OBJECTIVE

Reduction in serum level of estrogen has been thought to result in hyperlipidemia which triggers atherosclerosis, and even to lead to cardiovascular diseases, in postmenopausal women. The present study was designed to investigate the influence of bilateral oophorectomy (OPX), which induces as much reduction in serum estrogen level as menopause, upon lipid metabolism, especially the serum levels of total cholesterol.

METHODS

In 31 OPX subjects and 31 age- and body size-matched premenopausal controls, the serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL-C), apoprotein-A1 (Apo-A1), apoprotein-B (Apo-B), lipoprotein lipase (LPL) and lipoprotein-a [LP(a)] were measured as indices of lipid metabolism and the index of arteriosclerosis was calculated.

RESULTS

TC level was significantly higher in the OPX group than in the premenopausal control group, being 8995 +/- 244 (mean +/- S.E.) mmol/l and 7757 +/- 228 mmol/l, respectively. LDL-C and Apo-B levels and the index of arteriosclerosis were all significantly higher in the OPX group than in the premenopausal control groups. However, there were no significant intergroup differences with regard to HDL-C, Apo-A1, LPL and LP(a).

CONCLUSIONS

The above results demonstrated that, in spite of no reduction in HDL-C, the blood levels of Apo-B, LDL-C and TC change due to OPX. These changes suggest OPX induces cardiovascular diseases and, therefore, follow-up of the changes in lipid metabolism is required, paying special attention to Apo-B and LDL-C.

The protective effect of hydroxycinnamic acids, i.e. caffeic acid (CA) and sinapic acid (SA) present in wine, and chlorogenic acid (CHA) present in apple, compared to a red wine phenolic extract (RWPE) was investigated in hamsters fed an atherogenic diet for 12 weeks. Five groups of 8 hamsters fed such a diet received by force-feeding RWPE, CA or SA in water, mimicking a moderate consumption of alcohol-free red wine. Controls received water and CHA force-feeding was extrapolated from apple consumption. Plasma cholesterol concentration was lower in group that received RWPE (-22%) and hydroxycinnamic acids had no effect. Plasma apolipoprotein Apo-A1 concentration was not affected; consumption of RWPE only decreased Apo-B concentration (-46%). Liver superoxide dismutase activity was 33% lower and glutathione peroxidase activity was 67% greater in the group receiving RWPE compared to controls; there was no effect when CA, SA or CHA were given. All the phenolic compounds significantly increased plasma antioxidant capacity (about 28% on average) compared with controls. Aortic fatty streak area was significantly reduced in the group receiving RWPE (-30%) in comparison with controls and hydroxycinnamic acids. Our findings demonstrate that chronic ingestion of the nonalcoholic components of red wine, mainly polyphenols, prevent the development of atherosclerosis in hamster and that wine hydroxycinnamic acids are not the phenolic compounds involved in such a beneficial effect.

Cholesterol is indispensable for cellular membrane composition and function. It is also a precursor for the synthesis of steroid hormones, which promote, among others, the maturation of fetal organs. A role of the ATP-binding-cassette-transporter-A1 (ABCA1) in the transport of maternal cholesterol to the fetus was suggested by transferring cholesterol to apolipoprotein-A-1 (apo-A1), but the directionality of the apoA-1/ABCA1-dependent cholesterol transport remains unclear. We isolated primary trophoblasts from term placentae to test the hypotheses that (1) apoA-1/ABCA1 dispatches cholesterol mainly towards the fetus to support fetal developmental maturation at term, and (2) differentiated syncytiotrophoblasts (STB) exert higher cholesterol transport activity than undifferentiated cytotrophoblasts (CTB). As experimental models, we used (1) trophoblast monolayers grown on Transwell® system consisting of apical (maternal-like) and basal (fetal-like) compartments, and (2) trophoblasts grown on conventional culture plates at CTB and STB stages. Surprisingly, apoA-1-mediated cholesterol efflux operated almost exclusively at the apical-maternal side, where ABCA1 was also localized by immunofluorescence. We found greater cholesterol efflux capacity in STB, which was increased by liver-X-receptor agonist treatment and decreased by ABCA1 inhibition. We conclude that at term the apoA-1/ABCA1 pathway is rather involved in cholesterol transport to the mother than in transfer to the fully developed fetus.

We studied prospectively the effect of exogenous testosterone (testosterone undecanoate [TU] 160 mg/d orally) on lipoprotein profiles in eight hypogonadal males and 10 females (female-to-male transsexuals). Testosterone administration to androgen-deficient men and to eugonadal women produced similar serum levels of testosterone (7.67 +/- 5.47 nmol/L v 8.45 +/- 3.81 nmol/L) and 5 alpha-dihydrotestosterone (DHT) (3.27 +/- 3.52 nmol/L v 3.97 +/- 2.35 nmol/L) in the two groups, while serum estradiol levels were three to four times higher in the females (90 +/- 24 pmol/Lv 376 +/- 315 pmol/L). After testosterone treatment serum high-density lipoprotein (HDL) cholesterol levels decreased from 1.41 +/- 0.27 mmol/L to 1.27 +/- 0.22 mmol/L after 3 months and 1.17 +/- 0.23 mmol/L after 6 months (P < .01) in female-to-male transsexuals and from 1.31 +/- 0.39 mmol/L to 1.09 +/- 0.31 mmol/L after 3 months and 1.10 +/- 0.32 mmol/L (P < .05) after 6 months in hypogonadal males. In particular, serum HDL2 cholesterol levels decreased from 0.71 +/- 0.44 mmol/L to 0.45 +/- 0.20 mmol/L after 3 months and 0.49 +/- 0.39 mmol/L after 6 months (P < .01) in female-to-male transsexuals and from 0.52 +/- 0.12 mmol/L to 0.38 +/- 0.18 mmol/L after 3 months and 0.34 +/- 0.19 mmol/L after 6 months (P < .05) in hypogonadal males. Serum apolipoprotein (apo) A1 levels decreased concomitantly. In both sexes, serum levels of HDL cholesterol and HDL2 cholesterol decreased by approximately 15% and 35%, respectively, whereas serum levels of total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, apo A2, and apo B were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE

Inflammation plays an important role in the pathophysiology of atherosclerosis. Some studies suggest a link between chronic infections, an inflammatory state, and endothelial dysfunction. However, data related to acute infections are scant. We have investigated: (i) the effect of acute infection on endothelial function; (ii) the role of potential mediators of endothelial dysfunction.

METHODS

Forty patients 40 years old with acute infection (mean age 53.9 +/- 8.8 years), without coronary artery disease or its equivalents were enrolled. Endothelial function and blood levels of high sensitive C-reactive protein, interleukin-6, tumour necrosis factor-a, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), apolipoprotein-A1 (Apo-A1) and apolipoprotein-B100 (Apo-B100) were assessed in the acute infection phase and 1 month after recovery. Endothelial function was evaluated by brachial artery flow-mediated vasodilation (FMD).

RESULTS

The intraclass correlation coefficients for intra- and interobserver agreement for FMD measurements were 0.98 (95% CI: 0.95-0.99) and 0.93 (95% CI: 0.83-0.97), respectively. FMD improved significantly 1 month after recovery (P < 0.001). Compared to the levels at 1 month, inflammatory markers, LDL cholesterol, LDL/HDL ratio, Apo-B100 and Apo-B100/Apo-A1 ratio were significantly higher. However, HDL and apo-A1 were significantly lower in the phase of acute infection. Change in FMD from baseline to 1 month after recovery correlated significantly only with the change in Apo-A1 (r = 0.35, P = 0.027).

CONCLUSIONS

Acute infection causes transient endothelial dysfunction. It increases inflammatory markers and generates an atherogenic lipid profile. Among the parameters evaluated, only the change in Apo-A1 level was associated with acute infection-induced endothelial dysfunction.

To examine the effect of tamoxifen on serum lipoprotein profiles of premenopausal and postmenopausal patients of breast carcinoma (without and with cardiovascular disease) we performed a short term evaluation of serum lipoprotein profiles of 38 pre and 42 post menopausal subjects of breast carcinoma (without and with cardiovascular disease) at baseline and after 3 and 6 months of tamoxifen therapy. The serum lipoprotein profiles of premenopausal patients of breast carcinoma, both without and with cardiovascular disease, showed no significant variation, after 3 and 6 months of tamoxifen treatment than the corresponding baseline values of premenopausal subjects. However, in postmenopausal subjects of breast carcinoma (both without and with cardiovascular disease), serum TC, Apo-B, and Lp (a) were significantly decreased and serum TG, HDL and Apo A1 were significantly elevated, after 3 and 6 months of tamoxifen treatment, than the corresponding baseline values of postmenopausal subjects. Also, the comparison of the results of the present study for pre and postmenopausal patients of breast cancer revealed that the administration of tamoxifen, as an adjuvant therapy for breast cancer, is estrogenic and beneficial for postmenopausal patients of breast carcinoma (both without and with the risk of cardiovascular disease) as the drug minimises the risk of cardivascular disease by bringing significant improvement in serum lipoprotein profiles of the patients. But the drug fails to bring any significant beneficial effect on serum lipoproteins of hyperiipoproteinemic patients of breast cancer.

Psoriasis is a chronic inflammatory skin disease characterized by excessive cellular replication. Apolipoproteins are genetically determined molecule whose role has been implied in cardiovascular pathology. Vascular adhesion protein-1 (VAP-1) is an adhesion molecule with an enzymatic activity that partakes in the migration process of lymphocytes into sites of inflammation. Our purpose was to evaluate the plasma lipid profiles, apolipoproteins (A1, B) and Lp (a) and VAP-1 in order to compare the lipid profile in psoriatic patients with non-affected persons and correlation between VAP-1 and Lp (a). We determined serum concentrations of lipids, lipoproteins , apolipoproteins and VAP-1 in 90 patients with psoriasis and 90 age matched controls. Serum Lp (a), apo A1 and apo B were measured by immunoprecipitation assays, and the lipids and lipoproteins were measured by enzymatic methods.The VAP-1 were measured by ELISA method. The mean levels of total cholesterol, LDL, apo B and VAP-1 in patients with psoriasis were found to be significantly higher than those of healthy subjects (P<0.05. In psoriatic patients, elevation of VAP-1 correlated with elevation of Lp (a) (p = 0.025). This study shows that high serum lipid level and VAP-1, is significantly more common in psoriasis. This fact may be responsible for higher prevalence of cardiovascular accident in psoriatic patients.

OBJECTIVE

To determine the profile of lipidemia in patients with gallstones and the characteristics of lipidemia in different kinds of gallstone in gallbladder for predicting high risk subjects predisposed to gallstone formation by means of some serum parameters.

METHODS

Serum lipids and apolipoproteins levels in 47 patients with stone in gallbladder (stone group) were compared with those in 19 inpatients without stone (control group). The characteristics of lipidemia in different kinds of gallbladder stones were also compared.

RESULTS

Serum apolipoprotein (Apo) A1, C2 and E levels in the stone group significantly increased as compared with the control group (P < 0.01), but there were no statistically significant differences in TC, TG, LDL-C, HDL-C, HDL-C/TC, LDL-C/HDL-C, Apo A2, B and C3 and Apo A1/Apo B levels between the stone and control groups (P>> 0.05). Increased levels of serum LDL-C and Apo B and the LDL-C/HDL-C ratio (P < 0.05) were characterized as an index of cholesterol stones, while elevated levels of serum TG and Apo C2 (P < 0.05) as an index of pigment stones.

CONCLUSIONS

Serum apolipoproteins might be more sensitive parameters as compared with serum lipids in distinguishing patients with stones from subjects without stones. There are different profiles of serum lipids and apolipoproteins in different chemical types of gallbladder stones.

The aim of the present study was to investigate the relation of serum total sialic acid (TSA) concentrations with cardiovascular metabolic risk factors in Kuwaiti children and adolescents with uncomplicated type 1 diabetes. This case-control study included 150 (57 males and 93 females) type 1 diabetic children aged 6 to 18 years matched by age and sex to 150 nondiabetic children as controls. Measured variables included weight, height, systolic, diastolic blood pressure, and biochemical variables: blood glucose, glycated hemoglobin (HbA(1C)), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), apolipoproteins (apo) A1 and B, and urine microalbumin. There was no significant difference between mean serum TSA of the type 1 diabetic children (671.0 mg/L) and their controls (663.7 mg/L). In diabetic children, mean serum TSA was significantly higher in females (699.1 mg/L) than in males (625.2 mg/L) (P =.003). Significant correlations were found between serum TSA and the cardiovascular risk factors TC (P =.002), TG (P <.001), and apo B (P =.008). TSA mean level was significantly higher in diabetic children with poor glycemic control (HbA(1C)>> 9.0%; P =.015), raised TC (P =.013), raised TG (P =.014), and in children with family history of cardiovascular disease (CVD; P =.02). In conclusion, the study suggests that serum TSA levels were not elevated in young type 1 diabetic children as compared with controls. The study also confirmed significant correlation of TSA concentrations with CVD risk factors TC, TG, and apo B, and as such serum TSA may be considered as a marker for CVD risk, especially in diabetic patients. A long-term prospective study is recommended to ascertain the longitudinal relationship of serum TSA with the adverse metabolic changes in type 1 diabetic children as complications prevail.

OBJECTIVE

Women with impaired glucose tolerance (IGT) and type 2 diabetes (T2D) are more at risk of cardiovascular disease. The aim of this study was to test the hypothesis that increased visceral adipose tissue (VAT) could explain to a large extent alterations in the cardiovascular disease risk profile of postmenopausal women with IGT or T2D.

METHODS

Sixty-two women with normal glucose tolerance (NGT), 33 with IGT and 18 with de novo diagnosed T2D were tested. The sample was further divided into five groups: (i) NGT-low VAT (<130 cm(2) ); (ii) NGT-high VAT (≥130 cm(2)); (iii) IGT-low VAT (<130 cm(2) ); (iv) IGT-high VAT (≥130 cm(2) ) and (v) T2D.

RESULTS

Women with T2D, women with IGT-high VAT and those with NGT-high VAT all had lower insulin sensitivity as determined by the euglycaemic-hyperinsulinaemic clamp (M_I), higher triglyceride (TG), lower HDL(2)-cholesterol (chol) levels and higher levels of high-sensitivity C-reactive protein than women with NGT-low VAT. Only differences in M_I and early insulin response (EIR) were observed between women with IGT-high VAT and those with NGT-high VAT (lower values in IGT-high VAT). Women with T2D had lower M_I and EIR as well as higher plasma TG and lower plasma Apo A1 and HDL-chol concentrations than women with NGT-high VAT.

CONCLUSIONS

Our results suggest that increase in VAT accumulation usually found in women with IGT explains to a large extent the deterioration in their plasma lipid-lipoprotein and inflammatory profile. However, factors other than VAT are involved in explaining the high TG-low HDL dyslipidaemia observed in women with T2D.

OBJECTIVE

High-density lipoprotein (HDL)-associated paraoxonase (PON) activity may play an important role in the inhibition of low-density lipoprotein (LDL) oxidation. Previous studies have demonstrated that serum PON activity is decreased in patients with hyperlipoproteinaemia and coronary heart disease. The study presented here examined the effect of short-term treatment with simvastatin and atorvastatin on lipids and PON activity in patients with hyperlipoproteinaemia.

METHODS

A prospective, non-blinded, single-group, cross-over, comparative trial was performed. Following an 8-week dietary run-in period, 49 patients (23 men and 26 women, mean age: 59.8 +/- 7.9 years) with Fredrickson type IIa. and IIb. hyperlipoproteinaemias were randomized to receive either simvastatin 20 mg/day or atorvastatin 10 mg/day for 3 months. Following an 8-week washout period, patients were crossed-over to receive the other drug for a further 3 months. Serum lipids were measured and serum PON activity was determined spectrophotometrically using paraoxon as a substrate.

RESULTS

Simvastatin treatment significantly reduced serum cholesterol, LDL-cholesterol (LDL-C) and apolipoprotein (apo) B levels (p < 0.001). Atorvastatin had a more pronounced cholesterol, LDL-C- and apo B-lowering effect (p < 0.001) compared with simvastatin. Both statins also significantly reduced serum triglyceride levels (p < 0.01). Simvastatin and atorvastatin caused no significant change in the levels of HDL-cholesterol (HDL-C) and apo A1. HDL-associated PON activity did not change significantly after simvastatin therapy, but significantly increased after atorvastatin treatment (p < 0.05).

CONCLUSIONS

Short-term administration of simvastatin did not increase PON activity. Atorvastatin treatment had a favourable effect on lipid profile and increased the activity of HDL-associated PON.

Plasma levels of lipoprotein(a) [Lp(a)], tissue plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) were assessed in addition to anthropometry and levels of glucose, total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and apo A1 and B in 73 patients (36 men and 37 women) with primary hyperlipidaemia (group NDHL) in Kuwait. Lp(a) levels (212 mg L-1, 8-600 mg L-1, median and range) were similar to those obtained in a matched group of 32 non-insulin-dependent diabetes mellitus (NIDDM) patients with hyperlipidaemia (218 mg L-1, 50-610 mg L-1) and slightly higher, although not significantly so (P = 0.06), than levels seen in 68 healthy normolipidaemic control subjects (182 mg L-1, 70-488 mg L-1). tPA levels (8.4 ng mL-1, 3.8-18.4 ng mL-1, median and range) in group NDHL were lower than in the diabetic group (11.4 ng mL-1, 5.2-14.2 ng mL-1) but higher than in the healthy control subjects (7.4 ng mL-1, 2.8-12.6 ng mL-1). PAI-1 levels in group NDHL (40.4 ng mL-1, 8.6-55 ng mL-1, median and range) were higher than in the control subjects (32.5 ng mL-1, 14.6-46.4 ng mL-1) but lower than in diabetic patients (43.8 ng mL-1, 15.6-55 ng mL-1). Hyperlipidaemia phenotype (hypercholesterolaemia or hypertriglyceridaemia) did not influence tPA and PAI-1 levels, but Lp(a) levels were significantly lower with hypertriglyceridaemia. Gender, cigarette smoking and racial origin (Kuwaitis, other Arabs or South Asians) did not affect Lp(a), tPA and PAI-1 levels, but tPA levels were higher in postmenopausal subjects. Low-density lipoprotein (LDL) levels (whether in total cholesterol or as apo B) correlated significantly (P < 0.05) with Lp(a) levels. tPA levels were correlated with age and the plasma levels of glucose and uric acid (P < 0.05); this correlation with glucose may explain the high levels associated with diabetes, whereas the age association might account not only for the differences observed between group NDHL and the younger control group but also for the higher levels in the postmenopausal women. PAI-1 levels correlated with tPA and triglyceride (TG) levels in the groups of subjects (normo- and hyperlipidaemic). In the normolipidaemic control group, the significant associations of tPA and PAI-1 were with body mass, expressed as the body mass index or the waist-hip ratio. These results suggest that different factors influence the plasma levels of the prothrombotic factors Lp(a), tPA and PAI-1 in healthy control subjects and in patients with hyperlipidaemia. In the latter, hyperlipidaemia phenotype, age, glycaemic status and uric acid levels are important determinants of the levels of these prothrombotic variables, whereas in the healthy, young control population, body mass was the single important association with tPA and PAI-1.

Twenty consecutive infertile women (mean age +/- SD, 36.9 +/- 5.4 years) undergoing ovarian stimulation with recombinant follicle stimulating hormone (rFSH) were recruited. Serial measurements of plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (Apo-B), lipoprotein(a) (Lp(a)), oestradiol and progesterone were performed on day 3 before starting ovarian stimulation, on the day of human chorionic gonadotrophin (HCG) administration and on day 15 after HCG administration, respectively. The relationship between lipid and apolipoprotein concentrations and serum oestradiol and progesterone concentrations was sought. All women completed the ovarian stimulation protocol successfully. Plasma concentrations of HDL-C and Apo-A1 were significantly raised on the day of HCG administration and then returned to baseline values within 2 weeks. LDL-C, TG, Apo-B and Lp(a) were significantly increased on day 15 after HCG administration. Lp(a) variation between the first sample and the third sample correlated positively with serum progesterone concentrations (r = 0.472, P < 0.04). No other significant correlations were found between lipid and apolipoprotein variations and either oestradiol or progesterone concentrations. It was concluded that an increase of plasma lipid and apolipoprotein concentrations deserves particular consideration and all women undergoing ovarian stimulation should be monitored for long-term atherogenic and thrombogenic risks.

The efficacy of simvastatin in reducing plasma cholesterol is well documented. Other molecules within the apo lipoprotein family, particularly lipoprotein (a) Lp(a), have recently been found to have a predictive and/or causative role in atherosclerosis. Based on these considerations, we studied 15 patients affected by primary hypercholesterolemia to evaluate the effect of simvastatin in Lp(a) and apoprotein plasma levels (A1, B, C2, C3, E), in addition to the classic lipid parameters. Clinical and laboratory parameters were evaluated before therapy, after 12 weeks of therapy, and after 5 weeks of drug withdrawal. Simvastatin therapy produced a significant reduction in total cholesterol (CH) and LDL-CH (p < 0.0001), and a significant increase in HDL-CH (p < 0.01); no variation was observed in triglyceride (TG) levels. Simvastatin therapy further showed a significant decrease in apoC2 (p < 0.05), the apo C2/C3 ratio (p < 0.01), and apoE (p < 0.01), as well as a significant increase in Lp(a) plasma levels (p < 0.05). All of the parameters studied returned to pretreatment values 5 weeks after drug withdrawal; only HDL-CH persisted above the values reached during therapy. Our data agree with those documenting the beneficial effect of simvastatin in greatly decreasing CH and LDL-CH, but point out the need for further studies on the long-term effect of simvastatin on apoprotein molecules, such as on Lp(a), in order to fully establish its role in the secondary prevention of atherosclerosis.

BACKGROUND

Coronary artery disease (CAD) is the leading cause of death worldwide and has assumed alarming proportions in India with gradual increase in its incidence and prevalence over the last decade. India is in the middle of epidemic of coronary artery disease which is leading cause of hospital admissions, morbidity and mortality. In the Indian population, there is higher tendency to develop CAD at a younger age, which cannot be explained on the basis of conventional lipid parameters.

OBJECTIVE

The purpose of this study is to find advanced lipid parameters which correlate better with premature CAD, as compared to the conventional lipid parameters.

METHODS

Thirty middle aged individuals suffering from premature CAD and 30 age and gender matched healthy individuals without any history of clinical evidence suggestive of CAD were studied. Fasting venous blood samples of all the subjects under study were collected after an overnight fasting and conventional lipid parameters and advanced lipid parameters (i.e. oxidized LDL, Lp (a), ApoA-1, small dense LDL, ApoB) were estimated. Correlation of conventional and advanced lipid parameters with premature CAD and among each other was calculated using Pearson correlation coefficient.

RESULTS

In our study the values of ox-LDL, sdLDL, Lp (a) and ApoB, total cholesterol, TG, LDL-C were significantly higher while HDL-C and Apo A1 and were significantly lower in cases than in controls. Advanced lipid parameters have higher correlation with premature CAD as compared to conventional lipid parameters. Ox-LDL show the highest correlation coefficient (r=+0.89) among these parameters followed by Lp (a) (r=+0.86) and ApoB (r=+0.79).

CONCLUSIONS

Advanced lipid parameters (i.e. oxidized LDL, Lp (a), ApoA-1, small dense LDL, ApoB) are better discriminator of premature CAD as compared to conventional lipid parameters (total cholesterol, triglycerides, low density lipoprotein and high density lipoprotein). Oxidised LDL, small dense LDL and lipoprotein (a) can explain occurrence of CAD in normolipidemic patients and proved to be better markers for explaining high degree of prematurity, morbidity and mortality of CAD in Indian population. They can prove to be better marker for early detection and intervention in premature CAD and site for targeted drug therapy.

BACKGROUND

Chronic kidney disease (CKD) is associated with insulin resistance also in the absence of overt diabetes mellitus. The liver-derived transport protein retinol-binding protein (RBP) has recently been proposed as a novel adipokine involved in the metabolism of glucose. Although RBP is elevated in type 2 diabetics with mild CKD, its role in advanced CKD is not well studied. We hypothesized that altered RBP levels in CKD could be one factor contributing to the uremic insulin resistance.

METHODS

In a cross-sectional study, we evaluated 141 nondiabetic stage 5 CKD patients (GFR 6.8 +/- 2.0 ml/min; 62% males, mean age 52 +/- 11 years) close to the start of renal replacement therapy. We studied circulating RBP (RIA), retinol and metabolic markers. Body composition was also assessed using DEXA and patients were divided according to truncal fat mass above (obese) or below (lean) the sex-specific median. A fasting plasma glucose>> or =6.1 mM was defined as impaired glucose tolerance (IGT).

RESULTS

Serum RBP levels were significantly elevated in CKD as compared to previous reports in non-renal patients. Whereas levels of RBP did not differ between lean and obese patients without IGT, they were lower in lean CKD patients with IGT (5.9 +/- 2.9 microM) than in obese CKD patients with IGT (7.0 +/- 2.9 microM; p < 0.05). While RBP did not correlate with truncal or total fat mass or biomarkers of inflammation, in univariate analysis, we found weak correlations with HbA1c% (rho = 0.17; p < 0.05), fasting serum triglycerides (rho = 0.20; p < 0.001) and fasting apolipoprotein (Apo) A1 (rho = 0.29; p < 0.001). RBP also correlated negatively with ApoB (rho = -0.29; p < 0.001). In multivariate analysis, RBP was a significant and independent predictor of both HbA1c% and ApoA1 levels. Finally, RBP was strongly correlated with serum retinol, and calculating a retinol/RBP index further strengthened the observed correlations with HOMA-IR and HbA1c%.

CONCLUSIONS

RBP is elevated in nondiabetic stage 5 CKD and correlates weakly with HbA1c and ApoA1. As RBP is thought to induce insulin resistance and directly affect lipoprotein metabolism in other disease states, these findings may support a role for RBP in contributing to the uremic metabolic syndrome, putatively by altering ApoA1 metabolism, but further studies are needed to test this hypothesis.

OBJECTIVE

To investigate the prevalence of obesity and the lipoprotein-related characteristics among young male adults in the Taiwan area.

METHODS

After cluster sampling, a cross-sectional survey with a total of 936 males (mean age 20, 18-24) were enrolled.

METHODS

The distribution of anthropometric and lipoprotein-related variables and their correlations in young male adults were measured. The prevalence of obesity by different criterion and the lipoprotein characteristics of obese and non-obese were analyzed separately.

RESULTS

The prevalence of obesity was 9.6% by the criterion of body weight greater than 20% of ideal body weight, or 12.6% by the criterion of body mass index (BMI) greater than 25. The obese subjects had significantly higher serum total cholesterol (CHOL), triglyceride (TG) and apo-lipoprotein B (apo B) and lower higher density lipoprotein-cholesterol (HDL-C) levels than the non-obese. The apo A1 levels were 141.3 and 141.9 mg/dl and the lipoprotein [a] (Lp[a]) were 17.4 and 17.1 mg/dl in obese and non-obese respectively, the difference being not statistically significant. Pearson correlation coefficients of body weight, body height, BMI, waist circumference, hip circumference and waist-hip ratio (WHR) to lipoprotein variables showed that both BMI and WHR are positively correlated with CHOL, TG and apo B, but negatively correlated with HDL-C. Furthermore the lipoprotein variables were better correlated with BMI than WHR in lean subjects (BMI < 25). However, this phenomenon was quite different in obese (BMI>> 25) subjects, where the WHR was more highly correlated with lipoprotein variables than with BMI.

CONCLUSIONS

The prevalence of obesity is slightly higher than reported in previous studies in Taiwan. The obese subjects had various abnormal lipoprotein metabolic characteristics, such as higher CHOL, TG, and apo B and lower HDL-C levels than non-obese subjects. The BMI was more highly correlated with lipoprotein variables than was WHR in lean subjects, but the WHR was more highly correlated with lipoprotein variables than was BMI in obese subjects.

The aims of the present study were to determine whether the activity of cholesteryl ester transfer protein (CETP) is altered in the plasma of children and adolescents with insulin-dependent diabetes mellitus (IDDM), and whether high-density lipoprotein-cholesterol (HDL-C) levels reflect CETP activity. Plasma CETP activity was measured by a micromethod for radioisotopic assay, using exogenous lipoproteins as donor and acceptors. The study subjects were 22 Japanese children and adolescents with IDDM (8M, 14F) with a mean age of 13.0 y. They were non-obese and did not suffer from any significant nephropathy. The age-matched control group consisted of 20 children (10M, 10F) with a mean age of 12.7y. Serum triglycerides were significantly decreased, while the levels of HDL-C and apolipoprotein (apo) A1 were markedly increased, in the IDDM patients. Plasma CETP activity was significantly lower in the IDDM patients than in the control children. None of the anthropometric indices nor the biochemical data correlated significantly with CETP activity in the IDDM patients. Suppression of CETP along with the putative activation of lipoprotein lipase due to peripheral hyperinsulinism appears to induce synergistically the increase in HDL-C in IDDM children.

We investigated the relation of plasma lipids to the risk for cortical infarction with (22 cases) or without (38 cases) cardiac arrhythmias, for lacunar infarction (28 cases) and transient ischaemic attacks (TAI) (15 cases). In the group of cortical infarction with or without cardiac arrhythmias, we observed a maximum increase of total cholesterol, of very low density lipoprotein (VLDL) and low density lipoprotein (LDL), triglycerides, total Apolipoprotein (Apo) B, LDL-Apo B and Apo-A1. On the contrary, we observed a decrease of total ApoE, HDL-ApoE, a distribution of LDL in a single layer and the presence of LDL of small weight. TAI is different from the former group by a low level of HDL and the lack of abnormalities of Apo-A1, and on the distribution and the weight of LDL. Finally, lacunar infarction presents a normal plasma lipoprotein profile. These data suggest that previously demonstrated differences in LDL-cholesterol levels between patients with ischaemic stroke and control subjects may apply to patients with cortical but not lacunar infarction. The presence or not of a cardiac arrhythmia doesn't give a special lipoprotein profile, and TAI has no changes on the distribution and the weight of LDL. Therefore, separation of ischaemic strokes into types based on mechanism as large vessel atherosclerosis versus small vessel atherosclerosis may help clarify lipid-related risk factors in cerebrovascular disease.

We have examined basal and stimulated monocyte procoagulant activity (PCA) in 10 persons with high HDL (1.62-2.47 mmol/L) and 10 persons with low HDL (0.43-1.29 mmol/L). Heparinized whole blood was incubated at 37 degrees C for 2 hours with 100 ng/ml of E. Coli lipopolysaccharide (LPS). Monocytes were isolated by density gradient centrifugation (purity>> 70%), and PCA measured with a chromogenic peptide substrate assay. LPS-induced PCA was significantly higher in the high HDL group (p = 0.02), whereas basal levels were similar. Furthermore, the levels of total HDL, HDL2, as well as apo-A1 were all significantly correlated with LPS-induced monocyte PCA (p < 0.01, p < 0.01, and p = 0.03), whereas VLDL was inversely correlated (p = 0.02). PAI-I activity was significantly lower in the high HDL group (p < 0.01). LPS recovery in plasma after incubation, by LAL test, was significantly higher in the high HDL group (p = 0.02) and correlated to HDL2 (p = 0.04), and inversely correlated with triglycerides (p = 0.04). There was no significant difference between the two groups in plasma fibrinopeptide A (FPA) levels after LPS incubation.

Atherogenic lipoproteins can cause endothelial dysfunction in the initial stage of atherogenesis. In our study we examined 134 patients with defined hyperlipoproteinemia (non-HDL cholesterol>4.1 mmol/l or triglycerides>2.5 mmol/l or taking any of lipid lowering drugs)--94 men and 40 women. The subgroup of controls of comparable age contained 54 normolipidemic individuals--30 men and 24 women. Patients with hyperlipoproteinemia revealed significantly lower ability of endothelium-dependent flow-mediated vasodilation (EDV) measured on brachial artery (4.13+/-3.07 vs. 5.41+/-3.82 %; p=0.032) and higher carotid intima media thickness than normolipidemic controls (0.68+/-0.22 vs. 0.58+/-0.15 mm; p=0.005). In regression analysis, EDV correlated significantly with plasma concentrations of oxLDL (p<0.05) HDL-cholesterol (p<0.05), Apo A1 (p<0.05), ATI (p<0.01) and non-HDL cholesterol (p<0.05). Patients with hyperlipoproteinemia showed higher plasma levels of oxLDL (65.77+/-9.54 vs. 56.49+/-7.80 U/l; p=0.015), malondialdehyde (0.89+/-0.09 vs. 0.73+/-0.08 micromol/l; p=0.010) and nitrites/nitrates (20.42+/-4.88 vs. 16.37+/-4.44 micromol/l; p=0.018) indicating possible higher long-term oxidative stress in these patients.

The alterations in lipid metabolism that occur with the use of oral contraceptives (OCs) have aroused considerable concern that OCs might increase the risk of premature atherosclerosis. However, most studies examining the role of OCs in atherogenesis were performed using earlier-generation preparations employing larger doses of sex hormones than present formulation. Therefore, we undertook a comparative and standardized determination of the effects on lipid metabolism of six modern, low-dose OCs. This open, randomized, comparative study included patients recruited at 21 study centers throughout Europe. Four hundred sixty-six women, aged 18-38 years, participated. They were randomly assigned to the following OC formulations:(1) norgestimate 250 micrograms + ethinyl estradiol (EE) 35 micrograms (Cilest); (2) norgestimate 180/215/250 micrograms + EE 35 micrograms (Tricilest); (3) desogestrel 150 micrograms + EE 20 micrograms = (Marvelon); (4) desogestrel 150 micrograms + EE 30 micrograms (Mercilon); (5) gestodene 75 micrograms + EE 30 micrograms (Femovan); and (6) gestodene 50/70/100 micrograms + EE 30/40/30 micrograms (Trifemovan). There were three parallel studies with six parallel patient groups. Fasting blood samples were drawn at baseline (between days 24 and 28) and on days 18-22 of cycle 6, and cycle 12. Sample were analyzed for total cholesterol,high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein (apo)A1, and apoB at one central laboratory. Two hundred eighty-two women completed all 12 cycles and were included in the final evaluation. As expected, triglyceride and total cholesterol concentrations increased in all study groups but to lesser levels with the formulations containing gestodene. All OCs, except the monophasic gestodene preparation, slightly but significantly increased HDL. The HDL2 subfraction did ot change significantly except in the group using the monophasic gestodene preparation; in this group, the HDL2 subfraction slightly but significantly decreased. The LDL concentration increased slightly with the monophasic and triphasic norgestimate preparations and with desogestrel + 20 micrograms EE. The LDL/HDL ratio did not change significantly except with the use of the triphasic norgestimate preparation, in which case it decreased slightly. ApoA1 and apoB levels increased only slightly with all formulations. Importantly, while all of the OCs tested altered lipid levels to some extent, after 12 cycles there were no statistically significant differences in lipid effects among OC preparations. Modern, combined OCs that contain norgestimate, desogestrel, or gestodene all have some impact on lipid levels. However, it would appear likely that they do not contribute to atherogenesis in healthy women.

In 98 children from 98 kindreds, 49 with and 49 without parental premature myocardial infarction (age < or = 45 y), our specific aim was to determine whether, and to what degree, lipoprotein(a) [Lp(a)] and other atherogenic lipids and lipoproteins might be overexpressed in children from premature infarction kindreds. Median Lp(a) (270 mg/L) in case boys was nearly twice that in control boys (140 mg/L) (p < or = 0.001). In a logistic regression model including age, Quetelet index (relative ponderosity), Lp(a), apo A1, apo B, triglyceride, and pubertal status, the 24 case boys had higher Lp(a) (p = 0.03), higher triglyceride (p = 0.036), and marginally lower apo A1 (p = 0.06) than the 26 control boys. Median Lp(a) in case girls (200 mg/L) was much higher than in control girls (150 mg/L) (p < or = 0.01). In a logistic regression model including age, Quetelet index, Lp(a), apo A1, apo B, triglyceride, and menarchal status, Lp(a) was higher (p = 0.02), apo B was marginally higher (p = 0.07), and apo A1 was lower (p = 0.008) in 25 case girls than in 23 control girls. Reflecting familial clustering of major lipid-lipoprotein risk factors for coronary heart disease, children from kindreds with premature parental myocardial infarction were distinguished from children from control kindreds by high Lp(a) and also had higher apo B and triglyceride and lower apo A1 levels.

Postprandial triglyceride (TG) levels are easy to measure and are associated with future cardiovascular risk. The aim of this study was to compare the effects of statin monotherapy and low-dose statin/ezetimibe on lipid parameters including fasting and postprandial TG. After a 4-week dietary run-in period, 78 patients with combined hyperlipidemia were randomized into 1 of 2 treatment groups for 8 weeks: atorvastatin 20 mg or atorvastatin/ezetimibe 5 mg/5 mg. An oral fat load test was performed before and after the drug-treatment period. The low-dose combination had a tendency to decrease fasting TG more than atorvastatin monotherapy. The combination regimen showed a greater reduction in postprandial TG (-13% ± 42% and -34% ± 30%, in the atorvastatin and combination groups, respectively, P = .03) and total cholesterol (TC; P = .03). The changes in low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were not different between the 2 groups. The reduction in apo B/A1 was greater in the combination group (-32% ± 19% and -42% ± 13%, in the atorvastatin and combination groups, respectively, P = .02). In conclusion, these results demonstrated a potential beneficial effect of low-dose atorvastatin/ezetimibe combination treatment on postprandial TG control after comparable LDL-C lowering in patients with combined hyperlipidemia.