OBJECTIVE

The aim of this study was to study the diurnal variation of the cardiovascular risk markers apolipoprotein A1 and B and apo B/apo A1 ratio.

METHODS

We have studied the diurnal variation of apolipoprotein A1, apolipoprotein B and apo B/apo A1 ratio during night sleep and the day sleep conditions in seven healthy volunteers (age 22-32 yr). Samples were collected every hour to evaluate the effect of different sampling times on the test results.

RESULTS

The lowest diurnal coefficient of variation (CV) was observed for the apo B/apo A1 ratio, which usually was below 2% but also apolipoprotein A1, apolipoprotein B showed low CV. There were no significant differences between nightsleep and daysleep for any of the studied markers.

CONCLUSIONS

Even if there was a diurnal variation for these markers, the variation was very low. Thus, sampling does not have to be restricted to certain times of the day.

OBJECTIVE

The aim of this study was to test the utility of preferred walk-run transition speed (WRTS) in exercise training adjunct to dietary restriction for obesity management in healthy obese women.

METHODS

37 obese women (age: 35 ± 9 years, body mass index (BMI): 34.9 ± 4.6 kg/m(2)) were assigned to an intervention pilot study during 6 months of restricted diet alone (RD) followed by 6 months of RD combined with WRTS (RD and WRTS) as a training exercise. Body mass, waist circumference (WC), fat mass (FM), fat free mass (FFM), active cell mass (ACM), fasting glucose, serum lipids (triacylglycerol (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), apo-lipoproteins A1 (ApoA1) and B (ApoB)], leptin and insulin concentrations, and HOMA-IR were assessed at baseline (T0), at the end of the RD alone (T1), and at the end of the RD and WRTS programme (T2).

RESULTS

Mean weight loss was 8.6 ± 4.9 kg and 2.2 ± 2.9 kg for (T0-T1) and (T1-T2), respectively. Significant BMI and WC reductions were reported at T1 and T2. FM decreased significantly both with RD and with RD and WRTS training whereas FFM and ACM increased with RD and WRTS training only. TG decreased significantly with the two phases of the programme. A significant increase in HDL-C, and a decrease in LDL-C and TC/HDL-C ratio were noticed with RD and WRTS training. Heart rate monitored in training improved significantly after RD and WRTS training. A significant relationship (r = 0.542, p < 0.02) was demonstrated between reductions in serum leptin and insulin concentrations observed with both RD and WRTS training.

CONCLUSIONS

The addition of WRTS training to RD promoted a greater reduction in body mass, WC, FM, leptin and insulin concentrations, improved metabolic and cardiovascular risk factors, and enhanced cardiovascular fitness.

Low serum apolipoprotein (Apo) A1 concentrations and high serum ApoB concentrations may be better markers of the risk of cardiovascular disease than high-density lipoprotein (HDL) and low-density lipoprotein (LDL). However, the associations between modifiable lifestyle factors and Apo concentrations have not been investigated in detail. Therefore, this study investigated the associations between Apo concentrations and education, lifestyle factors and dietary intake (macronutrients and 34 food groups). These cross-sectional associations were examined among 24,984 individuals in a Swedish population-based cohort. Baseline examinations of the cohort were conducted between 1991 and 1996. Dietary intake was assessed using a modified diet history method. The main determinants of high ApoA1 concentrations (r between 0.05 and 0.25) were high alcohol consumption, high physical activity, non-smoking, and a low body mass index (BMI), and the main determinants of high ApoB concentrations were smoking and a high BMI. The intake of sucrose and food products containing added sugar (such as pastries, sweets, chocolate, jam/sugar and sugar-sweetened beverages) was negatively correlated with ApoA1 concentrations and positively correlated with ApoB concentrations and the ApoB/ApoA1 ratio, whereas the intake of fermented dairy products, such as fermented milk and cheese, was positively correlated with ApoA1 concentrations and negatively correlated with the ApoB/ApoA1 ratio. These results indicate that smoking, obesity, low physical activity, low alcohol consumption and a diet high in sugar and low in fermented dairy products are correlated with an unfavorable Apo profile.

BACKGROUND

The interactions between apolipoprotein (Apo) A1/C3/A5 haplotypes and alcohol consumption on serum lipid profiles have not been previously explored. The present study was undertaken to detect the polymorphisms of ApoA1 -75 bp G>A (rs1799837), ApoC3 3238C>G (rs5128), ApoA5 -1131T>C (rs662799), ApoA5 c.553G>T (rs2075291), and ApoA5 c.457G>A (rs3135507) and the interactions between their haplotypes and alcohol consumption on serum lipid levels.

METHODS

Genotyping was performed in 1,030 unrelated subjects (516 nondrinkers and 514 drinkers) aged 15 to 89. The interactions between ApoA1/C3/A5 haplotypes and alcohol consumption on serum lipid levels were detected by factorial regression analysis after controlling for potential confounders.

RESULTS

The frequencies of ApoC3 3238 CG/GG genotypes and ApoA1 -75 bp A allele in nondrinkers were higher in females than in males (p < 0.05). The frequencies of ApoC3 3238 CG/GG genotypes and G allele in drinkers were higher in females than in males (p < 0.05). The frequencies of ApoA1 -75 bp GA/AA genotypes and A allele in males were higher, and those of ApoC3 3238 CG/GG genotypes were lower in drinkers than in nondrinkers (p < 0.05 to 0.01). The frequency of ApoC3 3238 GG genotype in male drinkers was also higher in ≥25 g/d than in <25 g/d subgroups (p < 0.05). There were 11 haplotypes with a frequency >1% in our study population. The haplotypes of G-G-T-C-G (in the order of c.553G>T, c.457G>A, -1131T>C, 3238C>G, and -75 bp G>A), G-G-T-C-A, and G-G-C-G-G were shown consistent interactions with alcohol consumption to increase serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), and ApoA1 levels (p < 0.05 to 0.001). The interactions between G-G-T-G-G (HDL-C and ApoA1), G-G-C-C-A (ApoA1), G-A-T-C-G (triglyceride), G-G-T-C-G (ApoA1/ApoB ratio), and G-G-C-G-G (ApoB) haplotypes and alcohol consumption on serum lipid levels were also detected (p < 0.05 to 0.001); the levels of these serum lipid parameters were significantly higher in drinkers than in nondrinkers.

CONCLUSIONS

The differences in serum lipid parameters between drinkers and nondrinkers might partly result from different interactions between the ApoA1/C3/A5 haplotypes and alcohol consumption.

BACKGROUND

The single nucleotide polymorphism (SNP) of peroxisome proliferator-activated receptor delta (PPARD) gene affects serum lipid profiles, but to what extent alcohol consumption interferes with this association remains unknown. The present study was undertaken to compare the association of PPARD +294T>> C (rs2016520) polymorphism and serum lipid levels in the nondrinkers and drinkers.

METHODS

A total of 685 unrelated nondrinkers and 497 drinkers aged 15-82 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the PPARD +294T>> C was performed by polymerase chain reaction and restriction fragment length polymorphism. Interactions of the PPARD +294T>> C genotypes and alcohol consumption on serum lipid levels were detected by using a factorial regression analysis after controlling for potential confounders.

RESULTS

The levels of triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) A1, and the ratio of ApoA1 to ApoB were higher in drinkers than in nondrinkers (P < 0.05-0.001). There were no significant differences in the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and ApoB between the two groups (P>> 0.05 for all). The frequencies of TT, TC and CC genotypes were 56.0%, 36.4% and 7.6% in nondrinkers, and 57.2%, 38.0% and 4.8% in drinkers (P>> 0.05); respectively. The frequencies of T and C alleles were 74.2% and 25.8% in nondrinkers, and 76.2% and 23.8% in drinkers (P>> 0.05); respectively. There was also no significant difference in the genotypic and allelic frequencies between males and females in both groups (P>> 0.05 for all). The levels of TC in nondrinkers were different among the three genotypes (P = 0.01), the C allele carriers had higher serum TC levels than the C allele noncarriers. The levels of all seven lipid traits in drinkers were not different among the three genotypes (P>> 0.05 for all). The interactions of PPARD +294T>> C genotypes and alcohol consumption on serum lipid levels were not detected in the drinkers (P >0.05 for all). Multiple linear regression analysis showed that serum TC, HDL-C, LDL-C, ApoA1, and ApoB levels were correlated with genotypes in drinkers but not in nondrinkers (P < 0.05-0.01).

CONCLUSIONS

These results suggest that the great majority of our study populations are beneficial from alcohol consumption. But there is no interaction between the PPARD +294T>> C genotypes and alcohol consumption on serum lipid levels in the drinkers.

BACKGROUND

Arterial compliance or stiffness is an important determinant of cardiovascular disease and there is considerable interest in its noninvasive measurement. Pulse wave velocity (PWV) is widely used as an index of arterial stiffness.

OBJECTIVE

To determine whether PWV is useful for risk stratification in both healthy individuals and coronary patients.

METHODS

Control subjects, n=510, aged 46.1 +/- 11 years, with no history of coronary disease, were selected from electoral rolls, and coronary patients, n=301, aged 53.7 +/- 10 years, were selected from hospital patients with a history of coronary artery disease (CAD) confirmed by coronary angiogram (at least 75% obstruction of one of the main coronary vessels). The asymptomatic subjects without CAD formed Group A, and were subdivided into A1 (without hypertension, dyslipidemia and/or diabetes) and A2 (with hypertension, dyslipidemia and/or diabetes). The coronary patients formed Group B, who were also subdivided into B1, without these classic risk factors, and B2 with hypertension, dyslipidemia and/or diabetes. We used the Student's t test to compare continuous variables and the chi-square test to compare categorical data. The strength of correlation between continuous variables was tested by Pearson's linear correlation. Independent variables predictive of CAD were determined by backward logistic regression analysis. The statistical analysis was performed using SPSS for Windows version 11.0 and data were expressed as means +/- SD; a p value of 0.05 was considered significant.

RESULTS

Comparing the two groups A1 and A2, mean PWV was significantly lower in group A1. Comparing B1 and B2, mean PWV was also significantly lower in group B1. In group A1, PWV was significantly and positively correlated with age, body mass index, waist-to-hip ratio, alcohol consumption, total/HDL cholesterol ratio, systolic, diastolic and mean blood pressure (BP), blood glucose, apo B, triglycerides, and high-sensitivity C-reactive protein, unlike HDL which was inversely correlated (Pearson's coefficient). In group A2, PWV was significantly and positively correlated with age, alcohol consumption, total/HDL cholesterol ratio, systolic, diastolic and mean BP, blood glucose and pulse pressure (PP), but not HDL, which was inversely correlated with PWV. In group B1, PWV was only significantly and positively correlated with age, systolic, mean, and diastolic BP and PP, and presented a significant inverse correlation with ejection fraction. However, in the high-risk coronary population (group B2), there was a positive correlation with age, waist-to-hip ratio, systolic and mean BP, PP and homocysteine. After stepwise logistic regression, PWV remained in the model and proved to be a significant and independent risk factor for CAD.

CONCLUSIONS

The results of our study show that PWV is higher in high-risk groups and significantly correlated with many classic and new CAD risk markers, suggesting that there is a cumulative influence of risk factors in the development of arterial stiffness. We believe that PWV is a useful index of vascular status and hence cardiovascular risk and that it may be useful for risk stratification in both asymptomatic and coronary patients.

OBJECTIVE

Patients with heterozygous familial hypercholesterolemia (FH) have an increased risk of premature myocardial infarction, stroke, and surgical revascularization, and an increased rate of progression of carotid intima-media thickness (IMT). The most commonly used drugs for cholesterol lowering, statins, have a limited action in these patients. Ezetimibe, a novel compound, selectively inhibits cholesterol uptake and when associated with statins has an additional low-density lipoprotein cholesterol (LDL-C) reducing effect. The aim of this study is to evaluate the effects of long-term combined Ezetimibe/Simvastatin (EZE/SIMVA) therapy (30 months) on the lipidic pattern, inflammatory markers, and carotid IMT in patients with FH subdivided into two groups: one with a history of acute myocardial infarction (IMA) and the other with carotid atherosclerotic plaques but no history of cardiovascular events.

METHODS

All patients enrolled in this study (group A: patients with a history of IMA; group B, patients with carotid lesions but no history of cardiovascular events) were submitted to a 6-week period of isocaloric diet and to a 4-week lipid-lowering wash-out period before study entry. After the wash-out period at baseline (time 0) and then every two months total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B and A1 were determined. LDL-C levels were calculated. Fibrinogen and hs-CRP at baseline and at 6, 18, and 30 months were determined. All patients were submitted to an ultrasonographic evaluation of the carotid intima-media thickness at baseline, 18 and 30 months. The scheduled duration time of the study was 30 months. At the beginning of the study all patients were assigned to receive the combined EZE/SIMVA treatment 10/20 mg per day. After two months, patients who had not reached the respective LDL-C targets proposed by NCEP ATPIII (<70 mg/dL for patients with a history of IMA and <100 mg/dL for patients with carotid lesions) were assigned to receive EZE/SIMVA 10/40 mg per day and, after four months, patients who had not reached the respective LDL-C targets were assigned to receive EZE/SIMVA 10/80 mg per day.

RESULTS

At the end-point, significant reductions (P<0.001) of about 70% in LDL-C, of 57% in total cholesterol (TC), of 46% in Apo-B, and of 46% in hs-C-reactive protein (hs-CRP) were observed in both groups compared to baseline. Also, triglyceride and fibrinogen levels were significantly (P<0.01) reduced, respectively by 26% and 15% compared to baseline. The EZE/SIMVA association resulted in significant increases in HDL-C (P<0.01) of 11% and in Apo-A1 (P<0.05) by 9% and in significant (P<0.001) reductions of the mean of the carotid IMT in both groups. The EZE/SIMVA treatment was generally well-tolerated, with a safety profile on laboratory parameters. During the 30-month scheduled period of the study, no patient in either group presented any further cardiovascular events.

CONCLUSIONS

In patients with FH, combined EZE/SIMVA treatment resulted in a significant LDL-C lowering, achieving the goals proposed by NCEP ATP III, in a significant improvement of all the lipidic and inflammatory patterns, and above all in a progressive decrease of the carotid IMT. Although the results of ongoing randomized controlled trials are required before making any definitive conclusions, our results support the hypothesis of stabilizing effect of EZE/SIMVA on the atherosclerotic disease both in primary and in secondary prevention.

The requirements for FAD-attachment to His71 of 6-hydroxy-D-nicotine oxidase (6-HDNO) were investigated by site-directed mutagenesis. The following amino acid replacements were introduced into the sequence Arg67-Ser68-Gly69-Gly70-His71 of the 6-HDNO-polypeptide: 1) Arg67 was replaced with Ala (A1 mutant); 2) Ser68 was replaced with Ala (A2 mutant); and 3) Arg67 was replaced with Lys (K mutant). The substitution in mutant A2 had no effect on flavinylation, measured as [14C]FAD incorporation into apo-6-HDNO. Replacement of Arg67 with Ala prevented, but replacement with Lys permitted the flavinylation of His71. Mutant A1 showed no 6-HDNO activity, whereas the replacement of Ser with Ala in mutant A2 had only a slight effect on 6-HDNO activity. The substitution of Lys for Arg67, however, reduced the specific 6-HDNO activity in extracts of Escherichia coli cells expressing the mutant polypeptide from 50.3 to 17.5 milliunits/mg protein. It is concluded that a basic amino acid residue (Arg67 or Lys67) is required to mediate the attachment of FAD to His71, and while Lys can substitute for Arg67 in this function, it can only partially replace Arg67 in the enzyme reaction mechanism of 6-HDNO.

Cerebral hypoperfusion or aging often results into the disturbances of cholesterol and lipoprotein, which have been tightly associated with numerous neurological and psychiatric diseases, such as vascular dementia. The pathway of liver X receptor-β (LXR-β)/retinoic X receptor-α (RXR-α)/ABCA1 plays a vital role in lipoprotein metabolism. However, there were no reports about the relationship between the signal molecules of the pathway and lipoprotein homeostasis in cerebral hypoperfusion models. Therefore, we aimed to detect the expression of the pathway molecules in the aging rat models of chronic cerebral hypoperfusion and to explore its underlying mechanism. The model with cerebral hypoperfusion was established by ligating of the bilateral common carotid arteries (2VO). The temporal blood flow in the model rats was significantly decreased 14 d, 21 d and 28 d after 2VO compared with the control. The serum levels of high-density lipoprotein (HDL) and total cholesterol (TC) were reached a peak at 14 d, then, they were gradually decreased. The changes of LXR-β, RXR-α, ABCA1 and apolipoprotein A1 (apo A1) of the pathway were consistent with the changes of HDL and TC. We conclude that LXR-β/RXR-α/ABCA1 and downstream genes apo A1 undergo dynamic changes during the process of cerebral hypoperfusion. The LXR-β/RXR-α/ABCA1 mediated apo A1 cholesterol may play a protective effect, and the effect only exists in a certain period of time.

The aim of this work was to evaluate the prevalence of microalbuminuria in an obese population and to study the relation between albumin excretion rate (AER), various clinical (body mass index, adipose tissue distribution) nutritional (macronutrient intake) and metabolic parameters. A cross-sectional study was carried out, and AER was evaluated in 182 obese subjects (BMI>> 27) with no medication, no intercurrent disease, no cardiac, pulmonary or endocrinological disorders (including diabetes and hypertension) and also in 31 control subjects at the outpatient clinic of the department of Nutrition, Hôtel Dieu, Paris, France. The following were measured: BMI, waist/hip ratio (WHR), urinary AER, blood glucose, insulin and C peptide levels, cholesterol (CT), triglycerides, HDL cholesterol (HDL-CT), apoprotein A1 and B. In the obese population, 18 subjects (9.9%) were found to have an increased AER: 13 subjects (7.1%) with microalbuminuria (AER between 30 to 300 mg/24 h) and five with AER over 300 mg/24 h. AER was normal in all control subjects but one, who was found to have microalbuminuria. Log AER was positively correlated to WHR (P < 0.001), blood pressure (P < 0.05), cholesterol (P < 0.05), Apo B levels (P < 0.01) and with fasting Insulin levels and protein intake (P < 0.001). Positive association between log AER and protein intake, insulin levels, Apo B and blood pressure were found independently of BMI and WHR. It is suggested that abdominal obesity may be associated with incipient nephropathy in some obese subjects without diabetes and hypertension. Microalbuminuria may be included among metabolic abnormalities connected with abdominal-type excess weight distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors evaluated the lipid profile of children with a positive family history of coronary heart disease (CHD), cerebrovascular disease (CVD), or hyperlipidemia and compared them with controls in order to identify risk indicators for atherosclerosis. A group of 315 children (group A) aged more than 2 years old with a positive family history were evaluated for serum concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein B100 (ApoB100), apolipoprotein A1 (Apo A1), and lipoprotein (a) (Lp[a]). These values were compared with the levels of a control group of 214 children of comparable age (group B). The median age of children in groups A and B was 10.6 (range 2.3-16) and 9.8 (range 3-13.7) years of age, respectively. Among these children, 196 (52%), 47 (12.5%), and 72 (19.1%) had a positive family history of CHD (group A1), cerebrovascular disease (CVD) (group A2), and hypercholesterolemia (group A3), respectively. We identified 8 children with genetically determined dyslipidemia: 2 children with homozygous and 6 with heterozygous familial hypercholesterolemia. Children in group A3 had significantly higher concentrations of TC, TG, LDL-C, and ApoB100 and lower concentrations of Apo A1 compared with controls, while no significant differences were found in concentrations of lipid variables among children of group A1, A2, and A3. Significant differences were also noted in the concentrations of TC, LDL-C, and Lp(a) between children of group A1 and controls. Screening the progeny of young patients with CHD or familial hypercholesterolemia can identify children at excessive risk for future vascular disease.

It has been reported that focal and segmental glomerulosclerosis (FSGS) with pronounced proteinuria rapidly develop in Dahl salt-sensitive hypertensive (DS) rats fed a high-salt diet. We found that even when they are fed a standard rat chow (0.3% NaCl), DS rats, especially males, exhibit marked proteinuria, hypoalbuminemia, and hypertriglyceridemia without marked hypertension at 32 to 38 weeks of age. The nephrosis was associated with spontaneously developed FSGS. We therefore investigated the mechanism of hypertriglyceridemia in nephrotic animals. Plasma triglyceride (TG) and apoprotein (apo) B levels were markedly increased in DS rats compared with Sprague-Dawley (SD) rats, and this was mainly attributable to an increase in the concentration of very-low-density lipoprotein (VLDL). The TG secretion rate estimated by the Triton WR1339 method was significantly greater in DS rats. VLDL-TGs isolated from both the DS and SD rats were endogenously radiolabeled with different isotopes, and a mixture of these was then injected into DS and SD recipients. The half-life of VLDL-TG was about three times longer in DS recipients, regardless of the source of VLDL. In SD recipients, VLDL from DS rats was cleared at a slower rate than VLDL from SD rats. The activity of lipoprotein lipase in postheparin plasma was substantially decreased in DS rats. Isoelectric focusing gel electrophoresis (IEF) showed that the ratio of apo E/C or apo C-II/C-III in VLDL was markedly decreased and the ratio of apo E or apo C to apo A1 in high-density lipoprotein (HDL) was slightly decreased in DS rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid peroxidation (LP) has recently been suggested to trigger the atherosclerotic process as well as to worsen the progression of renal disease. Autoantibodies against oxidized low-density lipoproteins (Ox-LDLAb) were considered to provide a sensitive marker to detect LDL oxidation in vivo. To date few studies have been reported on Ox-LDLAb levels in patients with different degrees of renal failure. The aim of this study was to evaluate the influences of renal function, dietary manipulation, and lipids on Ox-LDLAb concentrations in uremic patients either on conservative or replacement therapy. Seventy-one patients (42 males, 29 females) aged 60 +/- 19 years with chronic renal failure (CRF) of different etiology and degree were divided into four groups according to serum creatinine levels [sCr(mg/dl)] and diet: CRF I>> or = 1.5-3.0, CRF II>> 3.0-5.5, and CRF III>> 5.5 were all patients on a conventional low-protein diet, while a fourth group included patients on a vegetarian diet supplemented with keto analogues and amino acids (CRF SD >3.0). A further group was represented by patients on dialysis therapy. All patients were examined for Ox-LDLAb, triglycerides (TG), total cholesterol, HDL and LDL cholesterol, and apolipoproteins Apo A1, Apo B, and Lp(a). The results were compared with those of 20 controls (9 males and 11 females) aged 52 +/- 11 years with sCr <1.5 mg/dl. Ox-LDLAb increased, although not significantly, with TG and Lp(a) from the early stages of CRF along with the deterioration of renal function. However, TG and Lp(a) levels were significantly higher in all groups of patients except those on vegetarian diet (CRF SD). This group also showed the lowest Ox-LDLAb levels. No relationship was observed between lipids or apolipoproteins and Ox-LDLAb. Hyperlipidemic patients did not show higher Ox-LDLAb levels than normolipidemics. Our results show a progressive increase of LP as the renal function declines, which may account for the increased risk of cardiovascular disease reported in uremia. Dialysis does not correct significantly the oxidative state observed in patients with end-stage renal disease. Vegan diet, by reducing LP, TG, and Lp(a), is supposed to decrease the risk of cardiovascular disease and worth being reconsidered as an alternative effective therapeutic tool in patients with advanced CRF.

OBJECTIVE

To identify new biomarkers of pancreatic cancer (PaCa), we performed MALDI-TOF/MS analysis of sera from 22 controls, 51 PaCa, 37 chronic pancreatitis, 24 type II diabetes mellitus (DM), 29 gastric cancer (GC), and 24 chronic gastritis (CG).

METHODS

Sera were purified by Sep-Pak C18 before MALDI-TOF/MS Anchorchip analysis.

RESULTS

Features present in at least 5% of all spectra were selected (n = 160, m/z range, 1200-5000). At univariate analysis, 2 features (m/z 2049 and 2305) correlated with PaCa, 3 (m/z 1449, 1605, and 2006) with DM. No feature characterized gastric cancer or chronic gastritis. Ten-fold cross-validation binary recursive partitioning trees were obtained for patients' classification. The tree (CA 19-9, age, m/z 2006, 2599, 2753, and 4997), built considering only patients with diabetes, allowed a distinction between DM [area under the receiver operating characteristic curve (AUC), 0.997], chronic pancreatitis (AUC, 0.968), and PaCa (AUC, 0.980), with an overall correct classification rate of 89%. The tree including CA 19-9, 1550, and 2937 m/z features, achieved an AUC of 0.970 in distinguishing localized from advanced PaCa. MALDI-TOF-TOF analysis revealed the 1550 feature as a fragment of Apo-A1, which was determined as whole protein and demonstrated to be closely correlated with PaCa.

CONCLUSIONS

The findings made demonstrate a role for serum peptides identified using MALDI-TOF/MS for addressing PaCa diagnosis.

Iron is required by the brain for normal function, however, the mechanisms by which it crosses the blood-brain barrier (BBB) are poorly understood. The uptake and efflux of transferrin (Tf) and Fe by murine brain-derived (bEND3) and lymph node-derived (m1END1) endothelial cell lines was compared. The effects of iron chelators, metabolic inhibitors and the cellular activators, lipopolysaccharide (LPS) and tumour necrosis factor-alpha (TNF-alpha), on Tf and Fe uptake were investigated. Cells were incubated with 59Fe-125I-Tf; Fe uptake was shown to increase linearly over time for both cell lines, while Tf uptake reached a plateau within 2 h. Both Tf and Fe uptake were saturable. bEND3 cells were shown to have half as many Tf receptors as m1END1 cells, but the mean cycling times of a Tf molecule were the same. Tf and Fe efflux from the cells were measured over time, revealing that after 2 h only 25% of the Tf but 80% of the Fe remained associated with the cells. Of 7 iron chelators, only deferriprone (L1) markedly decreased Tf uptake. However, Fe uptake was reduced by more than 50% by L1, pyridoxal isonicotinoyl hydrazone (PIH) and desferrithiocin (DFT). The cellular activators TNF-alpha or LPS had little effect on Tf turnover, but they accelerated Fe uptake in both endothelial cell types. Phenylarsenoxide (PhAsO) and N-ethyl maleimide (NEM), inhibitors of Tf endocytosis, reduced both Tf and Fe uptake in both cell lines, while bafilomycin A1, an inhibitor of endosomal acidification, reduced Fe uptake but did not affect Tf uptake. The results suggest that Tf and Fe uptake by both bEND3 and m1END1 is via receptor-mediated endocytosis with release of Fe from Tf within the cell and recycling of apo-Tf. On the basis of Tf- and Fe-metabolism both cell lines are similar and therefore well suited for use in in vitro models for Fe transport across the BBB.

BACKGROUND

Women often lag behind men in their risk of cardiovascular events. However, with age and the onset of menopause, women's cardiovascular risk eventually becomes similar to that of men. This change in risk may, in part, be attributable to a shift to a more atherogenic lipid profile. Our objective was to evaluate standard- and sub-lipid parameters and the apo A1 remnant ratio: (apo A1/[VLDL₃-C+IDL-C]) for their associations with death/myocardial infarction among peri- and post-menopausal women.

METHODS

Women (N=711) >50 years of age undergoing coronary angiography were evaluated. Baseline clinical and angiographic characteristics, lipids, and sub-lipid levels (Vertical Auto Profile method) were collected. Cox regression analysis, adjusted by standard cardiovascular risk factors, was utilized to determine associations of lipid and sub-lipid tertiles(T) with death/myocardial infarction at 1 and 3 years.

RESULTS

Patients averaged 67.7±9.4 years and 53.6% had underlying severe (≥70% stenosis) coronary artery disease. The apo A1 remnant ratio was found to have stronger associations for 1 year (T1 vs. T3: HR=2.13, p=0.03, T2 vs. T3: HR=1.57, p=0.21) and 3 year (T1 vs. T3: HR=2.32, p=0.002, T2 vs. T3: HR=1.97, p=0.01) death/myocardial infarction than any individual lipid (LDL-C, HDL-C, triglycerides, non-HDL-C) or sub-lipid (apo A1, apo B, VLDL₃-C+IDL-C) measure, or any other well-known ratio (triglyercies/HDL-C, apo B/A1, TChol/HDL-C, HDL-C/[VLDL₃-C+IDL-C]).

CONCLUSIONS

The apo A1 remnant ratio was a significant predictor of short and intermediate-term death/myocardial infarction risk among women >50 years of age. Furthermore, this ratio was found to have greater predictive ability than traditional lipid and sub-lipid parameters and represents a potential new risk marker.

Raising high-density lipoprotein cholesterol (HDL-C) is an important strategy for reducing residual cardiovascular risk. In the present study, we sought to assess the effect of extended-release niacin/laropiprant on endothelial function in patients after a myocardial infarction with target low-density lipoprotein cholesterol (LDL-C). In this double-blind, placebo-controlled trial, 63 men (35-60 years of age) after a myocardial infarction were randomized to either niacin/laropiprant (1000/20 mg daily for 4 weeks and 2000/40 mg daily thereafter) or placebo. Flow-mediated dilation (FMD) and nitroglycerin-induced (GTN) dilation of the brachial artery, total cholesterol (TC), LDL-C, HDL-C, triglycerides (TG), lipoprotein(a) [Lp(a)], and apolipoprotein (Apo) A1/B were measured at baseline and after 12 weeks of intervention. FMD significantly increased (from 3.9 ± 5.1 to 9.8 ± 4.4%, p < 0.001) in the niacin/laropiprant group, but not in the placebo group (4.6 ± 4.4 to 6.1 ± 4.4%, p = 0.16) (p = 0.02 for comparison of interventions). GTN dilation also increased in the niacin/laropiprant group (from 12.5 ± 6.1 to 16.7 ± 4.8%, p = 0.02), but not in the placebo group (13.4 ± 5.0 to 15.1 ± 5.2%, p = 0.18), (p = 0.60 for comparison of interventions). Niacin/laropiprant reduced TC and LDL-C (p = 0.05 for both) and increased HDL-C (p < 0.001) without influencing TG, with no changes in the placebo group. Lp(a) (p = 0.026) and ApoB (p = 0.014) were significantly lower in the niacin/laropiprant group, with no difference in the placebo group. ApoA1 did not change in either of the groups (p = 0.13; p = 0.26). FMD and GTN dilation improvements did not correlate with changes in the lipid profile. Niacin/laropiprant improves endothelium-dependent and endothelium-independent dilation of the brachial artery. This improvement does not correlate with changes in lipid parameters.

OBJECTIVE

Many studies have reported associations between elevated intraocular pressure (IOP) and systemic health parameters, which suggest a common mechanism links IOP elevation and various related cardiometabolic risk factors. Furthermore, according to a recent study, serum apolipoprotein B (APO B) level is a predictor of coronary artery disease. This study was undertaken to analyse the relationship between serum apolipoprotein levels and IOP.

METHODS

Healthy people (28,852) who attended a community hospital for a health checkup between January 2011 and December 2013 were enroled in the study. We measured age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A1 (APO A1) and APO B, APO B/APO A1 ratios, and IOP.

RESULTS

Univariate regression analysis showed IOP was positively correlated with BMI, SBP, DBP, TC, LDL-C, TG, APO B, and APO B/APO A1 (P<0.001), and negatively correlated with HDL-C (P<0.001). On the other hand, multivariate regression analysis adjusted for age, BMI, SBP, and DBP, revealed IOP was positive correlated with TC, TG, LDL-C, APO B, and APO B/APO A1, and negatively correlated with HDL-C (all <0.05).

CONCLUSIONS

Among the various lipid profiles investigated, APO B was found to be most strongly correlated with IOP, regardless of sex. Additional studies are required to confirm the validity of apolipoprotein level as an index for predicting IOP.

Fifty-five experimental (29 male, 25 female) and 38 control (20 male, 18 female) adolescent subjects participated in this study to investigate the differences in coronary heart disease (CHD) risk factors in groups of trained and untrained adolescents. As expected the trained group (both sexes) had higher maximal aerobic power (VO2max) and lower systolic blood pressure at rest. The level of total cholesterol was the same in both groups, but the levels of high-density lipoprotein and its lipoprotein subfractions apolipoprotein (Apo-A) and Apo-A1 were higher, and low-density lipoprotein, Apo-B and triglycerides were significantly lower in the experimental group. The value of risk factors from the family history was the same in both groups, but the behavioural and physical risk factors such as smoking and percentage of body fat were lower in the trained group. It would appear that the group of adolescents, trained for several years in athletics and swimming, had a more beneficial lipoprotein profile and a lower level of behavioural and physical risk factors than the control group. For methodological reasons it remains an open question whether these profile differences are the consequences of self-selection procedures or the effects of training.

alpha-Lactalbumin (alpha-LA) is a calcium binding protein that also binds Mn(II), lanthanide ions, A1(III), Zn(II), Co(II). The structural implications of cation binding were studied by high-resolution proton (200 MHz) NMR and photochemically induced dynamic nuclear polarization (CIDNP) spectroscopy. Marked changes were observed in the NMR spectra of the apoprotein upon addition of a stoichiometric amount of calcium to yield Ca(II)-alpha-LA, manifested particularly in ring current shifted aliphatic peaks and in several shifts in the aromatic region, all of which were under slow exchange conditions. The CIDNP results showed that two surface-accessible tyrosine residues, assigned as Tyr-18 and -36, became inaccessible to the solvent upon addition of 1:1 Ca(II) to apo-alpha-lactalbumin, while Tyr-103 and Trp-104 remained completely accessible in both conformers. The proton NMR spectra of apo-alpha-LA and A1(III)-alpha-LA were extremely similar, which was also consistent with intrinsic fluorescence results [Murakami, K., & Berliner, L. J. (1983) Biochemistry 22, 3370-3374]. The paramagnetic cation Mn(II) bound to the strong calcium binding site on apo-alpha-LA but also to the weak secondary Ca(II) binding site(s) on Ca(II)-alpha-LA. It was also found that Co(II) bound to some secondary sites on Ca(II)-alpha-LA that overlapped the weak calcium site. All of the lanthanide shift reagents [Pr(III), Eu(III), Tb(III), Dy(III), Tm(III), Yb(III)] bound under slow exchange conditions; their relative affinities for apo-alpha-lactalbumin from competitive binding experiments were Dy(III), Tb(III), and Pr(III) greater than Ca(II) greater than Yb(III).

In non-insulin-dependent diabetes mellitus (NIDDM), cardiovascular risk factors improve during treatment, but whether insulin (I) differs from sulfonylurea (SU) therapy is unclear. To separate the contributions of improved diabetic control versus treatment regimen to risk factors, we examined the effects of SU and I on insulin sensitivity, basal and post-glucose load levels of insulin-like molecules, fibrinolysis, and lipid concentrations. Twenty poorly controlled, diet-treated NIDDM subjects were given I or SU each for a period of 16 weeks in a randomized crossover study, with a 4-week washout period between each treatment. Subjects were studied at the baselines (B1 and B2) and after each treatment. Treatment with I or SU produced similar improvements in glycemia (hemoglobin A1 [HbA1] B1, 11.7% +/- 2.1%; SU, 8.5% +/- 0.9%; I, 8.6% +/- 1.2%) and the metabolic clearance rate of glucose ([MCR-G] B1, 1.86 x/divided by 1.4; SU, 2.36 x/divided by 1.4 (P = .005 vB1); I, 2.27 x/divided by 1.4 (P = .07 vB1) ml x kg(-1) x min(-1)). On SU therapy, subjects had higher fasting and post-glucose load levels of intact proinsulin compared with B1 and I (fasting, 13.9 x/divided by 2.6 v 9.5 x/divided by 2.2 (P = .004) and 9.1 x/divided by 2.4 pmol x L(-1) (P = .01), respectively). Plasminogen activator inhibitor-1 (PAI-1) activity and antigen were higher than at B1 on SU therapy (23.7 v 19.9 AU x mL(-1) (P = .02) and 47.6 v 32.2 ng x mL(-1) (P = .006), respectively), but not on I. There were no changes compared with B1 and no differences between the two therapies in total, very-low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL) cholesterol and triglyceride, low-density lipoprotein (LDL), high-density lipoprotein 2 (HDL2) and HDL3 cholesterol, apolipoprotein (apo) A1, A2, and B1, or lipoprotein (a) [Lp(a)] levels. In conclusion, (1) treatment with SU or I resulted in equal improvement in glycemia and insulin sensitivity, (2) intact proinsulin and PAI-1 antigen and activity were higher on SU, and (3) there were no differences in lipid concentrations with improved glycemia or between therapies.

OBJECTIVE

Plasma lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease. The purpose of this study is to evaluate the correlation of anthropometric measures, lipids and lipoprotein profiles and serum Lp(a) values among children in Taiwan. We will attempt to find parameters that will be able to predict Lp(a) levels in children.

METHODS

After a probability-proportional-to size, multi-stages sampling procedure, we randomly sampled 1500 schoolchildren from 10 schools in Taipei city. Anthropometric measures including body weight, body height, waist and hip circumference and skinfolds were measured. We used standard methods to measure serum total cholesterol (CHOL), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 and B (ApoA1 and ApoB) and Lp(a) levels. We also calculated low density lipoprotein-cholesterol (LDL-C) and CHOL HDL-C ratio (TCHR) by formula.

RESULTS

We sampled 1283 children (635 boys and 648 girls) with a mean age of 13.3 years (from 12 to 16 years) in this study. The mean and medium serum Lp(a) levels were 16.8 and 8.8 mg/dl among boys and 20.8 and 11.9 mg/dl among girls. Children in the highest quintile of Lp(a) (mean = 49.6 and 58.6 mg/dl for boys and girls, respectively) had higher CHOL, LDL-C, ApoB levels and TCHR than children in the lowest quintile (mean = 3.1 and 3.7 mg/dl for boys and girls, respectively). Lipids and lipoprotein profiles, such as CHOL, LDL-C, Apo-B and TCHR were positively correlated with Lp(a) levels in both genders. Furthermore, the children with Lp(a) levels greater than or equal to 30 mg/dl had higher CHOL, LDL-C and Apo-B levels when compared to children with Lp(a) levels less than 30 mg/dl. After adjusting for age, cigarette smoking, alcohol drinking, puberty development and heart rates, LDL-C and ApoB levels were significantly positively associated with Lp(a) levels while ApoA1 was negatively associated among boys. Among girls, only Apo-B was significantly positively associated with Lp(a) and TG was negatively associated with Lp(a) levels. Most importantly, none of the anthropometric measures were significantly correlated with Lp(a) levels.

CONCLUSIONS

From this study, we found that lipids and lipoproteins profiles, rather than degree of adiposity as reflected by anthropometric measures, are significantly associated with serum Lp(a) levels among school children.

OBJECTIVE

To assess the effect of regular physical exercise on plasma lipids and apoproteins in an elderly group.

METHODS

Sixty-three old people of both sexes, aged between 65 and 94, were randomly distributed between a test group (n = 31) and a control group (n = 32). The test group followed a program of physical exercise for eight months, with intensity of 60% to 80% of heart rate reserve, consisting of three weekly sessions, on alternate days, of 60 minutes each. Before the beginning of the program and eight months afterwards, blood samples were collected to assess total cholesterol, triglycerides, HDL-C, HDL2-C. HDL3-C, apo A1, apo B-100 and apo (a). The ratios total cholesterol/HDL-C, LDL-C/HDL-C, HDL2-C/HDL3-C and apo A1/apo B-100 were also calculated.

RESULTS

In the test group total cholesterol, triglycerides, LDL-C, apo B-100, total cholesterol/HDL-C and LDL-C/HDL-C decreased significantly; HDL-C, HDL2-C, apo A1, HDL2-C/HDL3-C and apo A1/apo B-100 increased significantly; HDL3-C and apo (a) did not change. The control group did not present any significant alterations in any of the parameters assessed.

CONCLUSIONS

Regular physical exercise decreases vascular risk and may help to reduce cardiovascular events in the elderly.

Disorders of the lipoprotein metabolism are an important cause of premature coronary artery disease and myocardial infarction. Of the genetic lipoprotein disorders, elevation of apoprotein (apo) B containing lipoproteins is the most frequent one in the western population. We aimed to define the prevalence of genetic lipoprotein disorders and other risk factors in a population from a country with a low average cholesterol levels. We examined 48 consecutive patients with premature myocardial infarction below age 55, their 78 siblings and age and body mass index matched controls for familial lipoprotein disorders. The patients with premature myocardial infarction had higher triglyceride, low-density lipoprotein, apo B, lipoprotein (Lp) (a) and lower apo A1 levels then controls (p < 0.05). Of the nonlipid risk factors, 67% smoked, 8% had diabetes mellitus, 17% had hypertension and 58% a family history of premature coronary artery disease. Fifty percent of these patients with premature myocardial infarction had a familial lipoprotein disorder. Familial excess of Lp(a) was the most frequent lipoprotein abnormality present in 16% of the patients followed by familial combined hyperlipidemia. We conclude that, Lp(a) increase was the most frequent familial lipoprotein abnormality in this population. The frequency of familial lipoprotein disorders in this population emphasises the need to screen siblings of patients with premature myocardial infarction.