Nutrition, Metabolism & Cardiovascular Diseases - Articles in Press

Ectopic fat and cardiovascular disease: What is the link? - Corrected Proof

A. Gastaldelli, G. Basta — 2010-07-26

Abstract: Aim: of this paper is to review the recent literature on the relationship between ectopic fat accumulation and cardiovascular disease.Data synthesis: Ectopic fat is an important predictor of metabolic (in particular insulin resistance) and cardiovascular disease, carrying more risk than general fat accumulation. Recent studies have shown a link between ectopic fat accumulation, as cardiac (epicardial or intra-myocardial fat) and/or visceral and/or hepatic fat, and development of atherosclerosis, coronary heart disease and hypertension.Conclusions: Ectopic fat accumulation is not only a marker of cardiometabolic disease, since through the release of adipocitokines, lipotoxic and glucotoxic agents, participates in the crosstalk with insulin-sensitive organs leading to metabolic, cardiac and vascular dysfunctions.

Dietary phosphate restriction in dialysis patients: A new approach for the treatment of hyperphosphataemia - Corrected Proof

2010-07-07

Abstract: Background and Aim: Elevated serum phosphate and calcium–phosphate levels play an important role in the pathogenesis of vascular calcifications in uraemic patients and appear to be associated with increased cardiovascular mortality. We aimed to evaluate the effects of a partial replacement of food protein with a low-phosphorus and low-potassium whey protein concentrate on phosphate levels of dialysis patients with hyperphosphataemia.Methods and Results: Twenty-seven patients undergoing chronic haemodialysis were studied for a 3-month period. In the intervention group (n = 15), food protein were replaced by 30 or 40 g of low-phosphorus and low-potassium protein concentrate aimed at limiting the phosphate intake. In the control group (n = 12) no changes were made to their usual diet. Anthropometric measurements, biochemical markers and dietary interviews were registered at baseline and during the follow-up period. From baseline to the end of the study, in the intervention group, serum phosphate and circulating intact parathyroid hormone levels lessened significantly (8.3 ± 1.2 mg/dL vs 5.7 ± 1.4 mg/dL and 488 ± 205 pg/ml vs 177 ± 100 pg/ml respectively; p < 0.05) with decreasing of phosphate and potassium intake. No significant differences were found in the control group. No significant changes were observed in serum albumin, calcium, potassium, Kt/V, body weight and body composition in both the intervention and control groups.Conclusion: Dietary intake of phosphate mainly comes from protein sources, so dietary phosphorus restriction may lead to a protein/energy malnutrition in a dialysis patient. A phosphorus-controlled diet plan including a nutritional substitute resulted in serum phosphate and intact parathyroid hormone decrease without nutritional status modifications in dialysis patients.

Meta-analysis on the effect of the Ala54Thr polymorphism of the fatty acid-binding protein 2 gene on body mass index - Corrected Proof

T. Zhao, J. Zhao, J. Lv, M. Nzekebaloudou — 2010-06-21

Abstract: Background and aim: The results from studies published on the association of fatty acid-binding protein 2 (FABP2) Ala54Thr polymorphism with body mass index (BMI) are conflicting. In this meta-analysis, we investigated the association of the FABP2 Ala54Thr polymorphism with BMI.Methods and results: We searched for articles published prior to June 2009 using PubMed, HugeNavigator and China National Knowledge Internet. The languages were limited to English and Chinese. Data on BMI were collected. A pooled weighted mean difference (WMD), together with 95% confidence interval (CI), was used for this meta-analysis.A total of 27 studies with 10 974 subjects were included in this meta-analysis. The pooled effect for dominant, recessive and co-dominant model comparisons did not suggest the significant association between the FABP2 Ala54Thr polymorphism and BMI in overall populations: WMDfixed effects=−0.00, 95% CI: (−0.16 to 0.15), p=0.99, WMDrandom effects=−0.00, 95% CI: (−0.16 to 0.15), p=0.99, pQ=0.77, I2=0%, WMDfixed effects=−0.12, 95% CI: (−0.39 to 0.14), p=0.35, WMDrandom effects=−0.12, 95% CI: (−0.39 to 0.14), p=0.35, pQ=0.47, I2=0% and WMDfixed effects=0.07, 95% CI: (−0.11 to 0.25), p=0.45, WMDrandom effects=0.07, 95% CI: (−0.11 to 0.25), p=0.45, pQ=0.90, I2=0%, respectively. The results from the comparisons of ThrThr versus AlaAla and AlaThr versus AlaAla showed no evidence that the FABP2 Ala54Thr polymorphism is significantly associated with BMI in overall populations (p>0.05). All the results from the subgroup analyses for these genetic models comparisons were not significant (p>0.05).Conclusions: Our meta-analysis does not support the association between the FABP2 Ala54Thr polymorphism and BMI.

Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: The AREA-in-CHF study - Corrected Proof

2010-06-18

Abstract: Background and aim: We analyzed the effect of the mineralocorticoid receptor antagonist canrenone on LV mechanics in patients with or without metabolic syndrome (MetS) and compensated (Class II NYHA) heart failure (HF) with reduced ejection fraction (EF≤45%) on optimal therapy (including ACE-i or ARB, and β-blockers).Methods and results: From a randomized, double-blind placebo-controlled trial (AREA-in-CHF), patients with (73 on canrenone [Can] and 77 on placebo [Pla]), based on modified ATPIII definition (BMI≥30kg/m2 instead of waist girth) or without MetS (146 by arm). In addition to traditional echocardiographic parameters, we also evaluated myocardial mechano-energetic efficiency (MME) based on a previously reported method. At baseline, Can and Pla did not differ in age, BMI, blood pressure (BP), metabolic profile, BNP, and PIIINP. Compared with MetS-Pla, and controlling for age, sex and diabetes, at the final control MetS-Can exhibited increased MME, preserved E/A ratio, and decreased atrial dimensions (0.04

Semisolid meal enriched in oat bran decreases plasma glucose and insulin levels, but does not change gastrointestinal peptide responses or short-term appetite in healthy subjects - Corrected Proof

2010-06-07

Abstract: Background and aims: Dietary fibre (DF) may play an important role in weight control. The amount, type and way of processing of DF modify food structure and subsequent postprandial appetitive, metabolic and hormonal effects, but current understanding about the magnitude of effects that specific types and amounts of DF exert are still poorly understood.Methods and results: We investigated the effects of wheat and oat brans alone and as combination in semisolid food matrix on postprandial appetite profile and gastrointestinal (GI) hormonal responses. Twenty healthy, normal-weight subjects (5 male/15 female, aged 23.3 ± 0.85y) participated in the study. Isoenergetic and isovolumic (1250 kJ, 300 g) puddings with different insoluble and soluble DF content were tested in a randomised order: pudding with 1) no added fibre, 2) 10 g wheat bran DF, 3) 10 g oat bran DF and 4) combination including 5 g wheat bran DF + 5 g oat bran DF. Blood samples were drawn before and 15, 30, 45, 60, 90, 120 and 180 min after the test meals to determine plasma glucose, ghrelin, peptide YY (PYY) and serum insulin concentrations. Subjective profiles of appetite were assessed using visual analogue scales (VAS). Plasma glucose (P = 0.001) and serum insulin (P < 0.001) responses were the lowest after the pudding with the greatest amount of β-glucan. In contrast, postprandial ghrelin or PYY responses or appetite sensations did not differ among the meals.Conclusion: Oat β-glucan decreased postprandial plasma glucose and serum insulin responses, yet had no significant effects on GI peptide responses or appetite ratings.

Association of plasma markers of cholesterol homeostasis with metabolic syndrome components. A cross-sectional study - Corrected Proof

2010-05-31

Abstract: Background and aims: Increased plasma phytosterols, which reflect enhanced cholesterol absorption, have been related to an increased risk of cardiovascular disease (CVD). However, high CVD risk conditions, such as obesity, diabetes and the metabolic syndrome (MetS) have been associated with reduced cholesterol absorption. We investigated associations between plasma noncholesterol sterols and MetS components.Methods and results: With a cross-sectional design, we related MetS components to plasma noncholesterol sterol-to-cholesterol ratios measured by gas chromatography in 674 dyslipidemic patients and 361 healthy subjects participating in a prospective cohort study.Plasma phytosterol-to-cholesterol ratios were inversely associated with all components of the MetS. In the dyslipidemic group, multivariable analyses showed that a 1-SD increase in sitosterol-to-cholesterol ratio was associated with a reduced risk for any MetS feature, ranging from 0.57 (95% CI, 0.45 to 0.71) for visceral adiposity to 0.82 (95% CI, 0.69 to 0.98) for high blood pressure. The risk of having MetS was nearly halved, with ORs of 0.49 (95% CI, 0.38 to 0.64) or 0.56 (95% CI, 0.44–0.70), depending on the definition. Results were opposed for plasma lathosterol, a marker of cholesterol synthesis. Most findings were reproduced in the healthy cohort. ApoE genotype was unrelated to plasma noncholesterol sterols.Conclusion: In both dyslipidemic and healthy populations, MetS is associated with increased plasma lathosterol, a cholesterol synthesis marker, and decreased plasma sitosterol, a marker of cholesterol absorption. Elevated plasma phytosterols related to a lower frequency of cardiometabolic risk factors, suggesting that they are associated with a reduced CVD risk.

Effect of the Mediterranean diet with and without weight loss on cardiovascular risk factors in men with the metabolic syndrome - Corrected Proof

C. Richard, P. Couture, S. Desroches, A. Charest, B. Lamarche — 2010-05-31

Abstract: Background and aims: No study has yet examined how weight loss modifies the impact of the Mediterranean diet (MedDiet) on cardiovascular risk factors in men with the metabolic syndrome (MetS). The objective of the study was to assess the efficacy of MedDiet, with and without weight loss, to modify the cardiometabolic risk profile of male patients with MetS.Methods and results: Twenty-six men aged between 24 and 62 years with the MetS consumed a North American control diet for 5 weeks followed by a 5-week MedDiet, both under weight-maintaining conditions. Participants then underwent a 20-week weight loss period, after which they consumed the MedDiet for five weeks under weight stable conditions. Body weight was reduced by 10.2% ± 2.9% after the weight loss period (p < 0.001). All foods were provided to participants during the weight stable phases of the study. The MedDiet in the absence of weight loss decreased total plasma cholesterol (C) (−7.1%), LDL-C (−9.3%) and the total/HDL-C ratio (−6.5%) compared to the control diet (all p < 0.04). The MedDiet combined with weight loss led to reductions in systolic blood pressure (−4.7%), diastolic blood pressure (−7.7%), triglycerides (−18.2%), ApoB (−10.7%), fasting glucose (−4.2%) and insulin (−29.9%) compared to the control diet (all p < 0.001). Conclusion: The MedDiet in the absence of weight loss leads to significant changes in plasma cholesterol concentrations but has little effects on other cardiometabolic risk factors associated with the MetS in men.

Plasma adiponectin is associated with less atherogenic lipoprotein phenotype - Corrected Proof

M.-J. Shin, O.Y. Kim — 2010-05-31

Abstract: Background and aims: This study examined the relationships between plasma levels of adiponectin and the features of the atherogenic lipoprotein phenotype (ALP), including HDL subclasses.Methods and results: Blood lipids and apolipoproteins were measured in 293 healthy individuals. LDL particle size and HDL subspecies (HDL2, HDL3) were measured using gradient gel electrophoresis. Plasma adiponectin levels were negatively correlated with levels of apoB (r=−0.199, p<0.001), TG (r=−0.262, p<0.001), and HOMA-IR (r=−0.323, p<0.001) and positively correlated with levels of apoAI (r=0.173, p=0.006), HDL-cholesterol (r=0.287, p<0.001), and LDL particle size (r=0.289, p<0.001). Multiple linear regression analysis revealed the relationship between plasma adiponectin and LDL particle size (p<0.05) was no longer significant after adjusting for plasma TG levels. However, adiponectin (p<0.005) together with apoAI and TG were independent factors for HDL-cholesterol. With regard to HDL subclasses, plasma adiponectin levels were positively correlated with HDL2b (r=0.204, p<0.001), HDL2a (r=0.132, p<0.05) and negatively with HDL3a (r=−0.128, p<0.05), HDL3b (r=−0.203, p<0.001), and HDL3c (r=−0.159, p<0.01). The relationship between circulating adiponectin and HDL2 (HDL2b+HDL2a) was independent of apoB and TG levels (p<0.05), but not of apoAI and HOMA-IR.Conclusions: Our results show that circulating adiponectin is associated with reduced manifestations of ALP.

Circulating immature osteoprogenitor cells and arterial stiffening in postmenopausal osteoporosis - Corrected Proof

2010-05-31

Abstract: Background and Aims: An increased number of circulating osteoprogenitor cells (OPCs) expressing bone-related proteins and the stem cell marker CD34 have been identified in women with postmenopausal osteoporosis, who also have stiffer arteries than nonosteoporotic subjects. We investigated whether an increased number of circulating OPCs underlies the association of osteoporosis with arterial stiffness.Methods and Results: The number of circulating OPCs was quantified by FACS analysis in 120 postmenopausal women with or without osteoporosis. OPCs were defined as CD34+/alkaline phosphatase(AP)+ or CD34+/osteocalcin(OCN)+ cells. Participants underwent cardiovascular risk factor assessment, measurement of bone mineral density (BMD), and aortic pulse wave velocity (aPWV) as a measure of arterial stiffness.Osteoporotic women had higher aPWV (9.8 ± 2.8 vs 8.5 ± 1.9 m/s, p = 0.005) and levels of CD34+/AP+ and CD34+/OCN+ cells than nonosteoporotic controls [1045 n/mL (487–2300) vs 510 n/mL (202–940), p < 0.001; 2415 n/mL (1225–8090) vs 1395 n/mL (207–2220), p < 0.001]. aPWV was associated with log-CD34+/AP+ (r = 0.27, p = 0.003), log-CD34+/OCN+ cells (r = 0.38, p < 0.001). In stepwise regression analysis CD34+/OCN+ cells, age, systolic blood pressure and heart rate were significant predictors of aPWV (Model R = 0.62, p < 0.001), independent of cardiovascular risk factors, parathyroid hormone levels and osteoporotic status.Conclusion: In women with postmenopausal osteoporosis an increased availability of circulating osteoprogenitor cells has a detrimental influence on arterial compliance, which may in part explain the association between osteoporosis and arterial stiffening.

High sensitivity C-reactive protein predicts the development of new carotid artery plaques in older persons - Corrected Proof

2010-05-31

Abstract: Background and Aim: Previous studies have shown that increased levels of C-reactive protein (CRP) predict cardiovascular events, including stroke, myocardial infarction and death from cardiovascular causes. Previous studies have also shown that increased levels of CRP are strong predictors of the progression of pre-existing carotid artery plaques. However, whether CRP is involved in the development of new plaques, that may or may not be associated with clinical events, in subjects with clean carotid arteries has been scarcely investigated.Methods and Results: 486 “InCHIANTI” Study participants (200 men and 286 women, 72% aged 65 years and over) free from carotid artery plaques at baseline, also underwent carotid artery scan three years later. We tested the association of baseline characteristics, cardiovascular risk factors and inflammatory markers with the development of new carotid artery plaques. Older participants were significantly more likely to develop new plaques. Independent of age, the relative risks of developing new plaques associated with heavy smoking and family history of atherosclerosis were 1.7 (95%CI 1.5–1.9) and 1.9 (95%CI 1.2–3.1), respectively. Participants with high (>3 μg/mL) and moderate (≥1 and ≤3 μg/mL) CRP levels had a relative risk of 2.2 (95%CI 1.9–2.6) and 1.9 (95%CI 1.6–2.3) respectively, when compared with subjects with low (<1 μg/mL) CRP levels. Surprisingly, risk factors such as hypertension, diabetes, dyslipidemia and overweight/obesity were not significant predictors of the development of new carotid artery plaques.Conclusions: High CRP levels independently predict the development of new plaques in older persons with carotid arteries free from atherosclerotic lesions.

Obesity induced by neonatal treatment with monosodium glutamate impairs microvascular reactivity in adult rats: Role of NO and prostanoids - Corrected Proof

2010-05-31

Abstract: Background and aim: given that obesity is an independent risk factor for the development of cardiovascular diseases we decided to investigate the mechanisms involved in microvascular dysfunction using a monosodium glutamate (MSG)-induced model of obesity, which allows us to work on both normotensive and normoglycemic conditions.Methods and results: Male offspring of Wistar rats received MSG from the second to the sixth day after birth. Sixteen-week-old MSG rats displayed higher Lee index, fat accumulation, dyslipidemia and insulin resistance, with no alteration in glycemia and blood pressure. The effect of norepinephrine (NE), which was increased in MSG rats, was potentiated by L-nitro arginine methyl ester (L-NAME) or tetraethylammonium (TEA) and was reversed by indomethacin and NS-398. Sensitivity to acetylcholine (ACh), which was reduced in MSG rats, was further impaired by L-NAME or TEA, and was corrected by indomethacin, NS-398 and tetrahydrobiopterin (BH4). MSG rats displayed increased endothelium-independent relaxation to sodium nitroprusside. A reduced prostacyclin/tromboxane ratio was found in the mesenteric beds of MSG rats. Mesenteric arterioles of MSG rats also displayed reduced nitric oxide (NO) production along with increased reactive oxygen species (ROS) generation; these were corrected by BH4 and either L-NAME or superoxide dismutase, respectively. The protein expression of eNOS and cyclooxygenase (COX)-2 was increased in mesenteric arterioles from MSG rats.Conclusion: Obesity/insulin resistance has a detrimental impact on vascular function. Reduced NO bioavailability and increased ROS generation from uncoupled eNOS and imbalanced release of COX products from COX-2 play a critical role in the development of these vascular alterations

Effects of the association of aging and obesity on lipids, lipoproteins and oxidative stress biomarkers: A comparison of older with young men - Corrected Proof

2010-05-31

Abstract: In this study, plasma lipids, lipoproteins and markers of oxidant/antioxidant status were investigated in young (n = 45) and older (n = 40) obese men and compared to those in young (n = 65) and older (n = 55) normal weight controls. The purpose was to determine whether obesity exacerbates or not lipid, lipoprotein abnormalities and oxidative stress in older men.Our findings showed that all obese patients had increased plasma triglyceride, cholesterol, LDL-cholesterol, -triglyceride and HDL-triglyceride levels concentrations compared to controls (P < 0.01). However, the younger obese men had relatively larger and accentuated changes in plasma lipids and lipoproteins than the older patients. Additionally, total antioxidant capacity (ORAC), vitamins C and E were lower while hydroperoxides and carbonyl proteins were higher in young and older obese patients compared to their respective controls (P < 0.001). Erythrocyte antioxidant SOD and catalase activities were enhanced in obese young patients, but reduced in obese older men. Glutathione peroxidase activity was low in obesity irrespective of age. In multiple regression analysis, BMI significantly predicted total cholesterol, LDL-C, LDL-TG and HDL-TG (P < 0.0001). These relationships were not modified by age. BMI alone was a not a significant predictor for ORAC, vitamins C, E, catalase and Glutathione peroxidase. However, the interaction BMI–age significantly predicted these parameters and explained 28–45% of their changes. BMI was a significant predictor of SOD, carbonyl proteins and hydroperoxides. This effect became more significant (P < 0.0001) and worsened with BMI–age interaction.In conclusion, lipoprotein metabolism and oxidant/antioxidant status are altered in obesity irrespective of age. However, obesity-related lipid and lipoprotein alterations were attenuated while oxidative stress was aggravated in older adults.

The effect of vitamin–mineral supplementation on CRP and IL-6: A systemic review and meta-analysis of randomised controlled trials - Corrected Proof

C.-H. Sun, Y. Li, Y.-B. Zhang, F. Wang, X.-L. Zhou, F. Wang — 2010-04-20

Abstract: Background and Aims: Inflammation is regarded as a risk predictor for metabolic syndrome and atherogenesis. The objective of this study was to conduct a systematic review and a meta-analysis to confirm the effect of vitamin–mineral supplementation on cytokine levels.Methods and Results: We searched the PubMed, EMBASE and Cochrane databases up to May 2009 for randomised controlled trials regarding the effect of vitamin–mineral supplementation on C-reactive protein (CRP) and interleukin-6 (IL-6). Eighteen trials with 1747 participants for CRP and nine trials with 1037 participants for IL-6 were included, respectively. Pooled estimates and 95% confidence intervals (CIs) were calculated by fixed- or random-effects model. No significant differences were observed for CRP and IL-6 reduction between the subjects with vitamin–mineral supplementation and placebo control. A dose-dependent manner for different body mass index (BMI) subgroups in CRP analysis was observed (weighted mean difference (WMD), −0.057; 95%CI: −0.753 to 0.639 for BMI<25; WMD, −0.426; 95%CI: −0.930 to 0.079 for 25≤BMI<30; WMD, −0.491; 95%CI: −1.407 to 0.424 for BMI≥30). However, no significance was detected in meta-regression (−0.046, 95%CI: −0.135 to 0.044). Moreover, the best effect for reduction in CRP levels in a supplementation duration of 4 weeks–6 months (WMD, −0.449; 95%CI: −1.004 to 0.106) was observed compared with supplementation duration less than 4 weeks (WMD, −0.137; 95%CI, −0.816 to 0.541) and more than 6 months (WMD, −0.389; 95%CI, −1.034 to 0.257) without statistical significance (P = 0.059).Conclusion: No statistically significant evidences for the potential dose-dependent manner of BMI and best supplement duration were detected in this study. Large and well-designed studies are recommended to confirm this conclusion.

Association of the FTO gene variant (rs9939609) with cardiovascular disease in men with abnormal glucose metabolism – The Finnish Diabetes Prevention Study - Corrected Proof

2010-04-20

Abstract: Background and aim: The common single nucleotide polymorphism (SNP) in the FTO (fat mass and obesity associated) gene has been consistently associated with an increased risk of obesity. We investigated whether the SNP rs9939609 (T/A) of the FTO is associated with risk factors of cardiovascular diseases (CVD), including serum levels of C – reactive protein (CRP), the chemokine RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted; CCL5), and serum and lipoprotein lipids in the Finnish Diabetes Prevention Study (DPS). Furthermore, we examined whether the rs9939609 increased the CVD risk in the DPS and if these results could be replicated in a larger cross-sectional population-based random sample of Finnish men (the METSIM).Methods and results: In the DPS, altogether 490 (BMI≥25kg/m2) subjects with impaired glucose tolerance were genotyped for rs9939609. Cardiovascular morbidity and mortality data were collected during the median follow-up of 10.2 years. The replication study was a population-based cross-sectional study of 6214 men.In the DPS, the AA genotype of rs9939609 was associated, independently of BMI, with increased RANTES (p=0.002) and decreased HDL cholesterol concentrations (p=0.007) in men. During the follow-up, the AA genotype was associated with an adjusted 2.09-fold risk (95% CI 1.17–3.73, p=0.013) of CVD in men. In the METSIM Study, the association with a history of myocardial infarction was replicated in the subgroup of men with type 2 diabetes.Conclusion: We suggest that the variation in the FTO gene may contribute to the development of CVD in men with an abnormal glucose metabolism.

An elevated apolipoprotein B/AI ratio is independently associated with microalbuminuria in male subjects with impaired fasting glucose - Corrected Proof

K-C. Sung, E-J. Rhee, H. Kim, J-B. Park, Y-K. Kim, S. Woo, A.M. Wilson — 2010-04-16

Abstract: Background and aims: The ratio of apolipoprotein B/AI (apo B/AI) has been used as a marker to predict the risk of coronary artery disease. Recent studies have suggested an association between apolipoprotein B level and microalbuminuria in diabetic subjects. This study was performed to assess a possible association between the apo B/AI ratio and microalbuminuria in male subjects with impaired fasting glucose (IFG).Methods and results: In 1266 patients with fasting serum glucose level in the pre-diabetic range, urine albumin-to-creatinine ratio (UACR, μgmg−1) was measured from single morning voided urine. The presence of microalbuminuria was defined as a UACR between 30 and 299μgmg−1. Participants were stratified into four groups by apo B/AI quartiles, from the lowest to the highest. Apo B/AI was higher with increasing body mass index, higher serum triglyceride and serum low-density lipoprotein cholesterol, systolic and diastolic blood pressure values, but lower with higher high-density lipoprotein cholesterol concentrations. After adjusting for these and other confounding factors, an increased apo B/AI ratio was independently associated with the presence of microalbuminuria. In receiver operating characteristic (ROC) curve analyses, apo B/AI ratio showed the highest correlation with the presence of microalbuminuria among the variables, although statistically not different.Conclusion: These findings indicate that apo B/AI ratio shows significant association with microalbuminuria in Korean male subjects with IFG.

High prevalence of vitamin D deficiency and its association with left ventricular dilation: An echocardiography study in elderly patients with chronic heart failure - Corrected Proof

2010-04-16

Abstract: Background and aims: Vitamin D deficiency has been associated with chronic heart failure (CHF). We evaluated vitamin D levels in relationship with New York Heart Association (NYHA) classes, N-terminal pro-brain natriuretic peptide (NT-proBNP) values and left ventricular (LV) measures in ≥60 year old patients with stable CHF. Differently from previous investigations, LV function was assessed by transthoracic echocardiography, to provide easily reproducible results.Methods and results: The study was performed at geographic latitude 44° N, from March to May and from September to November 2008. Acute HF and diseases or drugs altering vitamin D status were exclusion criteria. NYHA scores and 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D and NT-proBNP concentrations were assessed in 90 (45 F, 45M) Caucasian patients with CHF secondary to hypertension and/or coronary artery disease. Vitamin D levels were also measured in 31 subjects without heart disease (controls). LV echocardiography was performed in 52 (26 F, 26M) representative patients. Vitamin D concentrations were significantly lower in CHF cases than in controls. Among subject with CHF, 97.8% presented vitamin D deficiency (25(OH)D<75nmol/L), being severe (<25nmol/L) in 66.7%. LV end-diastolic and end-systolic diameters were significantly longer, LV end-diastolic and end-systolic volumes bigger and fractional shortening lower in CHF patients with 25(OH)D<25nmol/L than with 25(OH)D≥25nmol/L (p<0.05). Log-values of 25(OH)D were negatively correlated with LV end-systolic diameter and volume (r=−0.28; p<0.05). On subgroup analysis, these results persisted only in male patients.Conclusions: In elderly CHF patients, vitamin D deficiency was highly prevalent and often severe. This first addressed echocardiography study showed a sex-specific association between vitamin D deficiency and LV dilation. Since further echocardiography data are easily obtainable, larger investigations are demanded.

Increased levels of microparticles originating from endothelial cells, platelets and erythrocytes in subjects with metabolic syndrome: Relationship with oxidative stress - Corrected Proof

2010-04-16

Abstract: Background and aims: The Metabolic Syndrome (MetS) is associated with increased cardiovascular risk. Circulating microparticles (MP) are involved in the pathogenesis of atherothrombotic disorders and are raised in individual with CVD. We measured their level and cellular origin in subjects with MetS and analyzed their associations with 1/anthropometric and biological parameters of MetS, 2/inflammation and oxidative stress markers.Methods and results: Eighty-eight subjects with the MetS according to the NCEP-ATPIII definition were enrolled in a bicentric study and compared to 27 healthy controls. AnnexinV-positive MP (TMP), MP derived from platelets (PMP), erythrocytes (ErMP), endothelial cells (EMP), leukocytes (LMP) and granulocytes (PNMP) were determined by flow cytometry. MetS subjects had significantly higher counts/μl of TMP (730.6±49.7 vs 352.8±35.6), PMP (416.0±43.8 vs 250.5±23.5), ErMP (243.8±22.1 vs 73.6±19.6) and EMP (7.8±0.8 vs 4.0±1.0) compared with controls. LMP and PNMP were not statistically different between groups. Multivariate analysis demonstrated that each criterion for the MetS influenced the number of TMP. Waist girth was a significant determinant of PMP and EMP level and blood pressure was correlated with EMP level. Glycemia positively correlated with PMP level whereas dyslipidemia influenced EMP and ErMP levels. Interestingly, the oxidative stress markers, plasma glutathione peroxydase and urinary 8-iso-prostaglandin F2 α, independently influenced TMP and PMP levels whereas inflammatory markers did not, irrespective of MP type.Conclusion: Increased levels of TMP, PMP, ErMP and EMP are associated with individual metabolic abnormalities of MetS and oxidative stress. Whether MP assessment may represent a marker for risk stratification or a target for pharmacological intervention deserves further investigation.

Olmesartan, a novel angiotensin II type 1 receptor antagonist, reduces severity of atherosclerosis in apolipoprotein E deficient mice associated with reducing superoxide production - Corrected Proof

K. Shimada, T. Murayama, M. Yokode, T. Kita, M. Fujita, C. Kishimoto — 2010-04-16

Abstract: Background and Aim: Oxidative stress may play an important role in the development of atherosclerosis. Some angiotensin II type 1 (AT1) receptor antagonists have the capacity of reducing oxidative stress in addition to the hemodynamic actions. Accordingly, we assessed the hypothesis that olmesartan, a novel AT1 receptor antagonist, reduced the severity of atherosclerosis in apolipoprotein (apo) E-deficient mice associated with reducing oxidative stress.Methods and results: Atherosclerosis was induced in apo E-deficient mice fed a high fat diet. Mice were intraperitoneally treated with an injection of olmesartan (1mg/kg/day) daily over 8 weeks, and were compared with the untreated controls. Blood pressure was not changed significantly by the olmesartan treatment. Fatty streak plaque developed in apo E-deficient mice, and was suppressed in mice that received olmesartan. In addition, olmesartan reduced not only superoxide production but the overload of oxidative stress in aortic walls. There were no significant differences in serum lipid levels between olmesartan-treated and -untreated groups. In vitro study showed that both olmesartan and its active metabolite RNH-6270, an enantiomer of olmesartan, suppressed interferon-γ, macrophage inflammatory protein-2, and thioredoxin (a marker of oxidative stress) concentrations in cultured cells.Conclusion: Olmesartan may suppress atherosclerosis via reducing not only superoxide production but also the overload of oxidative stress in this animal model.

Serum ferritin levels are associated with vascular damage in patients with nonalcoholic fatty liver disease - Corrected Proof

2010-04-14

Abstract: Background and aims: Increased ferritin and body iron stores are frequently observed in nonalcoholic fatty liver disease (NAFLD), associated with heightened susceptibility to vascular damage. Conflicting data have been reported on the role of iron in atherosclerosis, with recent data suggesting that excess iron induces vascular damage by increasing levels of the hormone hepcidin, which would determine iron trapping into macrophages, oxidative stress, and promotion of transformation into foam cells. Aim of this study was to investigate the relationship between iron status and cardiovascular damage in NAFLD.Methods and results: Vascular damage was evaluated by common carotid arteries intima-media thickness (CC-IMT) measurement and plaque detection by ecocolor-doppler ultrasonography in 506 patients with clinical and ultrasonographic diagnosis of NAFLD, hemochromatosis gene (HFE) mutations by restriction analysis in 342 patients. Serum hepcidin-25 was measured by time-of-flight mass spectrometry in 143 patients. At multivariate analysis CC-IMT was associated with systolic blood pressure, glucose, LDL cholesterol, abdominal circumference, age, and ferritin (p=0.048). Carotid plaques were independently associated with age, ferritin, glucose, and hypertension. Ferritin reflected iron stores and metabolic syndrome components, but not inflammation or liver damage. Hyperferritinemia was associated with increased vascular damage only in patients with HFE genotypes associated with hepcidin upregulation by iron stores (p<0.0001), and serum hepcidin-25 was independently associated with carotid plaques (p=0.05).Conclusion: Ferritin levels, reflecting iron stores, are independent predictors of vascular damage in NAFLD. The mechanism may involve upregulation of hepcidin by increased iron stores in patients not carrying HFE mutations, and iron compartmentalization into macrophages.

The effect of increased dietary fruit and vegetable consumption on endothelial activation, inflammation and oxidative stress in hypertensive volunteers - Corrected Proof

2010-04-14

Abstract: Background and aims: Public health campaigns recommend increased fruit and vegetable (FV) consumption as an effective means of cardiovascular risk reduction. During an 8 week randomised control trial among hypertensive volunteers, we noted significant improvements in endothelium-dependent vasodilatation with increasing FV consumption. Circulating indices of inflammation, endothelial activation and insulin resistance are often employed as alternative surrogates for systemic arterial health. The responses of several such biomarkers to our previously described FV intervention are reported here.Methods and results: Hypertensive volunteers were recruited from medical outpatient clinics. After a common 4 week run-in period during which FV consumption was limited to 1 portion per day, participants were randomised to 1, 3 or 6 portions daily for 8 weeks. Venous blood samples for biomarker analyses were collected during the pre and post-intervention vascular assessments. A total of 117 volunteers completed the 12 week study. Intervention-related changes in circulating levels of high sensitivity C-reactive protein (hsCRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1) did not differ significantly between FV groups. Similarly, there were no significant between group differences of change in homeostasis model assessment (HOMA) scores.Conclusions: Despite mediating a significant improvement in acetylcholine induced vasodilatation, increased FV consumption did not affect a calculated measure of insulin resistance or concentrations of the circulating biomarkers measured during this study. Functional indices of arterial health such as endothelium-dependent vasomotion are likely to provide more informative cardiovascular end-points during short-term dietary intervention trials.

High cardiovascular risk in Spanish workers - Corrected Proof

2010-04-12

Abstract: Background and aims: To investigate the prevalence of high cardiovascular risk in the Spanish working population, and its distribution among different occupations and gender.Methods and results: Cross-sectional study of 309,955 workers (72.6% males, mean age 36.5 years, range 16–74 years), who underwent a routine medical check-up. Workers were classified as high, intermediate or low cardiovascular risk, according to the SCORE system. Workers with a relative risk greater than 4 were also considered as high-risk. The prevalence of high cardiovascular risk was 7.6% (95% CI 7.5–7.7) in males and 1.7% (95% CI 1.6–1.8) in females. After adjusting for age and gender, the prevalence of high cardiovascular risk was greater in workers from the Agriculture and Construction sectors than in those from Industry and Service sectors. The prevalence of high cardiovascular risk was higher in blue-collar than in white-collar occupations.Conclusions: A sizeable proportion of workers, especially blue-collar males, are at high cardiovascular risk. Knowledge of this risk for certain workers may serve as a basis for preventive strategies.

Changes in natriuretic peptide and cytokine plasma levels in patients with heart failure, after treatment with high dose of furosemide plus hypertonic saline solution (HSS) and after a saline loading - Corrected Proof

2010-03-26

Abstract: Background and Aims: Neurohormonal activation and inflammation characterizes heart failure, relates to outcome, and is a therapeutic target.The aim of this study was to evaluate the effects of high-dose furosemide plus small-volume hypertonic saline solutions (HSS) on natriuretic peptides and immuno-inflammatory marker levels and to analyze, after treatment, the response to acute saline loading.Methods and Results: 120 patients with heart failure treated with high-dose furosemide+HSS (Furosemide/HSS group) were matched with: 30 subjects with heart failure treated with high-dose furosemide (furosemide group), 30 controls with asymptomatic left-ventricular dysfunction (ALVD) (asymptomatic group) and 30 controls without heart failure or ALVD (Healthy group). We evaluated plasma levels of natriuretic peptides and cytokine levels in baseline, after treatment and after acute saline load.After treatment with high-dose furosemide+HSS compared to treatment with furosemide alone we observed a significant lowering of ANP [96 (46.5–159.5)pg/ml vs 64 (21–150)pg/ml], BNP [215.5 (80.5–487)pg/ml vs 87 (66–141.5)pg/ml], TNF-α [389.5 (265–615.5)pg/ml vs 231.5 (156–373.5)pg/ml], IL-1β [8 (7–9)pg/ml vs 4 (3–7)pg/ml], IL-6 [5 (3–7.5)pg/ml vs 3 (2–4)pg/ml], plasma values and after an acute saline load, a lower percentage change of ANP (+18.6% vs +28.03% vs +25% vs +29%), BNP (+14.5% vs +29.2% vs +30% vs +29.6%) TNF-α (+10.8% vs +15.8% vs +17.8% vs +11.3%), IL-1β (+20% vs 34.4% vs 40% vs 34.4%) compared to control groups.Conclusions: Treatment with HSS could be responsible for a stretching relief that could influence natriuretic and immuno-inflammatory markers.

Dietary fat and cholesterol and risk of cardiovascular disease in older adults: The Health ABC Study - Corrected Proof

2010-03-25

Abstract: Background and aims: Although dietary fats and cholesterol have previously been associated with risk of cardiovascular disease (CVD) in middle-aged populations, less is known among older adults. The purpose of this study was to determine the association between dietary fats, cholesterol, and eggs and CVD risk among community-dwelling adults aged 70–79 in the Health, Aging and Body Composition Study.Methods and results: Diet was assessed using an interviewer-administered 108-item food frequency questionnaire (n=1941). CVD events were defined as a confirmed myocardial infarction, coronary death, or stroke. Relative rates of CVD over 9 years of follow-up were estimated using Cox proportional hazards models. During follow-up, there were 203 incident cases of CVD. There were no significant associations between dietary fats and CVD risk. Dietary cholesterol (HR (95% CI): 1.47 (0.93, 2.32) for the upper vs. lower tertile; P for trend, 0.10) and egg consumption (HR (95% CI): 1.68 (1.12, 2.51) for 3+/week vs. <1/week; P for trend, 0.01) were associated with increased CVD risk. However, in sub-group analyses, dietary cholesterol and egg consumption were associated with increased CVD risk only among older adults with type 2 diabetes (HR (95% CI): 3.66 (1.09, 12.29) and 5.02 (1.63, 15.52), respectively, for the upper vs. lower tertile/group).Conclusions: Dietary cholesterol and egg consumption were associated with increased CVD risk among older, community-dwelling adults with type 2 diabetes. Further research on the biological mechanism(s) for the increased CVD risk with higher dietary cholesterol and frequent egg consumption among older adults with diabetes is warranted.

Sub-clinical organ damage in hypertension and obesity - Corrected Proof

2010-03-22

Abstract: Background: The development of sub-clinical organ damage precedes and predicts the occurrence of cardiovascular (CV) events in hypertensive as well as in obese patients.Aim and methods: We investigated the prevalence and clinical correlates of organ damage (OD), namely carotid atherosclerosis (US scan) and urine albumin to creatinine ratio (three non-consecutive first morning samples) in a group of 164 obese patients and in an age- and gender-matched group of non-obese hypertensive patients.Results: There was a significantly greater prevalence and severity of OD in obese patients as compared to non-obese hypertensive patients. In particular obese patients more frequently had microalbuminuria (16 vs7%, χ2 5.8, P=0.0157) and carotid abnormalities (53 vs 10%, χ2 69.5, P<0.0001) as well as higher urinary albumin excretion rate (−0.05±0.52 vs −0.28±0.43log ACR, P<0.0001) and carotid intima-media thickness (0.955±0.224 vs 0.681±0.171, <0.0001). Notably, the coexistence of hypertension and obesity did not entail a greater prevalence and severity of OD. Moreover, after adjusting for potentially confounding factors including blood pressure levels, diagnosis of diabetes, and lipid profile, morbidly obese patients showed a 5-fold, and 22-fold higher risk of having microalbuminuria, and carotid atherosclerosis, respectively.Conclusions: Sub-clinical OD is highly prevalent in obese patients, even in the absence of high blood pressure. Hypertension and obesity seem to exert an independent, possibly non-additive role on the occurrence of organ damage.

Adiposity indices in the prediction of metabolic abnormalities associated with cardiovascular disease in non-diabetic adults - Corrected Proof

A. Liu, F. Abbasi, GM. Reaven — 2010-03-22

Abstract: Background and Aims: The prevalence of insulin resistance and cardiovascular disease (CVD) increases with degree of obesity. Whether measurements of generalized and abdominal obesity differ in the ability to predict changes associated with increased CVD risk is widely debated. We compared the prevalence of metabolic abnormalities in 275 women and 204 men stratified by categories of body mass index (BMI) and waist circumference (WC), and assessed the ability of these adiposity indices in combination with metabolic risk variables to predict insulin resistance.Methods and Results: Healthy, non-diabetic volunteers underwent measurements of BMI, WC, blood pressure, fasting plasma glucose (FPG), lipoprotein concentrations, and direct quantification of insulin-mediated glucose uptake. Insulin resistance was defined as the top tertile of steady-state plasma glucose (SSPG) concentrations. BMI and WC were highly correlated (P < 0.001) in both women and men. Abnormal SSPG and triglyceride concentrations were associated with increasing adiposity by either index in both genders. Among women, abnormal FPG and high density lipoprotein cholesterol (HDL-C) concentrations were associated with increasing BMI and WC. In men, abnormal HDL-C was associated with increasing BMI only. Elevated systolic blood pressure (SBP) was associated with increasing BMI in both genders. The odds of insulin resistance were greatest in women with elevated FPG and triglycerides (4.5-fold). In men, the best predictors were BMI and SBP, and WC and HDL-C (3-fold).Conclusion: BMI is at least comparable to WC in stratifying individuals for prevalence of metabolic abnormalities associated with increased CVD risk and predicting insulin resistance.

The G3057A LEPR polymorphism is associated with obesity in Tunisian women - Corrected Proof

2010-03-22

Abstract: Objectives: The aim of this study was to evaluate the effect of the G3057A (rs62589000) LEPR polymorphism on obesity risk and plasma leptin, insulin, and lipid levels in a sample of the Tunisian population.Design and methods: Three hundred and ninety-three obese patients and 317 controls participated in this study. The G3057A genotype was determined by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis.Results: In the entire study sample, no significant differences in genotype frequencies were observed between obese patients and controls. However, stratified analysis by gender revealed a quantitative increase in the variant allele (33.3% vs. 25.8%; χ2=4.90, p=0.026) in obese women (but not men) compared to controls. When a dominant model of inheritance was assumed, the GA+AA genotypes were more prevalent in these obese female patients than in controls (58.3% vs. 47.8%; χ2=4.08, p=0.044). Unconditional logistic regression showed that in women only, obesity risk was significantly higher for homozygotes for the variant allele (OR=2.73, 95% CI 1.03–7.21) and for carriers of GA+AA genotypes (OR=1.53, 95% CI 1.01–2.31) compared with homozygotes for the normal allele. The association between the G3057A LEPR variant and obesity remained statistically significant even after adjustment for age. No relationship was found between the G3057A LEPR polymorphism and leptin and insulin levels. Additionally, this LEPR gene variant had no effect on plasma lipid concentrations.Conclusion: There is evidence in this study that the G3057A LEPR polymorphism is associated with obesity in Tunisian women.

-94 ins/del ATTG NFKB1 gene variant is associated with lower susceptibility to myocardial infarction - Corrected Proof

2010-03-22

Abstract: Background and Aims: An imbalance of Nuclear Factor Kappa B (NFкB) and Inhibitor Kappa B (IкB) is involved in various human diseases including atherogenesis. We aimed to evaluate the relationship between NFKB1 and NFKBIA polymorphism and susceptibility to myocardial infarction (MI).Methods and Results: Genotyping was performed for NFKB1 and NFKBIA gene variants in 253 subjects (86 patients affected by myocardial infarction and 167 control subjects). In 40 patients, biopsy specimens were taken from the left ventricle area of presumed ischemia for p50, p65 and IкBα quantification. The allele frequency and genotype distribution of NFKBIA gene polymorphism did not differ between MI and control group while control subjects had a higher D allele frequency of -94 ins/del ATTG NFKB1 polymorphism, compared to the MI group (P<0.001; OR=0.304; 95% CI=0.177–0.522). Subjects carrying the D allele had significantly lower plasma fibrinogen and CRP (C-reactive protein) levels compared to no carriers (P<0.05). Fibrinogen–genotype interaction was found to have a significant effect on susceptibility to myocardial infarction. Myocardial p50 (r=0.627; P=0.012) and p65 (r=0.683; P=0.005) levels significantly correlated with plasma fibrinogen levels while subjects carrying the D allele of the NFкB1 gene variant had lower myocardial p50 (P=0.007) and p65 (P=0.009) levels compared to no carriers.Conclusion: -94 ins/del ATTG NFKB1 gene variant may contribute to lower MI susceptibility via the potential reduction of activated NFкB which in turn is related to plasma inflammatory marker reduction.

The influence of the S19W SNP of the APOA5 gene on triglyceride levels in southern Brazil: Interactions with the APOE gene, sex and menopause status - Corrected Proof

2010-03-22

Abstract: Background and aims: Hypertriglyceridemia is an important independent risk factor for coronary artery diseases and is determined by a wide range of factors, both genetic and exogenous. The A5 apolipoprotein, which is associated with the synthesis and removal of triglycerides (TG), is encoded by the APOA5 gene. One of the polymorphisms of this gene that has been the focus of a large number of studies, and which appears to be associated with increased TG, is S19W (rs 3135506). In this study, we examined the influence of this single nucleotide polymorphism (SNP) on TG levels of a sample of southern Brazilians.Methods and results: Samples obtained from 567 people of European descent were genotyped; interactions between this variant and anthropometric variables were analyzed, and the effects of lifestyle, sex, menopause, and variations of the APOE gene were evaluated. We found that the 19W allele is associated with increased TG (p = 0.025) and that this influence was modulated by sex (p = 0.003), menopause (p = 0.022) and the presence of the E*4 allele (p = 0.027).Conclusion: Our data showed, for the first time, the importance and magnitude of the influence of the S19W variant in a southern Brazilian population.

Curcumin improves insulin resistance in skeletal muscle of rats - Corrected Proof

L-X. Na, Y-L. Zhang, Y. Li, L-Y. Liu, R. Li, T. Kong, C-H. Sun — 2010-03-15

Abstract: Background and aims: Curcumin has been reported to lower plasma lipids and glucose in diabetic rats, and to decrease body weight in obese rats, which may partly be due to increased fatty acid oxidation and utilization in skeletal muscle.Methods and results: Diabetic rats induced by high-fat diet plus streptozotocin (STZ, 30mg/kg BW) were fed a diet containing 50, 150, or 250mg/kg BW curcumin for 7 wk. Curcumin dose-dependently decreased plasma lipids and glucose and the dose 150mg/kg BW appeared to be adequate to produce a significant effect. Curcumin supplementation reduced glucose and insulin tolerance measured as areas under the curve. L6 myotubes were treated with palmitate (0.25mmol/L) in the presence of different levels of curcumin for 24 h in our in vitro experiment. Curcumin at 10μmol/L was adequate to cause a significant increase in 2-deoxy-[3H]d-glucose uptake by L6 myotubes. Curcumin up-regulated expression of phosphorylated AMP-activated protein kinase (AMPK), CD36, and carnitine palmitoyl transferase 1, but down-regulated expression of pyruvate dehydrogenase 4 and phosphorylated glycogen synthase (GS) in both in vivo and in vitro studies. Moreover, curcumin increased phosphorylated acetyl COA carboxylase in L6 myotubes. The effects of curcumin on these enzymes except for GS were suppressed by AMPK inhibitor, Compound C. LKB1, an upstream kinase of AMPK, was activated by curcumin and inhibited by radicicol, an LKB1 destabilizer.Conclusion: Curcumin improves muscular insulin resistance by increasing oxidation of fatty acid and glucose, which is, at least in part, mediated through LKB1-AMPK pathway.

Reduced circulating endothelial progenitor cell number in healthy young adult hyperinsulinemic men - Corrected Proof

2010-03-15

Abstract: Background and aims: The number of Endothelial Progenitor Cells (EPCs) is considered a novel marker of cardiovascular (CV) disease. It is not clear which are the main determinants of EPC number in apparently healthy subjects in the absence of overt clinical CV or metabolic abnormalities. We evaluated the main clinical determinants of EPC levels in a population of healthy subjects with normal glucose tolerance.Methods and results: EPC number was determined in 122 healthy subjects (73M/49F;36.6 ± 8yrs). Blood samples were collected to test biochemical variables. OGTT was performed and insulin resistance/compensatory hyperinsulinemia was defined according to fasting plasma insulin (FPI) levels. EPCs were identified as cells co-expressing CD133/CD34/KDR antigens by flow-cytometry. CD133+/KDR+ count inversely correlated with BMI (rho=−0.18;p < 0.05), waist circumference (−0.2;<0.05), diastolic (−0.23;<0.01) and systolic blood pressure (−0.21;<0.05), uric acid (−0.24;<0.005), PAI-1 (−0.197; <0.05) and FPI (−0.2;<0.05) and directly correlated with HDL cholesterol (0.182;<0.05). CD34+/CD133+/KDR+ count inversely correlated with uric acid (−0.28;<0.005) and FPI (−0.2;<0.05). EPC number was lower in males (p < 0.05) and gender was the only independent predictor of EPC count (p < 0.05). By dividing the population in four subgroups based on gender and insulin resistance, CD133+/KDR+ levels were lower in insulin resistant compared to insulin sensitive males (p < 0.05) with no differences in females.Conclusion: The male gender is an independent predictor of low EPC levels in healthy subjects. This might contribute to explaining the higher CV risk in males compared to pre-menopausal age-matched females. In this study a reduced EPC number seems to be associated with insulin resistance in male subjects.

Impaired fasting glucose and recurrent cardiovascular disease among survivors of a first acute myocardial infarction: Evidence of a sex difference? The Western New York experience - Corrected Proof

R.P. Donahue, J.M. Dorn, S. Stranges, M. Swanson, K. Hovey, M. Trevisan — 2010-03-15

Abstract: Background and aims: There is little epidemiological evidence regarding the association of impaired glucose metabolism with recurrent cardiovascular events. We therefore examined potential sex differences in the effect of impaired fasting glucose (IFG) on recurrent cardiovascular disease (CVD) in a community-based study of survivors of a first acute myocardial infarction (MI).Methods and results: This report focuses on 1226 incident MI cases (28.4% women) discharged alive from area hospitals in the Western New York Acute MI Study (1996–2004). Deaths and underlying cause of death were determined via query of the National Death Index (Plus) Retrieval Program with follow-up through December 31, 2004. Outcomes reported included fatal or non-fatal coronary heart disease (CHD) or coronary revascularization surgery and total stroke. Traditional CHD risk factors and other explanatory variables were determined by clinical examination after the first acute event. Impaired fasting glucose was defined as fasting blood glucose between 100 and 125mg/dl. During a mean follow-up of 4.5 years, there were 91 recurrent events (26.1%) in women and 173 recurrent events (19.7%) in men. After multivariable adjustment, the hazard ratios for recurrent cardiovascular events were 1.96 (95% CI: 1.15–3.16) and 2.59 (1.56–4.30) in women with IFG and with diabetes, respectively, compared to normoglycemic women. Among men, neither IFG nor diabetes was independently related to risk of recurrence.Conclusions: In this study, IFG was a strong risk factor for recurrent cardiovascular events only among women. These results suggest that increased cardiovascular risk in MI survivors begins at lower glucose levels in women than men.

Comparison of the effects of cows' milk, fortified soy milk, and calcium supplement on weight and fat loss in premenopausal overweight and obese women - Corrected Proof

Sh Faghih, A.R. Abadi, M. Hedayati, S.M. Kimiagar — 2010-03-15

Abstract: Background and aims: Recent studies suggest that calcium metabolism and perhaps other components of dairy products may contribute to shifting the energy balance and thus play a role in weight regulation. We compared the effects of cows' milk, calcium fortified soy milk and calcium supplement on weight and body fat reduction in premenopausal overweight and obese women.Methods and Results: In this clinical trial, 100 healthy overweight or obese premenopausal women were randomized to one of the following dietary regimens for 8 weeks: (1) a control diet providing a 500kcal/day deficit, with 500–600mg/day dietary calcium; (2) a calcium-supplemented diet identical to the control diet with 800mg/day of calcium as calcium carbonate; (3) a milk diet providing a 500kcal/day deficit and containing three servings of low-fat milk; (4) a soy milk diet providing a 500kcal/day deficit and containing three servings of calcium fortified soy milk. At baseline and after 8 weeks, weight, waist circumference, and hip circumference were measured. Three 24-h dietary records and physical activity records were also taken. Comparing the mean differences in weight, waist circumference, body mass index (BMI) and waist-to-hip ratio (WHR) using repeated measure of variance analysis showed that changes in waist circumference and WHR were significant among the four groups (p=0.029 and p=0.015, respectively). After adjustment for baseline values, changes in weight and BMI were also significant (p=0.017 and p=0.019, respectively). Weight reductions in high milk, soy milk, calcium supplement and control groups were 4.43±1.93(kg), 3.46±1.28(kg), 3.89±2.40(kg) and 2.87±1.55(kg), respectively. The greatest changes were seen in the high dairy group in all variables.Conclusion: Increasing low fat milk consumption significantly reduces the general and central obesity beyond a low calorie diet.

Homocysteine enriched diet leads to prolonged QT interval and reduced left ventricular performance in telemetric monitored mice - Corrected Proof

2010-03-15

Abstract: Background and aims: Homocysteine (Hcy) is a sulfur-containing, non-protein amino acid produced in the metabolic pathway of methionine. Hyperhomocysteinemia is associated with cerebro- and cardiovascular disease in industrialized countries, mostly resulting from protein rich diet and sedentary life style. Matrix metalloproteinases are involved in cardiac remodeling, leading to degradation of intercellular junctions, cardiac connexins and basement membranes. The study was designed to investigate the relationship between Hcy, cardiac remodeling, cardiac performance, and rhythm disturbances in an animal model of hyperhomocysteinemia. We tested the hypothesis that induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 leads to connexin 40, connexin 43, connexin 45 expression changes contributing to decreased cardiac performance and disturbed atrioventricular conduction.Methods and results: Hcy was added to drinking water of male C57/BL6J mice to achieve moderate Hcy blood levels. ECG was monitored in conscious mice with a telemetric ECG device; echocardiography was used for assessment of left ventricular function. Immunoblotting was used to evaluate matrix metalloproteinase-2, matrix metalloproteinase-9, connexin 40, connexin 43, and connexin 45 expression in cardiac tissue. Animals fed Hcy showed significant prolongation of QRS, QTc, and PR intervals along with reduced left ventricular function. Western blotting showed increased expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and decreased expression of connexin 40, 43, and 45.Conclusion: Hcy has been identified as a nutritional factor contributing to cardiovascular disease. Cardiac remodeling induced by matrix metalloproteinase-2 and matrix metalloproteinase-9 and decreased expression of connexin 40, 43, and 45 appears to play a role in the pathomechanism of atrioventricular conduction delay and ventricular dilatation in hyperhomocysteinemia.

Endothelial dysfunction and non-alcoholic liver steatosis in hypertensive patients - Corrected Proof

2010-03-15

Abstract: Background and aims: Non-alcoholic fatty liver disease, characterized by insulin resistance, has been correlated with several clinical and pathological manifestations, such as intima-media thickness. At present, no data are available regarding endothelial dysfunction, the first step in atherosclerosis, and non-alcoholic fatty liver disease. The aim of this study was to test a possible association between non-alcoholic fatty liver disease and endothelium-dependent vasodilation in a group of hypertensive patients.Methods and results: A total of 40 never-treated uncomplicated hypertensive outpatients were enrolled. Patients underwent a complete clinical and biochemical work-up including ultrasonographic scanning to detect liver steatosis. Insulin sensitivity was estimated by using the homeostasis model assessment (HOMA) index. Endothelial function was assessed by strain-gauge plethysmography during intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside. Endothelium-dependent vasodilation was significantly reduced in hypertensive patients with liver steatosis in comparison with those without. Statistical analysis demonstrated that the HOMA index was the strongest predictor of both endothelium-dependent vasodilation and liver steatosis. In particular, one point of HOMA accounts for 37.9% of forearm blood flow variation, and increases the risk of liver steatosis by 86.4%.Conclusion: Our data demonstrate that hypertensive patients with liver steatosis have a reduced endothelium-dependent vasodilation and highest insulin resistance. In keeping with this, it is possible to hypothesize that liver steatosis may be considered a marker of vascular damage in essential hypertension.

Polymorphisms in the platelet-specific collagen receptor GP6 are associated with risk of nonfatal myocardial infarction in Caucasians - Corrected Proof

2010-03-15

Abstract: Background and aims: Glycoprotein 6 (GP6) is a platelet-specific collagen receptor implicated in the thrombotic pathway to acute myocardial infarction (AMI), but a possible genetic relationship between GP6 and AMI is poorly understood. We tested for the genetic association between AMI and single nucleotide polymorphisms (SNPs) in 24 loci, including GP6.Methods and results: We conducted a case-control study of AMI and GP6 in a community-based population (n = 652 cases, 625 controls). We also examined men and women separately and stratified the latter by use of hormone replacement therapy (HRT). Among both sexes, the strongest association was for a protective missense polymorphism (rs1163662) in the GP6 gene (OR = 0.70; Bonferroni-adjusted p < 0.05). SNPs in GP6 were also strongly associated with AMI among women who reported ever taking HRT, but not among women who never took HRT. Haplotype analyses were consistent with the single-SNP findings.Conclusions: In this sample of white non-Hispanic men and women, several SNPs in GP6 were significantly related to risk of AMI. Development of pharmacologic therapy directed towards platelet activity and thrombosis may reduce the incidence of AMI among at-risk groups.

Genetic variation within IL18 is associated with insulin levels, insulin resistance and postprandial measures - Corrected Proof

2010-03-15

Abstract: Background and aims: IL-18 expression is up-regulated in atherosclerotic plaques, and higher levels are seen in obese and Type 2 Diabetic individuals. More recently, a possible role for IL-18 in glucose and energy homeostasis has been suggested.Methods and results: We investigated variation within the IL18 gene and its association with measures of obesity and the metabolic syndrome. Five IL18 tagging single nucleotide polymorphisms (rs1946519, rs2043055, rs549908, rs360729, rs3882891) were selected and genotyped in the Gene-Diet Attica Investigation on childhood obesity (GENDAI) (age range 10–14 yrs); in young European men in the second European Atherosclerosis Research offspring Study (EARSII), an offspring study (age range 18–28 yrs) and in a group of healthy women from the Greek Obese Women study (GrOW) (age range 18–74 yrs). Six common haplotypes were observed. In GrOW, Hap6 (Frequency-2.6%) was associated with higher insulin levels (p<0.0001), estimates of HOMA-Insulin Resistance (p<0.0001) and HOMA-β-cell (p<0.0001) compared to the common haplotype Hap1 (Frequency-33.2%). In EARSII, rs2043055 was associated with peak and area under the curve triglycerides (p=0.001 and p=0.002, respectively) after an oral fat tolerance test in ‘cases’ but not ‘controls’. None of the haplotypes were associated with measures of body fatness in any of the studies.Conclusion: Association of IL18 variation with insulin levels and estimates of insulin resistance were only observed in our adult study, suggesting that the effects of IL-18 are only associated with increasing age. Taken together with the association of IL18 variants with post-prandial measures, this provides support for IL-18 as a metabolic factor.

Plasma carotenoids and risk of acute myocardial infarction in the Singapore Chinese Health Study - Corrected Proof

W.-P. Koh, J.-M. Yuan, R. Wang, Y.-P. Lee, B.-L. Lee, M.C. Yu, C.-N. Ong — 2010-03-15

Abstract: Background and Aim: Modification of low-density lipoprotein due to oxidative stress is essential in the development of coronary atherosclerosis. Data of specific carotenoids except β-carotene on cardioprotective effects in humans are limited.Methods and Results: This study examined the associations between plasma concentrations of specific carotenoids and incidence of acute myocardial infarction. The study included 280 incident cases of acute myocardial infarction and 560 matched controls nested within the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese men and women aged 45–74 years old enrolled in 1993–1998 in Singapore. Retinol and carotenoids in prediagnostic plasma were quantified using high-performance liquid chromatography. High levels of plasma β-cryptoxanthin and lutein were associated with decreased risk of acute myocardial infarction after adjustment for multiple risk factors for coronary heart disease. For β-cryptoxanthin, the odds ratio (95% confidence interval) for the highest (Q5) versus the lowest (Q1) quintile was 0.67 (0.37–1.21) (P for trend=0.03). For lutein, the odds ratios (95% confidence intervals) for the combined Q2–Q3 and the combined Q4–Q5 versus Q1 were 0.71 (0.45–1.12) and 0.58 (0.35–0.94) respectively (P for trend=0.03). There was no statistically significant association between other carotenoids or retinol and risk of acute myocardial infarction.Conclusions: High plasma levels of β-cryptoxanthin and lutein were associated with decreased risk of acute myocardial infarction. The findings of this study support a cardioprotective role of these two carotenoids in humans.

Induction of HO-1 and redox signaling in endothelial cells by advanced glycation end products: A role for Nrf2 in vascular protection in diabetes - Corrected Proof

M. He, R.C.M. Siow, D. Sugden, L. Gao, X. Cheng, G.E. Mann — 2010-03-15

Abstract: Background and aims: Hyperglycemia and diabetes are associated with increased formation of advanced glycation end products and enhanced oxidative stress, leading to the progression of diabetic vascular disease. We have investigated the mechanisms by which AGE-modified bovine albumin (AGE-BSA) induces reactive oxygen species (ROS) generation, leading to nuclear factor-erythroid 2-related factor (Nrf2) dependent induction of the antioxidant genes heme oxygenase-1 (HO-1) and NADPH:quinone oxidoreductase 1 (NQO1) in bovine aortic endothelial cells.Methods and results: AGE-BSA (100 μg ml−1, 0–24 h), but not native BSA, elicited time-dependent increases in ROS generation, Nrf2 nuclear translocation and enhanced mRNA and protein expression of HO-1 and NQO1, but not glutathione peroxidase-1. Inhibition of ROS production with the superoxide scavenger Tiron or inhibitors of flavoproteins (diphenylene iodonium) and NADPH oxidase (apocynin), but not eNOS (l-NAME) or mitochondria complex I (rotenone) abrogated HO-1 induction by AGE-BSA. Although AGE-BSA induced rapid phosphorylation of JNK and Akt, only inhibition of JNK abrogated HO-1 expression, implicating the involvement of the JNK signaling pathway in AGEs activation of Nrf2/ARE-linked antioxidant gene expression.Conclusion: Our findings establish that AGEs activate redox sensitive Nrf2-dependent antioxidant gene expression in bovine aortic endothelial cells, providing an adaptive endogenous defense against oxidative stress in diabetes.

Cross-sectional association of nut intake with adiposity in a Mediterranean population - Corrected Proof

2010-03-11

Abstract: Background and aims: Nut intake has been inversely related to body mass index (BMI) in prospective studies. We examined dietary determinants of adiposity in an elderly Mediterranean population with customarily high nut consumption.Methods and results: A cross-sectional study was conducted in 847 subjects (56% women, mean age 67 years, BMI 29.7kg/m2) at high cardiovascular risk recruited into the PREDIMED study. Food consumption was evaluated by a validated semi-quantitative questionnaire, energy expenditure in physical activity by the Minnesota Leisure Time Activity questionnaire, and anthropometric variables by standard measurements. Nut intake decreased across quintiles of both BMI and waist circumference (P-trend <0.005; both). Alcohol ingestion was inversely related to BMI (P-trend=0.020) and directly to waist (P-trend=0.011), while meat intake was directly associated with waist circumference (P-trend=0.018). In fully adjusted multivariable models, independent dietary associations of BMI were the intake of nuts inversely (P=0.002) and that of meat and meat products directly (P=0.042). For waist circumference, independent dietary associations were intake of nuts (P=0.002) and vegetables (P=0.040), both inversely, and intake of meat and meat products directly (P=0.009). From the regression coefficients, it was predicted that BMI and waist circumference decreased by 0.78kg/m2 and 2.1cm, respectively, for each serving of 30g of nuts. Results were similar in men and women.Conclusion: Nut consumption was inversely associated with adiposity independently of other lifestyle variables. It remains to be explored whether residual confounding related to a healthier lifestyle of nut eaters might in part explain these results.

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.