipid profiles, Lp(a) lipoprotein, and acute phase reactants are associated with early atherosclerosis in rheumatoid arthritis (RA). The associations of Lp(a) levels with atherosclerotic disorders, diabetes, RA, and renal diseases suggest that Lp(a) might be involved in autoimmune reactions.Methods Eighty-seven women with RA diagnosed according to American Rheumatism Association criteria (mean age 45.4±9.4 years) were recruited and 50 healthy women (mean age 44±10.7 years) included as a control group. Serum Lp(a), total cholesterol (TC), triglyceride (TG), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and C-reactive protein levels were analyzed.Results In the RA and C groups, serum Lp(a) levels were 39.2±20.6 mg/dl and 14.8±9.7 mg/dl, respectively (P<0.001). The TC levels were 188.4±41.8 mg/dl and 185.3±19.3 mg/dl (P>0.05), TG levels were 124.5±50.1 mg/dl and 94.6±24.9 mg/dl (P<0.01), HDL-C levels were 40.0±7.4 mg/dl and 52.8±4.8 mg/dl (P<0.01), and LDL-C levels were 123.4±24.6 mg/dl and 113.3±21.1 mg/dl (P>0.05). While serum CRP levels showed a positive correlation with Lp(a), they correlated negatively with HDL-C levels (r=0.83 and P<0.0001, r=–0.49 and P<0.0001, respectively). It was meaningful that Lp(a) correlated negatively with serum HDL-C level (r=–0.36, P<0.001).Conclusions It is suggested that higher serum Lp(a), lower HDL-C, higher TG level, and a high ratio of TC/HDL-C might show high risk of atherosclerosis. Inflammation in RA may cause changes in HDL-C and Lp(a) metabolisms.