Circulating PCSK9 levels in acute coronary syndrome: Results from the PC-SCA-9 prospective study

BackgroundSerum proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations have been shown to be positively associated with LDL cholesterol (LDL-C), but the relationship between PCSK9 and coronary atherosclerosis lesions remains unclear.ObjectiveThis study aims to investigate the correlation between serum PCSK9 levels and coronary damage severity in patients hospitalized for acute coronary syndrome (ACS).MethodsIn this prospective proof-of-concept study, coronary lesions were assessed using SYNTAX scores. Serum PCSK9 concentrations were measured on admission (Day 0) for ACS by Elisa, and on every day of hospitalization. Spearman's correlations were used to determine the association between PCSK9 levels, SYNTAX score and metabolic parameters.ResultsA total of 174 patients (mean age: 59 ± 14 years, 79% male) with ACS (on Day 0, 119 patients were not taking statins, but 55 were) were included. After initiation of high-intensity statin therapy, serum PCSK9 concentrations increased significantly, reaching maximum levels on Day 2 (+31% vs. Day 0), and remained stable up to Day 4 (P < 0.001, by mixed model). Serum PCSK9 on Day 0 was associated with LDL-C (rho = 0.226, P = 0.017) and apolipoprotein B (rho = 0.282, P = 0.005) in the statin-naïve group only, and with triglycerides and non-HDL-C in all groups. More important, PCSK9 levels on Day 0 were positively associated with SYNTAX scores in the statin-naïve group (rho = 0.239, P = 0.009), but not in the statin-treated group (P = NS). This association was maintained after adjusting for LDL-C (P = 0.014) and major CV risk factors (P = 0.008).ConclusionSerum PCSK9 levels are positively associated with severity of coronary artery lesions independently of LDL-C concentrations in patients hospitalized for ACS. This reinforces the potential importance of PCSK9 inhibition in the management of ACS.     

Baru almond improves lipid profile in mildly hypercholesterolemic subjects: A randomized,controlled, crossover study

Backgroud and aimThe usual consumption of nuts reduces cardiovascular diseases (CVD) risk by improving serum lipids and oxidation status. Baru almonds (Dipteryxalata Vog.), a native species of Brazilian Savannah, have considerable contents of monounsaturated fatty acids (MUFA), dietary fiber, vitamin E and zinc, which could exert positive effects in serum lipids and markers of oxidation. However, there is no study about the effect of their consumption on human health. Thus, the aim of this study was to evaluate the effect of baru almonds supplementation on lipid profile and oxidation of mildly hypercholesterolemic subjects.Methods and ResultsA randomized, crossover, placebo controlled study was performed with 20 mildly hypercholesterolemic subjects (total cholesterol (TC) mean ±SEM = 5.8 ± 0.2 mmol/L). The assay had 2 periods of 6 weeks each and a 4-week washout period between the treatments. Subjects were randomly allocated in alternated periods receiving the following treatments per period: supplementation with 20 g/day of baru almonds or placebo (1 corn starch capsule/day). Compared to placebo, supplementation of baru almonds reduced TC (−8.1 ± 2.4%, P = 0.007), low-density lipoprotein cholesterol (LDL-c) (−9.4 ± 2.4%, P = 0.006) and non-high-density lipoprotein cholesterol (non-HDL-c) (−8.1 ± 3.0%, P = 0.013). There were no significant changes on the oxidation biomarkers evaluated.ConclusionDietary supplementation of mildly hypercholesterolemic subjects with baru almonds improved serum lipid parameters, so that this food might be included in diets for reducing the CVD risk.Clinical Trial registryBrazilian Registry of Clinical Trials (ReBEC) (website: http://www.ensaiosclinicos.gov.br). Register number: RBR-4zdy9p.     

Inflammatory status modulates plasma lipid and inflammatory marker responses to kiwifruit consumption in hypercholesterolaemic men

Background and aimsKiwifruit has the potential to improve markers of metabolic dysfunction, but the response may be influenced by inflammatory state. We aimed to investigate whether inflammatory state would modulate the effect of consuming two green kiwifruit daily on plasma lipids and markers of inflammation.Methods and resultsEighty-five hypercholesterolaemic men completed a 4-week healthy diet run-in, before randomisation to a controlled cross-over study of two 4-week interventions of two green kiwifruit/day plus healthy diet (intervention) or healthy diet alone (control). Anthropometric measures and fasting blood samples (plasma lipids, serum apolipoproteins A1 and B, high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, tumour necrosis factor-alpha (TNF-α) and IL-10) were taken at baseline, 4 and 8 weeks. Subjects were divided into low and medium inflammatory groups, using pre-intervention hs-CRP concentrations (hs-CRP <1 and 1–3 mg/L, respectively).In the medium inflammatory group the kiwifruit intervention resulted in significant improvements in plasma high-density lipoprotein cholesterol (HDL-C) (mean difference 0.08 [95% CI: 0.03, 0.12] mmol/L [P < 0.001]), total cholesterol (TC)/HDL-C ratio (−0.29 [−0.45, −0.14] mmol/L [P = 0.001]), plasma hs-CRP (−22.1 [−33.6, −4.97]% [P = 0.01]) and IL-6 (−43.7 [−63.0, −14.1]% [P = 0.01]) compared to control treatment. No effects were seen in the low inflammatory group. There were significant between inflammation group differences for TC/HDL-C (P = 0.02), triglyceride (TG)/HDL-C (P = 0.05), and plasma IL-6 (P = 0.04).ConclusionsInflammatory state modulated responses to the kiwifruit intervention by improving inflammatory markers and lipid profiles in subjects with modestly elevated CRP, suggesting this group may particularly benefit from the regular consumption of green kiwifruit.Registered 16th March 2010, Australian New Zealand Clinical Trials Registry (no. ACTRN12610000213044), www.ANZCTR.org.au.     

Nut consumption,serum fatty acid profile and estimated coronary heart disease risk in type 2 diabetes

Background and aimsNut consumption has been associated with decreased risk of coronary heart disease (CHD) and type 2 diabetes which has been largely attributed to their healthy fatty acid profile, yet this has not been ascertained. Therefore, we investigated the effect of nut consumption on serum fatty acid concentrations and how these relate to changes in markers of glycemic control and calculated CHD risk score in type 2 diabetes.Methods and results117 subjects with type 2 diabetes consumed one of three iso-energetic (mean 475 kcal/d) supplements for 12 weeks: 1. full-dose nuts (50–100 g/d); 2. half-dose nuts with half-dose muffins; and 3. full-dose muffins. In this secondary analysis, fatty acid concentrations in the phospholipid, triacylglycerol, free fatty acid, and cholesteryl ester fractions from fasting blood samples obtained at baseline and week 12 were analyzed using thin layer and gas chromatography. Full-dose nut supplementation significantly increased serum oleic acid (OA) and MUFAs compared to the control in the phospholipid fraction (OA: P = 0.036; MUFAs: P = 0.024). Inverse associations were found with changes in CHD risk versus changes in OA and MUFAs in the triacylglycerol (r = −0.256, P = 0.011; r = −0.228, P = 0.024, respectively) and phospholipid (r = −0.278, P = 0.006; r = −0.260, P = 0.010, respectively) fractions. In the cholesteryl ester fraction, change in MUFAs was inversely associated with markers of glycemic control (HbA1c: r = −0.250, P = 0.013; fasting blood glucose: r = −0.395, P < 0.0001).ConclusionNut consumption increased OA and MUFA content of the serum phospholipid fraction, which was inversely associated with CHD risk factors and 10-year CHD risk.Clinical Trial Reg. No.NCT00410722, clinicaltrials.gov.     

Low circulating insulin-like growth factor-1 levels are associated with high serum uric acid in nondiabetic adult subjects

Background and aimsLow insulin-like growth factor-1 (IGF-1) levels and high uric acid concentrations are associated with cardio-metabolic disorders. Acute IGF-1 infusion decreases uric acid concentration in healthy individuals. In this study, we aimed to examine the relationship between IGF-1 and uric acid levels.Methods and results1430 adult non diabetic subjects were stratified into quartiles according to their circulating IGF-1 values. Significant differences in uric acid concentration, measured by the URICASE/POD method were observed between low (quartile 1), intermediate (quartile 2 and 3), and high (quartile 4) IGF-1 levels groups after adjusting for age, gender, and body mass index (P = 0.02). These differences remained significant after adjustment for blood pressure, total cholesterol, high density lipoprotein, triglycerides, fasting and 2 h post-load glucose levels, HOMA-IR index (P = 0.005), liver enzymes (P = 0.03), glucose tolerance status (P = 0.02), growth hormone levels (GH) (P = 0.05), anti-hypertensive treatments (P = 0.04) or diuretics use (P = 0.04)). To clarify the molecular links between IGF-1 and uric acid, we performed an in vitro study, incubating human hepatoma cells with uric acid for 24 or 48 h in the presence of GH and observed a 21% and 26% decrease, respectively, in GH-stimulated IGF-1 mRNA expression (P = 0.02 and P = 0.012, respectively). This effect appears to be mediated by uric acid ability to down regulate GH intracellular signaling; in fact we observed a significant decrease of GH activated JAK2 and Stat5 phosphorylation.ConclusionsThese data demonstrate an inverse relationship between IGF-1 and uric acid levels in adults and suggest that uric acid might affect hepatic IGF-1 synthesis.     

Predictive value of low serum pancreatic enzymes in invasive intraductal papillary mucinous neoplasms

BackgroundDespite evidence suggesting a role of chronic pancreatitis in pancreatic carcinogenesis, its relationship with invasive intraductal papillary mucinous neoplasms (IPMN) remains unclear. Low levels of pancreatic enzymes are predictive markers of advanced chronic pancreatitis. We investigated whether low pancreatic enzyme levels were associated with a higher incidence of invasive IPMN.MethodsThis study included 146 consecutive patients who underwent surgical resection of IPMN between April 2001 and October 2014. Multivariable logistic regression analysis was conducted to assess the association between serum pancreatic enzymes and the incidence of invasive IPMN, with adjustment for clinical characteristics including alcohol consumption. The association of serum pancreatic enzymes with pathological pancreatic atrophy and inflammation in areas adjacent to or distant from the tumor was also evaluated.ResultsLow serum levels of pancreatic amylase and lipase were associated with a higher incidence of invasive IPMN (multivariable odds ratio [OR] = 9.6, 95% confidence interval [CI] = 2.99 to 35.1, P = 0.0001; OR = 14.2, 95% CI = 2.77 to 112, P = 0.001, respectively). Low serum pancreatic amylase and lipase levels were also associated with higher grade pancreatic atrophy in areas adjacent to the tumor (P = 0.011 and P = 0.017, respectively) and in areas distant from the tumor (P = 0.0002 and P = 0.001, respectively). Furthermore, low serum pancreatic amylase and lipase levels were associated with higher grade inflammation in areas distant from the tumor (P < 0.0001 and P = 0.001, respectively).ConclusionsLow serum pancreatic enzymes may be a predictive marker of invasive IPMN. Excessive alcohol consumption did not influence the association of low pancreatic enzyme levels with invasive IPMN.     

Dietary isoflavone intake is associated with evoked responses to inflammatory cardiometabolic stimuli and improved glucose homeostasis in healthy volunteers

Background and aimsConsumption of foods that modulate inflammatory stress in genetically-prone individuals may influence development of cardiometabolic diseases. Isoflavones in soy-derived foods function as phytoestrogens, have antioxidant and anti-inflammatory activity, inhibit protein-tyrosine kinase activity, and may be atheroprotective. We examined the relationship between soy food consumption and inflammatory responses to endotoxemia, postprandial responses to oral lipid tolerance test (OLTT), and insulin sensitivity from frequently sampled intravenous tolerance tests (FSIGTT).Methods and resultsWe administered low-dose endotoxin (LPS 1 ng/kg) to induce transient endotoxemia in young, healthy volunteers (N = 215) of African (AA), and European (EA) ancestry as part of the GENE Study. We further supported these findings in two independent samples: the MECHE Study and NHANES. Soy food consumption was a significant predictor of peak cytokine response following LPS. Individuals with moderate-high (>1.48 mg/day, N = 65) vs. low-no (<1.48 mg/day, N = 150) isoflavone consumption had significantly higher tumor necrosis factor alpha (TNFα) post-LPS (AUC, P = 0.009). Further, high-isoflavone consumers were protected against inflammation-induced decline in insulin sensitivity (S_I) in GENE. We observed significant differences by soy consumption in the interferon gamma (IFNγ) response to OLTT, and the insulin response to OGTT in MECHE, as well as significantly lower fasting insulin, and 2-hour glucose post-OGTT in EA NHANES subjects.ConclusionWe demonstrate that soy consumption may influence inflammatory and metabolic responses. In research of nutritional exposures, measuring evoked phenotypes may be more informative than describing resting characteristics.The GENE Study was registered under NCT00953667 and the MECHE Study under NCT01172951, both at clinicaltrials.gov.     

Sex-Related Differences of Coronary Atherosclerosis Regression Following Maximally Intensive Statin Therapy: Insights From SATURN

ObjectivesThe study sought to explore sex-related differences in coronary atheroma regression following high-intensity statin therapy.BackgroundGuidelines now recommend high-intensity statins in all individuals with atherosclerotic cardiovascular disease.MethodsSATURN (Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin) employed serial intravascular ultrasound measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. The treatment groups did not differ significantly in change from baseline of percent atheroma volume (PAV) or total atheroma volume (TAV) on intravascular ultrasound, nor in safety or clinical outcomes.ResultsCompared with men (n = 765), women (n = 274) were older (p < 0.001) and more likely to have hypertension (p < 0.001), diabetes (p = 0.002), and higher low-density lipoprotein cholesterol (LDL-C) (p = 0.01), high-density lipoprotein cholesterol (p < 0.001), and C-reactive protein (CRP) (p = 0.004) levels. At follow-up, women had higher high-density lipoprotein cholesterol (p < 0.001) and CRP (p < 0.001), but similar LDL-C (p = 0.46) levels compared with men. Compared with men, women had lower baseline PAV (34.0 ± 8.0% vs. 37.2 ± 8.2%, p < 0.001) and TAV (122.4 ± 55 mm³ vs. 151.9 ± 63 mm³, p < 0.001), yet demonstrated greater PAV regression (–1.52 ± 0.18% vs. –1.07 ± 0.10%, p = 0.03) and TAV regression (–8.27 ± 0.9 mm³ vs. –6.59 ± 0.50 mm³, p = 0.11) following treatment. Greater PAV regression in women versus men occurred with rosuvastatin (p = 0.004), those with diabetes (p = 0.01), stable coronary disease (p = 0.01), higher baseline LDL-C (p = 0.02), and higher CRP (p = 0.04) levels. On multivariable analysis, female sex was independently associated with PAV regression (p = 0.01), and a sex-treatment interaction was found (p = 0.036). For participants with on-treatment LDL-C levels <70 mg/dl, women achieved greater PAV regression (–1.81 ± 0.22% vs. –1.12 ± 0.13%, p = 0.007) and TAV regression (–10.1 ± 1.1 mm³ vs. –7.16 ± 0.65 mm³, p = 0.023) than men, whereas PAV and TAV regression did not differ by sex, with LDL-C levels ≥70 mg/dl.ConclusionsWomen with coronary disease demonstrate greater coronary atheroma regression than men when empirically prescribed guideline-driven potent statin therapy. This benefit appears in the setting of lower on-treatment LDL-C levels. (CRESTOR Athero Imaging Head to Head IVUS Study [SATURN]; NCT000620542)     

Lipoprotein lipase variants interact with polyunsaturated fatty acids for obesity traits in women: Replication in two populations

Background and aimsLipoprotein lipase (LPL) is a candidate gene for obesity based on its role in triglyceride hydrolysis and the partitioning of fatty acids towards storage or oxidation. Whether dietary fatty acids modify LPL associated obesity risk is unknown.Methods and resultsWe examined five single nucleotide polymorphisms (SNPs) (rs320, rs2083637, rs17411031, rs13702, rs2197089) for potential interaction with dietary fatty acids for obesity traits in 1171 participants (333 men and 838 women, aged 45–75 y) of the Boston Puerto Rican Health Study (BPRHS). In women, SNP rs320 interacted with dietary polyunsaturated fatty acids (PUFA) for body mass index (BMI) (P = 0.002) and waist circumference (WC) (P = 0.001) respectively. Higher intake of PUFA was associated with lower BMI and WC in homozygotes of the major allele (TT) (P = 0.01 and 0.005) but not in minor allele carriers (TG and GG). These interactions were replicated in an independent population, African American women of the Atherosclerosis Risk in Communities (ARIC) study (n = 1334).ConclusionDietary PUFA modulated the association of LPL rs320 with obesity traits in two independent populations. These interactions may be relevant to the dietary management of obesity, particularly in women.     

Correlation between secretin-enhanced MRCP findings and histopathologic severity of chronic pancreatitis in a cat model

Background/objectivesTo evaluate the usefulness of secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) in chronic pancreatitis (CP), we compared the severity of disease determined histopathologically with that indicated by S-MRCP imaging parameters in an induced CP cat model.Materials and methodsAn experimental group of randomly chosen cats (n = 24) underwent ligation of the pancreatic duct to induce CP, and cats in a similarly chosen control group (n = 8) were sham-operated. MRCP was performed prior to secretin stimulation, and 5 and 15 min afterward, noting in particular the pancreatic duct caliber change (PDC) and the increasing degree of fluid volume (IDFV). Histopathological changes were observed in pancreatic samples processed for hematoxylin–eosin and Sirius red staining, and CP was classified as normal, minimal, moderate, or advanced. Correlations were investigated between these groups and the PDC at 5 min and the IDFV at 15 min.ResultsBetween cats with minimal CP and the controls, the differences in mean IDFV and PDC were not significant although diseased cats showed a downward trend in both parameters. However, compared with the control group both the mean IDFV and PDC were significantly lower in cats with moderate (IDFV, P = 0.001; PDC, P = 0.013) or advanced (IDFV, P = 0.013; PDC, P = 0.001) CP.ConclusionThe S-MRCP parameters IDFV and PDC correlated with the histopathological severity of induced CP. S-MRCP could be used to evaluate the severity of CP, although it is somewhat insensitive for depicting very early disease.     

Oxidised LDL levels decreases after the consumption of ready-to-eat meals supplemented with cocoa extract within a hypocaloric diet

Background and aimsCocoa flavanols are recognised by their favourable antioxidant and vascular effects. This study investigates the influence on health of the daily consumption of ready-to-eat meals supplemented with cocoa extract within a hypocaloric diet, on middle-aged overweight/obese subjects.Methods and resultsFifty healthy male and female middle-aged volunteers [57.26 ± 5.24 years and body mass index (BMI) 30.59 ± 2.33 kg/m²] were recruited to participate in a 4 week randomised, parallel and double-blind study. After following 3 days on a low-polyphenol diet, 25 volunteers received meals supplemented with 1.4 g of cocoa extract (645.3 mg of polyphenols) and the other 25 participants received control meals, within a 15% energy restriction diet. On the 4th week of intervention individuals in both dietary groups improved (p < 0.05) anthropometric, body composition, blood pressure and blood biochemical measurements. Oxidised LDL cholesterol (oxLDL), showed a higher reduction (p = 0.030) in the cocoa group. Moreover, myeloperoxidase (MPO) levels decreased only in the cocoa supplemented group (p = 0.007). Intercellular Adhesion Molecule-1 (sICAM-1) decreased significantly in both groups, while Vascular Cell Adhesion Molecule-1 (sVCAM-1) did not present differences after the 4 weeks of intervention. Interestingly, cocoa intake showed a different effect by gender, presenting more beneficial effects in men.ConclusionsThe consumption of cocoa extract as part of ready-to-eat meals and within a hypocaloric diet improved oxidative status (oxLDL) in middle-aged subjects, being most remarkable in males.Registration number: Registered at www.clinicaltrials.gov (NCT01596309).     

Myeloperoxidase levels predict accelerated progression of coronary atherosclerosis in diabetic patients: Insights from intravascular ultrasound

ObjectiveWhile inflammation has been proposed to contribute to the adverse cardiovascular outcome in diabetic patients, the specific pathways involved have not been elucidated. The leukocyte derived product, myeloperoxidase (MPO), has been implicated in all stages of atherosclerosis. The relationship between MPO and accelerated disease progression observed in diabetic patients has not been studied.MethodsWe investigated the relationship between MPO and disease progression in diabetic patients. 881 patients with angiographic coronary artery disease underwent serial evaluation of atherosclerotic burden with intravascular ultrasound. Disease progression in diabetic (n = 199) and non-diabetic (n = 682) patients, stratified by baseline MPO levels was investigated.ResultsMPO levels were similar in patients with and without diabetes (1362 vs. 1255 pmol/L, p = 0.43). No relationship was observed between increasing quartiles of MPO and either baseline (p = 0.81) or serial changes (p = 0.43) in levels of percent atheroma volume (PAV) in non-diabetic patients. In contrast, increasing MPO quartiles were associated with accelerated PAV progression in diabetic patients (p = 0.03). While optimal control of lipid and the use of high-dose statin were associated with less disease progression, a greater benefit was observed in diabetic patients with lower compared with higher MPO levels at baseline.ConclusionsIncreasing MPO levels are associated with greater progression of atherosclerosis in diabetic patients. This finding indicates the potential importance of MPO pathways in diabetic cardiovascular disease.     

Effect of liraglutide administration and a calorie-restricted diet on lipoprotein profile in overweight/obese persons with prediabetes

Background and aimsTo evaluate the effects of 14 weeks of liraglutide plus modest caloric restriction on lipid/lipoprotein metabolism in overweight/obese persons with prediabetes.Methods and resultsVolunteers with prediabetes followed a calorie-restricted diet (−500 Kcal/day) plus liraglutide (n = 23) or placebo (n = 27) for 14 weeks. The groups were similar in age (58 ± 7 vs. 58 ± 8 years) and body mass index (31.9 ± 2.8 vs. 31.9 ± 3.5 kg/m²). A comprehensive lipid/lipoprotein profile was obtained before and after intervention using vertical auto profile (VAP). Weight loss was greater in the liraglutide group than in the placebo group (6.9 vs. 3.3 kg, p < 0.001), as was the fall in fasting plasma glucose concentration (9.9 mg/dL vs. 0.3 mg/dL, p < 0.001). VAP analysis revealed multiple improvements in lipid/lipoprotein metabolism in liraglutide-treated compared with placebo-treated volunteers, including decreases in concentrations of total cholesterol, low-density lipoprotein cholesterol and several of its subclasses, triglyceride, and non-high-density cholesterol. The liraglutide-treated group also had a significant shift away from small, dense low-density lipoprotein-particles, as well as decreases in apolipoprotein B concentration and ratio of apolipoprotein B/apolipoprotein A-1. There were no significant changes in the lipoprotein profile in the placebo-treated group.ConclusionTreatment with liraglutide plus modest calorie restriction led to enhanced weight loss, a decrease in fasting plasma glucose concentration, and improvement in multiple aspects of lipid/lipoprotein metabolism associated with increased cardiovascular disease (CVD) risk. The significant clinical benefit associated with liraglutide-assisted weight loss in a group at high risk for CVD – obese/overweight individuals with prediabetes – as seen in our pilot study, suggests that this approach deserves further study.     

Effect of maternal gestational diabetes on the cardiovascular risk factor profile of infants at 1 year of age

Background and aimOffspring of women with gestational diabetes (GDM) exhibit an adverse cardiovascular risk factor profile by as early as age 5 years. Recently, maternal glycemia has been associated with epigenetic modification of genes on the fetal side of the placenta, including those encoding emerging risk factors (adiponectin, leptin), suggesting that vascular differences may emerge even earlier in life. Thus, we sought to evaluate cardiovascular risk factors and determinants thereof in 1-year-old infants of women with and without GDM.Methods and resultsTraditional (glucose, lipids) and emerging (C-reactive protein (CRP), adiponectin, leptin) risk factors were assessed in pregnancy in 104 women with (n = 36) and without GDM (n = 68), and at age 1-year in their offspring. In pregnancy, women with GDM had higher triglycerides (2.49 vs 2.10 mmol/L, p = 0.04) and CRP (5.3 vs 3.6 mg/L, p = 0.03), and lower adiponectin (7.3 vs 8.5 μg/mL, p = 0.04) than did their peers. At age 1-year, however, there were no differences in cardiovascular risk factors (including adiponectin) between the infants of women with and without GDM. Of note, maternal and infant adiponectin levels were associated in the non-GDM group (r = 0.39, p = 0.001) but not in the GDM group (r = 0.07, p = 0.67). Furthermore, on multiple linear regression analyses, maternal adiponectin emerged as an independent predictor of infant adiponectin in the non-GDM group only (beta = 776.1, p = 0.0065).ConclusionInfants of women with and without GDM have a similar cardiovascular risk factor profile at age 1-year. However, there are differences in their early-life determinants of adiponectin that may be relevant to the subsequent vascular risk of GDM offspring.     

Interaction between vitamin D receptor gene polymorphisms and 25-hydroxyvitamin D concentrations on metabolic and cardiovascular disease outcomes

Aim25-hydroxyvitamin D (25OHD) concentrations have been shown to be associated with major clinical outcomes, with a suggestion that individual risk may vary according to common genetic differences in the vitamin D receptor (VDR) gene. Hence, we tested for the interactions between two previously studied VDR polymorphisms and 25OHD on metabolic and cardiovascular disease-related outcomes in a large population-based study.MethodsInteractions between two previously studied VDR polymorphisms (rs7968585 and rs2239179) and 25OHD concentrations on metabolic and cardiovascular disease-related outcomes such as obesity- (body mass index, waist circumference, waist-hip ratio (WHR)), cardiovascular- (systolic and diastolic blood pressure), lipid- (high- and low-density lipoprotein, triglycerides, total cholesterol), inflammatory- (C-reactive protein, fibrinogen, insulin growth factor-1, tissue plasminogen activator) and diabetes- (glycated haemoglobin) related markers were examined in the 1958 British Birth cohort (n up to 5160). Interactions between each SNP and 25OHD concentrations were assessed using linear regression and the likelihood ratio test.ResultsAfter Bonferroni correction, none of the interactions reached statistical significance except for the interaction between the VDR SNP rs2239179 and 25OHD concentrations on waist-hip ratio (WHR) (P = 0.03). For every 1 nmol/L higher 25OHD concentrations, the association with WHR was stronger among those with two major alleles (−4.0%, P = 6.26e⁻²⁴) compared to those with either one or no major alleles (−2.3%, P ≤ 8.201e⁻⁰⁷, for both) of the VDR SNP rs2239179.ConclusionWe found no evidence for VDR polymorphisms acting as major modifiers of the association between 25OHD concentrations and cardio-metabolic risk. Interaction between VDR SNP rs2239179 and 25OHD on WHR warrants further confirmation.     

Relationship between QRS characteristics and delayed-enhancement cardiac magnetic resonance in patients with ischemic cardiomyopathy

BackgroundWe explored the relationship between QRS characteristics and myocardial phenotype by delayed-enhancement cardiac magnetic resonance (DE-CMR) in patients with coronary heart disease (CHD).Methods and resultsEighty five consecutive patients with CHD that were referred for DE-CMR evaluation constituted the study population. Of a total of 1445 left ventricular (LV) segments evaluated, 346 (23.9%) segments had fibrosis.Compared to patients without pathological Q waves, patients with pathological Q waves showed a higher number of segments with fibrosis (5.9 ± 3.1 vs. 2.7 ± 2.8, p < 0.001), and lower left ventricular ejection fraction (LVEF) (42.9 ± 13.6% vs. 51.8 ± 18.3, p = 0.01); whereas no significant differences were observed regarding LV size.When discriminated in according to the QRS duration tertiles, no significant differences were observed regarding the number of segments with fibrosis (p = 0.34), whereas the highest QRS tertile was related to the presence of a low LVEF (p = 0.005) and larger LV size (p = 0.01). QRS fragmentation (fQRS), defined as the presence of an R′ or notching in the nadir of the R wave or the S wave, or the presence of >1 R′ in 2 contiguous leads, was significantly related to LV size (LV end diastolic volume 153.6 ± 81.6 ml, vs. 111.5 ± 41.4 ml, p = 0.003), function (LVEF 43.2 ± 15.9% vs. 53.6 ± 16.3%, p = 0.005), and extent of fibrosis (5.1 ± 3.4 segments vs. 3.2 ± 3.1 segments, p = 0.01).ConclusionsIn the present study, fQRS was the only QRS-derived variable systematically and more closely related to LV size, LV systolic function, and to the presence and extent of fibrosis.     

Potential coeliac disease in Type 1 diabetes mellitus: Does a positive antibody lead to increased complications?

Background and aimsCoeliac disease (CD) is more common in people with Type 1 diabetes and is associated with poorer glycaemic control, lipid profiles, nephropathy and retinopathy. Potential CD (positive serology but normal duodenal biopsy) is associated with neuropathy but patients with coexisting Type 1 diabetes were excluded. The aim was to determine whether potential CD is associated with increased microvascular complications in patients with Type 1 diabetes.Methods and resultsFour groups were recruited; 1) patients with Type 1 diabetes and potential CD, 2) patients with Type 1 diabetes and newly identified CD, 3) patients with Type 1 diabetes alone and 4) patients with CD alone. Glycaemic control, quality of life, lipid profile and microvascular complication rates were examined.As many as 76 individuals were included in the study: 22 in group 1, 14 in group 2, 24 in group 3 and 16 in group 4. There were no differences in age, gender, BMI and diabetes duration between the groups. Patients in group 1 had significantly lower total cholesterol compared to group 3 (p = 0.003) but higher than group 2 (p = 0.027). There were no significant differences in HbA1c, HDL cholesterol, cholesterol:HDL ratio, creatinine, quality of life scores or prevalence of neuropathy between individuals in group 1 and the other groups.ConclusionsThis is the first study to assess the effects of potential CD in patients with Type 1 diabetes. It appears that an enteropathy is required as well as antibody positivity in order to increase the risk of diabetes related complications. This pilot data requires further longitudinal validation.     

Inverse association between circulating adiponectin levels and skeletal muscle strength in Japanese men and women

Background and aimsIncreased levels of circulating adiponectin in the elderly cause a negative impact on physical function and health status, which suggests that circulating adiponectin may be related to skeletal muscle function. However, data on the relationship between circulating adiponectin levels and skeletal muscle function is limited. Our objective was to investigate the association between serum adiponectin levels and muscle strength in adults.Methods and resultsThis cross-sectional study is a part of the Oroshisho Study of adult employees in Japan from 2008 to 2011. In our study, we used data gathered in 2008–2010 that had included serum adiponectin measurements (n = 1378; age, 19–83 years). From this population, 1259 subjects were evaluated for grip strength (949 men, 310 women), and 965 subjects were evaluated for leg extension power (716 men, 249 women). Multivariate linear regression analyses showed that adiponectin was associated significantly and negatively with both grip strength (β and standard error [SE]: men, −0.09 [0.01], p = 0.010; women, −0.20 [0.03], kg, p = 0.002) and leg extension power (men, −0.09 [0.02], p = 0.014; women, −0.14 [0.07], W, p = 0.032) after adjusting for age, physical activity, nutrient intake, depressive symptoms, metabolic syndrome, C-reactive protein, body mass index, and other lifestyle-related potential confounders.ConclusionThis population-based cross-sectional study indicates an inverse association between serum adiponectin levels and muscle strength in adults. Further studies are necessary to confirm this association and to clarify causality.     

T-cadherin gene variants are associated with type 2 diabetes and the Fatty Liver Index in the French population

AimAdiponectin is an adipocyte-secreted protein associated with insulin sensitivity. T-cadherin is a receptor for high and medium molecular weight adiponectin. In GWAS, T-cadherin gene (CDH13) polymorphisms are associated with circulating adiponectin levels. This study investigated the associations between genetic variants of CDH13 and type 2 diabetes (T2D), and its related parameters, in a Caucasian population.MethodsTwo polymorphisms of CDH13 (rs11646213 and rs3865188) were genotyped in two French cohorts, a general population from the D.E.S.I.R. study (n = 5212) and people with T2D in the DIABHYCAR study (n = 3123). Baseline adiponectin levels were measured in D.E.S.I.R. participants who were normoglycaemic at baseline, but hyperglycaemic after 3 years (n = 230), and in controls who remained normoglycaemic (n = 226) throughout.ResultsIn a cross-sectional analysis, CDH13 genotype distributions differed between those with and without T2D, with T2D odds ratios (OR) of 1.11 (95% CI: 1.04–1.18; P = 0.001) and 0.92 (95% CI: 0.87–0.98; P = 0.01) for rs11646213 and rs3865188, respectively. The rs11646213 variant, associated with a higher OR for T2D, was also associated with higher BMI (P = 0.03) and HbA_1c (P = 0.006), and lower plasma adiponectin levels (P = 0.03) in the D.E.S.I.R. participants. Conversely, the rs3865188 variant, associated with a lower OR for T2D, was also associated with lower BMI (P = 0.03), HbA_1c (P = 0.02) and Fatty Liver Index (FLI; P ≤ 0.01), and higher plasma adiponectin levels (P = 0.002). Associations with HbA_1c, FLI and adiponectin levels persisted after adjusting for BMI.ConclusionCDH13 polymorphisms are associated with prevalent T2D in this French population study. The association may be mediated through effects on BMI and/or plasma adiponectin.