Nutrition, Metabolism & Cardiovascular Diseases - Articles in Press

Metabolic syndrome in adolescents in the Balearic Islands, a Mediterranean region - Corrected Proof

2010-03-08

Abstract: Background and aims: To determine the prevalence of metabolic syndrome (MetS) and its components in adolescents in the Balearic Islands, in the western Mediterranean Sea.Methods and results: A cross-sectional nutritional survey was carried out in the Balearic Islands (2007–2008). A random sample (n=362, 143 boys and 219 girls) of the adolescent population (12–17years) was interviewed, anthropometrically measured, and provided a fasting blood sample. The MetS prevalence was determined by the ATP III criteria adapted for youths. Adherence to the Mediterranean diet (MD) was defined according to a score constructed considering the consumption of MD components: high monounsaturated fatty acids (MUFA)/saturated fatty acids (SFA) ratio, moderate ethanol consumption, high legume, cereals and roots, fruit, vegetables, and fish consumption, and low meat and milk consumption.The overall MetS prevalence was 5.8% (boys 10.5%, girls 2.7%). MetS criteria were met by 10.0% of overweight, 45.5% of obese and in 1.8% of normal weight adolescents. Half of the adolescents (49.7%) had at least one MetS component. None of the adolescents had all five risk factors. High triglyceride level (90.5%), hypertension (85.7%), low HDL cholesterol level (78.9%) and central obesity (71.4%) were common among adolescents with MetS whereas hyperglycaemia (0.6%) was infrequent. Higher adherence to MD was associated with significantly lower odds ratio of having MetS, but half of the adolescents showed high adherence to MD.Conclusion: MetS prevalence was significant among adolescents in the Balearic Islands, especially among obese boys. A high adherence to MD in adolescents was associated with a low prevalence of the MetS criteria.

ApoB/apoA-I ratio is better than LDL-C in detecting cardiovascular risk - Corrected Proof

2010-02-22

Abstract: Background and aims: Cardiovascular (CV) events occur even when LDL-C are <100mg/dL. To improve the detection of CV risk we investigated the apoB/apoA-I ratio versus LDL-C in subjects considered normal glucose tolerant (NGT) by oral glucose tolerance test (OGTT).Methods and results: We enrolled 616 NGT (273 men and 343 women), and we measured insulin resistance, lipid profile, apoB/apoA-I and the factors compounding the metabolic syndrome (MetS). An unfavourable apoB/apoA-I (≥0.9 for males and ≥0.8 for females) was present in 13.9% of 108 patients with LDL-C <100mg/dL: compared to subjects with lower apoB/apoA-I (<0.9 for males and <0.8 for females), they had more elements of MetS and their lipid profile strongly correlated with high CV risk. Out of 314 patients with lower apoB/apoA-I, 40.12% had LDL-C ≥130mg/dL: these retained a more favourable lipid profile than corresponding subjects with elevated apoB/apoA-I ratio. Finally, we found a significant correlation between LDL-C and apoB/apoA-I ratio (r=0.48, p<0.0001).Conclusions: In NGT with LDL-C <100mg/dL, a higher apoB/apoA-I exhibited an atherogenic lipid profile, indicating that LDL-C alone is insufficient to define CV risk. Independent from LDL-level, when apoB/apoA-I is lower, the lipid profile is, in fact, less atherogenic. This study demonstrates that apoB/apoA-I is at least complementary to LDL-C in identifying the “effective” CV risk profile of asymptomatic NGT subjects.

Dietary antioxidant capacity is inversely associated with diabetes biomarkers: The ATTICA study - Corrected Proof

2010-02-22

Abstract: Background and aims: Elevated dietary antioxidant activity has been regarded as providing potential benefits to health. The present work aimed at evaluating the association of glycemic indices with total dietary antioxidant capacity in healthy adults.Methods and results: The ATTICA study consisted of men and women, randomly selected from all areas of Attica region in Greece. In this work, a random sub-sample from the ATTICA study's database was studied, consisting of 551 men (41 ± 11 years) and 467 women (38 ± 11 years), with complete nutritional and biochemical information. Dietary habits were evaluated using a validated food-frequency questionnaire. The dietary antioxidant capacity was based on published values for Italian foods measured by three different assays: ferric-reducing antioxidant power (FRAP), total radical-trapping antioxidant parameter (TRAP) and Trolox equivalent antioxidant capacity (TEAC). Inverse, age–energy adjusted correlations were observed between FRAP and log-glucose (r = −0.149, p = 0.001), log-insulin (r = −0.221, p = 0.001) and log-HOMA-IR (r = −0.186, p = 0.001) concentration, as well as with TRAP and TEAC. After controlling for age, gender, body mass index, physical activity status, smoking habits and energy intake, multi-adjusted analysis confirmed the previous relationships only among participants who were not on the Mediterranean dietary pattern.Conclusions: Although more prospective studies are required, the data presented support the view that dietary modification towards higher consumption of antioxidants should be implemented in public health strategies, in order to better control glycemic markers in individuals, and prevent the development of diabetes at the population level.

Greater Mediterranean diet adherence is observed in Dutch compared with Greek university students - Corrected Proof

2010-02-22

Abstract: Background and aims: Research has demonstrated that Mediterranean youth appear to abandon the traditional diet. The present study aimed to assess Mediterranean diet (MD) adherence in Greek university students, compared with a non-Mediterranean (Dutch) population.Methods and results: The MD was assessed through the MD score (MedDietScore, MDS) in 100 nutrition students from Amsterdam and 85 from Thessaloniki. Subjects at both sites demonstrated average MDS, which was higher in the Dutch sample (27.5 ± 3.9) compared to the Greek (26.1 ± 3.4) (p ≤ 0.001). The highest score was observed in Amsterdam (39). Potatoes, non-refined cereals, vegetables and olive oil were more frequently consumed by Dutch students (p ≤ 0.001), but the Greeks demonstrated a higher legume intake (p ≤ 0.05). The Dutch diet comprised 17% protein, 50% carbohydrate and 33% fat, whereas the Greeks consumed 14% protein, 48% carbohydrate and 38% fat (p ≤ 0.001 and p ≤ 0.031 for between-country protein and fat intake, respectively). In Amsterdam, significantly greater amounts of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids as a percentage of energy intake (p ≤ 0.001, p ≤ 0.01) were consumed.Conclusion: The findings indicate that the MD has been transmitted to non-Mediterranean populations, probably as a result of its declared health benefits. However, it is alarming that an average adherence score was demonstrated by the Greek nutrition students and this is indicative of the need for new approaches in transmitting the Mediterranean dietary pattern.

The role of HDL cholesterol in metabolic syndrome predicting cardiovascular events. The Gubbio population study - Corrected Proof

2010-02-19

Abstract: Background and aims: Metabolic syndrome (MS) has recently been claimed to be an important new risk factor for the occurrence of coronary heart disease (CHD) and cardiovascular disease (CVD) events, although it is simply a combination of known risk factors used in a dichotomized fashion. The aims of this analysis were to explore the predictive role of MS for CHD and CVD events in a population study, in comparison with using the same factors in a continuous fashion, with special emphasis on HDL cholesterol.Methods and results: In the second examination of the Gubbio population study from central Italy, 2650 cardiovascular disease-free men and women, aged 35–74 years around 1990, were examined and followed-up for 12 years. The classic risk factors (sex, age, systolic blood pressure, serum cholesterol and smoking habits) were studied as predictors of CHD and CVD events, alone and with the contribution of other factors (HDL cholesterol, blood glucose, serum triglycerides and waist circumference) included in the so-called MS, based on several multivariate models. MS was also tested after adjustment for other risk factors.MS produced a predictive significant relative risk of 1.67 for CHD events and 1.82 for CVD events, but considering its single risk factors, the only ones contributing to prediction were HDL cholesterol and systolic blood pressure. Dedicated analyses showed that MS does not add anything to the power of prediction beyond the role of the single risk factors treated in a continuous fashion, while the best predictive power is obtained using classic risk factors (sex, age, smoking habits, total cholesterol, systolic blood pressure) with the addition of HDL cholesterol.Conclusions: The predictive power of MS is bound only to the presence of HDL cholesterol and blood pressure and does not add anything to using the same risk factor treated in a continuous fashion.

Coffee consumption and the incidence of type 2 diabetes in men and women with normal glucose tolerance: The Strong Heart Study - Corrected Proof

Y. Zhang, E.T. Lee, L.D. Cowan, R.R. Fabsitz, B.V. Howard — 2010-02-19

Abstract: Background and aims: It was reported that high coffee consumption was related to decreased diabetes risk. The aim of this study is to examine the association between coffee consumption and the incidence of type 2 diabetes in persons with normal glucose tolerance in a population with a high incidence and prevalence of diabetes.Methods and results: In a prospective cohort study, information about daily coffee consumption was collected at the baseline examination (1989–1992) in a population-based sample of American Indian men and women 45–74 years of age. Participants with normal glucose tolerance (N = 1141) at the baseline examination were followed for an average of 7.6 years. The incidence of diabetes was compared across the categories of daily coffee consumption. The hazard ratios of diabetes related to coffee consumption were calculated using Cox proportional hazards models, adjusted for potential confounders.Levels of coffee consumption were positively related to levels of current smoking and inversely related to body mass index, waist circumference, female gender, and hypertension. Compared to those who did not drink coffee, participants who drank 12 or more cups of coffee daily had 67% less risk of developing diabetes during the follow-up (hazard ratio: 0.33, 95% confidence interval: 0.13, 0.81).Conclusion: In this population, a high level of coffee consumption was associated with a reduced risk of deterioration of glucose metabolism over an average 7.6 years of follow-up. More work is needed to understand whether there is a plausible biological mechanism for this observation.

Influence of coffee and caffeine consumption on atrial fibrillation in hypertensive patients - Corrected Proof

A.V. Mattioli, A. Farinetti, C. Miloro, P. Pedrazzi, G. Mattioli — 2010-02-19

Abstract: Background and aims: Coffee and caffeine are widely consumed in Western countries. Little information is available on the influence of coffee and caffeine consumption on atrial fibrillation (AF) in hypertensive patients. We sought to investigate the relationship between coffee consumption and atrial fibrillation with regard to spontaneous conversion of arrhythmia.Methods and results: A group of 600 patients presenting with a first known episode of AF was investigated, and we identified 247 hypertensive patients. The prevalence of nutritional parameters was assessed with a food frequency questionnaire. Coffee and caffeine intake were specifically estimated. Left ventricular hypertrophy was evaluated by electrocardiogram (ECG) and echocardiogram. Coffee consumption was higher in normotensive patients. High coffee consumers were more frequent in normotensive patients compared with hypertensive patients. On the other hand, the intake of caffeine was similar in hypertensive and normotensive patients, owing to a higher intake in hypertensive patients from sources other than coffee. Within normotensive patients, we report that non-habitual and low coffee consumers showed the highest probability of spontaneous conversion (OR 1.93 95%CI 0.88–3.23; p=0.001), whereas, within hypertensive patients, moderate but not high coffee consumers had the lowest probability of spontaneous conversion (OR 1.13 95%CI 0.67–1.99; p=0.05).Conclusion: Coffee and caffeine consumption influence spontaneous conversion of atrial fibrillation. Normotensive non-habitual coffee consumers are more likely to convert arrhythmia within 48h from the onset of symptoms. Hypertensive patients showed a U-shaped relationship between coffee consumption and spontaneous conversion of AF, moderate coffee consumers were less likely to show spontaneous conversion of arrhythmia. Patients with left ventricular hypertrophy showed a reduced rate of spontaneous conversion of arrhythmia.

SLC30A8 polymorphism and type 2 diabetes risk: Evidence from 27 study groups - Corrected Proof

Y.L. Jing, Q.M. Sun, Y. Bi, S.M. Shen, D.L. Zhu — 2010-02-19

Abstract: Background and aims: Intense research has been performed to identify the genetic risk factors in type 2 diabetes, and a single nucleotide polymorphism (SNP) in SLC30A8 (rs13266634) was reported to be associated with type 2 diabetes mellitus. However, published data on the association between SLC30A8 polymorphism and the risk of type 2 diabetes were inconsistent. Therefore, we conducted this meta-analysis to derive a more precise estimation of the relationship.Methods and results: We searched PubMed through October 2009 to identify all relevant papers. Odds ratios (ORs) and 95% confidence intervals (CIs) were extracted under an additive genetic model. In the current meta-analysis, we identified a total of 27 groups including 42,609 cases and 69,564 controls. In analyses of the case–control studies by ethnicity, the results indicated that SLC30A8 polymorphism was related to elevate risks of type 2 diabetes both in Europeans (OR=1.15, 95% CI 1.11–1.18, P<0.001) and Asians (OR=1.15, 95% CI 1.11–1.19, P<0.001). Next, we separated hospital-based case–control studies from population-based case–control studies, however, there was no apparent difference between population-based case–control study groups (OR=1.15, 95% CI 1.12–1.17, P<0.001) and hospital-based case–control study groups (OR=1.16, 95% CI 1.07–1.25, P<0.001).Conclusion: Our present meta-analysis provided evidence that SLC30A8 (rs13266634) C allele carriers could elevate the risk of type 2 diabetes, especially in Europeans and Asians.

Total polyphenol excretion and blood pressure in subjects at high cardiovascular risk - Corrected Proof

2010-02-18

Abstract: Background and aims: Dietary factors are critical for the prevention and treatment of hypertension, but data on the effects of specific nutrients on blood pressure (BP) are scarce. The aim of this study was to assess the relationship between total polyphenol excretion (TPE) in urine, as an objective measurement of total polyphenol intake and BP in an elderly population at high cardiovascular risk.Methods and results: Cross-sectional substudy of 589 high-risk participants entering in the PREDIMED trial. BP was measured and TPE was determined in urine by Folin–Ciocalteu assay. A significant positive association was observed between TPE in urine and daily intake of fruit and vegetables (F&V), coffee or wine after adjusting for potential confounders. The intake of 100g of F&V (Beta=0.150;P<0.001) had a greater contribution to TPE than 100mL of coffee (Beta=0.141;P=0.001), and the latter two foods contributed more than the consumption of 100mL of wine (Beta=0.120;P=0.019). An inverse association was observed between urinary TPE and the prevalence of hypertension. Participants in the highest quartile of urinary TPE had a reduced prevalence of hypertension compared to those in the lowest quartile (Odds Ratio=0.64; 95% confidence interval 0.45 to 0.92; P=0.015). Systolic and diastolic BP were inversely associated with urinary TPE after adjustment for potential confounders (P=0.024 and P=0.003, respectively).Conclusions: Polyphenol intake, assessed via TPE in urine, was negatively associated with BP levels and prevalence of hypertension in an elderly Mediterranean population at high cardiovascular risk. Participants with the highest intake of polyphenol-rich foods showed the lowest BP measurements.

Microangiopathy is independently associated with presence, severity and composition of carotid atherosclerosis in type 2 diabetes - Corrected Proof

2010-02-17

Abstract: Background and aims: Common mechanisms for the development of micro- and macroangiopathic diabetic complications have been suggested. We aimed to cross-sectionally investigate strength and characteristics of the association between carotid atherosclerosis and microangiopathy in type 2 diabetic patients.Methods and results: Common carotid artery intima–media thickness (cIMT), carotid plaque (CP) type and degree of stenosis were evaluated by ultrasound, along with the determination of anthropometric parameters, HbA1c, lipid profile, assessment of diabetic retinopathy and nephropathy, in 662 consecutive patients with type 2 diabetes mellitus (T2DM). Patients were divided according to high/low cIMT, presence/absence of CP and of retinopathy and nephropathy. Patients with CP were older, more prevalently males, past smokers, had longer diabetes duration, significantly lower HDL cholesterol and more prevalent ischemic heart disease (all p<0.05) as compared to those with cIMT<1mm. Microangiopathies were more prevalent in patients with CP than in those without. At multivariate logistic regression, factors independently associated with the presence of CP were age, past smoke, HDL cholesterol, retinopathy and retinopathy plus nephropathy. A significant independent correlation of CP stenosis with stage of retinopathy and nephropathy was found. Finally, echolucent CPs were associated with a lower prevalence of proliferative retinopathy than CP containing calcium deposits.Conclusion: In T2DM, retinopathy, alone or in combination with nephropathy, is independently associated to CP, and severity of microangiopathy correlates with severity of carotid atherosclerosis. These observations, together with the different prevalence of proliferative retinopathy according to CP types, point to possible common pathogenic mechanisms in micro- and macrovascular complications.

The effect of comprehensive lifestyle intervention or metformin on obesity in young women - Corrected Proof

SS Lim, RJ Norman, PM Clifton, M Noakes — 2010-02-17

Abstract: Background and aim: Young women are at high risk of weight gain but few weight management interventions have been investigated in this group. This study aimed to determine the effect of metformin on body weight, body composition, metabolic risk factors and reproductive hormone levels in overweight or obese young women compared to placebo and comprehensive lifestyle intervention.Methods and results: 203 overweight or obese young women (BMI 33.2+/−0.3 kg/m2, age 28+/−0.3 years) were randomised to 1500 mg/day metformin (M) plus general lifestyle advice, placebo (P) plus general lifestyle advice or comprehensive lifestyle intervention including structured diet, exercise and behavioural therapy (L) for 12-weeks. At 12-weeks, linear mixed models found that L group had greater weight loss (−4.2+/−0.4 kg) compared to M (−1.0+/−0.4 kg) and P groups (−0.2+/−0.3 kg) (P 3%), compared to 3% (2/65) from M group and none (0/59) from L group (P < 0.001). The L group had the greatest decrease in waist circumference (−5.2+/−0.7 cm) and fat mass (−5.4+/−0.7 kg) compared to the other groups (P < 0.05). No significant time-by-group effects were seen in plasma lipids, SHBG, testosterone, blood pressure, serum folate, serum ferritin and serum vitamin B12. Conclusion: Lifestyle intervention was more effective in reducing body weight and improving body composition compared to metformin among healthy overweight or obese young women.

Parental history of premature myocardial infarction is a stronger predictor of increased carotid intima-media thickness than parental history of hypertension - Corrected Proof

2010-02-17

Abstract: An increased carotid intima-media thickness (IMT) is detectable in young subjects with parental history of premature myocardial infarction (PHPMI) or hypertension (PHH). In this study we evaluated if PHPMI and PHH exert a different influence on carotid IMT and if their conjunction produces additive effects.High-resolution B-mode ultrasonographic evaluation of common carotid artery IMT was acquired from 48 subjects without PHPMI and PHH (22 males, 26 females; mean age 22.1±4.9 years; controls), 24 age- (±1 year) and sex-matched subjects with PHH without PHPMI (PHH-positive/PHPMI-negative subjects), 24 age- and sex-matched subjects with PHPMI without PHH (PHH-negative/PHPMI-positive subjects) and 24 age- and sex-matched subjects with both PHPMI and PHH (PHH/PHPMI-positive subjects). Lipid profile, resting blood pressure, smoking behaviour and body mass index (BMI) were also assessed. Carotid IMT was smaller in controls (0.41±0.07mm) compared to PHH-positive/PHPMI-negative subjects (0.47±0.10, p=0.023), to PHH-negative/PHPMI-positive subjects (0.54±0.11, p<0.001) and to PHH/PHPMI-positive subjects (0.52±0.10mm, p<0.001). Carotid IMT was greater in PHH-negative/PHPMI-positive (p=0.006) and in PHH/PHPMI-positive (p=0.031) than in PHH-positive/PHPMI-negative subjects. No difference in carotid IMT was evident between PHH-negative/PHPMI-positive and PHH/PHPMI-positive subjects (p=0.549). In the comparison among subjects using multiple regression analysis, only PHPMI, age and BMI were independently associated with carotid IMT.In healthy young subjects with PHPMI and/or PHH, carotid IMT is increased. PHPMI is a stronger predictor of increased carotid IMT than PHH. PHH in conjunction with PHPMI does not add any further detrimental effect on carotid IMT.

Plasma adiponectin concentration is strongly associated with VLDL-TG catabolism in postmenopausal women - Corrected Proof

2010-02-15

Abstract: Background and aims: To investigate associations between plasma adiponectin concentration and very-low density lipoprotein–triglyceride (VLDL-TG) secretion and catabolism in postmenopausal women.Methods and results: This cross-sectional study included 30 postmenopausal women. Plasma adiponectin concentration was measured by ELISA. Insulin sensitivity was assessed by a 2-h euglycemic-hyperinsulinemic clamp. Fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) were measured during an oral glucose tolerance test. The calculation of VLDL-TG fractional catabolic rate (FCR) and VLDL-TG total secretion rate (TSR) were based on the monoexponential decrease of TG-[2H5] glycerol values obtained following the administration of a 2H5-glycerol bolus. Plasma adiponectin concentration was negatively associated with VLDL-TG TSR (r=−0.50; p=0.005) and positively associated with VLDL-TG FCR (r=0.54; p<0.002). This latter association remained significant after further adjustments for insulin sensitivity, visceral adipose tissue, HDL-C, FPG and 2hPG concentrations. In a multivariate model including adiponectin, insulin sensitivity and 2hPG, plasma adiponectin level was the strongest correlate of VLDL-TG FCR.Conclusions: Elevated plasma adiponectin concentration is associated with a favourable VLDL-TG metabolism.

Low-fat dairy consumption reduces systolic blood pressure, but does not improve other metabolic risk parameters in overweight and obese subjects - Corrected Proof

L.E.C. van Meijl, R.P. Mensink — 2010-02-15

Abstract: Background and aims: Epidemiological studies have indicated a negative relation between low-fat dairy consumption and the metabolic syndrome. However, evidence from intervention studies is scarce. Our aim was to investigate the effects of daily consumption of low-fat dairy products on metabolic risk parameters in overweight and obese men and women.Methods and results: Thirty-five healthy subjects (BMI>27kg/m2) consumed low-fat dairy products (500mL low-fat milk and 150g low-fat yogurt) or carbohydrate-rich control products (600mL fruit juice and 3 fruit biscuits) daily for 8 weeks in random order. Compared with the control period, systolic blood pressure was decreased by 2.9mmHg (95% confidence interval (CI), −5.5 to −0.3mmHg; P=0.027), while the difference in diastolic blood pressure did not reach statistical significance (95% CI, −3.4 to 0.3mmHg; P=0.090). Low-fat dairy consumption decreased HDL-cholesterol concentrations by 0.04mmol/L (95% CI, −0.07 to −0.01mmol/L; P=0.021) and apo A-1 concentrations by 0.04g/L (95% CI, −0.07 to −0.01g/L; P=0.016) compared with control. Serum total cholesterol, LDL-cholesterol, apo B, triacylglycerols, non-esterified fatty acids, glucose, insulin, C-reactive protein and plasminogen activator inhibitor-1 were unchanged.Conclusion: We conclude that in overweight and obese subjects, daily intake of low-fat dairy products for 8 weeks decreased systolic blood pressure, but did not improve other metabolic risk factors related to the metabolic syndrome.

The Direct Economic Cost of Pharmacologically-Treated Diabetes in Italy-2006. The ARNO Observatory - Corrected Proof

2010-02-15

Abstract: Aims/hypothesis: To estimate the prevalence and the direct cost of pharmacologically-treated diabetes in Italy.Methods: The ARNO observatory database, containing the 20-year medical prescriptions of over 10 million Italian people, was used. Ten-year longitudinal data were available in 22 Local Health Districts (LHD). Subjects were classified as having diabetes when prescribed glucose-lowering drugs (oral agents or insulin) (311,979 individuals in 2006). The direct cost was calculated as the sum of drug use, financial compensation by LHD for the inpatient (hospital DRG) and outpatient activities (consultations, laboratory tests, radiology, etc.), all regulated by government contracts. Individuals with diabetes were compared with pharmacologically-treated subjects without diabetes, pair-matched for age, sex and general practitioner.Results: In the 10-year period, the prevalence of pharmacologically-treated diabetes increased from 3.08% to 4.45% (P for trend, <0.001). The average pro capita cost totaled €2,589 in 2006 (95% confidence interval (CI), 2,584–2,594), corresponding to a rate ratio vs. no-diabetes of 1.54 (95% CI, 1.50–1.56). The cost of drugs was € 827 (rate ratio, 1.80 vs. no-diabetes; 95% CI, 1.79–1.82), that of service use, € 488 (rate ratio, 1.07 (0.93–1.25). Only 20% of the pharmaceutical cost was due to glucose-lowering drugs, a percentage stable through the years. The cost of any hospital admission, as defined by DRGs, was independent of diabetes, but the overall cost was much higher in diabetes due to much higher admission rates. Cardiovascular complications and renal failure accounted for the large majority of excess hospital cost.Conclusion: The direct economic burden of pharmacologically-treated diabetes on the National Health System is very high, due to the growing prevalence of disease and the cost of complications.

Pericardial fat is associated with carotid stiffness in the Multi-Ethnic Study of Atherosclerosis - Corrected Proof

2010-02-15

Abstract: Background and aims: Arterial stiffness is a prominent feature of vascular aging and a risk factor for cardiovascular disease (CVD). Fat around the heart and blood vessels (i.e. pericardial fat, Pfat) may contribute to arterial stiffness via a local paracrine effect of adipose tissue on the surrounding vasculature. Thus, we determined the association between Pfat and carotid stiffness in 5770 participants (mean age 62years, 53% female, 25% African American, 24% Hispanic, and 13% Chinese) from the Multi-Ethnic Study of Atherosclerosis.Methods and results: Pfat was measured by computed tomography, and ultrasonography of the common carotid artery was used to calculate the distensibility coefficient (DC) and Young's modulus (YM). Lower DC and higher YM values indicate stiffer arteries. Pfat quartile was highly associated with demographic, behavioral, anthropometric, hemodynamic, metabolic, and disease variables in both men and women. After adjusting for height, clinical site, CVD risk factors, and medications, a 1 standard deviation (41.91cm3) increment in Pfat was associated with a 0.00007±0.00002 1/mmHg lower DC (p=0.0002) in men and a 48.1±15.1mmHg/mm higher YM in women (p=0.002). Additional adjustment for C-reactive protein, coronary artery calcification, and carotid intima-media thickness had only modest effects. More importantly, adjusting for body mass index and waist circumference did not significantly change the overall results.Conclusion: Higher Pfat is associated with higher carotid stiffness, independent of traditional CVD risk factors and obesity.

Nutrient intake in relation to central and overall obesity status among elderly people living in the Mediterranean islands: The MEDIS study - Corrected Proof

2010-02-15

Abstract: Background and Aim: The aim of the present work was to evaluate the relationship between energy-generating nutrients and the presence of central and overall obesity after correcting for socio-demographic, lifestyle and clinical characteristics, among healthy elders.Methods and Results: During 2005–2007, 553 elderly men and 637 elderly women (mean age 74±7years) from eight Mediterranean islands in Greece and Cyprus, were enrolled. The retrieved information included demographic, bio-clinical and dietary characteristics. MedDietScore assessed adherence to the Mediterranean dietary pattern.The prevalence of obesity was 27% in males and 39% in females (p<0.001), while 73% of males and 87% of females had central obesity. The prevalence of diabetes, hypercholesterolemia and hypertension was higher in the obese than in the non-obese participants (p<0.01). After adjusting for various confounders, a 1% increase in carbohydrate consumption was associated with a 12% (95% CI 0.78–0.99) lower likelihood of having central obesity, while a 1% increase in carbohydrate and protein consumption was associated with a 14% (95% CI 0.78–0.95) and 16% (95% CI 0.72–0.97) lower likelihood of being obese, respectively. Vegetable protein was found to be associated with a 15% (95% CI 0.77–0.93) lower likelihood of being obese while, only low glycemic index carbohydrates seem to be associated with a 6% (95% CI 0.90–0.98) lower likelihood of having central obesity.Conclusions: The presented findings suggest that a diet high in carbohydrates and vegetable protein is associated with a lower likelihood of being obese and may help elderly people to preserve normal weight.

Body fat distribution and C-reactive protein – a principal component analysis - Corrected Proof

A. Oliveira, C. Lopes, M. Severo, F. Rodríguez-Artalejo, H. Barros — 2010-02-15

Abstract: Background and Aims: To assess, using principal component analysis, the independent associations of general, central and peripheral subcutaneous fat with high-sensitivity C-reactive protein (hs-CRP), in men and women from the general population.Methods and results: We studied 833 women and 486 men, randomly selected from the non-institutionalized population of Porto, Portugal, with information on hs-CRP (≤10mg/l) and anthropometrics (1999–2003). Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and a skinfold composite index to estimate the proportion of arm subcutaneous fat (PSFA), were ascertained by trained personnel. Beta regression coefficients were obtained from generalized linear models with adjustment for the main confounders.Direct associations were found between BMI, WC, WHR and hs-CRP. PSFA was inversely associated with hs-CRP in women (=−0.080, p-trend=0.010). Since the anthropometric measures were strongly correlated, we used principal component analysis to identify new independent anthropometric factors. The first one, representing a generalized fat distribution (high BMI and WC), was directly associated with hs-CRP (=0.226, p-trend<0.001 in women; =0.138, p-trend=0.002 in men). The second factor, characterized by a high PSFA, showed an inverse association with hs-CRP in women (=−0.071, p-trend=0.048). The third factor, representing a central pattern of fat distribution (low BMI, but high WC and high WHR), was directly associated with hs-CRP in men (=0.090, p-trend=0.005).Conclusion: A central pattern of fat distribution is directly associated with hs-CRP levels in men, while a high proportion of peripheral subcutaneous fat seems to be inversely associated with hs-CRP, but only in women.

The treatment of hypercholesterolemic children: Efficacy and safety of a combination of red yeast rice extract and policosanols - Corrected Proof

O. Guardamagna, F. Abello, V. Baracco, B. Stasiowska, F. Martino — 2010-02-15

Abstract: Background and aims: The prevention of cardiovascular risk, as occurs in lipoprotein disorders, is required since childhood. Aim of the study was to evaluate, in a group of children affected by primary dyslipidemia, the efficacy, tolerability and safety of a short-term treatment with a dietary supplement containing red yeast rice extract and policosanols.Methods and Results: 40 children affected by heterozygous Familial Hypercholesterolemia (FH) (n=24) and Familial Combined Hyperlipidemia (FCH) (n=16), aged 8–16 years, were enrolled in a double-blind, randomized, placebo-controlled, cross-over trial. After a 4-week run-in period with only dietary advice, children received a dietary supplement containing 200mg red yeast rice extract, corresponding to 3mg of monacolins, and 10mg policosanols once-daily and placebo for 8 weeks, separated by a 4-week washout period. Lipid profile was assessed after each treatment period.The dietary supplement, compared with the placebo, significantly reduced total cholesterol by 18.5% (p<0.001), LDL-C levels by 25.1% (p<0.001), and apolipoprotein B by 25.3% (p<0.001) when patients were considered as a whole group. Similar results were obtained when FH and FCH were considered separately and no significant difference between groups was detected. No significant differences were observed in HDL-C and apolipoprotein A–I levels. No adverse effects were detected when liver and muscular enzymes (AST, ALT, and CK) were determined.Conclusions: The treatment with a dietary supplement containing red yeast rice extract and policosanols has been for the first time successfully employed in hypercholesterolemic children. Results indicate this strategy as an effective, safe and well tolerated in a short-term trial.

Cardiovascular events in patients with antiphospholipid antibodies: Strategies of prevention - Corrected Proof

2010-02-15

Abstract: Antiphospholipid antibodies are a heterogeneous group of auto-antibodies against phospholipids-binding proteins. The antiphospholipid syndrome is an autoimmune disorder characterized by the clinical association of antiphospholipid antibodies with a condition of hypercoagulability that can affect any blood vessel. Involvement of larger vessels, such as arteries or veins, manifests in the form of thrombosis or thromboembolism, whereas involvement of small vessels manifests as thrombotic micro-angiopathy. The antiphospholipid syndrome is also characterized by the presence of recurrent fetal loss. Patients who are persistently positive for antiphospholipid tests, and who have an arterial thrombosis or venous thrombosis history, are at increased risk of recurrence. Oral anticoagulant therapy is the mainstay of treatment for the thrombotic manifestations of the syndrome. Therapy with anticoagulant drugs should be long-term.On the other hand, although the thromboembolic potential of antiphospholipid antibodies has been well documented, there is still no general consensus on the prophylactic treatment of antiphospholipid antibodies carriers who have never developed vascular/obstetric manifestations. The effect of primary prophylaxis in antiphospholipid antibodies positive individuals is not well known and no evidence-based recommendations exist for thrombosis prevention in these individuals. However, the presence of risk factors for thrombosis increases the risk of first event of antiphospholipid antibodies positive patients.In conclusion, there is still much to learn on primary prophylaxis of asymptomatic antiphospholipid antibodies carriers. Hopefully, evidence-based guidelines will be available in the future.

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.

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.

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.