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Background: Coronavirus disease 2019 (COVID-19) pandemic continues to escalate intensively worldwide. Massive studies on general populations with SARS-CoV-2 infection have revealed that pre-existing comorbidities were a major risk factor for the poor prognosis of COVID-19. Notably, 49–75% of COVID-19 patients had no comorbidities, but this cohort would also progress to severe COVID-19 or even death. However, risk factors contributing to disease progression and death in patients without chronic comorbidities are largely unknown; thus, specific clinical interventions for those patients are challenging. Methods: A multicenter, retrospective study based on 4806 COVID-19 patients without chronic comorbidities was performed to identify potential risk factors contributing to COVID-19 progression and death using LASSO and a stepwise logistic regression model. Results: Among 4806 patients without pre-existing comorbidities, the proportions with severe progression and mortality were 34.29% and 2.10%, respectively. The median age was 47.00 years [interquartile range, 36.00–56.00], and 2162 (44.99%) were men. Among 51 clinical parameters on admission, age ≥ 47, oxygen saturation < 95%, increased lactate dehydrogenase, neutrophil count, direct bilirubin, creatine phosphokinase, blood urea nitrogen levels, dyspnea, increased blood glucose and prothrombin time levels were associated with COVID-19 mortality in the entire cohort. Of the 3647 patients diagnosed with non-severe COVID-19 on admission, 489(13.41%) progressed to severe disease. The risk factors associated with COVID-19 progression from non-severe to severe illness were increased procalcitonin levels, SpO2 < 95%, age ≥ 47, increased LDH, activated partial thromboplastin time levels, decreased high-density lipoprotein cholesterol levels, dyspnea and increased D-dimer levels. Conclusions: COVID-19 patients without pre-existing chronic comorbidities have specific traits and disease patterns. COVID-19 accompanied by severe bacterial infections, as indicated by increased procalcitonin levels, was highly associated with disease progression from non-severe to severe. Aging, impaired respiratory function, coagulation dysfunction, tissue injury, and lipid metabolism dysregulation were also associated with disease progression. Once factors for multi-organ damage were elevated and glucose increased at admission, these findings indicated a higher risk for mortality. This study provides information that helps to predict COVID-19 prognosis specifically in patients without chronic comorbidities.

Objective To examine whether 5 years of high-intensity interval training (HIIT) increases high-density lipoprotein cholesterol (HDL-C) concentration more than moderate-intensity continuous training (MICT) and control (CON) in older men and women. Methods A total of 1567 older adults (790 [50.4%] women) were randomized (2:1:1) to either CON (n=780; asked to follow the national recommendations for physical activity) or 2 weekly sessions of HIIT (10-minute warm-up followed by 4×4-minute intervals at ∼90% of peak heart rate) or MICT (50 minutes of continuous work at ∼70% of peak heart rate). Serum HDL-C concentration was measured by standard procedures at baseline and at 1 year, 3 years, and 5 years. The study took place between August 21, 2012, and June 31, 2018. Linear mixed models were used to determine between-group differences during 5 years using the per protocol approach. Results Men in HIIT had a smaller reduction in HDL-C (−1.2%) than men in CON (−6.9%) and MICT (−7.8%) after 5 years (P=.01 and P=.03 for CON vs HIIT and MICT vs HIIT, respectively). No effect of exercise intensity on HDL-C was seen in women. Changes in peak oxygen uptake were associated with changes in HDL-C in both men and women, whereas changes in body weight and fat mass were not. Conclusion In men, HIIT seems to be the best strategy to prevent a decline in HDL-C during a 5-year period. No effect of exercise intensity was seen for older women. Trial registration ClinicalTrials.gov identifier: NCT01666340.

Graphical abstract, Highlights • MetS occurs in a 1 out of 4 obese children and increases the future risk of serious health complications. • The serum level of adiponectin decreases while leptin increases as body weight increases, in the understudy children group. • The serum level of the inflammatory marker CRP increases significantly as body weight increases in the understudy population. • Adipokines and CRP can distinguish the children with Metabolic Syndrome as compared to children with no Metabolic Syndrome., Background Metabolic syndrome (MetS) occurs in a proportion of overweight and obese children and increases their future risk of serious health complications, even in adolescence and young adulthood. We aimed to explore the role of certain adipokines and inflammatory markers in identifying children with MetS. Methods This study is a secondary analysis of data coming from the Healthy Growth Study, a cross-sectional study conducted with schoolchildren in Greece. The present study included data from a representative sample of 1376 schoolchildren (mean age: 11.19 ± 0.66 years), recruited from 77 primary schools in four large regions in Greece. Anthropometric, clinical and biochemical data were recorded. Children’s body weight status and the presence of MetS were determined and their correlation with the serum levels of leptin, adiponectin and C-reactive protein (CRP) was explored. Results The prevalence of the MetS was 21.7 % and 3.7 % in obese and overweight children, respectively. The balance of adipokines was disturbed in obesity, as the serum level of adiponectin decreased as body weight increased, while the serum level of leptin increased. The serum level of the inflammatory marker CRP increased significantly as body weight increased. Discriminant analysis showed that these factors could distinguish the children with MetS as compared to children with no MetS. Conclusions In the under study Mediterranean childhood population, monitoring of the levels of adipokines and CRP could identify the overweight and obese children with MetS. Appropriate individualized dietary and lifestyle interventions can be applied in these children to prevent health complications associated with MetS.

Background Even when low-density lipoprotein-cholesterol (LDL-C) levels are lower than guideline thresholds, a residual risk of atherosclerosis remains. It is unknown whether triglyceride (TG) levels are associated with subclinical atherosclerosis and vascular inflammation regardless of LDL-C. Objectives This study sought to assess the association between serum TG levels and early atherosclerosis and vascular inflammation in apparently healthy individuals. Methods An observational, longitudinal, and prospective cohort study, including 3,754 middle-aged individuals with low to moderate cardiovascular risk from the PESA (Progression of Early Subclinical Atherosclerosis) study who were consecutively recruited between June 2010 and February 2014, was conducted. Peripheral atherosclerotic plaques were assessed by 2-dimensional vascular ultrasound, and coronary artery calcification (CAC) was assessed by noncontrast computed tomography, whereas vascular inflammation was assessed by fluorine-18 fluorodeoxyglucose uptake on positron emission tomography. Results Atherosclerotic plaques and CAC were observed in 58.0% and 16.8% of participants, respectively, whereas vascular inflammation was evident in 46.7% of evaluated participants. After multivariate adjustment, TG levels ≥150 mg/dl showed an association with subclinical noncoronary atherosclerosis (odds ratio [OR]: 1.35; 95% confidence interval [CI]: 1.08 to 1.68; p = 0.008). This association was significant for groups with high LDL-C (OR: 1.42; 95% CI: 1.11 to 1.80; p = 0.005) and normal LDL-C (OR: 1.85; 95% CI: 1.08 to 3.18; p = 0.008). No association was found between TG level and CAC score. TG levels ≥150 mg/dl were significantly associated with the presence of arterial inflammation (OR: 2.09; 95% CI: 1.29 to 3.40; p = 0.003). Conclusions In individuals with low to moderate cardiovascular risk, hypertriglyceridemia was associated with subclinical atherosclerosis and vascular inflammation, even in participants with normal LDL-C levels. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318), Central Illustration

Cardiovascular disease (CVD) risk factors cluster in an individual. Exercise is universally recommended to prevent and treat CVD. Yet, clinicians lack guidance on how to design an exercise prescription (ExRx) for patients with multiple CVD risk factors. To address this unmet need, we developed a novel clinical decision support system to prescribe exercise (prioritize personalize prescribe exercise [P3-EX]) for patients with multiple CVD risk factors founded upon the evidenced-based recommendations of the American College of Sports Medicine (ACSM) and American Heart Association. To develop P3-EX, we integrated (1) the ACSM exercise preparticipation health screening recommendations; (2) an adapted American Heart Association Life’s Simple 7 cardiovascular health scoring system; (3) adapted ACSM strategies for designing an ExRx for people with multiple CVD risk factors; and (4) the ACSM frequency, intensity, time, and time principle of ExRx. We have tested the clinical utility of P3-EX within a university-based online graduate program in ExRx among students that includes physicians, physical therapists, registered dietitians, exercise physiologists, kinesiologists, fitness industry professionals, and kinesiology educators in higher education. The support system P3-EX has proven to be an easy-to-use, guided, and time-efficient evidence-based approach to ExRx for patients with multiple CVD risk factors that has applicability to other chronic diseases and health conditions. Further evaluation is needed to better establish its feasibility, acceptability, and clinical utility as an ExRx tool.

Objective To investigate the effect of replacing sitting with standing on cardiovascular risk factors tested in clinical trials. Methods We searched databases from inception up to August 28, 2019, for studies examining the effect of replacing sitting with standing on fasting blood glucose, fasting insulin, and lipid levels; blood pressure; body fat mass; weight; and waist circumference in healthy adults. Differences in mean ± SD values were used for pooling the data and calculating the mean differences and CIs. Results The search found 3507 abstracts. Nine clinical trials (8 randomized and 1 nonrandomized) with 877 (64.4% [n=565] women) participants met all inclusion criteria. The mean ± SD age was 45.34±5.41 years; mean follow-up was 3.81 months, and mean difference in standing time between the intervention and control groups was 1.33 hours per day. The follow-up fasting blood glucose and body fat mass values were slightly but significantly lower than baseline records in the intervention groups compared with control groups (−2.53; 95% CI, −4.27 to −0.79 mg/dL; and −0.75; 95% CI, −0.91 to −0.59 kg). The analysis for fasting insulin levels, lipid levels, blood pressure, weight, and waist circumference revealed no significant differences. Conclusion Replacing sitting with standing can result in very small but statistically significant decreases in fasting blood glucose levels and body fat mass with no significant effect on lipid levels, blood pressure, weight, and waist circumference. Replacing sitting with standing can be used as an adjunctive intervention to decrease the burden of cardiovascular risk factors but cannot be used as an alternative to physical activity to decrease sedentary time.

BACKGROUND Dyslipidemia induces platelet hyperactivation and hyper-aggregation, which are linked to thrombosis. Anthocyanins could inhibit platelet function in vitro and in mice fed high-fat diets with their effects on platelet function in subjects with dyslipidemia remained unknown. This study aimed to investigate the effects of different doses of anthocyanins on platelet function in individuals with dyslipidemia. METHODS A double-blind, randomized, controlled trial was conducted. Ninety-three individuals who were initially diagnosed with dyslipidemia were randomly assigned to placebo or 40, 80, 160 or 320 mg/day anthocyanin groups. The supplementations were anthocyanin capsules (Medox, Norway). Platelet aggregation by light aggregometry of platelet-rich plasma, P-selectin, activated GPⅡbⅢa, reactive oxygen species (ROS), and mitochondrial membrane potential were tested at baseline, 6 weeks and 12 weeks. FINDINGS Compared to placebo group, anthocyanins at 80 mg/day for 12 weeks reduced collagen-induced platelet aggregation (-3.39±2.36%) and activated GPⅡbⅢa (-8.25±2.45%) (P

Aims: Inflammation has been implicated in the pathogenesis of diabetic peripheral neuropathy (DPN) as suggested in various cross-sectional studies. However, more convincing prospective studies in diabetes patients are scarce. Therefore, we aimed to evaluate whether proinflammatory cytokines could predict the incidence of DPN through a prospective study with a five-year follow-up. Methods: We followed up 315 patients with diabetes who did not have DPN, recruited from five community health centers in Shanghai in 2014, for an average of 5.06 years. Based on the integrity of blood samples, 106 patients were selected to obtain the proinflammatory cytokines. Plasma markers of proinflammatory cytokines at baseline included interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule 1 (ICAM-1). Neuropathy was assessed by MSNI at baseline and during follow-up. Results: Among the 106 randomly chosen patients, 63 developed DPN after 5.06±1.14 years of follow-up. The baseline plasma levels of TNF-α, IL-6, and ICAM-1 were higher in the neuropathic group (P

Visual Abstract, Highlights • Aortic stenosis was less prevalent in carriers of the PCSK9 R46L variant. • Variation at the PCSK9 locus influences LDL-C levels, but not Lp(a). • PCSK9 is produced and secreted by aortic valves. • In vitro, PCSK9 inhibition might lower calcification in aortic valve cells. • PCSK9 inhibition could represent a therapeutic strategy for aortic stenosis., Summary The authors investigated whether PCSK9 inhibition could represent a therapeutic strategy in calcific aortic valve stenosis (CAVS). A meta-analysis of 10 studies was performed to determine the impact of the PCSK9 R46L variant on CAVS, and the authors found that CAVS was less prevalent in carriers of this variant (odds ratio: 0.80 [95% confidence interval: 0.70 to 0.91]; p = 0.0011) compared with noncarriers. PCSK9 expression was higher in the aortic valves of patients CAVS compared with control patients. In human valve interstitials cells submitted to a pro-osteogenic medium, PCSK9 levels increased and a PCSK9 neutralizing antibody significantly reduced calcium accumulation.

Highlights • We examined links between medical claims and health check-up data for older adults. • Patients receiving pharmacotherapies were more likely to participate in health checkups. • Patients with intensive disease control were more likely to be aged ≥ 90 years. • Linking these databases can improve evaluations of diseases control in older adults., The Japanese government encourages older adults to participate in annual health checkups designed to detect lifestyle diseases such as hypertension, diabetes, and dyslipidemia. However, individuals who are already being treated for these diseases are unlikely to benefit from health checkup participation. This retrospective cohort study of older adults evaluated the associations of pharmacological treatments for these diseases with health checkup participation and identified the disease control factors among patients receiving treatments. Using medical claims data and health checkup data between September 2013 and August 2014 from 820,215 older adults aged ≥ 75 years residing in Tokyo, Japan, we examined the associations between pharmacological treatments and health checkup participation using binary logistic regression analysis. Next, patients receiving pharmacological treatments were categorized into intensive, moderate, or limited disease control based on their blood pressure, hemoglobin A1c levels, and lipid levels; multinomial logistic regression analyses were used to identify the disease control factors. The results showed that patients receiving pharmacological treatments were more likely (odds ratio: 1.374; P

Objective Metabolic syndrome (MetS) refers to a cluster of risk factors for cardiovascular disease, including obesity, hypertension, dyslipidemia, and hyperglycemia. While sizable prior literature has examined associations between individual risk factors and quantitative measures of cortical thickness (CT), only very limited research has investigated such measures in MetS. Furthermore, the relative contributions of these risk factors to MetS-related effects on brain morphology have not yet been studied. The primary goal of this investigation was to examine how MetS may affect CT. A secondary goal was to explore the relative contributions of individual risk factors to regional alterations in CT, with the potential to identify risk factor combinations that may underlie structural changes. Methods Eighteen participants with MetS (mean age = 59.78 years) were age-matched with 18 healthy control participants (mean age = 60.50 years). CT measures were generated from T1-weighted images and groups were contrasted using whole-brain general linear modeling. A follow-up multivariate partial least squares correlation (PLS) analysis, including the full study sample with complete risk factor measurements (N = 53), was employed to examine which risk factors account for variance in group structural differences. Results Participants with MetS demonstrated significantly reduced CT in left hemisphere inferior parietal, rostral middle frontal, and lateral occipital clusters and in a right hemisphere precentral cluster. The PLS analysis revealed that waist circumference, high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose were significant contributors to reduced CT in these clusters. In contrast, diastolic blood pressure showed a significantly positive association with CT while systolic blood pressure did not emerge as a significant contributor. Age was not associated with CT. Conclusion These results indicate that MetS can be associated with regionally specific reductions in CT. Importantly, a novel link between a risk factor profile comprising indices of obesity, hyperglycemia, dyslipidemia and diastolic BP and localized alterations in CT emerged. While the pathophysiological mechanisms underlying these associations remain incompletely understood, these findings may be relevant for future investigations of MetS and might have implications for treatment approaches that focus on specific risk factor profiles with the aim to reduce negative consequences on the structural integrity of the brain., Highlights • Cortical thickness is reduced bilaterally in metabolic syndrome. • Five out of six risk factor components contribute to altered cortical thickness. • Particular risk factor combination may be an important target for intervention.

Objective: Increased left ventricular (LV) mass is an important precursor to heart failure. Inflammation plays an important role in increasing LV mass. However, the contribution of subclinical coronary artery disease (CAD) to the inflammation-LV mass relationship is unknown. In subjects with psoriasis, a chronic inflammatory skin disease, we evaluated if systemic inflammation assessed by plasma glycoprotein A (GlycA) associated with LV mass measured on coronary CT angiography (CCTA). Additionally, we analyzed whether this relationship was mediated by early CAD assessed as noncalcified coronary burden (NCB). Methods: We performed an observational longitudinal study of 213 subjects with psoriasis free of known cardiovascular disease, 189 of whom were followed over one year. All participants had GlycA measurements by nuclear magnetic resonance spectroscopy and LV mass and NCB quantified by CCTA. Results: The cohort had a mean age of 50.3 (±12.9) years and 59% were male. There was moderate psoriasis severity and low cardiovascular risk. LV mass increased by GlycA tertiles [1st tertile:24.6 g/m2.7(3.8), 2nd tertile:25.5 g/m2.7(3.8), 3rd tertile:27.7 g/m2.7(5.5), p

Summary The importance of inflammation and inflammatory pathways in atherosclerotic disease and acute coronary syndromes (ACS) is well established. The success of statin therapy rests not only on potently reducing levels of low-density lipoprotein cholesterol, but also on the many beneficial, pleiotropic effects statin therapy has on various inflammatory mechanisms in atherosclerotic disease, from reducing endothelial dysfunction to attenuating levels of serum C-reactive protein. Due to the growing awareness of the importance of inflammation in ACS, investigators have attempted to develop novel therapies against known markers of inflammation for several decades. Targeted pathways have ranged from inhibiting C5 cleavage with a high-affinity monoclonal antibody against C5 to inhibiting the activation of the p38 mitogen-activated protein kinase signaling cascades. In each of these instances, despite promising early preclinical and mechanistic studies and phase 2 trials suggesting a potential benefit in reducing post-MI complications or restenosis, these novel therapies have failed to show benefits during large, phase 3 clinical outcomes trials. This review discusses several examples of novel anti-inflammatory therapies that failed to show significant improvement on clinical outcomes when tested in large, randomized trials and highlights potential explanations for why targeted therapies against known markers of inflammation in ACS have failed to launch., Central Illustration

Background Anthocyanins, one of the major plant bioactive substances, possess anti-oxidative and anti-inflammatory capacity. However, their dose–response relationship has remained unclear. The present study investigated the dose–response relationship of anthocyanins with oxidative stress and inflammation in subjects with dyslipidemia. Design and Participants: A total of 169 participants with dyslipidemia were randomly assigned to placebo (n = 43), anthocyanins 40 mg/day (n = 44), 80 mg/day (n = 40), or 320 mg/day (n = 42) groups. Urine 8-iso-prostaglandin F2α (8-iso-PGF2α), 8-hydroxy-2′-deoxyguanosine (8-OHdG) and serum malonaldehyde (MDA), total superoxide dismutase (T-SOD), UA (uric acid), interleukin (IL)-6, IL-10, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured at baseline, at 6 weeks, and at 12 weeks. Results Anthocyanin supplementation (320 mg/day) for 6 weeks significantly improved T-SOD versus baseline (P, Graphical abstract Image 1, Highlights • Anthocyanins improve oxidative stress in a dose-response manner. • Anthocyanins improve anti-inflammatory capacity in a dose-response manner. • 80 mg/day anthocyanin could reach the threshold level for producing beneficial functions after 12-week intervention. • Anthocyanins prevent the progression of metabolic diseases in subjects with dyslipidemia.

Despite continued advances in health care, the cardiovascular disease (CVD) mortality rate has plateaued in recent years and appears to be trending upward. Poor diet is a leading cause of obesity and type 2 diabetes mellitus, which are leading contributors to CVD morbidity and mortality. Although dietary modification is a cornerstone of CVD prevention, implementation in clinical practice is limited by inadequate formal training in nutrition science. In this report, we review the individual components of a heart-healthy diet, evidence-based dietary recommendations, and the impact of diet on CVD risk factor prevention and management. Furthermore, we examine the unique difficulties of dietary counseling in low-socioeconomic-status environments and provide an evidence-based approach to better serve these populations. We utilized PubMed searches in adults with no date restriction with the following search terms: “carbohydrate,” “fat,” protein,” “DASH,” “Mediterranean,” “plant-based,” “vegetarian,” “cardiovascular disease,” “obesity,” “weight loss,” “diabetes,” “socioeconomic status,” and “race.” In this review, we demonstrate that patients should focus on implementing a general diet plan that is high in fruits, whole grains, legumes, and nonstarchy vegetables while low in trans-fats, saturated fats, sodium, red meat, refined carbohydrates, and sugar-sweetened beverages. The Dietary Approaches to Stop Hypertension, Mediterranean, and vegetarian diets have the most evidence for CVD prevention. Clinicians should understand the barriers that patients may face in terms of access to healthy dietary choices. Further research is needed to determine the dietary changes that are most economically, socioculturally, and logistically feasible to reduce these barriers. Improvement in diet is a public health priority that can lead to a significant population-level reduction in CVD morbidity and mortality. It is imperative that clinicians understand current dietary practice guidelines and implement evidence-based dietary counseling in those at high risk for CVD.

Highlights • We compared the effects of volunteer- and expert-led weight-loss intervention. • Participants were instructed to maintain a well-balanced, low-energy diet. • The completion proportions was significantly higher in the expert-led group. • The degree of body weight change was similar for both groups. • Such programs could be an alternative strategy for low-cost obesity management., This study compared the effect of volunteer- and expert-led versions of a community-based weight-loss intervention in a non-randomized comparative trial conducted in Ibaraki, Japan from 2016 to 2017. Participants were 145 Japanese adults with overweightness or obesity, aged 20–69 years, with 77 in a volunteer-led group and 68 in an expert-led group. Both groups received the same program content and intervention period. Community volunteers were trained in four or five 3-hour training sessions while experts were highly trained and experienced professionals in the fields of exercise and nutrition prescription. Participants were also instructed to maintain a well-balanced, low-energy diet. The primary outcome measure was body weight change. In the volunteer- and expert-led groups, 58 of 77 (75%) and 61 of 68 (95%) participants completed the 12-week intervention, respectively. The mean (95% confidence interval, CI) weight loss of the volunteer-led group was 6.4 (95% CI: 5.6–7.2) kg, corresponding to 8.9% of initial body weight, while that of the expert-led group was 6.3 (95% CI: 5.5–7.1) kg, corresponding to 8.2% of the initial body weight. The proportion of participants who completed the course was significantly higher in the expert-led group (P

Background & Aims Remnant lipoprotein cholesterol (RLP-C) is an atherogenic lipid profile associated with non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). With increased rates of CVD seen in adults with NAFLD, RLP-C has the potential to identify individuals with NAFLD who are at increased risk of CVD. This study examined in adolescents sex-different associations among RLP-C, NAFLD, and cardiometabolic risk factors, and whether RLP-C is associated with NAFLD beyond traditional cardiometabolic risk factors. Methods Adolescents in the Raine Study had anthropometry, clinical, biochemistry and arterial stiffness measurements recorded at 17 years of age. Fatty liver, subcutaneous and visceral adipose thickness were assessed using abdominal ultrasound. Relationships among RLP-C, NAFLD, liver biochemistry, insulin resistance, adipokines, adiposity and arterial stiffness were assessed. Results NAFLD was diagnosed in 15.1% (19.6% females and 10.7% males) of adolescents. Increasing RLP-C levels were associated with increasing severity of hepatic steatosis and metabolic syndrome. Adolescents with NAFLD and serum RLP-C levels in the highest quartile compared with the lowest quartile, had higher serum leptin, homeostatic model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein, low-density-lipoprotein cholesterol, triglycerides, BMI, subcutaneous and visceral adipose thickness, systolic blood pressure and arterial stiffness, but lower adiponectin and high-density-lipoprotein cholesterol. Using multivariable logistic regression, RLP-C in the lowest quartile compared with the highest quartile was associated with 85% lower odds of NAFLD in males and 55% in females, after adjusting for waist circumference, leptin, ALT, adiponectin and HOMA-IR. Conclusions There is an association between RLP-C and NAFLD beyond traditional risk factors of adiposity and insulin resistance in adolescents. Although raised serum RLP-C levels were associated with the severity of hepatic steatosis and markers of cardiometabolic risk, lower serum RLP-C might reflect reduced cardiovascular risk. Lay summary Remnant lipoprotein cholesterol (RLP-C) is a part of the blood cholesterol that is linked with heart disease and non-alcoholic fatty liver disease (NAFLD) in adults. In the Raine Study, teenagers with high RLP-C levels had more severe fat accumulation in their liver. Thus, RLP-C might be the hidden link between NAFLD and future risk of heart disease., Graphical abstract, Highlights • Non-alcoholic fatty liver disease (NAFLD) and heart disease share risk factors. • Serum remnant lipoprotein cholesterol (RLP-C) is linked with severity of liver fat. • Males with NAFLD have higher cardiometabolic risk. • RLP-C may contribute to risk of cardiovascular disease in people with NAFLD.

Classification of the category of diabetes is extremely important for clinicians to diagnose and select the correct treatment plan. Glycosylation, oxidation and other post-translational modifications of membrane and transmembrane proteins, as well as impairment in cholesterol homeostasis, can alter lipid density, packing, and interactions of Red blood cells (RBC) plasma membranes in type 1 and type 2 diabetes, thus varying their membrane micropolarity. This can be estimated, at a submicrometric scale, by determining the membrane relative permittivity, which is the factor by which the electric field between the charges is decreased relative to vacuum. Here, we employed a membrane micropolarity sensitive probe to monitor variations in red blood cells of healthy subjects (n=16) and patients affected by type 1 (T1DM, n=10) and type 2 diabetes mellitus (T2DM, n=24) to provide a cost-effective and supplementary indicator for diabetes classification. We find a less polar membrane microenvironment in T2DM patients, and a more polar membrane microenvironment in T1DM patients compared to control healthy patients. The differences in micropolarity are statistically significant among the three groups (p, Graphical abstract Image 1, Highlights • Dynamic flux of cholesterol is differentially altered in T1DM and T2DM. • Red blood cell senses the dynamic flux of lipids by changing its micropolarity. • Laurdan can measure micropolarity in red blood cells membranes. • Differences in micropolarity between the three groups are statistically significant. • Red blood cell Micropolarity is an innovative assay for diabetes classification.

Pioglitazone, a thiazolidinedione (TZD), is widely used as an insulin sensitizer in the treatment of type 2 diabetes. However, body weight gain is frequently observed in TZD-treated patients. Fish oil improves lipid metabolism dysfunction and obesity. In this study, we demonstrated suppression of body weight gain in response to pioglitazone administration by combination therapy of pioglitazone and fish oil in type 2 diabetic KK mice. Male KK mice were fed experimental diets for 8 weeks. In safflower oil (SO), safflower oil/low-dose pioglitazone (S/PL), and safflower oil/high-dose pioglitazone (S/PH) diets, 20% of calories were provided by safflower oil containing 0%, 0.006%, or 0.012% (wt/wt) pioglitazone, respectively. In fish oil (FO), fish oil/low-dose pioglitazone (F/PL), and fish oil/high-dose pioglitazone (F/PH) diets, 20% of calories were provided by a mixture of fish oil and safflower oil. Increased body weight and subcutaneous fat mass were observed in the S/PL and S/PH groups; however, diets containing fish oil were found to ameliorate these changes. Hepatic mRNA levels of lipogenic enzymes were significantly decreased in fish oil-fed groups. These findings demonstrate that the combination of pioglitazone and fish oil decreases subcutaneous fat accumulation, ameliorating pioglitazone-induced body weight gain, through fish oil-mediated inhibition of hepatic de novo lipogenesis., Open Access.

Objectives: Obese, African-American (AA) adolescents are at increased risk for vitamin D deficiency. The primary objective of this pilot study was to examine the effect of vitamin D supplementation upon 25-hydroxy vitamin D (25OHD) levels in obese, AA adolescents. Methods: A randomized, double-blinded, controlled pilot study included 26 obese (BMI ≥ 95%ile), vitamin D deficient (25OHD

Aims: To analyze the correlation between neck circumference (NC) and non-alcoholic fatty liver disease (NAFLD) and compare the predictive value of NC for NAFLD with that of other simple anthropometric measures and other biochemical profiles. Methods: 2761 subjects, undergoing a medical check-up at the Changhai Hospital between October 01, 2012 and November 30, 2012, were recruited to the study. NC, other simple anthropometric measures, and biochemical profiles were analyzed. Results: NC in NAFLD subjects with or without elevated ALT were 38.94 ± 2.62 cm and 37.21 ± 3.06 cm respectively, which was significantly higher than that in subjects with other metabolic disorders (NC: 35.33 ± 3.03 cm) and in normal controls (NC: 32.60 ± 2.37) (both P

Background Both pathological excess and deficiency of growth hormone (GH) are associated with cardiovascular mortality. Objectives The goal of this study was to test whether fasting levels of growth hormone measured with a high-sensitivity assay (hs-GH) predict cardiovascular morbidity and mortality at the population level. Methods We studied 4,323 participants (age 46 to 68 years; mean age 58 years; 59% women) of the Swedish, population-based Malmö Diet and Cancer study examined in 1991 to 1994. Using multivariate-adjusted Cox proportional hazards models, we related baseline levels of fasting hs-GH to incidence of coronary artery disease, stroke, congestive heart failure, all-cause mortality, and cardiovascular mortality. Results During a median follow-up of 16.2 years, hs-GH (hazard ratio [HR]/SD increment of natural logarithm of fasting hs-GH) was independently associated with increased risk of coronary artery disease (397 events; HR: 1.11; 95% confidence interval [CI]: 1.01 to 1.23; p = 0.04), stroke (251 events; HR: 1.18; 95% CI: 1.04 to 1.34; p = 0.01), congestive heart failure (107 events; HR: 1.25; 95% CI: 1.03 to 1.52; p = 0.02), all-cause mortality (645 events; HR: 1.17; 95% CI: 1.08 to 1.26; p < 0.001) and cardiovascular mortality (186 events; HR: 1.43; 95% CI: 1.24 to 1.66; p < 0.001). The addition of hs-GH to a model with conventional cardiovascular risk factors significantly reclassified risk, with a category-free net reclassification improvement (>0) of 0.542 (95% CI: 0.205 to 0.840) in cardiovascular mortality. Conclusions Higher values of hs-GH were associated with an increased risk of cardiovascular morbidity and mortality.

Hydroxytyrosol (HT) is a main phenolic component of olive oil. In this study, we investigated the safety and effects produced by HT purified (99.5%) from olive mill waste. HT was administered at a daily dosage of 45 mg for 8 weeks to volunteers with mild hyperlipidemia (n=14). We measured markers of cardiovascular disease risk, enzyme markers of several clinical conditions, hematology, antioxidant parameters, vitamins and minerals at baseline (T0), 4 weeks (T4) and 8 weeks (T8). The values obtained at T4 and T8 were compared with baseline. We found that the HT dose administered was safe and mostly did not influence markers of cardiovascular disease, blood lipids, inflammatory markers, liver or kidney functions and the electrolyte balance. Serum iron levels remained constant but a significant (P, The authors wish to thank Puleva Biotech SA and the Spanish Ministry of Economy and Competitiveness (formerly Ministry of Science and Innovation) [the ERDF-cofinanced grant AGL2011-24428], for funding. The authors wish to thank Maria González-Santiago, Carlos Rodríguez and Antonio D. Valero for their valuable technical assistance, Dr Luis Perez for the purification of the HT used in the study, Alberto Zafra for his help with the HPLC and GC-MS analytical procedures, Dr Arjan Geerlings for fruitful discussions and Ruth Wilson for revising the manuscript.

Highlights • We examined pre-heparin LPL mass in type 2 diabetes mellitus (T2DM). • Association of adiponectin, pre-heparin LPL mass, and HDL-C was examined in T2DM. • Pre-heparin LPL mass may mediate the adiponectin and HDL-C association in T2DM., Aim Lipoprotein lipase (LPL) is a major enzyme in lipid metabolism. Dyslipidemia, characterized by decreased high-density lipoprotein cholesterol (HDL-C), is prevalent in persons with type 2 diabetes mellitus (T2DM). The aim of this study was to determine whether pre-heparin LPL mass mediates the association between adiponectin and HDL-C in individuals with T2DM. Methods Pre-heparin LPL mass was measured via an enzyme-linked immunosorbent assay, adiponectin by radioimmunoassay, and HDL-C was determined enzymatically. Participants’ (n = 50) demographics, HbA1c, adiposity, homeostasis model assessment for insulin resistance (HOMA-IR), serum creatinine, and lipids were measured. Path analysis was utilized to test whether pre-heparin LPL mass is a mediator in the relationship between adiponectin and HDL-C. Results All four criteria for mediation were satisfied in the path analysis. The indirect effect of adiponectin on HDL-C through pre-heparin LPL mass was significant, p = 0.001, whereas the direct effect of adiponectin on HDL-C was not significant, p = 0.074. These results remained consistent even after adjustments for age, gender, body mass index, HOMA-IR, and serum creatinine in the model. Conclusion The findings in this study suggest that pre-heparin LPL mass may mediate the association between adiponectin and HDL-C in T2DM. This relationship for measures of HDL-C functionality requires future investigation.

SNP (single-nucleotide polymorphism) of rs10903129 near the TMEM (transmembrane protein) 57 locus has been associated with TC (total cholesterol) in a previous GWAS (genome-wide association study), but the association of TMEM57 rs873308 SNP and serum lipid levels has not been previously reported. The current study was undertaken to detect the association of the TMEM57 rs873308 SNP and several environmental factors with serum lipid profiles in the Han Chinese and Mulao populations. The genotypes of the TMEM57 rs873308 SNP in 865 individuals of Han Chinese and 902 participants of Mulao nationality were determined by PCR and RFLP (restriction-fragment-length polymorphism) combined with gel electrophoresis and then confirmed by direct sequencing. The T allele frequency of TMEM57 rs873308 SNP was not different between Han and Mulao (23.18% versus 25.72%, P>0.05), but different between males and females in the two ethnic groups (P

Objective Thyroid hormones as modulators of adaptive thermogenesis can potentially contribute to development of obesity. The purpose of our study is to observe a relationship between TSH and BMI, blood lipids, BP and HbA1c in type 2 diabetic subjects with euthyroidism. Methods A total of 120 subjects with type 2 diabetes were recruited for this study from November 2012 to June 2014. Subjects were included in the study with TSH values between 0.4 and 4.5 mU/l, who did not take any thyroid medication and had a similar iodine diet. Subjects were weighed and anthropometric indices, lipid parameters, fasting plasma glucose, HbA1c, eGFR, blood pressure (BP) were documented. TSH was measured by an electrochemiluminescence immunoassay. Statistical analysis was performed by using SPSS 18(P value 7%) decreased from 27.5% to 12.5% (P = 0.02, adjusted for age and sex). Conclusion In type 2 diabetic subjects with biochemical euthyroidism we found significant association between high normal TSH levels and components of metabolic syndrome. High normal TSH levels were associated with more number of subjects with glycemic goal (HbA1c >7%)., Highlights • We report TSH levels association with MetS components in type 2 diabetic subjects. • Diabetes control was somehow complicated in subjects with high-normal TSH levels. • We suggest low normal TSH concentrations in insulin-resistant subjects.

Background Despite the high incidence and mortality of ST-segment elevation myocardial infarction (STEMI) among the very elderly, risk markers for this condition remain poorly defined. This study was designed to identify independent markers of STEMI among individuals carefully selected for being healthy or manifesting STEMI in, Highlights • Population aging are rapidly increasing worldwide, especially in developing countries. • Incidence and mortality due to cardiovascular diseases is extremely high in the very elderly population. • There is no specific algorithm for cardiovascular disease risk estimation for very elderly individuals. • Among the very elderly, markers of cardiovascular risk are distinct from younger adults.

Background and aims Studies have consistently demonstrated that variants in a number of candidate genes are significant determinants of lipid levels in adults. However, few studies have investigated the impact of these variants in children. Therefore, in the present investigation we examined the influence of ten common variants in the genes for lipoprotein lipase (LPL – S447X), cholesterol ester transfer protein (CETP – Taq1B) apolipoprotein (APO) E (ɛ2, ɛ3, ɛ4), APOA5 (−1131C > T and S19W), APOA4 (S347T) and APOC3 (−482C > T; 1100C > T and 3238G > C) on lipoprotein levels children from the Gene–Diet Attica Investigation on childhood obesity (GENDAI). Methods and results The ten variants selected were genotyped in 882 Greek children, mean age: 11.2 ± 0.7 years (418 females and 464 males). Genotypes were assessed using TaqMan technology. Significantly higher total cholesterol (TC) (p = 0.0001) and low-density lipoprotein cholesterol (LDL-C) (p