Nutrition, Metabolism & Cardiovascular Diseases - Articles in Press

A pilot comprehensive lifestyle intervention program (CLIP) – Comparison with qualitative lifestyle advice and simvastatin on cardiovascular risk factors in overweight hypercholesterolaemic individuals - Corrected Proof

X. Cleanthous, M. Noakes, G.D. Brinkworth, J.B. Keogh, G. Williams, P.M. Clifton — 2010-01-28

Abstract: Background and Aims: Escalating costs of pharmaceuticals for cardiovascular management highlight the need to develop effective lifestyle intervention programs to reduce reliance on these agents. The aim of this pilot study was to evaluate the efficacy of a Comprehensive Lifestyle Intervention Program (CLIP) compared with qualitative lifestyle advice (L) and Simvastatin plus qualitative lifestyle (S+L) on cardiovascular risk factors.Methods and Results: Sixty-five overweight adults with hypercholesterolemia were randomised to either L (qualitative advice on diet, exercise), S+L (20mg/day Simvastatin plus L) or CLIP (6500kJ structured menu plan: conventional and functional foods contributing <10% energy from saturated fat, ≥3g soluble fibre, 2.4g plant sterols, oily fish ≥2 times/week at lunch and dinner, plus exercise advice and self monitoring) for 6 weeks. LDL-cholesterol was lowered in CLIP (−0.57±0.67mmol/L, 15%) and S+L (−1.43±0.59mmol/L, 37%), but did not change significantly in L (−0.17±0.59, 4%) (P<0.001 time-by-treatment interaction). Weight and waist circumference were significantly lowered by CLIP (−4.2±2.2 kg; −5.1±2.3 cm) compared to L (−1.0±1.6 kg; −2.7±3.3 cm) and L+S (−0.7±1.4 kg; −2.4±2.3 cm), (P≤0.003 time-by-treatment interactions). B-carotene levels within treatment groups did not change over time and were not lowered by the CLIP diet compared to L (P>0.05, all). Blood pressure changes were not different between groups.Conclusions: The structured CLIP program was more effective than qualitative lifestyle advice in improving weight, waist circumference and LDL-cholesterol without adverse effects on plasma carotenoids over a 6 week period. This program may therefore assist in comprehensive risk factor management, although the sustainability of these benefits needs confirmation.

Association of increased Visfatin/PBEF/NAMPT circulating concentrations and gene expression levels in peripheral blood cells with lipid metabolism and fatty liver in human morbid obesity - Corrected Proof

2010-01-27

Abstract: Background and aims: Nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine with physiological effects on the control of glucose homeostasis as well as potentially involved in inflammation. The association of circulating NAMPT concentrations with obesity has not been clearly established. The aim of the present work was to evaluate the effect of obesity on circulating concentrations and gene expression levels of NAMPT in human peripheral blood cells (PBCs) as well as its involvement in inflammation, glucose and lipid metabolism.Methods and results: Forty-four serum samples obtained from 14 lean and 30 obese volunteers were used to analyse the circulating concentrations of NAMPT. In addition, PBC, omental adipose tissue (OM) and liver biopsy samples obtained from a subgroup of subjects were used to determine transcript levels of NAMPT by Real-time PCR. Glucose and lipid profile as well as several inflammatory factors and hepatic enzymes were analysed. NAMPT circulating concentrations (P<0.01) and gene expression levels in PBC (P<0.05) were significantly increased in obese patients as compared to lean subjects. Total-cholesterol (P=0.016), HDL-cholesterol (P=0.036) and triglycerides (P=0.050) were significant and independent determinants of circulating concentrations of NAMPT (P<0.01). Moreover, a positive correlation (P<0.01) was found with the hepatic enzymes alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase after BMI adjustment.Conclusion: Our work shows that NAMPT circulating concentrations and mRNA expression levels in PBC are increased in obese patients and that plasma NAMPT levels are related to inflammation, lipid metabolism and hepatic enzymes suggesting a potential involvement in fatty liver disease and in the obesity-associated inflammatory state.

Early phase insulin secretion is increased in subjects with normal fasting glucose and metabolic syndrome: a premature feature of beta-cell dysfunction - Corrected Proof

2010-01-22

Abstract: Background and Aims: Metabolic syndrome (MS) has been mainly related to insulin resistance, but the role of changes in insulin secretion has not been thoroughly investigated.Methods and Results: Using an oral glucose tolerance test (OGTT) we studied beta-cell function and insulin sensitivity in subjects with normal fasting glucose with and without MS, and their relationship to fatty liver which was evaluated by abdominal-ultrasonography. In MS early phase insulin secretion, as measured by insulinogenic index (IG30), was increased (p<0.05) independently from insulin sensitivity. Furthermore IG30 was progressively higher as the number of factors needed for the diagnosis of MS increased (p<0.01). Insulin and C-peptide AUC were also increased (p<0.01 and p<0.05, respectively) but, in contrast to IG30, these differences disappeared when ISI was used as a covariate. After OGTT, 51% of the subjects with MS had altered post-load glucose tolerance compared to 24.9% without MS (p<0.01). In both groups, the altered glucose tolerance was associated with a similar IG30 reduction. In normo-tolerant subjects with MS the IG30 was higher (+54.1%, p<0.01), and this elevation occurred irrespective of ISI; however, the beta-cell compensatory capacity for insulin resistance (disposition index) was impaired (p<0.001). Fatty liver was more frequent (p<0.001) and more severe (p<0.01) in MS, and it was significantly related to total AUC-insulin (p<0.001), independently from ISI.Conclusion: These findings indicate that the prevalence of altered tolerance is more frequent in subjects with normal fasting glucose and MS. The hyperinsulinemia might not only be an adaptive response to insulin resistance, but a primary defect of beta-cell function contributing to glucose intolerance.

Non-cholesterol sterols in serum and endarterectomized carotid arteries after a short-term plant stanol and sterol ester challenge - Corrected Proof

2010-01-22

Abstract: Background and Aims: It is not known whether dietary intake of plant stanols or sterols changes the composition of arterial sterols. Therefore, we compared serum and carotid artery cholesterol and non-cholesterol sterols after plant stanol (staest) or sterol (steest) ester feeding in endarterectomized patients.Methods and Results: Elderly statin-treated asymptomatic patients undergoing carotid endarterectomy were randomized double-blind to consume staest (n=11) or steest (n=11) spread (2g of stanol or sterol/day) for four weeks preoperatively. Non-cholesterol sterols from serum and carotid artery tissue were analysed with gas-liquid chromatography. Staest spread lowered serum total (17.2%), VLDL, and LDL cholesterol and serum triglycerides, while steest spread lowered serum total (13.8%) and LDL cholesterol levels from baseline (p<0.05 for all). Serum cholestanol and avenasterol were decreased in both groups, but campesterol and sitosterol were decreased by staest and increased by steest from baseline (p<0.05 from baseline and between the groups). Serum sitostanol to cholesterol ratio was increased by staest, but in arterial tissue this ratio was similar in both groups. On staest, lathosterol, campesterol, and sitosterol, and on steest sitosterol and avenasterol correlated significantly between serum and arterial tissue. Cholesterol metabolism, eg. lathosterol/campesterol, suggested that plant sterols were reduced in serum and in arterial tissue during staest.Conclusion: The novel observations were that plant stanol ester consumption, in contrast to plant sterols, tended to reduce carotid artery plant sterols in statin-treated patients. Furthermore, despite increased serum sitostanol contents during plant stanol ester consumption, their arterial levels were unchanged suggesting that sitostanol is not taken up into the arterial wall.

Glomerular filtration rate, albuminuria and risk of cardiovascular and all-cause mortality in type 2 diabetic individuals - Corrected Proof

2010-01-22

Abstract: Background and aims: To assess all-cause and cardiovascular mortality in type 2 diabetic individuals according to estimated glomerular filtration rate (eGFR) and albuminuria.Methods and results: We followed 2823 type 2 diabetic outpatients for a median period of 6 years for the occurrence of all-cause and cardiovascular mortality. eGFR was estimated using the abbreviated Modification of Diet in Renal Disease study equation. At baseline, an eGFR <60ml/min/1.73m2 and abnormal albuminuria were present in 22.5% and 26.0% of participants, respectively. During follow-up, a total of 309 patients died, 53% of deaths were secondary to cardiovascular causes. Risks of all-cause and cardiovascular mortality increased progressively with decreasing eGFR and increasing albuminuria. After adjustment for age, sex, body mass index, smoking, hypertension, diabetes duration, hemoglobin A1c, plasma lipids, medications use (hypoglycemic, anti-hypertensive, anti-platelet or lipid-lowering drugs) and albuminuria, the hazard ratios of all-cause and cardiovascular mortality per 1-SD decrease in eGFR were 1.53 (95%CI 1.2–2.0; p<0.0001) and 1.51 (95%CI 1.05–2.2; p=0.023), respectively. A similar pattern in the risk of all-cause and cardiovascular mortality was seen for albuminuria (1.14, 1.01–1.3, p=0.028 and 1.19, 1.01–1.4, p=0.043 per 1-SD increase in albuminuria, respectively) after adjustment for eGFR and other potential confounders.Conclusions: These findings suggest that both decreasing eGFR and rising albuminuria are associated with all-cause and cardiovascular mortality in type 2 diabetic individuals, independently of traditional risk factors and diabetes-related variables.

Mediterranean diet and the incidence of cardiovascular disease: A Spanish cohort - Corrected Proof

2010-01-22

Abstract: Background and aim: The Mediterranean diet is considered a model for healthy eating. However, prospective evidence in Mediterranean countries evaluating the relationship between this dietary pattern and non-fatal cardiovascular events is scarce. The aim of the present study was to evaluate the association between the adherence to the Mediterranean diet and the incidence of fatal and non-fatal cardiovascular events among initially healthy middle-aged adults from the Mediterranean area.Methods and results: We followed-up 13,609 participants (60 percent women, mean age: 38 years) initially free of cardiovascular disease (CVD) during 4.9 years. Participants were part of a prospective cohort study of university graduates from all regions of Spain. Baseline diet was assessed using a validated 136-item food-frequency questionnaire. A 9-point score was used to appraise adherence to the Mediterranean diet. Incident clinical events were confirmed by a review of medical records. We observed 100 incident cases of CVD. In multivariate analyses, participants with the highest adherence to the Mediterranean diet (score>6) exhibited a lower cardiovascular risk (hazard ratio=0.41, 95% confidence interval [CI]: 0.18–0.95) compared to those with the lowest score (<3). For each 2-point increment in the score, the adjusted hazard ratios were 0.80 (95% CI: 0.62–1.02) for total CVD and 0.74 (0.55–0.99) for coronary heart disease.Conclusions: There is an inverse association between adherence to the Mediterranean diet and the incidence of fatal and non-fatal CVD in initially healthy middle-aged adults.

Distinct signalling mechanisms are involved in the dissimilar myocardial and coronary effects elicited by quercetin and myricetin, two red wine flavonols - Corrected Proof

2010-01-22

Abstract: Background and Aims: Moderate red wine consumption associates with lower incidence of cardiovascular diseases. Attention to the source of this cardioprotection was focused on flavonoids, the non-alcoholic component of the red wine, whose intake inversely correlates with adverse cardiovascular events.We analysed whether two red wine flavonoids, quercetin and myricetin, affect mammalian basal myocardial and coronary function.Methods and results: Quercetin and myricetin effects were evaluated on isolated and Langendorff perfused rat hearts under both basal conditions and α- and β-adrenergic stimulation. The intracellular signalling involved in the effects of these flavonoids was analysed on perfused hearts and by western blotting on cardiac and HUVEC extracts. Quercetin induced biphasic inotropic and lusitropic effects, positive at lower concentrations and negative at higher concentrations. Contrarily, Myricetin elicits coronary dilation, without affecting contractility and relaxation. Simultaneous administration of the two flavonoids only induced vasodilation. Quercetin-elicited positive inotropism and lusitropism depend on β1/β2-adrenergic receptors and associate with increased intracellular cAMP, while the negative inotropism and lusitropism observed at higher concentrations were α-adrenergic-dependent. NOS inhibition abolished Myricetin-elicited vasodilation, also inducing Akt, ERK1/2 and eNOS phosphorylation in both ventricles and HUVEC. Myricetin-dependent vasodilation increases intracellular cGMP and is abolished by triton X-100.Conclusions: The cardiomodulation elicited on basal mechanical performance by quercetin and the selective vasodilation induced by myricetin point to these flavonoids as potent cardioactive principles, able to protect the heart in the presence of cardiovascular diseases.

Insulin-mimetic action of conglutin-γ, a lupin seed protein, in mouse myoblasts - Corrected Proof

2010-01-21

Abstract: Background and aims: Lupin seed is referred to as an antidiabetic product in traditional medicine. Conglutin-γ, a lupin seed glycoprotein, was found to cause a significant plasma glucose reduction when orally administered to rats in glucose overload trials. Conglutin-γ was identified as being responsible for the claimed biological activity, and the aim of this work was to envisage its hypothetical insulin-mimetic cellular mechanism of action. Insulin is responsible for proteosynthesis control through IRS/AKT/P70S6k/PHAS1 pathways modulation, glucose homeostasis through PKC/Flotillin-2/caveolin-3/Cbl activation and muscle differentiation/hypertrophy via muscle-specific MHC gene transcription control.Methods and results: To assess whether conglutin-γ modulates the same insulin-activated kinases, myoblastic C2C12 cells were incubated after 72h of differentiation with 100nM insulin or 0.5mg/mL (∼10μM) conglutin-γ. Metformin-stimulated cells were used as a positive control. The effect on the above mentioned pathways was evaluated after 5, 10, 20 and 30min. In the control cells medium insulin, conglutin-γ and metformin were not added. We demonstrated that insulin or conglutin-γ cell stimulation resulted in the persistent activation of protein synthetic pathway kinases and increased glucose transport, glut4 translocation and muscle-specific gene transcription regulation.Conclusions: Our results indicate that conglutin-γ may regulate muscle energy metabolism, protein synthesis and MHC gene transcription through the modulation of the same insulin signalling pathway, suggesting the potential therapeutic use of this natural legume protein in the treatment of diabetes and other insulin-resistant conditions, as well as the potential conglutin-γ influence on muscle cells differentiation and regulation of muscle growth.

Metabolic syndrome in children with Prader–Willi syndrome: the effect of obesity - Corrected Proof

2010-01-20

Abstract: Background and aims: Prader–Willi syndrome (PWS), the most frequent syndromic obesity, is associated with elevated morbidity and mortality in pediatric and adult ages. In PWS, the presence of metabolic syndrome (MS) has not yet been established. The aim of the study was to estimate the frequency of MS and its components in pediatric subjects according to obesity status.Methods and results: A cross-sectional study was performed in 109 PWS children aged 2–18years (50 obese and 59 non-obese) and in 96 simple obese controls matched for age, gender, and also for BMI with obese PWS. Obesity was defined when SDS-BMI was >2.Non-obese PWS showed significantly lower frequency of hypertension (12%) than obese PWS (32%) and obese controls (35%)(p=0.003). The same was observed for low HDL-cholesterol (3% vs 18% and 24%, p=0.001) and high triglycerides (7% vs 23% and 16%, p=0.026). Frequency of altered glucose metabolism was not different among groups (2% vs 10% and 5%), but type 2 diabetes (four cases) was present only in obese PWS. Non-obese PWS showed lower insulin and HOMA-index respect to obese PWS and obese controls (p≤0.017). Overall MS frequency in PWS was 7.3%. None of the non-obese PWS showed MS compared with 16% of obese PWS and controls (p<0.001). When obesity was excluded from the analysis, a significantly lower frequency for clustering of ≥2 factors was still found in non-obese PWS (p=0.035).Conclusion: Non-obese PWS showed low frequency of MS and its components, while that observed in obese PWS was very close to those of obese controls, suggesting the crucial role of obesity status. Prevention of obesity onset remains the most important goal of PWS treatment. Early identification of MS could be helpful to improve morbidity and mortality in such patients.

Coronary vasoreactivity is not altered in young people with type 1 diabetes - Corrected Proof

2010-01-18

Abstract: Background and aim: : Abnormal coronary microvascular circulation has been demonstrated in diabetes and is associated with increased rate of cardiovascular events. Our objective was to evaluate coronary vasoreactivity in young people with type 1 diabetes with and without microvascular complications.Methods and results: Twenty-five type 1 diabetic patients without microvascular complications (DC–), 23 with microvascular complications (DC+), and 18 control subjects (C) were studied. Coronary vasoreactivity was assessed by means of coronary flow reserve (CFR). Blood flow velocity in the left anterior descending coronary artery was measured at rest and after high-dose dipyridamole using transthoracic color-guided pulsed Doppler echocardiography. CFR was defined as the ratio of hyperaemic to resting diastolic peak flow velocities.The three groups had similar cardiac function parameters, and also systolic and diastolic blood pressure at rest, which remained unchanged during dipyridamole infusion. Resting coronary flow velocity was comparable in C, DC–, and DC+ (p=ns). Dipyridamole infusion produced a threefold increase in coronary diastolic peak velocity, which reached similar values in C (0.69±0.16m/s), DC– (0.69±0.18m/s), and DC+ (0.66±0.11m/s). Mean CFR ratio was similar in C (3.33±0.66), DC– (3.30±0.51), and DC+ (3.24±0.60). At multiple linear regression analysis, no association was found between CFR and age, sex, HbA1c, duration of diabetes, and complications.Conclusion: Coronary vasodilatory function is preserved in young D patients, even those with early microvascular complications, suggesting that coronary vasoreactivity deteriorates at more advanced stages of microvascular complications and/or in the presence of other cardiovascular risk factors.

Effects of one serving of mixed nuts on serum lipids, insulin resistance and inflammatory markers in patients with the metabolic syndrome - Corrected Proof

2009-12-23

Abstract: Background and aims: Knowledge of the effect of nut consumption on metabolic syndrome (MetS) components is limited. We assessed the effects of nut intake on adiposity, serum lipids, insulin resistance, and inflammatory biomarkers in patients with MetS.Methods and results: In a randomized, parallel-group, 12-week feeding trial, 50 patients with MetS were given recommendations for a healthy diet with or without supplementation with 30g/day of raw nuts (15g walnuts, 7.5g almonds and 7.5g hazelnuts) (Nut and Control diet groups, respectively). Adiposity measures, serum lipids, insulin, Homeostasis Model Assessment (HOMA), interleukin-6 (IL-6) and other inflammatory biomarkers, and 48-h fecal fat were determined basally and at study's completion. Moderate weight loss, decreased adiposity, and lower blood pressure occurred similarly after both diets. The Control, but not the Nut diet, was associated with significant (P<0.05) reduction of LDL-cholesterol, with mean changes of −0.36 versus −0.13mmol/L, respectively (between-group differences, P=0.154). The Nut diet reduced fasting insulin by 2.60μU/mL (95% CI, −4.62 to −0.59) and HOMA-insulin resistance by 0.72 (−1.28 to −0.16) (P<0.05 versus Control diet; both). Among inflammatory markers, the Nut diet resulted in changes of median plasma IL-6 of −1.1ng/L (−2.7 to −0.1; P=0.035 versus Control diet), but adjustment for weight loss attenuated the significance of the association. Stool fat decreased with the Control diet and slightly increased with the Nut diet (P<0.05 for between-group differences).Conclusion: Patients with MetS show decreased lipid responsiveness but improved insulin sensitivity after daily intake of 30g of mixed nuts.

Metabolic toxicity of the heart: Insights from molecular imaging - Corrected Proof

P. Iozzo — 2009-12-23

Abstract: There is convincing evidence that alterations in myocardial substrate use play an important role in the normal and diseased heart. In this review, insights gained by using quantitative molecular imaging by positron emission tomography and magnetic resonance spectroscopy in the study of human myocardial metabolism will be discussed, and attention will be paid to the effects of nutrition, gender, aging, obesity, diabetes, cardiac hypertrophy, ischemia, and heart failure.The heart is an omnivore organ, relying on metabolic flexibility, which is compromised by the occurrence of defects in coronary flow reserve, insulin-mediated glucose disposal, and metabolic-mechanical coupling. Obesity, diabetes, and ischemic cardiomyopathy appear as states of high uptake and oxidation of fatty acids, that compromise the ability to utilize glucose under stimulated conditions, and lead to misuse of energy and oxygen, disturbing mechanical efficiency. Idiopathic heart failure is a complex disease frequently coexisting with diabetes, insulin resistance and hypertension, in which the end stage of metabolic toxicity manifests as severe mitochondrial disturbance, inability to utilize fatty acids, and ATP depletion.The current literature provides evidence that the primary events in the metabolic cascade outlined may originate in extra-cardiac organs, since fatty acid, glucose levels, and insulin action are mostly controlled by adipose tissue, skeletal muscle and liver, and that a broader vision of organ cross-talk may further our understanding of the primary and the adaptive events involved in metabolic heart toxicity.

Relative contribution of individual oxidized components in ox-LDL to inhibition on endothelium-dependent relaxation in rat aorta - Corrected Proof

W.T. Wong, C.H. Ng, S.Y. Tsang, Y. Huang, Z-Y. Chen — 2009-12-14

Abstract: Background and Aim: Oxidized low-density lipoprotein (ox-LDL) causes atherosclerosis and endothelial dysfunction. No study up to the present date has examined the relative contribution of all the oxidized components in ox-LDL to inhibition on vascular function. Our aim was to investigate the effects of individual oxidized components at concentrations similar to those in ox-LDL on the impairment of endothelium-dependent relaxation in rat aorta.Methods and Results: Rat thoracic aorta was pre-treated with lysophosphatidylcholine (LPC), cholesterol oxidized products (COPs), oxidized linoleic acid (ox-18:2) and oxidized linolenic acid (ox-18:3) at concentrations similar to those in human ox-LDL. Ox-LDL as a whole caused 61% inhibition while LPC, COPs and ox-18:2 at concentrations similar to those in ox-LDL caused 12%, 24% and 19% inhibition, respectively, on endothelium-dependent relaxation, suggesting that COPs produced the most adverse effect followed by ox-18:2 and LPC in an additional way. Three COPs including 7-ketocholesterol, 7α-hydroxycholesterol and 7β-hydroxycholesterol showed inhibition on endothelium-dependent relaxation with Emax being reduced to 79–87% compared with the control Emax (95%). At Western blot analysis phosphorylation of eNOS at Ser1177 site and total eNOS were not altered by ox-LDL treatment, indicating that ox-LDL did not affect nitric oxide (NO) synthesis capacity. Ox-LDL might react directly with NO and lower NO bioavailability.Conclusion: The present study demonstrated the relative contribution of individual oxidized components in ox-LDL in the inhibition of endothelium-dependent relaxation in rat aorta. This inhibitory effect could be caused by the reduction of NO bioactivity.

Physical inactivity and chronic kidney disease in Australian adults: The AusDiab study - Corrected Proof

2009-11-27

Abstract: Background and Aims: Physical inactivity is associated with cardiovascular risk however its relationship to chronic kidney disease is largely unknown. We examined the association between leisure-time physical activity and risk of chronic kidney disease in a prospective, population-based cohort of Australians aged ≥25 years (AusDiab).Methods and Results: The baseline sample included 10,966 adults (4951 males and 6015 females). From this sample, 6318 participants with complete baseline and 5-year follow-up urinalysis and serum creatinine measurements formed the study population for longitudinal analysis. Self-reported leisure-time physical activity was measured using a validated, interviewer–administered questionnaire. Compared with sufficiently active individuals (≥150min physical activity per week), those who were inactive (0min/week) were more likely to have albuminuria at baseline (multivariate-adjusted OR=1.34, 95% CI 1.10–1.63). Inactivity (versus sufficient physical activity) was associated with increased age- and sex-adjusted odds of an estimated glomerular filtration rate <3rd percentile (OR=1.30, 95% CI 1.02–1.65), although this was not significant after multivariate adjustment (OR=1.17, 95% CI 0.91–1.50). Obese, inactive individuals were significantly more likely to have albuminuria at baseline (multivariate-adjusted OR=1.74, 95% CI 1.35–2.25), compared with sufficiently active, non-obese individuals. Baseline physical activity status was not significantly associated with longitudinal outcomes.Conclusions: Physical inactivity is cross-sectionally associated with albuminuria prevalence, particularly when combined with obesity. Future studies are needed to determine whether this association is causal and the importance of physical activity in CKD prevention.

Non-soy legume consumption lowers cholesterol levels: A meta-analysis of randomized controlled trials - Corrected Proof

L.A. Bazzano, A.M. Thompson, M.T. Tees, C.H. Nguyen, D.M. Winham — 2009-11-27

Abstract: Background and Aims: Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids.Methods and Results: Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was −11.8mg/dL (95% confidence interval [CI], −16.1 to −7.5); mean net change in low-density lipoprotein cholesterol was −8.0mg/dL (95% CI, −11.4 to −4.6).Conclusion: These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.

Perspectives of nuclear diagnostic imaging in diabetic cardiomyopathy - Corrected Proof

2009-11-27

Abstract: Diabetic cardiomyopathy is a ventricular dysfunction in the absence of coronary artery disease, valvular or hypertensive heart disease. The mechanisms underlying diabetic cardiomyopathy may involve metabolic disturbances, myocardial fibrosis, small vessel disease, microcirculation abnormalities, cardiac autonomic neuropathy and insulin resistance.Diagnostic problems emerge because no specific disease pattern characterizes the disease and because there may be coexistence in diabetes of coronary artery disease and hypertension as independent but compounding causes of biochemical, anatomical and functional alterations impairing cardiac function.In this paper we will review the role of nuclear imaging today, concentrating on the diagnostic capabilities of radionuclide ventriculography, to study the effect of insulin resistance and, more extensively, gated-single photon emission computed tomography with Tc-99m labelled agents.A broad analysis will be dedicated to: 1) positron emission tomography using perfusion agents, with the potential to quantify resting and stress blood flow and coronary flow reserve; 2) radionuclide procedures evaluating aerobic and anaerobic cardiac metabolism; and 3) cardiac neurotransmission imaging, studying the autonomic neuropathy.

Implications of prevalent and incident diabetes mellitus on left ventricular geometry and function in the ageing heart: The MONICA/KORA Augsburg cohort study - Corrected Proof

2009-11-27

Abstract: Background and Aim: It is unclear to what extent diabetes modulates the ageing-related adaptations of cardiac geometry and function.Methods and Results: We examined 1005 adults, aged 25–74 years, from a population-based survey at baseline in 1994/5 and at follow-up in 2004/5. We compared persistently non-diabetic individuals (ND; no diabetes at baseline and at follow-up, n=833) with incident (ID; non-diabetic at baseline and diabetic at follow-up, n=36) and with prevalent diabetics (PD; diabetes at baseline and follow-up examination, n=21). Left ventricular (LV) geometry and function were evaluated by echocardiography. Statistical analyses were performed with multivariate linear regression models.Over ten years the PD group displayed a significantly stronger relative increase of LV mass (+9.34% vs. +23.7%) that was mediated by a more pronounced increase of LV end-diastolic diameter (+0% vs. +6.95%) compared to the ND group. In parallel, LA diameter increased (+4.50% vs. +12.7%), whereas ejection fraction decreased (+3.02% vs. −4.92%) more significantly in the PD group. Moreover, at the follow-up examination the PD and ID groups showed a significantly worse diastolic function, indicated by a higher E/EM ratio compared with the ND group (11.6 and 11.8 vs. 9.79, respectively).Conclusions: Long-standing diabetes was associated with an acceleration of age-related changes of left ventricular geometry accumulating in an eccentric remodelling of the left ventricle. Likewise, echocardiographic measures of systolic and diastolic ventricular function deteriorated more rapidly in individuals with diabetes.

Prevalence of blood lipid disturbances in Swedish and foreign-born 60-year-old men and women in Stockholm, Sweden - Corrected Proof

P.E. Wändell, A.C. Carlsson, U. de Faire, M-L. Hellénius — 2009-11-27

Abstract: Background and aims: Some immigrant groups in Sweden show a higher incidence of cardiovascular diseases, especially coronary heart disease. There is a lack of data of pattern of blood lipids among these. The aim of this study was to estimate the prevalence of dyslipidaemia in men and women of foreign-born origin compared to Swedish-born.Methods and results: A cross-sectional study of a random sample of the population in Stockholm County, Sweden, with total of 4228 60-year-old men and women. Medical, lifestyle and socio-economic data were collected by questionnaires, and anthropometric and laboratory data through medical examination. Outcomes were odds ratios (OR) with 95% confidence interval (95% CI) for dyslipidaemia in different groups, with Swedish-born as reference group, with adjustment for anthropometric, medical, lifestyle and socio-economic factors.Among non-European immigrants, the fully adjusted OR of high cholesterol was 0.57 (95% CI 0.37–0.88), of high LDL-cholesterol was 0.62 (95% CI 0.40–0.96), and of low HDL-cholesterol was 2.06 (95% CI 1.35–3.15). When only adjusting for sex, Finnish-born and non-European immigrants showed higher risk of high triglycerides, OR 1.31 (95% CI 1.01–1.71) and OR 1.98 (95% CI 1.34–2.93), respectively, and of high apoB/apoA-I ratio, OR 1.29 (95% CI 1.00–1.66) and OR 1.57 (95% CI 1.06–2.33), respectively.Conclusion: The finding of blood lipid disturbances among immigrants in this study partly explain the higher cardiovascular morbidity shown in previous studies. Non-European immigrants showed a different lipid pattern, with lower HDL-cholesterol, which could possibly be of genetic background.

Daily consumption of milk enriched with fish oil, oleic acid, minerals and vitamins reduces cell adhesion molecules in healthy children - Corrected Proof

2009-11-26

Abstract: Background and aims: Several studies have suggested that polyunsaturated fatty acids, vitamins and minerals have beneficial effects on lipid profile and systemic inflammation in adults.Methods and results: We examined the effects of a daily intake of milk enriched with long-chain polyunsaturated fatty acids, oleic acid, carbohydrates, vitamins, minerals and low in saturated fatty acids (SFAs) for 5 months, on several cardiovascular (CVD) risk biomarkers in healthy children aged 8–14 years. In a randomized double-blind placebo-controlled trial, a total of 107 children of both genders were assigned to two study groups: 1) a supplemented group (SG, n=53) who consumed 0.6L/day of an enriched dairy product, and 2) a control group (CG, n=54) who consumed 0.6L/day of standard whole milk. Both groups consumed the dairy drinks for 5 months, in addition to their usual diet. Serum levels of adhesion molecules as indices of vascular endothelial cell activation were assessed in both groups at 0 and 5 months as well as white blood cell counts, lipid profile, serum proteins, total serum calcium, 25-OH vitamin D, glucose, insulin and adiponectin. In the enriched dairy drink supplemented group, adhesion molecules E-selectin and ICAM-1 as well as lymphocyte levels decreased while plasma docosahexaenoic acid (DHA) and serum calcium concentrations increased. In the control group, serum total protein, transferrin, total cholesterol, HDL-cholesterol and adiponectin concentrations decreased.Conclusion: The consumption of a milk enriched with fish oil, oleic acid, minerals and vitamins reduced indices of endothelial cell activation in the studied group of healthy children.

Influence of body mass index on extent of coronary atherosclerosis and cardiac events in a cohort of patients at risk of coronary artery disease - Corrected Proof

2009-11-26

Abstract: Background and Aim: To estimate if a meaningful relationship exists between body mass index (BMI) and the entity of coronary atherosclerosis, coronary events and mortality in a cohort of consecutive patients with suspected coronary artery disease (CAD).Methods and results: In this prospective study, we enrolled 1299 consecutive patients (905 [69.7%] males) who had undergone coronary angiography. Our sample consisted of 477 patients (36.8%) of normal weight; 567 (43.6%) overweight and 255 (19.6%) obese, according to the WHO classification. Conventional cardiovascular risk factors, BMI, endothelial function and subclinical inflammation were studied. Different angiographic CAD scores were used to quantify coronary atherosclerotic burden. In overweight and obese patients, respect to normal weight population, there is a higher prevalence of hypertension, hypercholesterolemia and diabetes mellitus, but BMI was not significantly associated with greater extent of coronary atherosclerosis. At follow-up (mean: 40; range: 24–82 months) obese and overweight patients showed a higher incidence of coronary events compared to the normal weight population (74.9% [obese] versus 62.7% [overweight] versus 53.2% [normal weight]; adjusted relative risk [obese versus overweight]: 1.08 [95% confidence interval: 1.02–1.23]; P<0.05; and adjusted RR [obese versus normal weight]: 1.17 [95% CI: 1.10–1.42], P<0.01). Mortality from cardiac events was not significant within the categories. The Cox regression model showed flow mediated dilation (P<0.0001), high-sensitive C reactive protein (P=0.022) and BMI (P=0.045) as independent predictors of acute coronary events.Conclusion: BMI is not associated with the extent of coronary atherosclerosis and mortality. The higher incidence of coronary events in obese subjects is only partly explained by conventional associated risk factors. Impaired endothelial function and sub-clinical inflammation could be involved in this association but BMI itself is related to cardiovascular events suggesting that other unknown (or not considered) pathways are involved.

Effect of a plant stanol ester-containing spread, placebo spread, or Mediterranean diet on estimated cardiovascular risk and lipid, inflammatory and haemostatic factors - Corrected Proof

2009-11-26

Abstract: Background and aims: Mediterranean diet is associated with a reduced risk for cardiovascular disease (CVD). Use of plant stanols decreases low density lipoprotein cholesterol (LDL-C) concentrations. We compared the effects of the Mediterranean diet and plant stanol esters on vascular risk factors and estimated CVD (eCVD) risk.Methods and results: In this prospective, randomized, placebo-controlled study, 150 mildly hypercholesterolaemic subjects were randomized to Mediterranean diet, a spread containing plant stanol esters (2g/day) or a placebo spread. Vascular risk factors were assessed every month for 4 months and the eCVD risk was calculated using the PROspective- Cardiovascular-Munster (PROCAM), Framingham, and Reynolds risk engines. Placebo had no significant effect on risk factors or eCVD risk. Mediterranean diet gradually induced a significant reduction in total cholesterol (TC), LDL-C, triglycerides, high sensitivity C-reactive protein (hsCRP), blood pressure and eCVD risk (24–32%). The plant stanol ester spread reduced (by 1 month) TC (−14%), LDL-C (−16%), hsCRP (−17%), and estimated CVD risk (26–30%). eCVD risk reduction was sustained at 4th months when the gradual Mediterranean diet eCVD risk reduction became comparable to that of the stanol group.Conclusions: Plant stanol esters yielded an early, by 1st treatment month, reduction of eCVD risk that resulted from a TC, LDL-C, and hsCRP decrease. eCVD risk reduction on the Mediterranean diet resulted from a change in several CVD risk factors and equaled that of plant stanol at 4 months. The consumption of plant stanol esters by moderately hypercholesterolaemic patients may be a useful option to reduce CVD risk in those who do not adopt a Mediterranean diet.

Distribution of HDL–cholesterol and non-HDL–cholesterol in Brazilian children and adolescents – The Floripa study - Corrected Proof

I. Giuliano, S Freitas, M Coutinho, J Zunino, B Caramelli, G Berenson — 2009-10-26

Abstract: Background and aims: HDL–cholesterol (HDL–C) and non-HDL–cholesterol (nHDL–C) are involved in atherosclerosis. The aim of this study was to determine the distribution of HDL–C and nHDL–C and its association with cardiovascular and socio-cultural variables in a pediatric Brazilian sample.Methods and results: Children and adolescents from Florianopolis were randomly selected and a structured questionnaire was administered, a physical examination was performed and a blood sample was collected. Enzymatic and Direct methods in vitro were used to determine the total cholesterol and HDL–cholesterol levels. The associations among HDL–C and nHDL–C and the described variables were tested by odds ratio and logistic regression. A total of 1009 individuals were examined. Based on the Brazilian criteria, 23% were classified with low levels of HDL–C and 25% with high levels of non-HDL–C. After multivariate analysis there were significant associations among low HDL–C and high C-reactive protein (OR, 3.3; 95% CI, 2.1–5.2), paternal tobacco use (OR, 1.5; 95% CI,1.1–2.1), and high triceps-to-subscapular index (OR, 1.5; 95% CI, 1.1–2.2). There were also significant associations among high nHDL–C and high waist circumference (OR, 1.95; 95% CI, 1.16–3.29), black skin color (OR, 1.78; 95% CI, 1.06–3.06), and high income (OR, 1.48; 95% CI, 1.09–2.02).Conclusions: In this sample, low levels of HDL–C were associated with other clinical variables such as a centripetal fat pattern and C-reactive protein, and n-HDL–C was associated with abdominal obesity, skin color and economic class.

Associations of plasma homocysteine level with brachial-ankle pulse wave velocity, LDL atherogenicity, and inflammation profile in healthy men - Corrected Proof

2009-10-26

Abstract: Aims: To investigate the association of plasma total homocysteine (tHcy) with arterial stiffness, measured as brachial-ankle pulse wave velocity (baPWV), LDL atherogenicity, and inflammation profile in healthy men.Methods and Results: In this cross-sectional study, 612 healthy men aged 31–79 years were classified into quartiles according to plasma tHcy concentration. In the total study population, tHcy concentration showed positive correlation with age (r=0.083, P=0.040), interleukin (IL)-1β (r=0.249, P<0.001), TNF-α (r=0.150, P<0.001), IL-6 (r=0.154, P<0.001), oxidized LDL (oxLDL) (r=0.161, P=<0.001), and baPWV (r=0.087, P=0.032); and negative correlation with folate (r=−0.353, P<0.001) and vitamin B12 (r=−0.269, P<0.001). In subgroup analysis based on plasma tHcy level, tHcy was associated with baPWV in men with high levels of tHcy (≥13.1μmol/L, n=153; r=0.258, P=0.001), but not in those with low-tHcy (<13.1μmol/L, n=459; r=−0.033, P=0.478). The association between tHcy and baPWV in the high-tHcy group remained significant after adjustment for age, BMI, smoking, drinking, folate, and vitamin B12. In the high-tHcy group, tHcy level was also positively correlated with IL-1β, TNF-α, oxLDL, and blood pressure; and negatively correlated with LDL particle size. In addition, baPWV showed negative correlation with LDL particle size and positive correlation with oxLDL in the high-tHcy group.Conclusion: This study shows an association between high levels of plasma tHcy and more advanced arterial stiffness, smaller LDL particle size, and higher levels of oxLDL and cytokines in men with hyperhomocysteinemia. Enhanced arterial stiffness in hyperhomocysteinemia might be attributed, in part, to Hcy-related LDL atherogenicity.

Vitamin D deficiency in the spontaneously hypertensive heart failure [SHHF] prone rat - Corrected Proof

R. Przybylski, S. Mccune, B. Hollis, R.U. Simpson — 2009-10-16

Abstract: Background and aims: Vitamin D deficiency has been associated with the etiology and pathogenesis of heart disease including congestive heart failure. We previously observed cardiac hypertrophy in vitamin D deficient rats and vitamin D receptor knockout mice. These studies indicate that the absence of vitamin D-mediated signal transduction and genomic activation results in increased sensitivity of the heart to ionotropic stimuli and cardiomyocyte hypertrophy. This study's aim is to investigate the relationship between vitamin D status and the heart failure phenotype in the rat.Methods and results: Vitamin D status was assessed by measuring 25-hydroxyvitamin D levels and related to heart weight in young, middle-aged and aging spontaneously hypertensive, heart failure (SHHF) prone rats. We also measured the effects of the vitamin D hormone,1,25(OH)2D3, on cardiac function in SHHF rats. Cardiac hypertrophy in this model of the failing heart increased with age and related to decreasing vitamin D status. Vitamin D deficiency presented after cardiac hypertrophy was first observed. Additionally, we found that 1,25(OH)2D3 treatment between 4.0 and 7.0 months of age prevented cardiac hypertrophy and permits decreased workload for the heart while allowing adequate blood perfusion and pressure, resulting in reduced cardiac index.Conclusions: Our findings suggest that low vitamin D status is associated with the progression and final terminal phase of the heart failure phenotype and not with initial heart hypertrophy. Also, we report that in the vitamin D sufficient SHHF rat, 1,25(OH)2D3 treatment provided protection against the progression of the heart failure phenotype.

Glycemic index, glycemic load, and the risk of acute myocardial infarction in Finnish men: The Kuopio Ischaemic Heart Disease Risk Factor Study - Corrected Proof

2009-10-16

Abstract: Background and aim: The role of dietary glycemic index (GI) and glycemic load (GL) in coronary heart disease (CHD) is unclear. Our aim was to study the association between the dietary GI and GL and the risk of acute myocardial infarction (AMI).Methods and results: The study population consisted of 1981 Finnish men from the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study, aged 42–60 years and free of CHD at baseline. During an average follow-up time of 16.1 years, 376 new AMI events occurred. In multivariable-adjusted Cox proportional hazards models, the relative risk (RR) for AMI in the highest quartile of GI was 1.25 (95% CI: 0.92–1.69; P for trend=0.08) and for GL 1.11 (95% CI: 0.79–1.57; P for trend=0.21) when compared with the lowest quartile. For overweight (BMI≥27.5kg/m2) men, the multivariable-adjusted RR for AMI in the highest compared to the lowest tertile of GI and GL were 1.58 (95% CI: 1.03–2.43; P for trend=0.04, P for interaction=0.01) and 2.05 (95% CI: 1.30–3.23; P for trend=0.002, P for interaction=0.002), respectively. For physically less active men; energy expenditure for leisure-time physical activity <50kcal/d, the RR for AMI was 1.72 (95% CI: 1.07–2.76; P for trend=0.04, P for interaction 0.80) with higher GL.Conclusions: Our results suggest that both high dietary GI and GL are associated with increased risk of AMI among overweight and GL possibly among less physically active men.

The effect of breakfasts varying in glycemic index and glycemic load on dietary induced thermogenesis and respiratory quotient - Corrected Proof

2009-10-16

Abstract: Background and aim: Glycemic index (GI) and Glycemic Load (GL) are parameters of carbohydrate bioavailability able to influence risk of chronic diseases. GL can be lowered either by reducing carbohydrate intake or by reducing the GI of the carbohydrate moiety of a mixed meal. These two approaches might have a different impact on Dietary-Induced Thermogenesis (DIT) and preferential substrate oxidation in the postprandial period, which are variables known to be involved in the regulation of body weight and body composition. This dietary, crossover intervention trial was designed to evaluate the effect on DIT and Respiratory Quotient (RQ) of three isocaloric breakfasts different in GI and/or GL (high GI and high GL [HGI–HGL] vs. low GI and low GL [LGI–LGL]; vs. high GI and low GL [HGI–LGL]) followed by a standard meal.Methods and results: RQ and DIT were measured in 16 lean young males by indirect calorimetry for 8h. DIT resulted significantly higher after the LGI–LGL compared to the HGI–HGL breakfast (p<0.05). Postprandial changes in RQ differed among all breakfasts (p<0.001). RQ increased from baseline after the two breakfasts with highest carbohydrate content and significantly more after the HGI–HGL than after the LGI–LGL (p<0.02), whereas it decreased after the HGI–LGL breakfast, which contained a higher amount of fat.Conclusions: Reducing the GL of a meal by reducing GI seems an effective strategy to increase energy expenditure while maintaining a good rate of lipid oxidation. This might be related to different profiles of postprandial hormones affecting substrate oxidation.

Carotid artery atherosclerosis in hypertensive patients with a functional LDL receptor-related protein 6 gene variant - Corrected Proof

2009-10-15

Abstract: Background and aims: Rare (611C) and common (1062V) variants of the Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) display reduced activation of Wnt/ß-catenin signaling. The rare gene variant was associated with hypertension, metabolic abnormalities, and early coronary artery disease. We investigated whether the common 1062V LRP6 variant was related to carotid artery atherosclerosis (CAA) in hypertensive patients.Methods and results: Retrospective study of 334 hypertensive patients (<65 years old) who underwent carotid artery ultrasonography. Hypertension, type 2 diabetes, dyslipidemia, glomerular filtration rate, and smoking habit were evaluated. CAA was defined by the presence of atherosclerotic plaques (focal intima–media thickness ≥1.3mm). Logistic regression models were used to estimate the independent effect of 1062V allele. The relationship between LRP6 genotypes and LRP6 gene expression in carotid plaques was also investigated. No difference was observed between genotypes in clinical variables except for a slightly higher fasting glucose in 1062V carriers. The 1062V LRP6 variant was an independent risk factor for CAA in both unadjusted (OR 2.08, 95%CI 1.27–3.41, p=0.003) and adjusted models (OR 1.92, 95%CI 1.09–3.39, p=0.02). LRP6 was expressed in carotid atherosclerotic plaques at significantly lower levels (p=0.015) in 1062V carriers.Conclusion: Beside the role of established risk factors, 1062V variant of LRP6 and CAA are strongly associated in hypertensive patients, making LRP6 a novel relevant candidate gene for atherosclerosis in the presence of hypertension.

Association of Taq 1B CETP polymorphism with insulin and HOMA levels in the population of the Canary Islands - Corrected Proof

2009-10-12

Abstract: Background and aims: Cholesteryl ester transfer protein (CETP) is an enzyme with a key role in lipoprotein metabolism. A common genetic polymorphism, the Taq 1B, influences CETP activity and HDL-cholesterol levels, with individual homozygotes for the B1 allele exhibiting higher enzyme activity and lower HDL-cholesterol levels than carriers of at least one B2 allele. Our aim was to analyze the influence of Taq 1B CETP polymorphism on cardiovascular risk factors in a representative sample of adult subjects from Canary population.Methods and result: A total of 518 adult subjects from the Canary Islands, enrolled in a nutritional survey (the ENCA study), were included. The Taq 1B polymorphism was analyzed by PCR–RFLP. Compared with individuals with at least one B2 allele, and after adjusting for age, sex, BMI, waist perimeter, smoking and alcohol intake, carriers of the B1B1 genotype showed lower HDL-cholesterol levels (geometric mean (95% CI): 46.6 (44.5–48.8) vs. 50.6 (49.1–52.9)mg/dl; P=0.003); and higher insulin (geometric mean (95% CI): 11.1 (10.5–11.9) vs. 10.0 (9.5–10.5μU/ml; P=0.008) and HOMA levels (geometric mean (95% CI): 2.3 (2.1–2.5) vs. 2.1 (1.9–2.1); P=0.009). In addition, the B1B1 genotype was more frequent in individuals who had low levels of HDL-cholesterol according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria (Odds Ratio (OR): 1.563; 95% CI: 1.04–2.34; P=0.030), and in those included in the upper quartile of insulinemia (OR: 1.90; 95% CI: 1.20–3.03; P=0.007) and HOMA (OR: 1.61; 95% CI: 1.02–2.57; P=0.043).Conclusion: The observed influence of Taq 1B polymorphism on insulin levels and HOMA highlights the possible role of CETP in the regulation of glucose homeostasis.

Cyclosporine A administered during reperfusion fails to restore cardioprotection in prediabetic Zucker obese rats in vivo - Corrected Proof

R. Huhn, A. Heinen, M.W. Hollmann, W. Schlack, B. Preckel, N.C. Weber — 2009-10-12

Abstract: Background and aims: Hyperglycaemia blocks sevoflurane-induced postconditioning, and cardioprotection in hyperglycaemic myocardium can be restored by inhibition of the mitochondrial permeability transition pore (mPTP). We investigated whether sevoflurane-induced postconditioning is also blocked in the prediabetic heart and if so, whether cardioprotection could be restored by inhibiting mPTP.Methods and results: Zucker lean (ZL) and Zucker obese (ZO) rats were assigned to one of seven groups. Animals underwent 25min of ischaemia and 120min of reperfusion. Control (ZL-/ZO Con) animals were not further treated. postconditioning groups (ZL-/ZO Sevo-post) received sevoflurane for 5min starting 1min prior to the onset of reperfusion. The mPTP inhibitor cyclosporine A (CsA) was administered intravenously in a concentration of 5 (ZO CsA and ZO CsA+Sevo-post) or 10mg/kg (ZO CsA10+Sevo-post) 5min before the onset of reperfusion. At the end of reperfusion, infarct sizes were measured by TTC staining. Blood samples were collected to measure plasma levels of insulin, cholesterol and triglycerides.Sevoflurane postconditioning reduced infarct size in ZL rats to 35±12% (p<0.05 vs. ZL Con: 60±6%). In ZO rats sevoflurane postconditioning was abolished (ZO Sevo-post: 59±12%, n.s. vs. ZO Con: 58±6%). 5mg and 10mg CsA could not restore cardioprotection (ZO CsA+Sevo-post: 59±7%, ZO CsA10+Sevo-post: 57±14%; n.s. vs. ZO Con). In ZO rats insulin, cholesterol and triglyceride levels were significant higher than in ZL rats (all p<0.05).Conclusion: Inhibition of mPTP with CsA failed to restore cardioprotection in the prediabetic but normoglycaemic heart of Zucker obese rats in vivo.

ADAM17_i33708A>G polymorphism interacts with dietary n-6 polyunsaturated fatty acids to modulate obesity risk in the Genetics of Lipid Lowering Drugs and Diet Network study - Corrected Proof

2009-10-12

Abstract: Background and aims: The disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes. Importantly, elevated levels of ADAM17 expression have been linked to obesity and insulin resistance. Therefore, the aim of this study was to evaluate the association of six ADAM17 single nucleotide polymorphisms (SNPs) (m1254A>G, i14121C>A, i33708A>G, i48827A>C, i53440C>T, and i62781G>T) with insulin-resistance phenotypes and obesity risk, and their potential interactions with dietary polyunsaturated fatty acids (PUFA).Methods and results: ADAM17 SNPs were genotyped in 936 subjects (448 men/488 women) who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Anthropometrical and biochemical measurements were determined by standard procedures. PUFA intake was estimated using a validated questionnaire. G allele carriers at the ADAM17_m1254A>G polymorphism exhibited significantly higher risk of obesity (P=0.003), were shorter (P=0.017), had higher insulin (P=0.016), and lower HDL-C concentrations (P=0.027) than AA subjects. For the ADAM17_i33708A>G SNP, homozygotes for the A allele displayed higher risk of obesity (P=0.001), were heavier (P=0.011), had higher BMI (P=0.005), and higher waist measurements (P=0.023) than GG subjects. A significant gene-diet interaction was found (P=0.030), in which the deleterious association of the i33708A allele with obesity was observed in subjects with low intakes from (n-6) PUFA (P<0.001), whereas no differences in obesity risk were seen among subjects with high (n-6) PUFA intake (P>0.5)Conclusion: These findings support that ADAM17 (m1254A>G and i33708A>G) SNPs may contribute to obesity risk. For the ADAM17_i33708A>G SNP, this risk may be further modulated by (n-6) PUFA intake.

Glycaemic fall after a glucose load. A population-based study - Corrected Proof

2009-10-12

Abstract: Background and aims: A blood glucose (BG) fall after an oral glucose load has never been described previously at a population level. This study was aimed at looking for a plasma glucose trend after an oral glucose load for possible blood glucose fall if any, and for its impact on coronary mortality at a population level.Methods and results: In subjects from an unselected general population, BG and insulin were detected before and 1 and 2h after a 75-g oral glucose load for insulin sensitivity and β-cell function determination. Blood pressure, blood examinations and left ventricular mass were measured, and mortality was monitored for 18.8±7.7 years. According to discriminant analysis, the population was stratified into cluster 0 (1-h BG

Platelet aggregability is modulated by eNOS locus in non-type 2 diabetic patients with acute coronary syndrome - Corrected Proof

2009-10-12

Abstract: Background and aim: Platelet nitric oxide (NO) synthesis is compromised in patients with acute coronary syndrome (ACS), and platelet NO availability may be critically relevant in determining the extent of thrombosis in ACS patients. It has been demonstrated that an impaired responsiveness to the antiaggregatory effects of NO may affect platelet dysfunction in diabetic patients with ACS. Since NO availability may be genetically determined, we have investigated the role of endothelial nitric oxide synthase (eNOS) gene in influencing platelet aggregability in relation to the presence (n=247) or absence (n=883) of type 2 diabetes in ACS patients.Methods and results: We have genotyped 1130 consecutive high risk ACS patients on dual antiplatelet therapy, previously investigated in relation to platelet function. eNOS 4a allele frequency was significantly higher in diabetic vs. non-diabetic patients (p=0.02). In non-diabetic patients the eNOS 4a allele significantly modulated platelet aggregability in response to arachidonic acid (AA), but not to collagen and adenosine diphosphate (ADP) stimulus, after Bonferroni correction for multiple testing. After adjustment for age, gender, smoking habit, hypertension and ejection fraction ≤40%, the eNOS 4a allele remained significantly and independently associated with platelet aggregability in response to AA stimulus [β (SE)=0.17 (0.07), p=0.01]. When platelet aggregation values were considered according to the presence or absence of high residual platelet reactivity (RPR) eNOS 4a, but not −786C and 894T, allele was significantly associated with RPR by AA stimulus. The haplotype reconstruction analysis for eNOS gene showed that the −786C/894G/4a and −786C/894G/4b haplotypes significantly influenced platelet aggregation after AA stimulus.Conclusions: Our study indicates that eNOS 4a allele, may be a determinant of higher platelet aggregability and residual platelet reactivity in non-diabetic ACS patients.

Folic acid is positively associated with uteroplacental vascular resistance: The Generation R Study - Corrected Proof

2009-10-12

Abstract: Background and aims: Periconception folic acid supplementation may influence early placentation processes and thereby the occurrence of hypertensive pregnancy disorders. For this reason we examined the associations between periconception folic acid supplementation and uteroplacental vascular resistance, blood pressure, and the risks of gestational hypertension and preeclampsia, in 5993 pregnant women, participating in a population-based cohort study.Methods and results: Folic acid supplementation was assessed by questionnaire. Mean pulsatility index (PI) and resistance index (RI) of the uterine (UtA) and umbilical arteries (UmA) were measured by Doppler ultrasound in mid- and late pregnancy. Systolic and diastolic blood pressures (SBP, DBP) were measured in early, mid- and late pregnancy. Compared to women who did not use folic acid, preconception folic acid users had a slightly lower UtA-RI in mid-pregnancy [β −0.02, 95% confidence interval (CI) −0.03, −0.01] and late pregnancy [β −0.02, 95% CI −0.03, −0.001], a lower UtA-PI in mid-pregnancy [β −0.06, 95% CI −0.1, −0.03] and late pregnancy [β −0.03, 95% CI −0.05, −0.01], as well as tendencies towards a lower UmA-PI in mid-pregnancy [β −0.02, 95% CI −0.04, −0.001] and late pregnancy [β −0.01, 95% CI −0.02, 0.01]. Additionally, these women had slightly higher SBP and DBP throughout pregnancy. Neither the patterns of blood-pressure change during pregnancy, nor the risk of gestational hypertension and preeclampsia differed between the folic acid categories.Conclusion: Periconception folic acid supplementation is associated with lower uteroplacental vascular resistance and higher blood pressures during pregnancy. The effects are small and within physiologic ranges and seem not associated with the risk of hypertensive pregnancy disorders.

Fasting and postprandial adiponectin alterations anticipate NEFA and TNF-α changes in prepubertal obese children - Corrected Proof

M. Gil-Campos, M.C. Ramírez Tortosa, C.M. Aguilera, R. Cañete, A. Gil — 2009-10-12

Abstract: Background and aims: It has been suggested that adipokine changes might precede changes in plasma non-esterified fatty acids and other obesity metabolic biomarkers. The aim of the present study was to evaluate changes in fasting and postprandial plasma levels of adiponectin, non-esterified fatty acids, and tumor necrosis factor-alpha in prepubertal obese children and age-matched normal-weight children.Methods and results: Fifty-four children of prepubertal age (34 obese, comprising 23 males and 11 females, and 20 normal-weight comprising 11 males and 9 females) were studied. A standard 438kcal breakfast was given to both groups. Baseline measurements included anthropometry and plasma lipids. The following parameters were determined in plasma before and after breakfast: glucose, insulin, and C-peptide at baseline and 2h and non-esterified fatty acids, adiponectin, and tumor necrosis factor-alpha at baseline and 1, 2, and 3h. Fasting plasma non-esterified fatty acid levels were lower in the obese versus normal-weight children (P=0.021). Both at baseline and postprandially, plasma adiponectin levels were lower in the obese versus normal-weight children (P<0.001). A trend was observed (P=0.06) that levels of tumor necrosis factor-alpha were lower in the obese versus normal-weight children. Adiponectin was inversely associated with insulin in the obese children after adjustment for BMI and sex (r=−0.401, P=0.025).Conclusion: At prepubertal age, obese children show lower fasting and postprandial plasma adiponectin levels in comparison to normal-weight children, whereas non-esterified fatty acids and tumor necrosis factor-alpha were not yet increased. Therefore, adiponectin appears to be a good marker of early metabolic alterations associated with childhood obesity.

Moderate consumption of red wine, but not gin, decreases erythrocyte superoxide dismutase activity: A randomised cross-over trial - Corrected Proof

2009-10-12

Abstract: Background and Aims: Several studies have shown that moderate alcohol consumption reduces the risk of coronary heart disease, a disease related to oxidative stress. However, the effects of different alcoholic beverages on antioxidant status are not fully known. Our aim was therefore to compare the effects of a moderate intake of an alcoholic beverage with high polyphenol content (red wine) and another without polyphenol content (gin) on plasma antioxidant vitamins, lipid profile and oxidability of low-density lipoprotein (LDL) particles.Methods and results: Forty healthy men (mean age, 38 years) were included in a randomised cross-over trial. After a 15-day washout period, subjects received 30g/ethanol/d as either wine or gin for 28 days. Diet and exercise were monitored. Before and after each intervention, we measured serum vitamins, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase activities, lipid profile, oxidized LDL and LDL resistance to ex-vivo oxidative stress. Compared to gin intervention, wine intake reduced plasma SOD activity [−8.1U/gHb (95% confidence interval, CI, −138 to −25; P=0.009)] and MDA levels [−11.9nmol/L (CI, −21.4 to−2.5; P=0.020)]. Lag phase time of LDL oxidation analysis also increased 11.0min (CI, 1.2–20.8; P=0.032) after wine, compared to gin, whereas no differences were observed between the two interventions in oxidation rate of LDL particles. Peroxide concentration in LDL particles also decreased after wine [−0.18nmol/mL (CI, −0.3 to−0.08;P=0.020)], as did plasma oxidized LDL concentrations [−11.0U/L (CI,−17.3 to −6.1; P=0.009)].Conclusion: Compared to gin, red wine intake has greater antioxidant effects, probably due to its high polyphenolic content.

Pioglitazone modulates the balance of effector and regulatory T cells in apolipoprotein E deficient mice - Corrected Proof

2009-10-12

Abstract: Background and aims: Pioglitazone (PIO) affects T cell-mediated immunity through actions of peroxisome proliferator activated receptor γ (PPARγ). Effector and regulatory T cells control the development of atherosclerosis, a chronic inflammatory disease affecting the arterial blood vessels. The aim of this study was to examine whether PIO ameliorates atherosclerosis by altering the balance of effector and regulatory T cells.Methods and results: To explore the effect of PIO on early and advanced atherosclerosis, apolipoprotein E deficient (ApoE−/−) mice were fed western diet and received PIO (20mg/kg/day) by gastric gavage at 6 or 14 weeks of age, respectively for 8 weeks. Data showed PIO markedly inhibited early fatty streak formation. Further, although the advanced fibrofatty plaque sizes were not significantly reduced, the numbers of smooth muscle cells within lesions were increased and higher collagen concentrations were produced. In general, macrophage expression in lesions was decreased. Additionally, the expression of Foxp3+ cells was increased in lesions and spleens in mice at all PIO treatment stages, whereas the CD4+IFN-γ+/CD4+IL-4+ cell ratios were reduced.Conclusion: PIO inhibited early atherosclerotic lesion formation and increased the stability of advanced atherosclerotic plaques in ApoE−/− mice, which was associated with altering the balance of effector and regulatory T cells.

Consumption of diets with different type of fat influences triacylglycerols-rich lipoproteins particle number and size during the postprandial state - Corrected Proof

2009-10-12

Abstract: Background and aims: Previous evidence suggests that dietary fat could influence the composition and size of triacylglycerols-rich lipoproteins (TRL). In a controlled intervention study on healthy subjects, we evaluated the influence of 3 dietary interventions, with different types of fat on postprandial TRL particle size and number.Methods and results: Volunteers followed three different diets for four weeks each, according to a randomized crossover design. Western diet: 15% protein, 47% carbohydrates (CHO), 38% fat (22% saturated fatty acid (SFA)); Mediterranean diet: 15% protein, 47% CHO, 38% fat (24% monounsaturated fatty acid (MUFA)); high CHO enriched with ALNA diet: 15% protein, 55% CHO, <30% fat (8% polyunsaturated fatty acid (PUFA)). After a 12-h fast, volunteers consumed a breakfast with 1g fat and 7mg cholesterol per kg body weight and a fat composition similar to that consumed in each of the diets: Butter meal: 35% SFA; Olive oil meal: 36% MUFA; Walnut meal: 16% PUFA, 4% α-linolenic acid. Tryglicerides (TG) in TRL (large and small TRL) were determined by ultracentrifugation and size and number of lipoprotein particles were measured with Nuclear Magnetic Resonance Spectroscopy at different time points. The olive oil meal reduced the number of total TRL postprandial particles compared with the other meals (P=0.002). Moreover, the olive oil meal also increased the TRL particle size compared with the walnut meal (P=0.001).Conclusion: Our data showed that short-term intake of the Mediterranean diet and the acute intake of an olive oil meal lead to the formation of a reduced number and higher-size TRL particle compared with other fat sources. These novel findings have implications for understanding the postprandial lipoprotein mechanisms, and could favour the lower cardiovascular risk in Mediterranean countries.

Cardiovascular disease prevalence and its relation to risk factors in Alaska Eskimos - Corrected Proof

2009-10-05

Abstract: Background and aims: Although Eskimos were thought to be protected from cardiovascular disease (CVD), state health data show a large proportion of deaths from CVD, despite traditional lifestyles and high omega-3 fatty acid intake. This article explores CVD prevalence and its relation to risk factors in Alaska Eskimos.Methods and results: A population-based cohort of 499 Alaska Eskimos > age 45 from the Norton Sound region was examined in 2000–2004 for CVD and associated risk factors as part of the Genetics of Coronary Artery Disease in Alaska Natives study. CVD and atherosclerosis were evaluated and adjudicated using standardized methods. Average age was 58 years; diabetes prevalence was low and high-density lipoprotein cholesterol (HDL-C) concentrations were high, but a large proportion smoked and had high pathogen burden. CVD was higher in men (12.6%) than in women (5.3%) (prevalence ratio 2.4, CI 1.3–4.4). Rates of stroke (6.1% in men, 1.8% in women) were similar to those for coronary heart disease (CHD) (6.1% men, 2.5% women). MI prevalence was low in both genders (1.9% and 0.7%). CVD was higher in men and in those >60 years. Hypertension, diabetes, high LDL-C, high apoB, and low HDL-C were all strong correlates (<.002) and albuminuria and CRP were also correlated with CVD (p<.05) after adjustment for age and gender. Carotid atherosclerosis was correlated with CVD (p=.0079) independent of other risk factors.Conclusion: These data show high CHD and stroke prevalence in Alaska Eskimos, despite low average LDL-C and high HDL-C. Hypertension and high LDL-C were independent correlates; identifying these risk factors early and treating to target is recommended.

The APOA5−1131 T>C variant enhances the association between RBP4 and hypertriglyceridemia in diabetes - Corrected Proof

2009-09-22

Abstract: Background and aim: Type 2 diabetic patients have an increased prevalence of hypertriglyceridemia. RBP4 has been associated with insulin resistance and hypertriglyceridemia in obesity, the metabolic syndrome and type 2 diabetes. APOA5 is proposed to be a genetic modulator of triglycerides. The aim of this study was to evaluate the relationship between RBP4 plasma levels and lipid disturbances and to determine the impact of the APOA5−1131 T>C variant on this relationship in type 2 diabetic patients.Methods and results: A total of 165 type 2 diabetic patients were included in the study. RBP4 plasma levels and the APOA5−1131 T>C variant were determined and the complete lipid profile was assessed by sequential ultracentrifugation. RBP4 was positively correlated with triglyceride levels in plasma and with all the components of triglyceride-rich lipoproteins. Despite the fact that a statistically significant relationship between the APOA5 genetic variant and RBP4 plasma levels was not found, the hypertriglyceridemic effect of high RBP4 levels was enhanced by the presence of the APOA5−1131 T>C genetic variant. Correlation coefficients were 2-fold higher for TC carriers compared to TT carriers with regard to RBP4 plasma levels and all the components of triglyceride-rich lipoproteins. Those type 2 diabetic patients with high RBP4 plasma concentrations and who were TC carriers showed an increased incidence of hypertriglyceridemia (OR=7.46, P=0.010).Conclusion: RBP4 is associated with hypertriglyceridemia in type 2 diabetic patients. The RBP4 effect is conditioned by the presence of the APOA5−1131 T>C genetic variant.

Increased plasma xanthine oxidase activity is related to nuclear factor kappa beta activation and inflammatory markers in familial combined hyperlipidemia - Corrected Proof

2009-09-18

Abstract: Background and aims: Xanthine oxidase (XO) has been described as one of the major enzymes producing free radicals in blood. Oxidative stress and inflammatory processes have been implicated in the pathogenesis of endothelial dysfunction and the progression of atherosclerosis but until now, there is little data about the influence of vascular prooxidant systems and inflammation in familial combined hyperlipidemia (FCH). Our goal was to evaluate whether XO activity was altered in FCH and if it was related to the inflammatory process represented by NFkB, IL-6 and hsCRP, and assessing the correlation between XO activity and insulin resistance (IR).Method and results: 40 Non-related subjects with FCH and 30 control subjects were included, all of them non-diabetic, normotensive and non-smokers. We measured lipid profile, glucose, insulin, uric acid, XO activity, malondialdehyde (MDA), IL-6 and hsCRP in plasma and NFkB activity in circulating mononuclear cells. Patients with FCH showed significantly higher levels of uric acid, XO activity, MDA, NFkB activity, IL-6 and hsCRP than controls. XO activity was independently related to NFkB activity with an odds ratio of 4.082; to IL-6 with an odds ratio of 4.191; and to IR with an odds ratio of 3.830. Furthermore, mean NFkB activity, IL-6 levels, and IR were highest in the highest percentile of XO activity.Conclusions: Subjects with FCH showed increased XO and NFkB activities and low grade inflammatory markers related to atherosclerosis. XO activity was correlated with higher inflammatory activity and IR. These data could explain, in part, the high cardiovascular disease risk present in these patients.

An NPC1L1 gene promoter variant is associated with autosomal dominant hypercholesterolemia - Corrected Proof

2009-09-14

Abstract: Background and aims: A substantial number of subjects with autosomal dominant hypercholesterolemia (ADH) do not have LDL receptor (LDLR) or apolipoprotein B (APOB) mutations. Some ADH subjects appear to hyperabsorb sterols from the intestine, thus we hypothesized that they could have variants of the Niemann–Pick C1-Like 1 gene (NPC1L1). NPC1L1 encodes a crucial protein involved in intestinal sterol absorption.Methods and results: Four NPC1L1 variants (−133A>G, −18C>A, 1679C>G, 28650A>G) were analyzed in 271 (155 women and 116 men) ADH bearers without mutations in LDLR or APOB aged 30–70years and 274 (180 women and 94 men) control subjects aged 25–65years. The AC haplotype determined by the −133A>G and −18C>A variants was underrepresented in ADH subjects compared to controls (p=0.01). In the ADH group, cholesterol absorption/synthesis markers were significantly lower in AC homozygotes that in all others haplotypes. Electrophoretic mobility shift assay (EMSA) results revealed that the −133A-specific oligonucleotide produced a retarded band stronger than the −133G allele. Luciferase activity with NPC1L1 −133G variant was 2.5-fold higher than with the −133A variant.Conclusion: The −133A>G polymorphism exerts a significant effect on NPC1L1 promoter activity. NPC1L1 promoter variants might explain in part the hypercholesterolemic phenotype of some subjects with nonLDLR/nonAPOB ADH.

Dietary patterns and markers for the metabolic syndrome in Australian adolescents - Corrected Proof

2009-09-14

Abstract: Background and aims: Overweight and other risk factors for cardiovascular disease (CVD) as well as their clustering, are increasingly prevalent among adolescents. We examined dietary patterns, CVD risk factors, and the clustering of these risk factors in 1139 14-year-olds living in Western Australia.Methods and results: Usual dietary intake was assessed using a food frequency questionnaire. Two dietary patterns, ‘Western’ and ‘Healthy’, were identified using factor analysis. Associations between these dietary patterns and BMI, waist circumference, systolic blood pressure, fasting levels of serum glucose, insulin, total cholesterol, HDL-C, LDL-C, triglycerides and insulin resistance were assessed using ANOVA. Cluster analysis identified a high risk group (the ‘high risk metabolic cluster’) with features akin to adult metabolic syndrome. Belonging to the ‘high risk metabolic cluster’ was examined in relation to dietary patterns using logistic regression, adjusting for aerobic fitness and socio-demographic factors. Higher ‘Western’ dietary pattern scores were associated with greater odds for the ‘high risk metabolic cluster’ (p for trend=0.02) and greater mean values for total cholesterol (p for trend=0.03), waist circumference (p for trend=0.03) and BMI (p for trend=0.02) in girls, but not boys. Scores for the ‘Healthy’ dietary pattern were not related to the ‘high risk metabolic cluster’ but were inversely associated with serum glucose in boys and girls (p for trend=0.01 and 0.04, respectively) and were positively associated with HDL-C in boys (p for trend=0.02).Conclusions: Dietary patterns are associated with CVD risk factors and the clustering of these risk factors in adolescence.

Insulin resistance is a risk factor for high blood pressure regardless of body size and fat distribution in obese children - Corrected Proof

2009-09-14

Summary: Background and aim: The prevalence of children with hypertension is increasing, especially in obese children. This study was to assess the relationship between blood pressure, indexes of adiposity, body fat distribution and insulin resistance.Methods and results: Sample: 1044 children (M/F: 484/560; aged 6–11years). Anthropometry and blood pressure were measured and fasting blood samples were tested for triacylglycerol, total cholesterol, HDL cholesterol, glucose, insulin and ALT.The prevalence of high blood pressure in overweight males and females was 14.3 and 6.4%, respectively (χ2=16.73, p<0.001) and in obese it was 40.4 and 32.8%, respectively (χ2=5.56, p<0.001). High blood pressure increased progressively with BMI z-score categories (χ2=67.99, p<0.001) as well as with waist/height ratio (W/Hr) categories (χ2=23.51, p<0.001). Hypertensive subject had significantly higher insulin (15.6±9.8 vs 11.9±7.2, p<0.001 and 20.63±14.7 vs 15.26±9.8, p<0.001 in males and females respectively) and HOMAIR (3.23±2.1 vs 2.42±1.49, p<0.001 and 4.12±2.87 vs 3.07±1.98, p<0.001 in males and in females, respectively) than non-hypertensive ones. Among metabolic and cardiovascular risk factors, HOMAIR was the only variable able to predict high blood pressure in obese boys and girls, in addition to BMI or body fat distribution (waist, W/Hr). The highest HOMAIR category was the most important predicting factor of high blood pressure in overweight and obese children in addition to body size or body fat distribution.Conclusions: Blood pressure is associated with the degree of overweight and the indices of body fat distribution. Insulin resistance is an independent additional risk factor for hypertension.

Plant sterols from rapeseed and tall oils: Effects on lipids, fat-soluble vitamins and plant sterol concentrations - Corrected Proof

2009-09-14

Abstract: Background and aims: Data comparing the impact of different sources of plant sterols on CVD risk factors and antioxidant levels is scarce. We evaluated the effects of plant sterols from rapeseed and tall oils on serum lipids, lipoproteins, fat-soluble vitamins and plant sterol concentrations.Methods and results: This was a double-blinded, randomized, crossover trial in which 59 hypercholesterolemic subjects consumed 25g/day of margarine for 4weeks separated by 1week washout periods. The two experimental margarines provided 2g/day of plant sterols from rapeseed or tall oil. The control margarine had no added plant sterols. The control margarine reduced LDL cholesterol by 4.5% (95% CI 1.4, 7.6%). The tall and rapeseed sterol margarines additionally reduced LDL cholesterol by 9.0% (95% CI 5.5, 12.4%) and 8.2% (95% CI 5.2, 11.4%) and apolipoprotein B by 5.3% (95% CI 1.0, 9.6%) and 6.9% (95% CI 3.6, 10.2%), respectively. Lipid-adjusted β-carotene concentrations were reduced by both sterol margarines (P<0.017). α-Tocopherol concentrations were reduced by the tall sterol compared to the rapeseed sterol margarine (P=0.001). Campesterol concentrations increased more markedly with the rapeseed sterol versus tall sterol margarine (P<0.001). The rapeseed sterol margarine increased while the tall sterol margarine decreased brassicasterol concentrations (P<0.001).Conclusions: Plant sterols from tall and rapeseed oils reduce atherogenic lipids and lipoproteins similarly. The rapeseed sterol margarine may have more favorable effects on serum α-tocopherol concentrations.

Acute effects of 5-methyltetrahydrofolate on endothelial function and asymmetric dimethylarginine in patients with chronic heart failure - Corrected Proof

B. Paul, M.J. Whiting, C.G. De Pasquale, A.A. Mangoni — 2009-09-14

Summary: Background and aims: Folic acid enhances endothelial function in vascular disease states but its effects in chronic heart failure (CHF) are largely unknown. We studied the acute effects of i.v. methyltetrahydrofolate (5MTHF), the active metabolite of folic acid, on endothelial function and asymmetric dimethylarginine (ADMA) in CHF patients.Methods and results: Twenty two CHF patients and 22 controls received one of the following three-step infusions (1h per each step) in a randomized, parallel group, placebo-control study: (1) active treatment (saline, 5MTHF, and 5MTHF+the endothelial nitric oxide inhibitor NG-monomethyl l-arginine, LNMMA); or (2) placebo (saline×3). Endothelium-dependent vasodilatation was assessed by pulse-wave analysis (salbutamol-mediated changes in augmentation index, AIx). 5MTHF did not exert any significant effects on endothelium-dependent vasodilatation both in controls [ΔAIx post-salbutamol baseline −7.6% (−24.8/−4.1) vs. 5MTHF −5.5% (−16.7/−3.6), medians and interquartile range, and CHF patients [−1.8% (−17.3/+1.3) vs. −2.4% (−3.8/−1.2)]. However, a significant reduction in ADMA concentrations was observed in both groups [controls baseline 0.68μmol/L (0.64/0.77) vs. 5MTHF 0.65 (0.57/0.74); CHF baseline 0.76 (0.63/0.82) vs. 5MTHF 0.69 (0.66/0.71), P=0.05 for both vs. baseline and placebo. These effects persisted during co-infusion with LNMMA.Conclusion: 5MTHF did not affect endothelial function but significantly reduced serum ADMA concentrations both in CHF patients and controls. This suggests a direct effect of 5MTHF on ADMA metabolism.

Normal weight obesity: Relationship with lipids, glycaemic status, liver enzymes and inflammation - Corrected Proof

2009-09-14

Abstract: Background and aims: Normal weight obesity (NWO) is defined as an excessive body fat associated with a normal body mass index (BMI) and has been associated with early inflammation, but its relationship with cardiovascular risk factors await investigation.Methods and results: Cross-sectional study including 3213 women and 2912 men aged 35–75 years to assess the clinical characteristics of NWO in Lausanne, Switzerland. Body fat was assessed by bioimpedance. NWO was defined as a BMI<25kg/m2 and a % body fat>=66th gender-specific percentiles. The prevalence of NWO was 5.4% in women and less than 3% in men, so the analysis was restricted to women. NWO women had a higher % of body fat than overweight women. After adjusting for age, smoking, educational level, physical activity and alcohol consumption, NWO women had higher blood pressure and lipid levels and a higher prevalence of dyslipidaemia (odds-ratio=1.90 [1.34–2.68]) and fasting hyperglycaemia (odds-ratio=1.63 [1.10–2.42]) than lean women, whereas no differences were found between NWO and overweight women. Conversely, no differences were found between NWO and lean women regarding levels of CRP, adiponectin and liver markers (alanine aminotransferase, aspartate aminotransferase and gamma glutamyl transferase). Using other definitions of NWO led to similar conclusions, albeit some differences were no longer significant.Conclusion: NWO is almost nonexistent in men. Women with NWO present with higher cardiovascular risk factors than lean women, while no differences were found for liver or inflammatory markers. Specific screening of NWO might be necessary in order to implement cardiovascular prevention.

Carbohydrate restriction favorably alters lipoprotein metabolism in Emirati subjects classified with the metabolic syndrome - Corrected Proof

T. Al-Sarraj, H. Saadi, J.S. Volek, M.L. Fernandez — 2009-09-14

Abstract: Background and aims: Carbohydrate restriction (CR) has been shown to improve dyslipidemias associated with metabolic syndrome (MetS). We evaluated the effects of CR on lipoprotein subfractions and apolipoproteins in Emirati adults classified with the MetS.Methods and results: 39 subjects (15 men/24 women) were randomly allocated to a CR diet [20–25% energy from carbohydrate (CHO)] for 12wk (CRD group) or a combination treatment consisting of CRD for 6wk followed by the American Heart Association diet (50–55% CHO, AHA group) for an additional 6wk. All subjects reduced body weight, LDL cholesterol and triglycerides (P<0.01). At baseline all subjects had low concentrations of medium VLDL and total HDL particles associated with the very low plasma triglycerides and HDL cholesterol in this population. After 12wk, the large VLDL subfraction was decreased over time for subjects in the CRD group (P<0.01) while these changes were not observed in those subjects who changed to the AHA diet. The number of medium and small LDL particles decreased for all subjects rendering a less atherogenic lipoprotein profile. In agreement with these results, a significant decrease in apolipoprotein (apo) B was observed (P<0.01). The medium HDL subfraction and apo A-II, which can be considered pro-atherogenic, were also decreased over time in the CRD group only.Conclusions: These results suggest that weight loss favorably affects lipoprotein metabolism and that the CRD had a better effect on atherogenic VLDL and HDL than the low fat diet recommended by AHA.

Effects of obesity, physical activity, and cardiorespiratory fitness on blood pressure, inflammation, and insulin resistance in the National Health and Nutrition Survey 1999–2002 - Corrected Proof

C-Y. Lin, P-C. Chen, H-K. Kuo, L-Y. Lin, J-W. Lin, J-J. Hwang — 2009-09-14

Abstract: Background and aims: This study was designed to elucidate the effects of obesity, self-reported physical activity and cardiorespiratory fitness on blood pressure, inflammation, and insulin resistance.Methods and results: Data from 950 Caucasian subjects ranging in age from 19 to 49 years from the National Health and Nutrition Survey (NHANES), 1999–2002, were included to construct a population-based observational study. Cardiorespiratory fitness (VO2 max) was predicted from a submaximal exercise stress test. Self-reported physical activity was measured by metabolic equivalent score transformed from a questionnaire. A structural equation model (SEM) was developed to examine the relationship between obesity, cardiorespiratory fitness, self-reported physical activity, and hypertension, inflammation, and insulin resistance. The model showed that obesity was positively linked to hypertension (B=0.50, P<0.001) and C-reactive protein (CRP; B=0.15, p<0.05), which in turn led to insulin resistance (B=0.44, P<0.05). Increased cardiorespiratory fitness was negatively associated with CRP (Γ=−0.23, P<0.01), but not correlated to hypertension after adjustment for potential confounding factors. No significant association was found between self-reported physical activity and hypertension, insulin resistance, and CRP.Conclusion: Obesity contributes to the development of hypertension, inflammation, and insulin resistance. Improved cardiorespiratory fitness might lead to clinical and biochemical improvement in insulin resistance by reducing the inflammatory state.

Atherosclerosis regression study in rabbits upon olive pomace polar lipid extract administration - Corrected Proof

2009-09-14

Abstract: Background and aims: Virgin olive oil polar lipid extract (OOPL) and olive pomace polar lipid extract (PPL) have similar antiatherosclerotic effects in cholesterol-fed rabbits. Our aim was to compare the effect of PPL with that of simvastatin on the progression of atherogenesis.Methods and results: Rabbits were fed an atherogenic diet for 6 weeks in order to develop dyslipidemia and atheromatous lesions. Following documentation of these events in random animals (group A, n=6), the remaining were fed for 3 weeks with: standard chow alone (group B, n=6), chow supplemented with PPL (group C, n=6), and chow supplemented with simvastatin (group D, n=6). Blood was collected at 0, 6 and 9 weeks, to determine plasma lipid levels, plasma PAF-AH activity, platelet aggregation (PAF-EC50), resistance of plasma to oxidation (RPO) and extent of atheromatous lesions in aortas. The atherogenic diet induced dyslipidemia and increased PAF-AH activity. Dyslipidemia and PAF-activity reduced more effectively in groups C and D. RPO decreased in group B only. PAF-EC50 values decreased in group C only. Atherogenesis progression in group C was prevented to an extent indistinguishable from that in group D. PAF-AH activity was positively correlated, whereas RPO was negatively correlated with the extent of atheromatous lesions.Conclusion: PPL, as a dietary supplement, is equipotent to simvastatin in preventing the progression of atherogenesis.

Incidence of severe nocturnal hypoglycemia in patients with type 1 diabetes treated with insulin lispro or regular human insulin in addition to basal insulin glargine - Corrected Proof

2009-08-25

Abstract: Background and aims: Once-daily (OD) basal insulin glargine (GLA) can be used as part of a multiple daily injection regimen in patients with type 1 diabetes mellitus. This randomized, multicenter study compared GLA+prandial regular human insulin (RHI) with GLA+prandial insulin lispro (LIS) in reducing the incidence of severe nocturnal hypoglycemia at endpoint. In addition, the effects on glycemic control of both treatments were investigated.Methods and results: Patients (489) previously on neutral protamine Hagedorn (NPH) insulin or GLAR plus RHI/LIS were switched to, or continued on GLA (target fasting blood glucose [FBG]=5.0–6.7mmol/L [90–120mg/dL]) for 8 weeks (qualification phase) prior to randomization; patients continued with their previous bolus insulin. Patients (n=395) were then randomized to LIS (n=193) or RHI (n=202) and treated for 16 weeks. The proportion of patients experiencing severe nocturnal hypoglycemia at the end of the study was 1.55% (n=3) in the RHI group and 1.11% (n=2) in the LIS group (p=0.938 between groups); the mean difference was 0.44% (95% CI: −1.77, 2.21), suggesting non-inferiority of RHI versus LIS. At the end of the study, both treatments did not differ with respect to glycemic control, as measured by hemoglobin A1c and FBG.Conclusion: These results suggest that GLA+LIS and GLA+RHI treatments were associated with a similar and low rate of severe nocturnal hypoglycemia. Further studies with greater patient sizes are necessary to verify the findings from the current study.