Nutrition, Metabolism & Cardiovascular Diseases - Articles in Press

A gene variation (rs12691) in the CCAT/enhancer binding protein α modulates glucose metabolism in metabolic syndrome - Corrected Proof

2012-01-24

Abstract: Background and aims: CCAAT/enhancer-binding protein alpha (CEBPA) is a transcription factor involved in adipogenesis and energy homeostasis. Caloric restriction reduces CEBPA protein expression in patients with metabolic syndrome (MetS). A previous report linked rs12691 SNP in CEBPA to altered concentration of fasting triglycerides. Our objective was to assess the effects of rs12691 in glucose metabolism in Metabolic Syndrome (MetS) patients.Methods and results: Glucose metabolism was assessed by static (glucose, insulin, adiponectin, leptin and resistin plasma concentrations) and dynamic (disposition index, insulin sensitivity index, HOMA-IR and acute insulin response to glucose) indices, performed at baseline and after 12 weeks of 4 dietary interventions (high saturated fatty acid (SFA), high monounsaturated fatty acid (MUFA), low-fat and low-fat-high-n3 polyunsaturated fatty acid (PUFA)) in 486 subjects with MetS. Carriers of the minor A allele of rs12691 had altered disposition index (p = 0.0003), lower acute insulin response (p = 0.005) and a lower insulin sensitivity index (p = 0.025) indicating a lower insulin sensitivity and a lower insulin secretion, at baseline and at the end of the diets. Furthermore, A allele carriers displayed lower HDL concentration.Conclusion: The presence of the A allele of rs12691 influences glucose metabolism of MetS patients. Clinical Trials Registry number NCT00429195.

Can vitamin D deficiency cause diabetes and cardiovascular diseases? Present evidence and future perspectives - Corrected Proof

2012-01-24

Abstract: Several studies have shown that vitamin D may play a role in many biochemical mechanisms in addition to bone and calcium metabolism. Recently, vitamin D has sparked widespread interest because of its involvement in the homeostasis of the cardiovascular system. Hypovitaminosis D has been associated with obesity, related to trapping in adipose tissue due to its lipophilic structure. In addition, vitamin D deficiency is associated with increased risk of cardiovascular disease (CVD) and this may be due to the relationship between low vitamin D levels and obesity, diabetes mellitus, dyslipidaemia, endothelial dysfunction and hypertension. However, although vitamin D has been identified as a potentially important marker of CVD, the mechanisms through which it might modulate cardiovascular risk are not fully understood. Given this background, in this work we summarise clinical retrospective and prospective observational studies linking vitamin D levels with cardio-metabolic risk factors and vascular outcome. Moreover, we review various randomised controlled trials (RCTs) investigating the effects of vitamin D supplementation on surrogate markers of cardiovascular risk. Considering the high prevalence of hypovitaminosis D among patients with high cardiovascular risk, vitamin D replacement therapy in this population may be warranted; however, further RCTs are urgently needed to establish when to begin vitamin D therapy, as well as to determine the dose and route and duration of administration.

Lower plasma NAMPT/visfatin levels are associated with impaired hepatic mitochondrial function in non-diabetic obese women: A potential link between obesity and non-alcoholic fatty liver disease - Corrected Proof

J.R. Ruiz, A. Lasa, E. Simon, E. Larrarte, I. Labayen — 2012-01-09

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes. Hepatic mitochondrial dysfunction precedes the development of NAFLD, insulin resistance and inflammation . The 2-keto[1-13C]isocaproate oxidation measurement is a helpful tool in the in vivo assessment of liver mitochondrial function .

Homocysteinylation of low-density lipoproteins (LDL) from subjects with type 1 diabetes and human aortic endothelial cells: An in vitro study - Corrected Proof

2012-01-04

Type 1 (T1D) and Type 2 (T2D) diabetes are independent risk factors for cardiovascular disease (CVD), stroke and coronary artery disease . The higher risk of CVD associated with diabetes has been related to hyperglycaemia, hyperinsulinaemia and to alterations of the levels and/or heterogeneity of the major lipoprotein classes. An increase in small and dense LDL and glycated apoproteins has been described in patients with diabetes . These compositional and physicochemical changes reflect alterations in the susceptibility to lipid peroxidation and impaired interactions with cell receptors. In the past decade, homocysteine (Hcy) has been recognized as a risk factor for cardiovascular disease . Several studies have observed a relationship between Hcy levels and chronic complications of diabetes, and it has been reported that hyperhomocysteinaemia is associated with coronary heart disease in diabetes .

The relation of body mass index and abdominal adiposity with dyslipidemia in 27 general populations of the WHO MONICA Project - Corrected Proof

V. Wietlisbach, P. Marques-Vidal, K. Kuulasmaa, J. Karvanen, F. Paccaud — 2012-01-04

Abstract: Background and aims: The association between adiposity measures and dyslipidemia has seldom been assessed in a multipopulational setting.Methods and results: 27 populations from Europe, Australia, New Zealand and Canada (WHO MONICA project) using health surveys conducted between 1990 and 1997 in adults aged 35–64 years (n = 40,480). Dyslipidemia was defined as the total/HDL cholesterol ratio >6 (men) and >5 (women).Overall prevalence of dyslipidemia was 25% in men and 23% in women. Logistic regression showed that dyslipidemia was strongly associated with body mass index (BMI) in men and with waist circumference (WC) in women, after adjusting for region, age and smoking. Among normal-weight men and women (BMI<25 kg/m2), an increase in the odds for being dyslipidemic was observed between lowest and highest WC quartiles (OR = 3.6, p 84.8 cm) in normal-weight men, menopause in women and regular smoking further defined subgroups at increased risk.Conclusion: standard categories of BMI and WC, or their combinations, do not lead to optimal risk stratification for dyslipidemia in middle-age adults. Sex-specific adaptations are necessary, in particular by taking into account abdominal obesity in normal-weight men, post-menopausal age in women and regular smoking in both sexes.

What is common becomes normal: The effect of obesity prevalence on maternal perception - Corrected Proof

N. Binkin, A. Spinelli, G. Baglio, A. Lamberti — 2012-01-04

Abstract: Background and aims: This analysis investigates the poorly-known effect of local prevalence of childhood obesity on mothers’ perception of their children’s weight status.Methods and results: In 2008, a national nutritional survey of children attending the third grade of elementary school was conducted in Italy. Children were measured and classified as underweight, normal weight, overweight and obese, using the International Obesity Task Force cut-offs for body mass index (BMI). A parental questionnaire included parental perception of their child’s weight status (underweight, normal, a little overweight and a lot overweight). Regions were classified by childhood obesity prevalence (<8%, 8–12%, ≥13%). The association between incorrect maternal perception and regional obesity prevalence, and maternal and child characteristics were examined using bivariate and logistic regression analyses. Complete data were available for 37 590 children, of whom 24% were overweight and 12% obese. Mothers correctly identified the status of 84% of normal weight, 52% of overweight and 14% of obese children. Among overweight children, factors associated with underestimation of the child’s weight included lower maternal education (adjusted odds ratio, aOR, 1.9; 95% confidence interval (CI) 1.6–2.4), residence in a high-obesity region (aOR 2.2; 95% CI 1.9–2.6), male gender (aOR 1.4; 95% CI 1.2–1.6) and child’s BMI.Conclusion: Higher regional obesity prevalence is associated with lower maternal perception, suggesting that what is common has a greater likelihood of being perceived as normal. As perception is a first step to change, it may be harder to intervene in areas with high-obesity prevalence where intervention is most urgent.

Folate, vitamin B12 and homocysteine status in an Italian blood donor population - Corrected Proof

2012-01-04

Abstract: Background and aims: The relevance of folate, other B-vitamins and homocysteine (Hcy) for the occurrence or prevention of several diseases has induced growing interest. Unfortunately, little evidence is available regarding B-vitamin concentrations in Italy.This study evaluated in a region of middle-southern Italy, folate, vitamin B12 and Hcy concentrations and the prevalence of their ideal blood levels. The main determinants of B-vitamins and Hcy were also considered.Methods and results: Male and female blood donors (n=240), aged 18–66 years and living in Molise region (Italy), were enrolled in the study. They completed a brief questionnaire concerning fruit and vegetables intake, physical activity and smoking; serum and red blood cell (RBC) folate and serum vitamin B12 were measured by an immunoassay on an automated analyzer. Total Hcy was measured by high performance liquid chromatography (HPLC).Geometric means of serum folate, RBC folate and serum vitamin B12 were 10.8nmoll−1, 426.0nmoll−1 and 245.0pmoll−1, respectively. Only 22.5%, 24.2% and 16.3% of blood donors showed an adequate level of serum folate, RBC folate or serum vitamin B12 respectively. When a cut-off of RBC folate ≥906nmoll−1 was used no women of childbearing age had adequate levels. A geometric mean of 14.0μmoll−1 was found for total Hcy, with an ideal concentration in 12.1% of subjects. Folate concentration was higher in women and non-smokers and in subjects with higher consumption of fruit and vegetable.Conclusion: This study shows a low-moderate B-vitamins status in middle-southern Italy, associated with an inadequate fruit and vegetable consumption. A public health strategy should be undertaken to encourage a B-vitamin-rich diet with the addition of vitamin supplements or vitamin fortified foods in population subgroups with special needs.

Soluble receptor for advanced glycation end-products levels are related to albuminuria and arterial stiffness in essential hypertension - Corrected Proof

2012-01-04

Abstract: Background and aims: Emerging evidence suggests that the soluble receptor for advanced glycation end-products (sRAGE) is implicated in the development of vascular disease. We investigated the interrelationships of sRAGE with albumin to creatinine ratio (ACR) and arterial stiffness in essential hypertension.Methods and results: In 309 untreated non-diabetic hypertensives, ACR values were determined as the mean of three non-consecutive morning spot urine samples and aortic stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (c-f PWV). In all subjects, venous blood sampling was performed for the estimation of sRAGE levels. Patients with low (n = 155) compared to those with high sRAGE values (n = 154) had greater 24-h systolic BP (140 ± 8 vs. 134 ± 7 mmHg, p < 0.0001), exhibited higher ACR (36.3 ± 51.6 vs. 17.2 ± 1.2 mg g−1, p < 0.0001) and c-f PWV (8.3 ± 1.5 vs. 7.8 ± 1.1 m s−1, p = 0.003), independently of confounding factors. Multiple regression analyses revealed that age, male sex, 24-h systolic BP and sRAGE were the ‘independent correlates’ of ACR (R2 = 0.493, p < 0.0001), while age, 24-h systolic BP and sRAGE were the ‘independent correlates’ of c-f PWV (R2 = 0.428, p < 0.0001).Conclusion: In hypertensives, decreased sRAGE levels are accompanied by pronounced albuminuria and arterial stiffening. The association of sRAGE with ACR and c-f PWV suggests involvement of sRAGE in the progression of hypertensive vascular damage.

Dietary glycemic index/load and peripheral adipokines and inflammatory markers in elderly subjects at high cardiovascular risk - Corrected Proof

2012-01-04

Abstract: Background and Aims: Epidemiological and clinical studies suggest that low-glycemic index diets could protect against weight gain. However, the relationship between these diets and adipokines or inflammatory markers is unclear. In the present study we examine how the dietary glycemic index (GI) and dietary glycemic load (GL) are associated with several adipokines and related metabolic risk markers of obesity and diabetes in a cross-sectional and longitudinal manner.Methods and Results: 511 elderly community-dwelling men and women at high cardiovascular risk were recruited for the PREDIMED trial. Dietary data were collected at baseline and after 1 year of follow-up. The GI and GL were calculated. Plasma leptin, adiponectin and other metabolic risk markers were measured at baseline and after 1 year. At baseline, subjects in the highest quartiles of GI showed significantly higher levels of TNF and IL-6 than those in the lowest quartiles. Dietary GI index was negatively related to plasma leptin and adiponectin levels. After 1 year of follow-up, subjects with a higher increase in dietary GI or GL showed a greater reduction in leptin and adiponectin plasma levels. There was no association between GI or GL and the other metabolic markers measured.Conclusion: Our results suggest that the consumption of high-GI or high-GL diets may modulate plasma concentrations of leptin and adiponectin, both adipostatic molecules implicated in energy balance and cardiometabolic risk.

Changes of body mass index in celiac children on a gluten-free diet - Corrected Proof

2012-01-03

Abstract: Background and aim: Studies of adults and children with celiac disease (CD) performed mostly in tertiary care centers have reported an increased risk of overweight during gluten-free diet (GFD). We measured body mass index (BMI) of CD children followed by family pediatricians in order to estimate prevalence of underweight and overweight at diagnosis and to describe BMI changes during GFD.Methods and Results: We compared 150 CD children (age range 2–16 yrs) under GFD from a median (IQR) time of 4.4 (4.2) years with 288 healthy children matched for gender and age. We also evaluated retrospectively BMI changes between CD diagnosis and the current evaluation. The median (IQR) BMI of CD patients was significantly lower than that of controls [−0.38 (1.46) vs. 0.09 (1.18) SDS, p < 0.0001, Italian reference data]. Using the International Obesity Task Force classifications, CD children were less frequently overweight or obese (12% vs. 23.3%, p = 0.014) and more frequently underweight (16% vs. 4.5%, p < 0.001) than controls. During GFD, there was a marked decrease of number of underweight subjects (13 vs. 27) and a minimal increase of number of overweight subjects (9 vs. 6) (p < 0.001).Conclusions: The frequency of overweight and obesity at diagnosis of CD and during GFD in children followed by family pediatricians is substantially lower than that reported in tertiary care centers. On the other hand, the high frequency of underweight at diagnosis confirms the need of careful personalized nutritional management.

Acute renal failure after intragastric balloon in morbidly-obese metformin-treated diabetic patients. Report of two cases - Corrected Proof

A. Benetti, S.G. Garbossa, A. Veronelli, A.E. Pontiroli — 2011-12-26

The BioEnterics Intragastric Balloon (BIB) is an endoscopic device used to treat morbidly-obese patients who fail to achieve an adequate weight loss with diet and pharmacotherapy .

Epicardial fat thickness significantly decreases after short-term growth hormone (GH) replacement therapy in adults with GH deficiency - Corrected Proof

2011-11-28

Abstract: Background and Aim: Growth Hormone Deficiency (GHD) is characterized by increased visceral fat accumulation. Echocardiographic epicardial fat thickness is a new marker of visceral adiposity. Aim of the present study was to evaluate whether epicardial fat thickness can significantly change and therefore serve as a marker of visceral fat reduction after short-term rhGH replacement therapy in patients with adult-onset GHD.Methods and Results: Echocardiographic epicardial fat thickness was measured in 18 patients (10 M, 8 F, age 48 ± 11.8 yrs, BMI 29 ± 5.9 kg/m2) with adult-onset GHD, at baseline and after 6 and 12 months of rhGH therapy and in 18 healthy matched controls, at baseline. Echocardiographic epicardial fat thickness, conventional anthropometric and metabolic parameters, body fat percentage and quality of life were also evaluated. Epicardial fat thickness in adult GHD patients was higher than in controls (9.8 ± 2.8 vs 8 ± 3 mm, p < 0.05). Epicardial fat thickness significantly decreased after 6-months of rhGH replacement therapy (from 9.8 ± 2.8 to 7.0 ± 2.3 mm, P < 0.01, i.e. −29% from baseline). After 12 months of rhGH replacement therapy, epicardial fat thickness showed a further significant decrease (from 7.0 ± 2.3 to 5.9 ± 3.1 mm, P < 0.01, i.e. −40% from baseline). No significant changes in BMI or waist circumference after 6 or 12 months of rhGH therapy were observed.Conclusions: Echocardiographic epicardial fat thickness may represent a valuable and easy marker of visceral fat and visceral fat changes during rhGH replacement treatment in patients with adult-onset growth hormone deficiency.

Smoking is associated with impaired long-term glucose metabolism in patients with type 1 diabetes mellitus - Corrected Proof

P.A. Gerber, R. Locher, B. Schmid, G.A. Spinas, R. Lehmann — 2011-11-28

Abstract: Background and Aims: Smoking is known to negatively influence glucose metabolism both in healthy subjects and in patients with diabetes. The aim of this study was to compare glycemic control in patients with type 1 diabetes mellitus who were smokers with those who did not smoke during a prospective long-term follow-up.Methods and Results: In a single center, 763 patients with type 1 diabetes mellitus were included, 160 (21.0%) of them were smokers. Patients were treated with intensive insulin therapy according to existing guidelines. Glucose control was monitored quarterly, diabetes related complications and cardiovascular risk factors were assessed at least once a year. Glucose control in smokers was significantly worse than in non-smokers at baseline and during follow-up (mean HbA1c during 5047 patient-years of follow-up 7.9 ± 1.3% in smokers and 7.3 ± 1.1% in non-smokers, p < 0.001) despite a higher insulin dosage in smokers (0.71 ± 0.30 U/kg vs. 0.65 ± 0.31 U/kg in non-smokers, p = 0.046). HDL cholesterol was lower in smokers at baseline (1.53 ± 0.45 vs. 1.68 ± 0.51 in non-smokers, p = 0.048). Diabetes related complications tended to occur with a higher frequency in smokers, with a significant difference in macroalbuminuria (9.8% vs. 4.8% in non-smokers, p = 0.047).Conclusion: Smoking is associated with worse glucose control in patients with type 1 diabetes mellitus despite the same treatment strategies as in non-smokers. Hyperglycemia, therefore, may contribute to an earlier incidence of diabetes related complications in these patients, in addition to direct toxic effects of smoking.

Decreased serum bilirubin is associated with arterial stiffness in men - Corrected Proof

Y. Li, S.-y. Meng, C.-c. Meng, W.-g. Yu, R.-t. Wang — 2011-11-28

Abstract: Background and aims: The brachial-ankle pulse wave velocity (baPWV) is a marker for early atherosclerotic changes. Serum total bilirubin (TB) is an effective antioxidant and has been associated with carotid intima-media thickness, cardiovascular disease, stroke and peripheral arterial disease, all of which may be caused by arteriosclerosis. This study aimed to investigate the association of TB with arterial stiffness.Methods and results: In this cross-sectional study, we investigated the relationship between TB and baPWV in 2207 participants (1331 men, 876 women) in a general health examination. Different metabolic parameters were compared across TB quartiles. Age-adjusted mean values of baPWV gradually decreased with TB quartiles in men (Q1 = 1348, Q2 = 1266, Q3 = 1215, and Q4 = 1154 cm/s). However, the age-adjusted means of baPWV had no significance in women according to TB quartiles. Univariate analysis showed that age, smoking status, BMI, SBP, DBP, AST, ALT, GGT, TB, TG, and HDL-C were significantly associated with baPWV in men, whereas only age, BMI, SBP, DBP, TG and FPG were significantly associated with baPWV in women. In addition, BMI, SBP, TB, age, TG, and AST were significant factors in the multivariate model with baPWV in men; only BMI and FPG were significant factors with baPWV in women.Conclusion: The findings show that serum total bilirubin concentration is negatively correlated to arterial stiffness in Chinese men. Early detection of abnormal bilirubin levels could potentially serve as an early biomarker for arterial stiffness.

Plasma retinol: A novel marker for cardiovascular disease mortality in Australian adults - Corrected Proof

L. Brazionis, K.Z. Walker, C. Itsiopoulos, K. O’Dea — 2011-11-28

Abstract: Background and aims: Vitamin A affects inflammation and immune function and is thus a factor of interest in relation to cardiovascular disease (CVD). As vitamin A circulates in the plasma in the form of retinol, this study aims to describe the relationship between plasma retinol and the 5-year incidence of CVD mortality.Methods and results: Community-dwelling adults (n = 441, 45% with type 2 diabetes) were recruited in Melbourne, assessed at baseline and followed for 5 years. At baseline, CVD risk factors were assessed by clinical evaluation, by personal lifestyle questionnaire and from biochemistry (plasma fasting glucose, lipids, total homocysteine, C-reactive protein, retinol and carotenoids plus the urinary albumin excretion rate over 24 h.). Dietary intake was assessed by a validated food frequency questionnaire. CVD mortality over 5-years was determined by consulting state or national registries. The majority of participants had adequate plasma retinol concentrations (≥30 μg/dL). The final Cox regression model indicated that those in the highest tertile of plasma retinol (mean ± SD) 76 ± 14 μg/dL) had a significantly lower risk of 5-year CVD mortality (hazard ratio 0.27 [95% confidence interval 0.11, 0.68], P = 0.005), an effect that was not readily explained in terms of traditional CVD risk factors or dietary intake.Conclusion: In well-nourished older Australian adults, plasma retinol was inversely associated with CVD mortality via mechanisms apparently unrelated to established CVD risk factors and dietary intake.

Effect of quercetin on traits of the metabolic syndrome, endothelial function and inflammatory parameters in men with different APOE isoforms - Corrected Proof

2011-11-28

Abstract: Background and aims: The polyphenol quercetin may prevent cardiovascular diseases due to its vasorelaxant and anti-oxidative properties. We investigated the effects of quercetin on risk factors of atherosclerosis, biomarkers of inflammation and oxidative stress, depending on the apolipoprotein E (APOE) genotype.Methods and results: In a double-blind crossover study 49 healthy male subjects with APOE genotype 3/3 (n = 19), 3/4 (n = 22) and 4/4 (n = 8) consumed 150 mg/d quercetin or placebo for 8 weeks each, intermitted by a three-week washout phase. After each intervention, endothelial function, anthropometry, metabolic and inflammatory parameters were measured in the fasting and postprandial state following a standardized lipid-rich meal.Endothelial function was not changed. In all subjects combined, quercetin significantly decreased waist circumference (P = 0.004) and postprandial systolic blood pressure (P = 0.044). Postprandial triacylglycerol concentrations were significantly decreased and HDL-cholesterol concentrations increased after quercetin as compared to placebo consumption (P = 0.025). Quercetin also moderately increased levels of TNFα (P = 0.024). There was a significant gene–diet interaction for waist circumference and for body mass index (BMI).Conclusions: Quercetin supplementation improved some risk factors of cardiovascular disease, yet exerted slightly pro-inflammatory effects. Genotype-dependent effects were seen only on waist circumference and BMI.

Effect of dietary lipids on paraoxonase-1 activity and gene expression - Corrected Proof

G. Ferretti, T. Bacchetti — 2011-11-28

Abstract: Aims: Aim of the paper was to summarize the literature about the effect of dietary lipids on activity of paraoxonase-1 (PON1), a multifunctional enzyme associated with high density lipoprotein (HDL). PON1 exerts a protective effect against oxidative damage of cells and lipoproteins and modulates the susceptibility of HDL and LDL to atherogenic modifications such as homocysteinylation.Data synthesis: The present review shows evidence that the amount and the composition of dietary lipids are key factors in the modulation of PON1. The effect of dietary lipids is also modulated by PON1 polymorphisms. The molecular mechanisms involved include an effect on PON1 hepatic synthesis or secretion and/or modification of PON1 interactions with HDL. Changes of PON1 activity could also be related to dietary intake of oxidized lipids that behave as PON1 inhibitors.Conclusion: Dietary fatty acids by the modulation of PON1 gene expression and activity could constitute an useful approach for the prevention of human diseases associated with oxidative damage.

Corrected Proof

H. Blackburn — 2011-11-24

Mario Mancini and his international colleagues have produced a landmark volume on this complex subject, the universal plague of cardiovascular diseases (CVD). Unequaled in scope and detail, it engages most of the pioneers and those on the leading edge of research today. In 55 chapters, 120-odd experts treat the following 6 topics: nutrition and obesity; metabolic syndrome and diabetes; hypercholesterolemia and early atherosclerosis; nutrition, hypertension, and cardiovascular disease; hemostasis and thrombosis; and nutrition, metabolism, and aging.

Adiponectin in outpatients with coronary artery disease: Independent predictors and relationship with heart failure - Corrected Proof

2011-10-28

Abstract: Background and aims: Chronic heart failure (HF) is characterised by a neurohormonal dysfunction associated with chronic inflammation. A role of metabolic derangement in the pathophysiology of HF has been recently reported. Adiponectin, an adipose-tissue-derived cytokine, seems to play an important role in cardiac dysfunction. We investigated the variation of circulating adiponectin in patients with coronary artery disease (CAD), with or without HF, in order to identify its independent predictors.Methods and results: A total of 107 outpatients with CAD were enrolled in the study and divided into three groups: CAD without left ventricular systolic dysfunction (group 1); CAD with left ventricular dysfunction without HF symptoms (group 2) and CAD with overt HF (group 3). Plasma adiponectin was determined by enzyme-linked immunosorbent assay. Adiponectin concentrations increased progressively from group 1 (7.6 ± 3.6 ng ml−1) to group 2 (9.1 ± 6.7 ng ml−1) and group 3 (13.7 ± 7.6 ng ml−1), with the difference reaching statistical significance in group 3 versus 1 and 2 (p < 0.001). A multivariable model of analysis demonstrated that the best predictors of plasma adiponectin were body mass index, N-terminal pro-brain natriuretic peptide and high-density lipoprotein cholesterol. However, even after adjusting for all three independent predictors, the increase of adiponectin in group 3 still remained statistically significant (p = 0.015).Conclusion: Our data confirm the rise of adiponectin in overt HF. The levels of circulating adipokine seem to be mainly predicted by the metabolic profile of patients and by biohumoral indicators, rather than by clinical and echocardiographic indexes of HF severity.

Vegetarian diets and incidence of diabetes in the Adventist Health Study-2 - Corrected Proof

S. Tonstad, K. Stewart, K. Oda, M. Batech, R.P. Herring, G.E. Fraser — 2011-10-10

Abstract: Aim: To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2.Methods and Results: Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses.Conclusion: Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.

Association between modifiable lifestyle factors and residual lifetime risk of diabetes - Corrected Proof

L. Djoussé, J.A. Driver, J.M. Gaziano, J.E. Buring, I.M. Lee — 2011-10-10

Abstract: Background and aims: While clinical trials have reported beneficial effects of diet, exercise, and weight loss on incident diabetes in subjects with obesity or impaired glucose tolerance, little is known about the incremental benefit of not smoking and moderate drinking on diabetes risk. We sought to examine the association between modifiable lifestyle factors and residual lifetime risk of diabetes.Methods and Results: Prospective cohorts involving 20,915 men (1982–2008) and 36,594 women (1992–2008). Modifiable lifestyle factors and adiposity were ascertained at baseline in each cohort and incident diabetes was ascertained during follow up. The mean age at baseline was 53.5 y in men and 54.6 y in women. During an average follow up of 22.6 y in men and 13.0 y in women, 2096 men and 2390 women developed diabetes. At age 45 y, the residual lifetime risk of diabetes (95% CI) for men with 0, 1, 2, 3, and 4 + healthy lifestyle factors was 30.5 (27.3–33.7); 21.5 (19.9–23.0); 15.1 (13.9–16.3); 10.3 (9.1–11.5); and 7.3 (5.7–8.9) percent; respectively. Corresponding values for women were 31.4 (28.3–34.5); 24.1 (21.8–26.5); 14.2 (12.7–15.7); 11.6 (9.7–13.5); and 6.4 (4.2–8.6) percent, respectively.Conclusions: These data show an inverse and graded relation between desirable lifestyle factors and residual lifetime risk of diabetes in men and women. Not smoking and moderate drinking may have additional benefits when added to exercise, weight control, and diet.

The g.-469G>A polymorphism in the GPIHBP1 gene promoter is associated with hypertriglyceridemia and has an additive effect on the risk conferred by LPL defective alleles - Corrected Proof

S.P. Guay, D. Gaudet, D. Brisson — 2011-10-05

Abstract: Background and aims: Hypertriglyceridemia (hyperTG) is a component of the metabolic syndrome and a cardiovascular or pancreatitis risk factor. Although both genetic and environmental factors influence its expression, the biological component of hyperTG is still underestimated and has been reported in 10–20% of cases only. Given its key role in the lipolysis of TG-rich lipoproteins, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) is a biological candidate for hyperTG. The aim of this study was to assess the association of new GPIHBP1 gene variants with hyperTG (fasting plasma TG values≥2.0mmol/L).Methods and results: Sequencing the GPIHBP1 gene identified a g.-469G>A (rs72691625) polymorphism in the promoter. A sample of 541 Caucasians (263 normoTG and 278 hyperTG) was then screened for this polymorphism using a 5′nuclease TaqMan. In multivariate analyses, GPIHBP1 g.-469G>A polymorphism carriers were at significantly higher risk of hyperTG (≥2.0mmol/L) than non-carriers, the odds ratio (OR) being 1.67 (p=0.025) among heterozygotes and 5.70 (p=0.004) in homozygotes. The simultaneous presence of loss-of-function LPL polymorphisms had an incremental additive effect on the risk of hyperTG (OR: 7.30; p<0.001), highlighting the importance of gene–gene interactions in the expression of hyperTG.Conclusions: In this study, the g.-469G>A polymorphism in the GPIHBP1 gene promoter was associated with an increased risk of hyperTG and had an additive effect on the risk conferred by LPL defective alleles.

Increased plasma visfatin concentration is a marker of an atherogenic metabolic profile - Corrected Proof

2011-10-03

Abstract: Background and aims: Visfatin is associated with atherosclerosis-related diseases. We assessed in non-diabetic individuals the association of plasma visfatin levels with cardiovascular disease (CVD) risk and the atherosclerosis-related metabolic variables.Methods and results: When study population (n = 179, age 49 ± 11 years) was divided according to visfatin tertiles, the 10-year CVD Framingham risk scores were significantly increased in the top visfatin tertile. We observed a positive association between visfatin tertiles with waist circumference and blood pressure, as well as with total cholesterol and triglyceride levels, but not with apolipoprotein C-III, fibrinogen or pre-beta1 high density lipoprotein (HDL). The percentage of large HDL subclasses was significantly lower and the percentage of small HDL subclasses over the HDL-C concentration was significantly higher in the top visfatin tertile compared with the other tertiles. The atherogenic small dense low density lipoprotein subclasses (sdLDL-C) were significantly increased in the top visfatin tertile compared with the lower tertiles. High sensitivity C-reactive protein (hsCRP) concentration was significantly increased in the top visfatin tertile compared with the lower tertiles. Although age and sex distribution did not differ between visfatin tertiles, the simultaneous adjustment for these parameters attenuated the significance of the differences observed in sdLDL-C and hsCRP levels. Similarly, after adjustment for hsCRP or waist circumference, only triglycerides and blood pressure levels, as well as the distribution of HDL subclasses, remained significantly different between visfatin tertiles.Conclusions: Our results support a role for visfatin in the detection of subjects with many metabolic abnormalities, which result in increased CVD risk.

Lifestyle and nutrition related to male longevity in Sardinia: An ecological study - Corrected Proof

2011-09-28

Abstract: Background and aims: A demographic analysis in the Mediterranean island of Sardinia revealed marked differences in extreme longevity across the 377 municipalities and particularly identified a mountain inner area where the proportion of oldest subjects among male population has one of the highest validated value worldwide. The cause(s) of this unequal distribution of male longevity may be attributed to a concurrence of environmental, lifestyle and genetic factors.Methods and results: In this study we focussed on some lifestyle and nutrition variables recorded in the island’s population in early decades of 20th century, when agricultural and pastoral economy was still prevalent, and try to verify through ecological spatial models if they may account for the variability in male longevity. By computing the Extreme Longevity Index (the proportion of newborns in a given municipality who reach age 100) the island’s territory was divided in two areas with relatively higher and lower level of population longevity. Most nutritional variables do not show any significant difference between these two areas whereas a significant difference was found with respect to pastoralism (P = 0.0001), physical activity estimated by the average slope of the territory in each municipality (P = 0.0001), and average daily distance required by the active population to reach the usual workplace (P = 0.0001).Conclusion: Overall, these findings suggest that factors affecting the average energy expenditure of male population such as occupational activity and geographic characteristics of the area where the population mainly resides, are important in explaining the spatial variation of Sardinian extreme longevity.

Comparison of A1C, fasting and 2-h post-load plasma glucose criteria to diagnose diabetes in Italian Caucasians - Corrected Proof

2011-09-26

Abstract: Background and aims: The American Diabetes Association (ADA) has revised criteria for diagnosis of type 2 diabetes recommending an A1C cut point of ≥6.5% in addition to criteria based on glucose levels. We compared A1C, fasting plasma glucose (FPG) or 2-h post-challenge glucose (2-hPG) criteria for the diagnosis of diabetes in a cohort of Italian Caucasians.Methods and results: A total of 1019 individuals without known diabetes completed an oral glucose tolerance test (OGTT) and had A1C measured. Moderate agreement existed for A1C and FPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.522), with 85.5% of individuals classified as not having diabetes by both A1C and FPG criteria, and 5.8% classified as having diabetes by both A1C and FPG criteria. Discordant classifications occurred for 5.5% of individuals who had an A1C ≥ 6.5% and FPG <126 mg dl−1, and for 3.2% who had an A1C <6.5% and FPG ≥126 mg dl−1. Modest agreement existed for A1C and 2-hPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.427), with 81.8% of individuals classified as not having diabetes by both A1C and 2-hPG criteria, and 6.0% classified as having diabetes by both A1C and 2-hPG criteria. The area under the receiver operating characteristic curve of A1C for identifying subjects with diabetes according to FPG or 2-hPG criteria was 0.856 and 0.794, respectively. Modest agreement existed for A1C and FPG and/or 2-hPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.446).Conclusions: A1C ≥ 6.5% demonstrates a moderate agreement with fasting glucose and 2-hPG for diagnosing diabetes among adult Italian Caucasians subjects.

Metabolism of triglyceride-rich lipoproteins and transfer of lipids to high-density lipoproteins (HDL) in vegan and omnivore subjects - Corrected Proof

J.C. Vinagre, C.G. Vinagre, F.S. Pozzi, E. Slywitch, R.C. Maranhão — 2011-09-22

Abstract: Background and aims: Vegan diet excludes all foodstuffs of animal origin and leads to cholesterol lowering and possibly reduction of cardiovascular disease risk. The aim was to investigate whether vegan diet improves the metabolic pathway of triglyceride-rich lipoproteins, consisting in lipoprotein lipolysis and removal from circulation of the resulting remnants and to verify whether the diet alters HDL metabolism by changing lipid transfers to this lipoprotein.Methods and results: 21 vegan and 29 omnivores eutrophic and normolipidemic subjects were intravenously injected triglyceride-rich emulsions labeled with 14C-cholesterol oleate and 3H-triolein: fractional clearance rates (FCR, in min−1) were calculated from samples collected during 60 min for radioactive counting. Lipid transfer to HDL was assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids; % lipids transferred to HDL were quantified in supernatant after chemical precipitation of non-HDL fractions and nanoemulsion. Serum LDL cholesterol was lower in vegans than in omnivores (2.1 ± 0.8, 2.7 ± 0.7 mmol/L, respectively, p < 0,05), but HDL cholesterol and triglycerides were equal. Cholesteryl ester FCR was greater in vegans than in omnivores (0.016 ± 0.012, 0.003 ± 0.003, p < 0.01), whereas triglyceride FCR was equal (0.024 ± 0.014, 0.030 ± 0.016, N.S.). Cholesteryl ester transfer to HDL was lower in vegans than in omnivores (2.7 ± 0.6, 3.5 ± 1.5%, p < 0,05). Free-cholesterol, triglyceride and phospholipid transfer were equal, as well as HDL size.Conclusion: Remnant removal from circulation, estimated by cholesteryl oleate FCR was faster in vegans, but the lipolysis process, estimated by triglyceride FCR was equal. Increased removal of atherogenic remnants and diminution of cholesteryl ester transfer may favor atherosclerosis prevention by vegan diet.

Does cardiovascular phenotype explain the association between diabetes and incident heart failure? The Strong Heart Study - Corrected Proof

2011-09-22

Abstract: Background and aims: Diabetes remains a predictor of incident heart failure (HF), independent of intercurrent myocardial infarction (MI) and concomitant risk factors. Initial cardiovascular (CV) characteristics, associated with incident heart failure (HF) might explain the association of diabetes with incident HF.Methods and results: Participants to the 2nd Strong Heart Study exam, without prevalent HF or coronary heart disease, or glomerular filtration rate <30 mL/min/1.73 m2, were analyzed (n = 2757, 1777 women, 1278 diabetic). Cox regression of incident HF (follow-up 8.91 ± 2.76 years) included incident MI censored as a competing risk event. Acute MI occurred in 96 diabetic (7%) and 84 non-diabetic participants (6%, p = ns). HF occurred in 156 diabetic (12%) and in 68 non-diabetic participants (5%; OR = 2.89, p < 0.001). After accounting for competing MI and controlling for age, gender, BMI, systolic blood pressure, smoking habit, plasma cholesterol, antihypertensive treatment, heart rate, fibrinogen and C-reactive protein, incident HF was predicted by greater LV mass index, larger left atrium, lower systolic function, greater left atrial systolic force and urinary albumin/creatinine excretion. Risk of HF was reduced with more rapid LV relaxation and anti-hypertensive therapy. Diabetes increases hazard of HF by 66% (0.02 < p < 0.001). The effect of diabetes could be explained by the level of HbA1c.Conclusions: Incident HF occurs more frequently in diabetes, independent of intercurrent MI, abnormal LV geometry, subclinical systolic dysfunction and indicators of less rapid LV relaxation, and is influenced by poor metabolic control. Identification of CV phenotype at high-risk for HF in diabetes should be advised.

Type 2 diabetes mellitus: A disease of the governance of the glucose-insulin system: An experimental metabolic control analysis study - Corrected Proof

2011-09-21

Abstract: Background and aims: The relatives role of each component of the glucose-insulin system in determining hyperglycemia in type 2 diabetes is still under debate. Metabolic Control Analysis (MCA) quantifies the control exerted by each component of a system on a variable of interest, by computing the relevant coefficients of control (CCs), which are systemic properties. We applied MCA to the intravenous glucose tolerance test (IVGTT) to quantify the CCs of the main components of the glucose-insulin system on intravenous glucose tolerance.Methods and results: We combined in vivo phenotyping (IVGTT/euglycaemic insulin clamp) and in silico modeling (GLUKINSLOOP.1) to compute the CCs of intravenous glucose tolerance in healthy insulin-sensitive (n = 9, NGR-IS), healthy insulin-resistant (n = 7, NGR-IR) and subdiabetic hyperglycemic (n = 8, PreT2DM) individuals and in patients with newly diagnosed type 2 diabetes (n = 7, T2DM).Altered insulin secretion and action were documented in NGR-IR and PreT2DM groups, but only 1st phase insulin secretion was significantly lower in T2DM than in PreT2DM (p < 0.05). The CCs changed little in the nondiabetic groups. However, several CCs were significantly altered in the patients (e.g. CCs of beta cell: −0.75 ± 0.10, −0.64 ± 0.15, −0.56 ± 0.09 and −0.19 ± 0.04 in NGR-IS, NGR-IR, PreT2DM and T2DM, respectively; p < 0.01 by MANOVA), and they could not be corrected by matching in silico nondiabetic and T2DM groups for 1st phase secretion.Conclusions: Type 2 diabetes is characterized not only by loss of function of the elements of the glucose-insulin system, but also by changes in systemic properties (CCs). As such, it could be considered a disease of the governance of the glucose-insulin system.

Low serum 25-hydroxyvitamin D levels are associated with left ventricular hypertrophy in essential hypertension - Corrected Proof

2011-09-21

Abstract: Background and aim: Low serum 25-hydroxyvitamin D [25(OH)D] levels may have an important role in predisposing to hypertension and myocardial disease. We investigated the relationship between 25(OH)D and left ventricular (LV) structure and function, assessed by echocardiography, in a series of patients with essential hypertension (EH).Methods and results: Sixty-two newly diagnosed never-treated patients (32 male/30 female), aged 18–65 years, with grade 1–2 hypertension, no diabetes, no obesity, no hyperlipidemia, and no cardiopulmonary, renal, or hepatic disease, were studied. Twenty-four healthy normotensive sex-, age-, BMI-matched subjects served as controls. Hypertensive patients with 25(OH)D deficiency, defined as serum 25(OH)D levels <50 nmol/L, had higher prevalence of LV hypertrophy (LVH) than their 25(OH)D-sufficient counterparts (57.1 vs 17.6%, P = 0.02); no differences between the two groups were found in blood pressure levels as well as in other biochemical and hormone parameters. There was an inverse correlation between LV mass index and 25(OH)D levels (r = –0.366, P < 0.003) and a direct correlation between LV mass index and BMI (r = 0.333, P < 0.006) in the entire hypertensive population. The two variables remained independently associated with LVH at multivariable logistic regression analysis (OR 1.05, P < 0.005 and OR 1.25, P = 0.03, respectively). Prevalence of 25(OH)D deficiency was similar in EH patients and controls (45.1 vs 41.6%, P = 0.89), whereas no correlation between echocardiographic parameters and hormone levels was found.Conclusions: In the absence of major cardiovascular risk factors, 25(OH)D deficiency is a frequent finding in EH patients and is independently associated with LVH.

Lipid risk factors among elderly with normal fasting glucose, impaired fasting glucose and type 2 diabetes mellitus. The Italian longitudinal study on aging - Corrected Proof

M. Noale, S. Maggi, S. Zanoni, F. Limongi, S. Zambon, G. Crepaldi — 2011-09-21

Abstract: Background and aims: Three groups of subjects were identified within a representative sample of older Italians: subjects with normal fasting glucose (NFG), with impaired fasting glucose (IFG) or with type 2 diabetes mellitus (T2D). The aim of the present study was to evaluate the relationship among plasma lipids, lipoproteins, other metabolic factors in the three groups, and their role in predicting total fatal events.Methods and results: 2422 subjects, aged 65–84 years, taking part into the Italian Longitudinal Study on Aging were included in the analyses. Factor analysis was conducted separately for men and women. Factor scores were used as independent variables in Cox Proportional Hazard models, to determine factors predicting death at the follow-up in NFG, IFG and T2D subjects.Four major factors were found for men (“insulin resistance”, “body size”, “total cholesterol”, “HDL cholesterol”) and four also for women (“insulin resistance”, “total cholesterol”, “body size”, “HDL cholesterol”). For NFG and IFG men, and for both T2D men and women, the “HDL cholesterol” was a significant protective factor for total deaths (NFG men: HR = 0.79, 95% CI 0.67–0.93; IFG men: HR = 0.59, 95% CI 0.45–0.79; T2D men: HR = 0.55, 95% CI 0.34–0.89; T2D women: HR = 0.61, 95% CI 0.44–0.86). Among NFG women, the “body size” factor was also a protective factor with respect to total deaths (HR = 0.74, 95% CI 0.57–0.95).Conclusion: A factor including HDL Cholesterol and Apo A-I showed protection against all-cause mortality in older men, independently from the glycemia level, and in women only in those diagnosed with T2D.

Folate and risk of coronary heart disease: A meta-analysis of prospective studies - Corrected Proof

2011-09-19

Abstract: Background and aims: Epidemiologic studies are inconsistent regarding the association between folate and coronary heart disease (CHD) risk. The aim was to perform a meta-analysis to determine whether an association exists between folate and total CHD endpoints in prospective studies.Methods and results: We searched the PUBMED and EMBASE databases for studies conducted from 1966 through August 2010. Data were independently abstracted by 2 investigators using a standardized protocol. Study-specific risk estimates were combined by using a random effects model.A total of 14 studies were included in the meta-analysis: 7 studies on dietary folate intake and 8 studies on blood folate levels. For dietary intake, the summary relative risk (RR) indicated a significant association between the highest folate intake and reduced risk of CHD (summary RR: 0.69; 95% CI: 0.60, 0.80). Furthermore, an increase in folate intake of 200 ug/day was associated with a 12% decrease in the risk of developing CHD (summary RR: 0.88; 95% CI: 0.82, 0.94). For blood folate levels, we also found a borderline inverse association of highest blood folate levels on CHD risk (summary RR: 0.74; 95% CI: 0.53, 1.02); our dose-response analysis indicated that an increment in blood folate levels of 5 mmol/l was associated with an 8% decrease in the risk of developing CHD (summary RR: 0.92; 95% CI: 0.84, 1.00).Conclusion: This meta-analysis suggests that dietary folate intake and blood folate level are inversely associated with CHD risk.

Effect of fish oil supplementation on serum triglycerides, LDL cholesterol and LDL subfractions in hypertriglyceridemic adults - Corrected Proof

B. Oelrich, A. Dewell, C.D. Gardner — 2011-09-19

Abstract: Background and aims: The well-established triglyceride (TG) lowering effect of fish oil is accompanied by an increase in LDL-cholesterol (LDL-C) concentration. Less is known about the differential impact on LDL particle distribution – the smaller particles being associated with a greater risk for atherosclerosis. We aimed to examine the changes in serum concentrations of four subclasses of LDL particles as well as shifts in LDL phenotype patterns (A, B, AB) among hypertriglyceridemic adults.Methods and results: This was a secondary analysis from a double-blind, parallel design, placebo controlled trial with 42 adults that experienced significant TG lowering and modest increases in total LDL-C concentrations after 12 weeks of 4 g/d EPA + DHA. Reduction in serum TG concentrations (mean ± SEM) was −26 ± 4% (−0.81 ± 10.12 mmol/L), p < 0.0001. Total LDL-C concentration increased by 13 ± 3% (+0.31 ± 0.08 mmol/L), p < 0.0001. The 12-week changes in concentrations of LDL1, LDL2, LDL3 and LDL4 were +0.06 ± 0.02 mmol/L [+2.2 ± 0.7 mg/dL], +0.07 ± 0.03 mmol/L [+2.6 ± 1.0 mg/dL], +0.16 ± 0.05 mmol/L [+6.3 ± 1.8 mg/dL], and +0.04 ± 0.04 mmol/L [+1.4 ± 1.7 mg/dL], respectively (+20 ± 5%, +64 ± 13%, +26 ± 6%, and +17 ± 9%), p < 0.05 for all but LDL4. Changes in LDL phenotype patterns A, B and A/B were negligible and not statistically significant.Conclusion: In this population of hypertriglyceridemic adults, dietary supplementation with fish oil resulted in an increase in total LDL-C concentration which was distributed relatively evenly across the range of smaller and more atherogenic as well as larger and less atherogenic LDL particles.

Patient- and physician-level determinants of blood pressure response to treatment in normal weight and overweight patients (the PREVIEW study) - Corrected Proof

2011-09-19

Abstract: Background and aims: Obesity combined with hypertension places patients at greater risk for target-organ damage and cardiovascular disease. The purpose of this secondary analysis was to identify physician- and patient-levels determinants of blood pressure (BP) values and predictors of uncontrolled BP through subgroup analysis by body mass index (BMI).Methods and results: We conducted a subgroup analysis of 3006 patients with High-BMI (BMI >25kg/m2; n=2124) and Normal-BMI (BMI<25kg/m2; n=882) treated by 504 physicians and enrolled in PREVIEW, a Belgian prospective, multi-center, pharmaco-epidemiological study of 90-day second-line treatment with valsartan. Physician- and patient-level determinants of BP values and BP control were identified by means of hierarchical linear and logistic regression.Blood pressure values and control after 90 days of treatment were consistently lower for the High-BMI group. The 25.5% of variance in 90-day systolic and 28.3% of the variance in 90-day diastolic BP were attributable to physician-level determinants for the High-BMI group; versus 27.3% and 29.8% for the Normal-BMI group (ICC=0.273 and 0.298, respectively). Determinants of 90-day BP values and predictors of uncontrolled BP varied considerably by BMI status.Conclusion: Several common and unique patient- and physician-level determinants of BP values and control were identified for the High-BMI and Normal-BMI groups. These findings highlight the need for differentiating healthcare interventions to account for patient and physician variables, particularly with respect to effective BP management in vulnerable populations.

Association of fatty acid composition in serum phospholipids with metabolic syndrome and arterial stiffness - Corrected Proof

O.Y. Kim, H.H. Lim, M.J. Lee, J.Y. Kim, J.H. Lee — 2011-09-19

Abstract: Background and aim: We examined the association of fatty acid (FA) composition in serum phospholipids with the features of metabolic syndrome (MetS) and arterial stiffness.Methods: Korean men (n=593, 30–79yrs) were categorized based on the number of MetS risk factors (RFs) and measured for the markers of MetS, serum phospholipid FA composition and brachial-ankle pulse wave velocity (baPWV), an index for the severity of arterial stiffness.Results: Insulin resistance (HOMA-IR), baPWV, LDL size, and adiponectin were significantly altered corresponding to the number of MetS RFs. The proportions of total monounsaturated FA, palmitoleic acid (16:1), oleic acid (18:1ω-9) and dihomo-γ-linolenic acid (DGLA, 20:3ω-6) in serum phospholipids, and DGLA/linoleic acid (LA) (20:3ω-6/18:2ω-6), deta9-desaturase activity (D9D-16: 16:1/16:0 and D9D-18: 18:1ω-9/18:0) significantly increased corresponding to the number of MetS RFs, but D5D (20:4ω-6/20:3ω-6) decreased. baPWV positively correlated with HOMA-IR, palmitic acid (16:0), oleic acid, D6D (18:3ω-6/18:2ω-6), DGLA/LA and D9D-18, and negatively with adiponectin, LDL size, LA, docosahexaenoic acid (DHA, 22:6ω-3) and D5D. Multiple stepwise regression models revealed that baPWV was significantly influenced by systolic blood pressure, age, body weight, triglyceride and LA in serum phospholipids (R2=0.378). Interestingly, baPWV (1419±1cm/s) and MetS (22%) were highest in individuals with lower proportion of LA (<12.361%) and higher proportion of DGLA (≥1.412%) in serum phospholipid FAs.Conclusion: The features of MetS significantly related to serum phosopholipid FA composition. Particularly, arterial stiffness was associated with LA additively together with DLGA. It may suggest a potential benefit of sufficient amounts of LA in serum or in diet can reduce cardiovascular risk.

FXR activation improves myocardial fatty acid metabolism in a rodent model of obesity-driven cardiotoxicity - Corrected Proof

2011-09-19

Abstract: Background and aims: Obesity-driven lipotoxicity is a risk factors for cardiovascular disease. The Farnesoid X Receptor (FXR) is a bile acids sensor and member of the nuclear receptor superfamily. Activation of FXR lowers plasma triacylglycerols and glucose levels through a mechanism that involves both the repression of key regulatory genes in the liver and the modulation of insulin sensitivity in peripheral tissues. In the present study we have investigated whether administering obese (fa/fa) Zucker rats, a genetic model of obesity associated with dyslipidemia and insulin resistance, with an FXR ligand protects against lipid-induced cardiomyopathy.Methods and results: FXR is expressed in neonatal cardiomyocytes and the treatment with FXR agonists, chenodeoxycholic acid (CDCA), and GW4064, increased the mRNA expression of FXR and its canonical target gene, the small heterodimer partner (SHP), as well as proliferator-activated receptor alpha PPARα, acyl-CoA oxidase (AOX) and pyruvate dehydrogenase kinase (PDK-4). Feeding obese fa/fa rats with CDCA, 12 weeks, reduced hyperinsulinemia and hyperlipidaemia. The histological–pathological analysis of hearts demonstrated that treatment with the FXR ligand reduced lipid heart content decreased the rate of apoptosis, fibrosis scores and restored heart insulin signalling. Chronic CDCA administration, in the heart, induced PPARα and PPARα-regulated genes involved in β-oxidation.Conclusion: FXR agonism exerts beneficial effects in a genetic model of lipid-induced cardiomyopathy. The striking benefit of this therapy on cardiac function in this model warrants an effort to determine whether a counterpart of this activity translates in human settings.

Leucine 10 allelic variant in signal peptide of PCSK9 increases the LDL cholesterol-lowering effect of statins in patients with familial hypercholesterolaemia - Corrected Proof

L. Pisciotta, R. Sallo, C. Rabacchi, A. Wunsch, S. Calandra, S. Bertolini — 2011-09-15

Abstract: Background and aims: In the normal population, carriers of an additional leucine residue in a stretch of nine leucines in the signal peptide of PCSK9 (L10) have lower total (TC) and low-density lipoprotein cholesterol (LDL-C) than homozygotes for the wild-type allele (L9/L9). A similar effect was detected in familial hypercholesterolaemia (FH) patients with the p.C681X mutation of LDL-receptor (LDLR). We investigated the effect of L10 variant on basal lipid profile and response to statins in molecularly characterised FH patients.Methods and results: Plasma lipids were determined in 322 FH patients screened for the L9/L10/L11 polymorphism and in a subgroup of 54 patients carrying the same LDLR mutation (p.Q474HfsX63). Plasma lipids were also determined in 42 FH patients carrying the L10 variant and in a parallel group of 42 FH patients, L9/L9 homozygotes, matched for gender, age, type of LDLR gene mutation, as well as for type, dose and duration of statin treatment. In FH patients, no difference in the basal plasma TC and LDL-C levels was observed between carriers of L10 variant (L9/L10+L10/L10) and L9/L9 homozygotes. The same was true in FH patients carrying the p.Q474HfsX63 LDLR mutation. In the subgroups of statin-treated patients, the reduction of TC and LDL-C was greater in carriers of L10 (−34.0% and −42.5%, respectively) than in L9/L9 homozygotes (−27.5% and −34.3%, respectively) (P<0.001).Conclusion: The variant L10 of the leucine repeats in PCSK9 signal peptide is to be considered as a factor capable of modulating the lipid-lowering effects of statins in FH.

Postprandial triglyceridemia after single dose of alcohol in healthy young men - Corrected Proof

E. Mudráková, R. Poledne, J. Kovář — 2011-09-15

Abstract: Background and Aims: Moderate alcohol consumption provides protection against cardiovascular disease primarily due to increase of HDL-cholesterol. However, it also has some adverse effects on metabolism of triglycerides (TG). Therefore, we addressed the question how a single dose of alcohol affects postprandial lipemia and activities of two enzymes playing a critical role in regulation of triglyceridemia, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL).Methods and Results: Eight healthy volunteers were given a single dose of alcohol (vodka; 0.6 g of ethanol/kg of body weight) together with a fat load (0.7 g of fat/kg of body weight) in an experimental breakfast or together with dinner 12 h before the experimental breakfast. In comparison to control experiment, alcohol given with breakfast induced increased and prolonged postprandial response of triglyceride-rich lipoproteins (TRL; d < 1.006 g/ml). At the same time TG accumulated also in intermediate density lipoproteins (IDL; d 1.006–1.019 g/ml). Alcohol given in the evening before the experiment increased fasting TG concentration but did not affect changes in TRL and IDL concentrations. LPL activity measured both in vivo using intravenous fat tolerance test and in vitro and HTGL activity were determined at the end of experiments (after 7.5 h of postprandial lipemia study). Neither was affected by a single dose of alcohol.Conclusions: Single dose of alcohol induces immediate and profound changes in metabolism of TRL and IDL. The same dose of alcohol given 12 h before meal does affect baseline TG concentration but not the postprandial changes of triglyceridemia.

Hyperleptinemia is associated with hypertension, systemic inflammation and insulin resistance in overweight but not in normal weight men - Corrected Proof

2011-09-15

Abstract: Background and Aim: High leptin (LPT) is associated with high blood pressure (BP), insulin resistance and systemic inflammation but also excess body weight and adiposity. To disentangle these multiple relations, we analyzed BP, HOMA and circulating C-reactive protein concentration (hs-CRP) in white male adults with different LPT levels but similar age, body mass index (BMI) and body fat distribution. The novel aspect is the different statistical approach used to investigate the relation between LPT and the other alterations present in obesity.Methods and Results: 972 Olivetti Heart Study participants were stratified according to the median LPT distribution (2.97 ng/ml) into low LPT (l-LPT) and high LPT (h-LPT). The two groups were then carefully matched for age and BMI. We identified two groups of 207 h-LPT and 207 l-LPT individuals with overlapping age, BMI and waist/hip ratio. The two groups had different BP (132.9 ± 16.2/85.7 ± 9.0 vs 128.7 ± 18.2/82.8 ± 9.8 mmHg, p = 0.014 for SBP and p = 0.002 for DBP) and prevalence of hypertension (57% vs 43%, p = 0.027). Upon separate evaluation of untreated individuals with BMI < 25 or BMI ≥ 25, within the latter subgroup h-LPT compared with l-LPT participants (n = 133 each group) had higher BP (p = 0.0001), HOMA index (p = 0.013), hs-CRP (p = 0.002) and heart rate (p = 0.008) despite similar age and BMI. By contrast, within the normal weight subgroup, h-LPT individuals did not differ from l-LPT (n = 37 each) for any of these variables.Conclusions: High LPT is associated with higher BP, HR, hs-CRP and HOMA index independently of BMI and fat distribution but only among overweight individuals.

ENPP1 mRNA levels in white blood cells and prediction of metformin efficacy in type 2 diabetic patients: A preliminary evidence - Corrected Proof

2011-09-15

Metformin is the “first choice” oral hypoglycemic agent (OHA) in type 2 diabetes mellitus (T2DM) . The efficacy of metformin varies across individuals , supposedly due to environmental and genetic factors. Genetic predictors of metformin efficacy are mostly unknown, with few exceptions . Unraveling such predictors would help tailoring metformin treatment. We investigated the role of mRNA levels in white blood cells (WBCs) of ENPP1, an inhibitor of insulin-receptor signaling, in predicting the efficacy of metformin. Sixty-two Italian patients of European ancestry with T2DM (age: 40–70 yrs; disease duration: 2–25 yrs; HbA1c: 6.5–9%; no insulin therapy) were studied. Previous OHA were discontinued for 5 days before adding metformin (2550 mg/daily). BMI, overnight fasting glucose, insulin, triglycerides, HDL-cholesterol were measured before and after 3-month metformin treatment. ENPP1 mRNA levels were measured by quantitative RT-PCR in WBCs. After metformin treatment, there was an improvement in BMI (32.7 ± 7.2 vs. 31.8 ± 7.1 kg/m2, p men) and baseline fasting glucose (the higher baseline glucose level, the higher treatment efficacy), but not age, disease duration, BMI and HOMA-IR. Gender (p < 0.005), fasting glucose (p < 0.001) and ENPP1 mRNA (p < 0.05) remained independent predictors of metformin efficacy in a model comprising also duration of T2DM and BMI (age and HOMA-IR were not tested because of their collinearity with disease duration and fasting glucose). The multivariate r2 were 0.46 and 0.41 (p = 0.002) in the model with and without ENPP1. The mechanism through which ENPP1 modulates metformin efficacy might be due to their opposite effect on insulin signaling. Metformin is reported to up-regulate IRS-1 expression via AMP-activated protein kinase to suppress hyperglycemia-induced IRS-1 deactivation and to exert a positive effect on insulin-receptor number and function . All these effects on insulin signaling may well explain why metformin treatment seems to be particularly advantageous in individuals whose insulin-receptor activation is down-regulated, as it is the case for those over-expressing ENPP1 .

IRS1 gene variants, dysglycaemic metabolic changes and type-2 diabetes risk - Corrected Proof

2011-09-15

Abstract: Background and aims: A recent genome-wide association study identified rs2943641C > T, 500 kb from the insulin receptor substrate-1 gene (IRS1), as a type-2 diabetes (T2D) susceptibility locus. We aimed to replicate this association by meta-analysis and examine whether common variants within IRS1, present on the HumanCVD BeadChip, were associated with T2D risk.Methods and results: We genotyped rs2943641 in 2389 prevalent or incident T2D patients and 6494 controls from two prospective and three case studies based in UK and in the European Atherosclerosis Research Study-II (EARSII; n = 714). Thirty-three IRS1 variants had been genotyped in the prospective Whitehall-II study (n = 4752) using the HumanCVD BeadChip. In a fixed-effects meta-analysis of the UK study cohorts rs2943641T allele was associated with 6% lower risk of T2D (p = 0.18), with T-allele carriers having an odds ratio (OR) of 0.89 (95% confidence interval [CI]: 0.80–1.00, p = 0.056) compared to CC subjects. The T-allele was also associated with lower fasting insulin and homeostasis model assessment index of insulin resistance in Whitehall-II and with lower post-load insulin after an oral glucose tolerance test in EARSII (all p G showed association with reduced T2D risk (OR per G-allele: 0.82, 95%CI: 0.69–0.96, p = 0.015).Conclusions: We confirm the association of rs2943641T with T2D protection. There is a possible independent effect on risk of a putative IRS1 promoter variant.

Impact of metabolic syndrome on clinical outcomes after new generation drug-eluting stent implantation: The ‘obesity paradox’ phenomenon is still apparent - Corrected Proof

2011-09-14

Abstract: Background and aim: New generation drug-eluting stents (DES) have improved clinical outcomes. However, their impact on patients with metabolic syndrome (MS) is still unclear as there is no sufficient data. Therefore, we evaluated the impact of the new generation DES on patients with an isolated lesion in the proximal segment of the left anterior descending artery (pLAD) suffering from MS.Methods and results: We evaluated 511 patients with a pLAD lesion. Of these, 147 patients had MS. The major adverse cardiac events (MACE) including death, non-fatal myocardial infarction (MI) and target lesion revascularization (TLR) were defined as primary end points. Stent thrombosis was also evaluated. MACEs had a trend to be higher in non-MS group (8.24% vs 3.40%, p = 0.05) during 20 months mean follow-up period. Rates of cardiac death (1.37% vs 0.68%, p = 0.67), non-fatal MI (1.92% vs 0.0%, p = 0.20), TLR (4.94% vs 2.04% MS, p = 0.21) and thrombosis (3.29% vs 1.36%, p = 0.36) were not significantly different in non-MS and MS group. The Kaplan–Meier curve revealed: MS group: 96.59% vs non-MS group: 91.75% (p = 0.04). MS was a favorable independent predictor for MACE (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.12–0.93, p < 0.03). In addition, independent predictors for MACE were BMI ≥ 30 kg/m2 (HR 0.87 95% CI 0.79–0.96 p = 0.008) and diabetes mellitus (HR 2.01 95% CI 0.99–4.11, p = 0.05).Conclusion: The ‘obese paradox’ phenomenon is found in the era of new generation DES. In order to investigate the underlying mechanism for this phenomenon further studies are required.

Direct costs in diabetic and non diabetic people: The population-based Turin study, Italy - Corrected Proof

2011-09-12

Abstract: Background and aims: We compared direct costs of diabetic and non diabetic people covered by the Italian National Health System, focusing on the influence of age, sex, type of diabetes and treatment.Methods and results: Diabetic people living in Turin were identified through the Regional Diabetes Registry and the files of hospital discharges and prescriptions. Data sources were linked to the administrative databases to assess health care services used by diabetic (n = 33,792) and non diabetic people(n = 863,123). Data were analyzed with the two-part model; the estimated direct costs per person/year were €3660.8 in diabetic people and €895.6 in non diabetic people, giving a cost ratio of 4.1. Diabetes accounted for 11.4% of total health care expenditure. The costs were attributed to hospitalizations (57.2%), drugs (25.6%), to outpatient care (11.9%), consumable goods (4.4%) and emergency care (0.9%). Estimated costs increased from € 2670.8 in diabetic people aged <45 years to € 3724.1 in those aged >74 years, the latter representing two third of the diabetic cohort; corresponding figures in non diabetic people were € 371.6 and € 2155.9. In all expenditure categories cost ratios of diabetic vs non diabetic people were higher in people aged <45 years, in type 1 diabetes and in insulin-treated type 2 diabetes.Conclusion: Direct costs are 4-fold higher in diabetic than in non diabetic people, mainly due to care of the elderly and inpatient care. In developed countries, demographic changes will have a profound impact on costs for diabetes in next years.

Plasma cytokines, glomerular filtration rate and adipose tissue cytokines gene expression in chronic kidney disease (CKD) patients - Corrected Proof

2011-09-09

Abstract: Background and Aim: Systemic inflammation is a hallmark of chronic kidney disease (CKD) and obesity represents a major risk factor for CKD. We investigated the relationship between plasma interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) and the glomerular filtration rate (GFR) in 75 stage 2–5 CKD patients.Methods and Results: We studied the steady-state relationship between plasma and subcutaneous adipose tissue (SAT) gene expression of the same cytokines in 19 patients and in 17 well-matched healthy subjects (HS) and compared SAT gene expression of these cytokines and of two additional cytokines (IL-1β and IL-8) in CKD patients and in HS.Plasma IL-6 and TNF-α were higher in CKD patients than in HS (P < 0.001). IL-6 was similarly increased in patients with mild, moderate and severe CKD and largely independent of the GFR (r = −0.03, P = NS). TNF-α was inversely related to GFR, which was the first factor in rank (β = −0.37, P = 0.001) explaining the variability in TNF-α in CKD. SAT messenger RNA (mRNA) levels of IL-6, TNF-α, IL- β and IL-8 were similar in CKD patients and in HS. Plasma and SAT mRNA levels of IL-6 and TNF-α levels were largely unrelated.Conclusions: Plasma IL-6 rises early in CKD and does not show any further increase at more severe stages of CKD, whereas TNF-α is inversely associated with the GFR indicating a substantial difference in the dynamics of the relationship between these cytokines and renal function. Cytokines are not overexpressed in SAT in these patients, and circulating IL-6 and TNF-α are dissociated from the corresponding mRNA levels in SAT, both in CKD patients and in HS.

Anthropometric indices of fat distribution and cardiometabolic risk in Parkinson’s disease - Corrected Proof

E. Cereda, E. Cassani, M. Barichella, R. Caccialanza, G. Pezzoli — 2011-09-09

Abstract: Background & aims: To investigate the association between anthropometric indices of body fat distribution and cardiometabolic risk factors in a population of Parkinson’s disease (PD) patients.Methods & results: One hundred and fifty-seven PD patients (57.3% males) were studied measuring: waist circumference (WC), waist-hip ratio (WHR), waist-to-height ratio (WtHR), body fat percentage (BF%) by impedance, fasting glucose, serum lipids. Information was collected also on diabetes, hypertension and metabolic syndrome (MetS). Increased cardiometabolic risk was defined by ≥2 MetS component traits other than abdominal adiposity. In the whole population, prevalence of overweight and obesity were 35.0% and 19.2%, respectively. However, prevalence of MetS and elevated cardiometabolic risk were 14.6% and 18.5%, respectively. Prevalence was similar between genders, with one exception: adverse fat distribution according to WC and WHR was more common in females (P < 0.001). Using a multivariable model (adjustments: age, smoking status and disease duration), indices were highly correlated with BF% in both genders. WC and WtHR were associated with the number of MetS criteria and elevated risk. The only cardiometabolic parameters associated with anthropometric indices were HDL in men and triglycerides in women. After adjusting also for BMI all the associations found with anthropometric indices disappeared.Conclusions: Despite their correlation with BF%, anthropometric indices of body fat distribution appear to poorly account for the reduced cardiometabolic risk of the PD patient. This finding suggests a low metabolic activity within the adipose tissue. The implications of fat distribution on the cardiometabolic risk of PD patients clearly deserves further investigation.

Gender-specific differences in carotid intima-media thickness and its progression over three years: A multicenter European study - Corrected Proof

2011-09-09

Abstract: Background and aims: This multicentre European study evaluated, in a young-to-middle-aged healthy population without carotid atherosclerosis, the gender-related differences in carotid intima-media thickness (IMT) and its short-term (3-year) progression, and whether these differences are related to different vascular ageing rate, cardiovascular risk profile or different susceptibility to family predisposition to cardiovascular diseases (CVD).Methods and results: 366 men and 422 women (age between 30 and 60 years) underwent B-mode carotid ultrasound at baseline and after 3-year follow-up period. IMT in 3 carotid segments was higher in men than in women (p < 0.0001 for all segments). When evaluated according to age decade, differences between men and women disappeared in the 6th decade, as in this decade a 3-year IMT progression rate accelerated in women (p < 0.05 as compared to the 4th and 5th age decade). Age was a major determinant of baseline all-segment IMT in women; in men all-segment IMT was influenced by age and LDL-cholesterol. IMT progression did not correlate with established cardiovascular risk factors, their short-term changes or family predisposition to CVD. Yet, a 3-year IMT progression in common carotid artery (CCA) was higher in men (p = 0.01) and women (p < 0.01) in whom relative Framingham risk increased during the corresponding period.Conclusion: This study provides reference values on IMT and its short-term progression in healthy young-to-middle-aged population, and demonstrates gender-related differences in the susceptibility of carotid wall to ageing and LDL-cholesterol. Increase in Framingham risk accelerated a short-term CCA IMT progression rate in both genders, whereas family predisposition to CVD did not influence carotid IMT.

The preventive effects of dark chocolate on impaired endothelial function in medical personnel working sequential night shifts - Corrected Proof

2011-09-07

Recent study have reported that brachial artery endothelial function, which is measured as flow-mediated dilatation (FMD), was impaired in medical residents working night shifts and in situation of mental stress . Flavanols, the polyphenolic family of antioxidants abundantly present in fruits and vegetables, may provide vascular protection against cardiovascular disease (CVD) . The physiological mechanism remains obscure, but studies have suggested that the vascular protection is partly due to antioxidant properties and increased NOx bioavailability through increased NOx synthase activity . Therefore, this study was designed to assess the preventive effects of flavanol-rich dark chocolate on endothelial dysfunction in healthy medical personnel working night shifts.

Consumption of fried foods and weight gain in a Mediterranean cohort: The SUN project - Corrected Proof

2011-08-09

Abstract: Background and aims: The consumption of fried foods is believed to be linked with obesity and higher weight gain, however, the evidence from long-term randomized trials or prospective epidemiological studies is scarce. Therefore, the aim of our study was to prospectively evaluate the association between the consumption of fried foods and weight change and the incidence of overweight/obesity in a Mediterranean cohort.Methods and results: Prospective cohort study of 9850 men and women with a mean age of 38.1 years (SD 11.4) were followed-up for a median of 6.1 years to assess average yearly change in body weight, and incidence of overweight/obesity. The consumption of fried foods was associated with higher weight gain, but the differences were of small magnitude and statistically non-significant. The incidence of overweight/obesity during follow-up was also assessed in the subset of 6821 participants with initial body mass index <25 kg/m2 (initially free of overweight/obesity), after adjusting for potential confounders, the odds ratio for developing overweight/obesity among participants who consumed fried foods >4 times/week was 1.37 (95% confidence interval: 1.08 to 1.73) in comparison with those who consumed fried foods <2 times/week (p for trend = 0.02).Conclusion: In this Mediterranean prospective cohort, a more frequent consumption of fried foods at baseline was associated with a higher risk of subsequently developing overweight/obesity during follow-up.

Cocoa consumption reduces NF-κB activation in peripheral blood mononuclear cells in humans - Corrected Proof

2011-08-08

Abstract: Background and aims: Epidemiological studies have demonstrated an association between high-polyphenol intake and reduced incidence of atherosclerosis. The healthy effects of cocoa-polyphenols may be due to their antioxidant and anti-inflammatory actions, although the exact mechanisms are unknown and depend on the matrix in which cocoa-polyphenols are delivered. Nuclear factor κB (NF-κB) is a key molecule in the pathophysiology of atherosclerosis involved in the regulation of adhesion molecules(AM) and cytokine expression and its activation is the first step in triggering the inflammatory process. The aim of this study was to evaluate the effect of acute cocoa consumption in different matrices related to the bioavailability of cocoa-polyphenols in NF-κB activation and the expression of AM.Methods and results: Eighteen healthy volunteers randomly received 3 interventions: 40g of cocoa powder with milk (CM), with water (CW), and only milk (M). NF-κB activation in leukocytes and AM (sICAM, sVCAM, E-selectin) were measured before and 6h after each intervention. Consumption of CW significantly decreased NF-κB activation compared to baseline and to CM (P < 0.05, both), did not change after CM intervention, and significantly increased after M intervention (P = 0.014). sICAM-1 concentrations significantly decreased after 6h of CW and CM interventions (P ≤ 0.026; both) and E-selectin only decreased after CW intervention (P = 0.028). No significant changes were observed in sVCAM-1 concentrations.Conclusions: The anti-inflammatory effect of cocoa intake may depend on the bioavailability of bioactive compounds and may be mediated at least in part by the modulation of NF-κB activation and downstream molecules reinforcing the link between cocoa intake and health.

Lower endothelial progenitor cell number, family history of cardiovascular disease and reduced HDL-cholesterol levels are associated with shorter leukocyte telomere length in healthy young adults - Corrected Proof

2011-08-08

Abstract: Background and aims: Leukocyte telomere length (LTL) is a novel marker of cardiovascular (CV) risk. The aim of the study was to investigate the major determinants of LTL in a healthy young population at very low CV risk.Methods and results: LTL was determined in 82 healthy subjects (49M/33F; age37 ± 9yrs), normotensive and not taking any medication with different family history of cardiovascular disease (CVD) (24yes/58no). Fasting blood samples were drawn in all subjects for the determination of lipid profile, high sensitive C-reactive protein, uric acid, Plasminogen Activator Inhibitor-1 (PAI-1), LTL and Endothelial Progenitor Cell (EPC) number. LTL was assessed with a specific real-time PCR reaction in leukocyte DNA samples.LTL resulted inversely correlated with family history of CVD (t = 2.70; p = 0.009), age (r = −0.238; p = 0.032), waist circumference (r = −0.256; p = 0.02), triglycerides (r = −0.218; p = 0.049), PAI-1 (r = −0.288; p = 0.009) and directly correlated with HDL-cholesterol (r = 0.316; p = 0.004) and EPC number (r = 0.358; p = 0.002). At a multivariate analysis, family history of CVD (p = 0.013), EPC count (p = 0.003), and HDL-cholesterol (p = 0.017) were independently associated with LTL (r = 0.62).Conclusion: LTL is independently associated to CV risk factors also in healthy young adults.

Flaxseed dietary fibers suppress postprandial lipemia and appetite sensation in young men - Corrected Proof

2011-08-01

Abstract: Background and aim: Dietary fibers (DF) are linked to a reduced risk of life-style diseases, which relate to their physiological effects in the gastrointestinal tract. The aim was to examine whether flaxseed DF-enriched meals suppress postprandial lipemia and reduce appetite.Methods and results: Four different iso-caloric meals were tested in 18 young men in a double-blind randomized crossover design. Test meals were served after an overnight fast. DF content and source were: control (C): 1.4 g/MJ; whole flaxseed (WF): 2.4 g/MJ from whole flaxseeds; low-mucilage dose (LM): 2.4 g/MJ from flaxseed DF; high-mucilage dose (HM): 3.4 g/MJ from flaxseed DF. During the 7 h test day, subjective appetite sensation was assessed using visual analogue scales and appetite-regulating hormones, and lipemia and glycemia were measured, after which ad libitum energy intake was recorded. There was a significant time × meal effect on triacylglycerols (TG) (p = 0.02) and an 18% smaller area under the curve (AUC) for TG after meal HM compared to meal C was observed (p < 0.01). AUC for insulin was smaller after both LM and HM meals compared to C and WF meals. Higher mean ratings of satiety (p < 0.01) and fullness (p = 0.03) was seen following the HM meal compared to meal C. AUC for ghrelin, CCK and GLP-1 and ad libitum energy intake did not differ between meals, but ghrelin response exhibited a different response pattern after the mucilage-containing meals.Conclusion: These findings suggest that flaxseed DF may suppress postprandial lipemia and appetite although subsequent energy intake was not affected.