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Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectionalmeta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Studyspecific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a-3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI:-10.03,-5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10-3 unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10-3, -1.01 × 10-3) difference in ageand sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10-3 unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10-3, -1.25 × 10-3). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL arewarranted.

The Nobel Prize in Medicine in 2009 was awarded to Elizabeth Blackburn, Carol Greider and Jack Szostak for discovering the molecular structure of the far ends of chromosomes, called telomeres (Fig. 1), and how these protect chromosomes from degradation. Their discoveries shed light on a basic biological mechanism which stimulated research in a new exciting field aiming to explore the role of telomeres in normal ageing, cancer and age-related disease pathology. Fig. 1 Schematic presentation of telomeres. Elizabeth Blackburn first announced the identification of the repeated sequence of DNA in telomeres at a conference in 1980 and together with Jack Szostak in 1982 revealed that telomeres constitute a fundamental mechanism offering protection to chromosomes from degradation throughout different species [1]. In 1984 Carol Greider working with Elizabeth Blackburn discovered the enzyme which forms telomeric sequences [2,3]. This enzyme prevents telomere shortening with cell division, which otherwise takes place due to the incapability of DNA polymerase to fully copy the very end sequences of chromosomes during DNA replication, the so-called end-replication problem [4]. The impact of Blackburn's, Greider's and Szostak's work during the early 1980s is indicated by the increasing rate of publications in the field of telomeres thereafter (Fig. 2). Fig. 2 The rate of publications in the field of telomeres over the last 40 years, using data from the “Web of Science”. We now know that telomeres’ biological function goes beyond the protection of chromosome ends from degradation or fusion, playing an important role in the cell's ageing process [5]. The length of telomeres serves as a mechanism of normal cell senescence [6]. In somatic cells, where the enzyme telomerase is not expressed, telomeres become shorter with each cell division, due to the end-replication problem. Once the length reduces below a critical value replicative senescence, also called the Hayflick limit, is induced [7]. The rate of telomere shortening in telomerase negative cells is not only dependent on the number of cell divisions, but also on DNA damage. The ends of telomeres constitute 3′ single-strand overhangs which are prone to single-strand breaks, particularly those caused by oxidative damage, due to their G-rich content. The accumulation of such breaks along the telomeres leads to additional loss during replication [8,9]. Therefore, the length of telomeres indicates the replicative capacity and cumulative genomic damage of somatic cells, reflecting in this way the tissue's “biological age”. In recent years, the role of telomere length in the pathology of cardiovascular disease (CVD) and diabetes, where tissue ageing and senescence play major roles, has attracted a continuously growing research interest, and in the last two years alone six articles on telomere length have been published in Atherosclerosis. An article by Adaikalakoteswari et al. in the November 2007 issue associated shorter leukocyte telomere length (LTL) with impaired glucose tolerance, type 2 diabetes (T2D) and atherosclerotic plaques in T2D patients [10]. In June 2008, Satoh et al. showed that telomere length was shorter and telomerase activity lower in endothelial progenitor cells from patients with coronary heart disease (CHD) and even more reduced in CHD patients with metabolic syndrome. At the same time, oxidative DNA damage in these subjects displayed the opposite trend [11]. Following this, LTL was shown to negatively correlate with homocysteine levels by Richards et al. [12] and to positively correlate with HDL in the study of Chen et al. [13]. In a recent issue of Atherosclerosis, Olivieri et al. [14] showed that LTL is shorter in T2D patients compared to healthy subjects and even shorter in T2D patients with CHD. More recently, in this issue, our study [15] confirms the shorter LTL in T2D patients and also correlates LTL with plasma oxidative stress and variation in a gene regulating mitochondrial production of reactive oxygen species.

Objective - Death rates from coronary heart disease continue to rise in women despite a marked decrease in men for the past two decades. Our study aimed to evaluate essential risk factors in high-risk adult women. Methods - Lipid profiles of 547 dyslipidaemic adult women aged 57.5 ± 10.6 years (mean ± standard deviation) were evaluated and stratified according to fasting plasma lipid levels. Classification of the cohort was performed based on triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) levels and correlations between TG and HDL-C were estimated. Results - Patients with TG ≥ 150mg/dl had lower HDL-C levels compared to those with TG

Many epidemiological and clinical studies have shown that light-to-moderate alcohol (Alc) consumption is associated with reduced risk of coronary heart disease (CHD) and total mortality in middle-aged and elderly men and women. The plausible mechanisms for the putative cardioprotective effects include increased levels of high-density lipoprotein cholesterol, prevention of clot formation, reduced platelet aggregation, promotion of blood clot dissolution, and lowering of plasma lipoprotein (a) concentration. Individuals who need to be treated with lipid-lowering drugs, such as dyslipidemic or CHD patients, may benefit from these effects of Alc. Because hypolipidemic treatment is usually continued for life, an important issue is the suitability of Alc consumption in these patients. In the present review, the beneficial effects of Alc consumption on CHD risk, its side effects, and its safety and suitability when coadministered with hypolipidemic drugs are discussed.

Genovefa D Kolovou1, Katherine Anagnostopoulou1, Nektarios D Pilatis1, Klelia D Salpea1, Ioannis S Hoursalas1, Ilias Petropoulos1, Helen I Bilianou2, Dennis V Cokkinos11Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece; 2Cardiology Department, Tzanio State Hospital, Piraeus, GreeceObjective: The aim of the present investigation was to evaluate the influence of serum triglycerides (TG) on other plasma lipids in patients to be treated for dyslipidemia.Methodology: Lipid profiles of a cohort of 801 patients (487 males and 314 females) aged 57 ± 9 years (mean ± SD) were evaluated. Patients were stratified according to their plasma lipid levels. They were divided into various groups on the basis of serum TG (≥ 150 or < 150 mg/dL) and high-density lipoprotein cholesterol (HDL-C) (≥ 40 or < 40 mg/dL).Results: Patients with TG ≥ 150 mg/dL had a higher total cholesterol and lower HDL-C levels compared with those with TG < 150 mg/dL, (p < 0.001). Patients with HDL-C < 40 mg/dL had a lower serum total cholesterol and higher TG compared with those with HDL-C ≥ 40 mg/dL (p = 0.011 and p < 0.0001, respectively). In all patients as well as in the subgroups, an inverse correlation between TG and HDL-C was found (r = –0.377, p < 0.001).Conclusions: Although, the metabolic pathway for TG and HDL-C is closely linked, an inverse correlation between TG and HDL-C levels seems to exist in the entire sampled population. This correlation also appears to persist in fasting patients with low levels of TG.Keywords: triglycerides, high-density lipoprotein cholesterol, dyslipidemia

Background The olive fly, Bactrocera oleae, is the most devastating pest of cultivated olives. Its control has been traditionally based on insecticides, mainly organophosphates and pyrethroids. In recent years, the naturalyte spinosad is used against the olive fly. As with other insecticides, spinosad is subject to selection pressures that have led to resistance development. Mutations in the α6 subunit of the nicotinic acetylcholine receptor (nAChR) have been implicated in spinosad resistance in several species (e.g., Drosophila melanogaster) but excluded in others (e.g., Musca domestica). Yet, additional mechanisms involving enhanced metabolism of detoxification enzymes (such as P450 monooxygenases or mixed function oxidases) have also been reported. In order to clarify the spinosad resistance mechanisms in the olive fly, we searched for mutations in the α6-subunit of the nAChR and for up-regulated genes in the entire transcriptome of spinosad resistant olive flies. Results The olive fly α6-subunit of the nAChR was cloned from the laboratory sensitive strain and a spinosad selected resistant line. The differences reflected silent nucleotide substitutions or conserved amino acid changes. Additionally, whole transcriptome analysis was performed in the two strains in order to reveal any underlying resistance mechanisms. Comparison of over 13,000 genes showed that in spinosad resistant flies nine genes were significantly over-expressed, whereas ~40 were under-expressed. Further functional analyses of the nine over-expressed and eleven under-expressed loci were performed. Four of these loci (Yolk protein 2, ATP Synthase FO subunit 6, Low affinity cationic amino acid transporter 2 and Serine protease 6) showed consistently higher expression both in the spinosad resistant strain and in wild flies from a resistant California population. On the other side, two storage protein genes (HexL1 and Lsp1) and two heat-shock protein genes (Hsp70 and Hsp23) were unfailingly under-expressed in resistant flies. Conclusion The observed nucleotide differences in the nAChR-α6 subunit between the sensitive and spinosad resistant olive fly strains did not advocate for the involvement of receptor mutations in spinosad resistance. Instead, the transcriptome comparison between the two strains indicated that several immune system loci as well as elevated energy requirements of the resistant flies might be necessary to lever the detoxification process. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-714) contains supplementary material, which is available to authorized users.

Background— Telomere length is a heritable trait, and short telomere length has been associated with multiple chronic diseases. We investigated the relationship of relative leukocyte telomere length with cardiometabolic risk and performed the first genome-wide association study and meta-analysis to identify variants influencing relative telomere length in a population of Sikhs from South Asia. Methods and Results— Our results revealed a significant independent association of shorter relative telomere length with type 2 diabetes mellitus and heart disease. Our discovery genome-wide association study (n=1616) was followed by stage 1 replication of 25 top signals ( P –6 ) in an additional Sikhs (n=2397). On combined discovery and stage 1 meta-analysis (n= 4013), we identified a novel relative telomere length locus at chromosome 16q21 represented by an intronic variant (rs74019828) in the CSNK2A2 gene (β=−0.38; P =4.5×10 −8 ). We further tested 3 top variants by genotyping in UK cardiovascular disease (UKCVD) (whites n=2952) for stage 2. Next, we performed in silico replication of 139 top signals ( P –5 ) in UK Twin, Nurses Heart Study, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, and MD Anderson Cancer Controls (n=10 033) and joint meta-analysis (n=16 998). The observed signal in CSNK2A2 was confined to South Asians and could not be replicated in whites because of significant difference in allele frequencies ( P Conclusions— By identification of a novel signal in telomere pathway genes, our study provides new molecular insight into the underlying mechanism that may regulate telomere length and its association with human aging and cardiometabolic pathophysiology.

OBJECTIVE Shortened leukocyte telomere length (LTL) and diagnosis of periodontitis are associated with an increased risk of complications and mortality in diabetes. This study investigated the association between LTL, endotoxemia, and severity of periodontitis in a large cohort of people with diabetes. RESEARCH DESIGN AND METHODS Six hundred thirty individuals (371 with type 2 and 259 with type 1 diabetes) were recruited from the University College Hospital in London, U.K. During a baseline visit, blood was collected for standard biochemical tests and DNA extraction, while a dental examination was performed to determine diagnosis and extent of periodontitis. LTL was measured by real-time PCR, and endotoxemia was assessed by the limulus amoebocyte lysate method. RESULTS Two hundred fifty-five individuals were diagnosed with gingivitis, 327 with periodontitis (114 with moderate and 213 with severe disease), and 48 with edentulous. Diagnosis of periodontitis was associated with shorter LTL (P = 0.04). A negative association between LTL and endotoxemia was found in the severe periodontitis and type 2 diabetes groups (P = 0.01 for both). Shorter LTL was associated with increased extent of periodontitis (P = 0.01) and increased insulin resistance (homeostatic model assessment). Multiple adjustments for biochemical, anthropometric, and medication-use variables did not affect the results. CONCLUSIONS LTL is associated with endotoxemia and diagnosis of periodontitis in people with diabetes. LTL shortening might represent a novel biological pathway accounting for previous epidemiological data that documented higher prevalence of diabetes and its complications in people with periodontitis and vice versa.

UNLABELLED:Cardiovascular disease and diabetes have been linked to shorter telomeres, but it is not yet clear which risk factors contribute to shorter telomeres in patients. Our aim was to examine whether pro-inflammatory conditioning, in combination or not with high glucose, result in a higher rate of telomere shortening during in vitro cellular ageing. Human fibroblasts from four donors were cultured for 90 days in: 1) medium lacking ascorbic acid only, 2) 10 mM buthionine sulphoximine (BSO) (pro-oxidant), 3) 25 mM D-glucose, 4) 1 ng/ml IL1B and 5) 25 mM D-glucose+1 ng/ml IL1B. Telomere length was measured with qPCR and intracellular reactive oxygen species (ROS) content and cell death with flow cytometry. Cultures treated with high glucose and BSO displayed a significantly lower growth rate, and cultures treated with IL1B showed a trend towards a higher growth rate, compared to the control [Glucose:0.14 PD/day, p

Objective— Short leukocyte telomere length (LTL) is associated with cardiovascular (CV) disease in adulthood. However, the biological basis of this association remains unclear. We sought to define early determinants of the association between CV disease and LTL in an adolescent population. Methods and Results— One thousand eighty adolescents, aged 13 to 16 years and participating in the Ten Towns Heart Health Study, provided blood samples for DNA extraction and measurement of a range of CV risk factors. LTL was measured by real-time polymerase chain reaction. LTL was inversely associated with age ( P =0.04), longer in females than in males ( P =0.03), and longer in South Asians than in white Europeans ( P =0.01). No associations were found between LTL and traditional CV risk factors. There was a significant and inverse association between LTL and inflammatory markers, including C-reactive protein ( P P =0.001). The associations between LTL and inflammatory markers were not affected by multiple adjustments for behavioral and metabolic factors. Conclusion— High levels of inflammation are associated with shorter LTL from early adolescence; traditional CV risk factors have little association with LTL in adolescence. Inflammation in early life may play a causal role in the adult association between short LTL and CV disease.

The aim of this study was to determine leukocyte telomere length (LTL) in individuals with periodontitis and controls, exploring its relationship with systemic inflammation and oxidative stress. Five hundred sixty-three participants were recruited for this case-control study: 356 subjects with and 207 subjects without periodontitis. LTL was measured by a qPCR technique from leukocytes' DNA. Global measures of oxidative stress (reactive oxygen metabolites) and biological antioxidant potential in plasma were performed together with high-sensitivity assays for C-reactive protein (CRP). Leukocyte counts and lipid profiles were performed using standard biochemistry. Cases had higher levels of CRP (2.1±3.7mg/L vs 1.3±5.4mg/L, P

Shorter telomeres have been reported in premature myocardial infarction (MI) patients. Our work aimed at confirming the association of shorter telomere with MI in two case–control studies and in familial hypercholesterolemia (FH) patients with coronary heart disease (CHD). The HIFMECH study compared 598 white male patients (

Objective High oxidative stress potentially leads to accelerated telomere shortening and consequent premature cell senescence, implicated in type 2 diabetes (T2D) development. Therefore, we studied the association of leukocyte telomere length (LTL) with the presence of T2D, as well as the effect on the patients’ LTL of plasma oxidative stress and of variation in UCP2, a gene involved in the mitochondrial production of reactive oxygen species. Methods Mean LTL was determined in 569 Caucasian, 103 South Asian and 70 Afro-Caribbean T2D patients aged from 24 to 92 years, 81 healthy Caucasian male students aged from 18 to 28 years and 367 healthy Caucasian men aged from 40 to 61 years by real-time PCR. Plasma total antioxidant status (TAOS) was measured in the T2D patients by a photometric microassay. The patients were also genotyped for the UCP2 functional variants −866G>A and A55V. Results Afro-Carribeans had 510 bp longer mean length compared to Caucasians (p

Previous studies of ours have shown that simvastatin (S) and nicotinic acid (NA) lower the alcohol (Alc)-induced increase of triglycerides. The aim of this study was to evaluate which drug is more effective and safe in decreasing Alc-induced hypertriglyceridaemia in Wistar rats.Male Wistar rats were randomised into 6 groups, which were fed with: (1) olive oil (Oil group, n=10); (2) Oil + Alc, (Alc group, n=10); (3) S solution in Oil (65 microg/100g body weight), (S group, n=10); (4) NA solution in Oil (8.5 mg/100g body weight), (NA group, n=8); (5) S solution in Oil + AIc (S+Alc group, n=10); and (6) NA solution in Oil + Alc (NA+Alc group, n=9). Another 13 male Wistar rats were fed only a standard laboratory diet (control group). After 8 weeks, blood samples were drawn and the livers were removed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), total cholesterol (TC) and triglycerides (TG) were measured. Liver histopathology was also assessed.Liver histopathology was similar in all groups and within the normal range. The TG plasma concentration in the Alc group was higher than in the control rats (p0.001) or any other groups (Oil, p0.001, or S, p0.001, or NA, p = 0.003). The Oil, S+Alc, NA+Alc and control groups had similar TG levels, but these were significantly lower compared to the Alc group (p0.001). AST plasma concentration was higher in the Alc group compared to controls (p0.001), Oil (p0.001), S (p0.001) and NA (p0.001) groups, while the AST concentration in the S+Alc and Na+Alc groups was lower than in the Alc group (p = 0.042, p0.001, respectively).NA and S, two drugs of different classes, seem to decrease Alc-induced secondary hypertriglyceridaemia to the same extent. Moreover, NA displays a better alleviation of Alc-induced AST raises compared to S, although it enhances small increases in AP and ALT levels.

Background and aims The wnt signaling pathway regulates adipogenesis and insulin secretion. The WNT5B gene has been reported to confer susceptibility to type 2 diabetes (T2D) in the Japanese population, and we therefore evaluated this in Caucasian subjects with respect to obesity status. Methods and results Two thousand seven hundred and one Caucasian middle-aged men from the prospective Northwick Park Heart Study II (NPHSII) of whom 153 developed T2D over 15 years and 1268 Caucasian middle-aged patients with T2D (60% male) were genotyped using a TaqMan assay for the IVS3C>G variant (rs2270031) in the WNT5B gene. The frequency of the G allele was 0.026 (0.022–0.031) in controls and 0.031 (0.025–0.039) in patients with diabetes, p =0.24. In the prospective analysis, G allele carriers with BMI below 26kg/m 2 had significantly higher T2D hazard risk [3.46 (1.34–8.96), p =0.01]. Comparing T2D cases with NPHSII controls, the G allele was associated with a significantly higher T2D odds ratio (OR) of 1.50 (1.06–2.12), p =0.02 in subjects with BMI lower than 30kg/m 2 . Increasing BMI had a smaller effect on risk in G allele carriers. The effect on risk was not explained by genotype being associated with any classical T2D risk factor. When the combined effect of this SNP and the TCF7L2 IVS3C>T SNP (rs7903146) was evaluated, a 2.07 (1.40–3.07), p Conclusion Variation in WNT5B predisposes to T2D in the absence of obesity. The increase in risk conferred by the presence of both WNT5B and TCF7L2 variants strengthens the role of wnt signaling in T2D.

The insulin resistance/metabolic syndrome is characterized by the variable co-existence of hyperinsulinemia, obesity, dyslipidemia (small dense low-density lipoprotein, hypertriglyceridemia, and decreased high-density lipoprotein cholesterol), and hypertension. The pathogenesis of the syndrome has multiple origins. However, obesity and sedentary lifestyle coupled with diet and still largely unknown genetic factors clearly interact to produce the syndrome. This multifactorial and complex trait of metabolic syndrome leads to increased risk of cardiovascular disease. The scope of this review is to examine the differences in prevalence of the metabolic syndrome in various groups (eg, according to age, sex, ethnicity, social status, or presence of obesity) that could help with the better understanding of the pathogenesis of this syndrome. This review also considers the impact of metabolic syndrome on cardiovascular disease.

Several studies showed that postprandial plasma triglyceride (TG) concentrations are higher in patients with coronary heart disease. TG-rich lipoprotein remnants accumulated in the postprandial state are involved in atherogenesis and in events leading to thrombosis. Lipid lowering drugs, such as 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) are of significant benefit in the primary and secondary prevention of atherosclerosis. Statins can decrease total cholesterol and low density lipoprotein cholesterol as well as TG concentrations and improve postprandial lipoprotein metabolism. Since abnormal postprandial lipemia is associated with pathological conditions, its treatment is relevant. This review considers the effect of statins on postprandial lipemia.

A 13-year-old Greek boy with severe dyslipidemia, large tuberous xanthomas over the knees and elbows, Achilles’ tendon xanthomas, and a bilateral corneal arcus was referred to the Lipid Clinic. He had a supravalvular aortic stenosis, 50% to 60% stenosis of both carotid arteries, and normal coronary arteries. Familial hypercholesterolemia was clinically diagnosed. A V408M null low-density lipoprotein receptor (LDLR) mutation was identified in homozygosity. He responded to lipid-lowering drugs by decreasing total cholesterol by 32%, low-density lipoprotein cholesterol by 33%, and triglyceride levels by 30%. Additional treatment with low-density lipoprotein-apheresis further decreased total cholesterol by 52%, low-density lipoprotein cholesterol by 55%, and triglycerides by 43%. Low-density lipoprotein cholesterol levels between apheresis sessions showed a declining pattern. A significant regression of tuberous xanthomas was noted. A suitable combination of lipid-lowering drugs is effective even in this case of homozygosity for a null LDLR mutation. Furthermore, the coadministration of statins, cholestyramine, and ezetimibe during low-density lipoprotein-apheresis tends to counterbalance the postapheresis relapse in low-density lipoprotein cholesterol levels.

BackgroundPostprandial hyperlipidaemia may be a predictor of vascular risk.DesignWe evaluated postprandial lipaemia after an oral fat tolerance test (OFTT) in men (n = 41) and women (n = 21) with metabolic syndrome (MetS).MethodsTriglyceride (TG) levels were measured before and 2, 4, 6 and 8 h after the fat load.ResultsMen showed a greater plasma TG response 8 h after the fat load (284 ± 117 versus 224 ± 126 mg/dl, P = 0.029). Only fasting TG levels significantly predicted the TG area under the curve (AUC) and incremental AUC.ConclusionsMen had a more pronounced postprandial hypertriglyceridaemia and seem to have delayed TG clearance.

The present investigation aimed to evaluate the influence of serum triglycerides (TG) on other plasma lipids in male patients less than 65 years of age intended for hypolipidaemic treatment.Lipid profiles of a cohort of 412 dyslipidaemic male patients aged 53.4 +/- 7.7 years (mean +/- standard deviation) were evaluated. Patients were stratified in accordance with their fasting plasma lipid levels. They were divided into multiple groups on the basis of serum TG (or = 150 or150 mg/dl) and high-density lipoprotein cholesterol (HDL-Cor = 40 or40 mg/dl).Patients with TGor = 150 mg/dl had higher total cholesterol and lower HDL-C levels compared with those with TG150 mg/dl (p = 0.005 and p0.001, respectively). Patients with HDL-C40 mg/dl had similar total cholesterol levels and higher TG levels compared to those with HDL-Cor = 40 mg/dl (p0.001). In all patients, an inverse correlation between TG and HDL-C was found (r = -0.286, p0.001). Additionally, HDL-C levels were inversely correlated with the TG concentration in patients with TG150 mg/dl (r = -0.135, p = 0.042) and TGor = 150 mg/dl (r = -0.188, p = 0.002).An inverse correlation between TG and HDL-C levels seems to exist in the sampled population, revealing a close link between the metabolic pathways for TG and HDL-C. This inverse correlation appears to persist even in patients with low fasting TG levels.

Cholesteryl ester transfer protein (CETP) gene is involved in the reverse cholesterol transport in humans. Thus, it is a candidate for studying the susceptibility to coronary heart disease (CHD). The goal of the current investigation was to determine any association between CETP polymorphisms (I405V and TaqIB), and severity of coronary stenosis, since the extent of coronary artery narrowing has been considered as a primary determinant of survival in CHD patients.The severity of coronary stenosis was estimated by Gensini (GS) and Duke Jeopardy (JS) scores in 130 men with documented CHD (mean age 61 +/- 10 yr). Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism analysis.The allele frequencies for both TaqIB and I405V were found in Hardy-Weinberg equilibrium. Homozygotes for I had lower GS compared with heterozygotes (IV) and homozygotes for V [72(95% CI 51-92) vs. 122(95% CI 88-157) and 136 (95% CI 74-198), P = 0.009, P = 0.010, respectively]. In addition, GS differed between carriers of I and carriers of V allele [86(95% CI 72-101) vs. 128(95% CI 102-154), P = 0.003]. A correlation was found between the GS and I405V polymorphism (r = 0.250, P = 0.005), but not with JS.Homozygosity for I405 favours less severe coronary stenosis. Our findings indicate that the I405V polymorphism may have potential importance in screening individuals at high risk for developing CHD, establishing efficient prevention measures, and searching for other risk factors for CHD. However, further prospective investigations in larger populations are required to confirm these findings.

Background Several groups of patients at high risk for cardiovascular disease have been found to show an exaggerated postprandial hypertriglyceridemia. Postprandial lipemia (PPL) therefore has been implicated as a potential additional risk factor that has been evading us. The purpose of this study was to test the effect of high fasting high-density lipoprotein cholesterol (HDL-C) levels on PPL in postmenopausal females. Methods Oral fat tolerance test, as quantified by the areas under the curve (AUC) of triglyceride (TG) levels, was given to 3 groups: normal postmenopausal females (control), postmenopausal females with exceptionally high HDL-C and a familial history of longevity (longevity syndrome), and postmenopausal females that were heterozygotes of familial hypercholesterolemia (hFH) with exceptionally high HDL-C. Results The PPL was not different between the control and longevity syndrome groups but was significantly higher in the hFH group; AUC (SD), in mg/dl/h; 749 (195), 882 (278) and 1244 (497) respectively, p=0.002. In linear regression analysis only fasting TG levels were a significant predictor of the AUC (Coefficient B = 11.779, p Conclusions In subjects with longevity syndrome the PPL is similar to controls, which means that high fasting HDL-C has not any beneficial influence on PPL. The fasting TG concentration is the main determinant of PPL. Furthermore, postmenopausal females with hFH have higher TG response postprandially, even in the case of high fasting HDL-C. Whether there is a threshold below or above, where HDL-C becomes a significant independent determinant of PPL is a question to be answered by future research.

Apolipoprotein E (apo E) plays an important role in lipid metabolism and its polymorphism may be a risk determinant of coronary heart disease (CHD). Since evidence suggested a gender-specific effect of apo E polymorphism, we studied the influence of gender-specific interaction of the polymorphism on CHD. From a total of 463 Greek Caucasians (314 men and 149 postmenopausal women) with angiographically documented CHD, we selected 79 women (68+/- 9 yr old) and 79 men (66+/- 9 yr old) who were matched for clinical characteristics. Apo E genotyping was performed by PCR and RFLP analysis. Biochemical parameters were also measured. The results were as follows: the E3/3 genotype occurred in 78.5% of the patients, followed by E3/4, E2/3, E2/4, and E4/4 genotypes, which occurred in 9.5%, 9.5%, 1.9%, and 0.6% of the patients, respectively. No significant differences were observed in the apo E allele or apo E genotype distributions between the matched Greek men and women with CHD. The E3/3 men patients were more frequently part of a family with a history of CHD, compared to women (p=0.035).

Background The metabolic syndrome (MetS), as well as postprandial hypertriglyceridemia, is associated with coronary heart disease. This study aimed to evaluate the postprandial lipemia after oral fat tolerance test (OFTT) in subjects with MetS and compare them to hypertensive (HTN) and healthy subjects. Results OFTT was given to 33 men with MetS (defined by the Adult Treatment Panel III), 17 HTN and 14 healthy men. The MetS group was further divided according to fasting triglycerides (TG) into TG ≥ 150 [MetS+TG, (n = 22)] or The postprandial response was significantly higher in MetS compared to HTN and healthy men [AUC (SD) in mg/dl/h; 2534 ± 1016 vs. 1620 ± 494 and 1019 ± 280, respectively, p ≤ 0.001]. The TG levels were increased significantly in MetS+TG compared to MetS-TG subjects at 4 (p = 0.022), 6 (p < 0.001) and 8 hours (p < 0.001). The TG were increased significantly in MetS-TG compared to healthy subjects at 4 (p = 0.011), 6 (p = 0.001) and 8 hours (p = 0.015). In linear regression analysis only fasting TG levels were a significant predictor of the AUC (Coefficient B = 8.462, p < 0.001). Conclusion Fasting TG concentration is the main determinant of postprandial lipemia. However, an exaggeration of TG postprandialy was found in normotriglyceridemic MetS and HTN compared to healthy subjects. This suggests that intervention to lower fasting TG levels should be recommended in MetS subjects.

The ingestion of alcohol (Alc) as well as gemfibrozil (Gem), a fibrate drug used to treat hypertriglyceridaemia, may occur on a long-term basis in humans. Since both Alc and Gem can disturb liver function, we assessed the effects of administering Alc together with Gem in Wistar rats.Male Wistar rats were randomized and divided into 4 groups of 10 each. They were fed (once a day) via a stomach tube with: i) 2 ml of polyethylene glycol (Peg); group Peg, ii) 2 ml of Peg + 2 ml of 25% v/v pure Alc in water; group Alc + Peg, iii) 2 ml of Gem solution in Peg (3.4 mg/100 g body weight); group Gem +Peg, iv) 2 ml of Gem solution in Peg 2 + 2 ml of Alc; group Gem +Alc +Peg. Another 13 male Wistar rats were only fed a standard laboratory diet (control group). After 8 weeks, blood samples were drawn and the livers removed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), total cholesterol (TC) and triglycerides (TG) were measured. Liver histopathology was also assessed.All tube-fed groups had higher body mass index compared to controls (p0.001). The control group had lower AP compared to Gem+Peg and Gem +Alc+Peg groups (p=0.005 and p=0.018, respectively). The Peg group had lower AP compared to G+Peg (p=0.041). All tube-fed groups had lower ALT compared to controls (p0.001). The TC levels were lower in tube-fed groups with Gem (Gem +Peg and Gem+Alc +Peg) compared to controls (p=0.002 and p=0.039, respectively). Among the tube-fed groups, the TC level was lower in Gem +Peg compared to Peg and Alc+Peg groups (p=0.047 and p=0.01, respectively). No differences were found among tube-fed groups and control rats in blood AST and TG. Liver histopathology was similar in all groups and within the normal range.A moderate amount of Alc daily together with Gem is safe in rats. Peg administration in Wistar rats protects from the Alc-induced TG and AST rises.

The effects of co-administration of nicotinic acid (NA) and alcohol (Alc) on liver function in male Wistar rats were evaluated. The rats were randomized into five groups: (i) Olive oil (Oil), (ii) Alc+Oil, (iii) NA+Oil, (iv) NA+Alc+Oil, and (v) Controls (fed only normal rat chow). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), total cholesterol and triglycerides (TG) were measured. Liver histopathology was also assessed. The Alc+Oil group had higher TG levels compared with the NA+Alc+Oil group and all other groups, as well. NA+Oil group had higher levels of AP compared with Alc+Oil and Oil groups. The NA+Oil group had higher ALT levels compared with the Oil group. The Oil group had lower ALT levels compared with the control group. The Alc+Oil group had higher AST levels compared with the NA+Alc+Oil group, as well as with all other groups. Liver histopathology was within the normal range. A moderate amount of Alc daily together with NA is safe in rats. The NA and Alc co-administration reduces the TG and AST levels in rats, compared with the administration of Alc alone.

Inter-individual variability in telomere length is highly heritable and has been correlated with risk of coronary heart disease (CHD). Our aim was to determine the association of mean leukocyte telomere length with paternal history of premature myocardial infarction (MI). Mean leukocyte telomere length was measured with real-time polymerase chain reactions in 369 male students (18–28 years) with a paternal history of MI before the age of 55, recruited from 14 European universities, serving as cases and 396 age-matched controls with no paternal history of CHD. Overall, cases had borderline significantly shorter mean length (~550 bp), adjusted for age and geographical region, than controls (p = 0.05). A significant difference in telomere length across the geographical regions of Europe was observed (p