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The aim of this systematic review and meta-analysis was to evaluate the effects of Nigella sativa (N. sativa) on glycemic control, lipid profiles, and biomarkers of inflammatory and oxidative stress. Two independent authors systematically examined online databases consisting of, EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until October 30, 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of the studied trials. The heterogeneity among the included studies were assessed using the Cochrane's Q test and I-square (I2 ) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. A total of 50 trials were included in this meta-analysis. We found a significant reduction in total cholesterol (WMD: -16.80; 95% CI: -21.04, -12.55), triglycerides (WMD: -15.73; 95% CI: -20.77, -10.69), LDL-cholesterol (WMD: -18.45; 95% CI: -22.44, -14.94) and VLDL-cholesterol (WMD: -3.72; 95% CI: -7.27, -0.18) following supplementation with N. sativa. In addition, there was significant reductive effect observed with N. sativa on fasting glucose (WMD: -15.18; 95% CI: -19.82, -10.55) and HbA1C levels (WMD: -0.45; 95% CI: -0.66, -0.23). Effects of N. sativa on CRP (WMD: -3.61; 95% CI: -9.23, 2.01), TNF-α (WMD: -1.18; 95% CI: -3.23, 0.86), TAC (WMD: 0.31; 95% CI: 0.00, 0.63), and MDA levels (WMD: -0.95; 95% CI: -2.18, 0.27) were insignificant. This meta-analysis demonstrated the beneficial effects of N. sativa on fasting glucose, HbA1c, triglycerides, total-, VLDL-, LDL-cholesterol levels. [ABSTRACT FROM AUTHOR]

Background In many cocoa intervention studies, health outcomes are related to cocoa components without taking into account the bioavailability of the main bioactive components: phenolic compounds and methylxanthines. Methods The present work associates the results of bioavailability and randomised controlled crossover studies in humans carried out with similar cocoa products, so that the main phenol and methylxanthine metabolites observed in plasma and urine are associated to the health effects observed in the chronic studies. We outstand that doses of cocoa and consumption rate used are realistic. In the bioavailability study, a conventional (CC) and a methylxanthine-polyphenol rich (MPC) cocoa product were used, whereas in the chronic study a dietary fibre-rich (DFC) and a polyphenol-rich (PC) product were studied in healthy and cardiovascular risk subjects. Results and Discussion The main phenolic metabolites formed after CC and MPC intake, 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate, 3′-methyl-epicatechin-5-sulfate, 4-hydroxy-5-(4′-hydroxyphenyl)valeric acid-sulfate, 5-phenyl-γ-valerolactone--sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-glucuronide, may contribute to the changes in cholesterol (and indirectly HDL-cholesterol) observed after the regular intake of both DFC and PC, in healthy and cardiovascular risk subjects, whereas 7-methylxanthine (the main cocoa methylxanthine metabolite) and theobromine, together with its content in insoluble dietary fibre, may be responsible for the decrease of IL-1β and hypoglycemic effects observed with DFC. With both phenolic and methylxanthine metabolites a strong dose–response effect was observed. Conclusion After the regular consumption of both DFC and PC, positive changes were observed in volunteer’s lipid profile, which may be related to the long-lasting presence of colonic phenolic metabolites in blood. In contrast, the anti-inflammatory and hypoglycemic effects were only observed with DFC, and these may be related to methylxanthine metabolites, and it is likely that insoluble dietary fibre may have also played a role.

High density lipoprotein (HDL) are responsible for the reverse transport of cholesterol from the peripheral cells to the liver. Here, cholesterol is metabolised. Monitoring of HDL-C in serum is of clinical importance since an inverse correlation exists between serum HDL-C concentrations and the risk of atherosclerotic disease. Elevated HDL-C concentrations are protective against coronary heart disease. In this study, an automated enzymatic method for the direct determination of HDL-C in serum was found to have good precision and accuracy. Reproducibility was determined daily using control Precinorm L® in an internal protocol (n=20), within-run CV = 1.3% and between-day CV = 2.013%. The comparison of the HDL-C enzymatic assay with HDL-C precipitating agent was good with a correlation coefficient r = 0.965, Y = 1.981+ 0.959X, n =172. The normal range of HDL-C concentration in serum by this enzymatic method was 36.16 -86.08 mg/dl. Thus, a HDL-C level of over 35 mg/dl, shows the risk is not high and is protective against coronary heart disease.

The aim of this systematic review and meta-analysis was to evaluate the effects of resistant starch (RS) on glycemic status, serum lipoproteins and inflammatory markers in patients with metabolic syndrome (MetS) and related disorders. Two independent authors systematically searched online database including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until 30 April 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I-square (I2) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. Nineteen trials were included in this meta-analysis. Administration of RS resulted in significant reduction in fasting plasma glucose (FPG) (14 studies) (WMD: -4.28; 95% CI: -7.01, -1.55), insulin (12 studies) (WMD: -1.95; 95% CI: -3.22, -0.68), and HbA1C (8 studies) (WMD: -0.60; 95% CI: -0.95, -0.24). When pooling data from 13 studies, a significant reduction in total cholesterol levels (WMD: -8.19; 95% CI: -15.38, -1.00) and LDL-cholesterol (WMD: -8.57; 95% CI: -13.48, -3.66) were found as well. Finally, RS administration was associated with a significant decrease in tumor necrosis factor alpha (TNF-α) (WMD: -2.02; 95% CI: -3.14, -0.90). This meta-analysis showed beneficial effects of RS on improving FPG, insulin, HbA1c, total cholesterol, LDL-cholesterol and TNF-α levels in patients with MetS and related disorders, but it did not affect HOMA-IR, triglycerides, HDL-cholesterol, CRP and IL-6 levels. [ABSTRACT FROM AUTHOR]

Background: In many cocoa intervention studies, health outcomes are related to cocoa components without taking into account the bioavailability of the main bioactive components: phenolic compounds and methylxanthines. Methods: The present work associates the results of bioavailability and randomised controlled crossover studies in humans carried out with similar cocoa products, so that the main phenol and methylxanthine metabolites observed in plasma and urine are associated to the health effects observed in the chronic studies. We outstand that doses of cocoa and consumption rate used are realistic. In the bioavailability study, a conventional (CC) and a methylxanthine-polyphenol rich (MPC) cocoa product were used, whereas in the chronic study a dietary fibre-rich (DFC) and a polyphenol-rich (PC) product were studied in healthy and cardiovascular risk subjects. Results and Discussion: The main phenolic metabolites formed after CC and MPC intake, 5-(4'-hydroxyphenyl)-valerolactone-3'-sulfate, 3'-methyl-epicatechin- 5-sulfate, 4-hydroxy-5-(4'-hydroxyphenyl)valeric acid-sulfate, 5-phenyl- valerolactone-sulfate and 5-(4'-hydroxyphenyl)-valerolactone-3'-glucuronide, may contribute to the changes in cholesterol (and indirectly HDL-cholesterol) observed after the regular intake of both DFC and PC, in healthy and cardiovascular risk subjects, whereas 7-methylxanthine (the main cocoa methylxanthine metabolite) and theobromine, together with its content in insoluble dietary fibre, may be responsible for the decrease of IL-1β and hypoglycemic effects observed with DFC. With both phenolic and methylxanthine metabolites a strong dose-response effect was observed. Conclusion: After the regular consumption of both DFC and PC, positive changes were observed in volunteer's lipid profile, which may be related to the long-lasting presence of colonic phenolic metabolites in blood. In contrast, the anti-inflammatory and hypoglycemic effects were only observed with DFC, and these may be related to methylxanthine metabolites, and it is likely that insoluble dietary fibre may have also played a role. [ABSTRACT FROM AUTHOR]

This trial aimed to determine the effect of a standardized Cynanchum wilfordii Radix extract (CWE) on the lipid profiles of individuals with elevated total cholesterol (T-Chol) using a double-blind randomized placebo-controlled design. Ninety-six Korean individuals with elevated T-Chol level (200-240 mg/dL) were recruited and randomly allocated to groups that received VasH300 (300 mg CWE/day, n = 32), VasH600 (600 mg CWE/day, n = 32), or a placebo (n = 32) groups. Primary outcomes included T-Chol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, and safety (adverse events, biochemical parameters, and hematological parameters). Data were compared using a one-way analysis of variance followed by Duncan's post-hoc tests (among groups) and paired t tests (within groups). Values for T-Chol and LDL-cholesterol were significantly reduced in the VasH300 and groups (VasH300: 4.0 and 6.4%, respectively; VasH600; 3.8 and 5.8% respectively; both p < .05) compared with the placebo group and were not dose-dependent. VasH300 significantly improved the lipid profiles of individuals with elevated T-Chol without any serious side effects. Daily supplementation with VasH might be an alternative strategy with which to modify cholesterol-related parameters, especially in individuals with elevated T-Chol levels. [ABSTRACT FROM AUTHOR]

Apabetalone is the first selective BET protein inhibitor in the field of cardiovascular diseases (CVD). BET proteins are epigenetic regulators that link upstream epigenetic modifications to downstream gene expression. Inhibition of BET proteins by apabetalone has been shown to modulate reverse cholesterol transport, coagulation, inflammation and vascular calcification. Furthermore, apabetalone reduces circulating markers of CVD risk and plaque vulnerability. Post-hoc pooled analyses suggest a potential reduction in risk of major adverse cardiac events (MACE) in patients with Type 2 diabetes (T2D) and stable CVD. However, the current cardiovascular outcomes trial BET-on-MACE failed to detect the assumed 30% reduction of MACE by apabetalone in patients with T2D after an acute coronary syndrome. [ABSTRACT FROM AUTHOR]

Congenital disorders of glycosylation are a growing group of rare genetic disorders caused by deficient protein and lipid glycosylation. Here, we report the clinical, biochemical, and molecular features of seven patients from four families with GALNT2-congenital disorder of glycosylation (GALNT2-CDG), an O-linked glycosylation disorder. GALNT2 encodes the Golgi-localized polypeptide N-acetyl-d-galactosamine-transferase 2 isoenzyme. GALNT2 is widely expressed in most cell types and directs initiation of mucin-type protein O-glycosylation. All patients showed loss of O-glycosylation of apolipoprotein C-III, a non-redundant substrate for GALNT2. Patients with GALNT2-CDG generally exhibit a syndrome characterized by global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities. In behavioural studies, GALNT2-CDG mice demonstrated cerebellar motor deficits, decreased sociability, and impaired sensory integration and processing. The multisystem nature of phenotypes in patients and rodent models of GALNT2-CDG suggest that there are multiple non-redundant protein substrates of GALNT2 in various tissues, including brain, which are critical to normal growth and development. [ABSTRACT FROM AUTHOR]

d-Allulose, a C-3 epimer of d-fructose, is a rare sugar and a non-caloric sweetener. d-Allulose is reported to have several health benefits, such as suppressing a rise in postprandial glucose levels and preventing fat accumulation in rodents and humans. Additionally, low HDL-cholesterol levels post-d-allulose feeding were observed in humans but it is unclear how d-allulose decreased HDL-cholesterol levels. It is necessary to research the mechanism of HDL-cholesterol reduction by d-allulose ingestion because low HDL-cholesterol levels are known to associate with increased atherosclerosis risk. We therefore investigated the mechanism by which d-allulose lowers HDL-cholesterol using rat's primary hepatocytes. Sprague Dawley rats were fed an AIN-93G based diet containing 3% d-allulose for 2 weeks. Thereafter, primary hepatocytes were isolated by perfusion of collagenase. We measured the ability of HDL-cholesterol uptake in hepatocytes and the protein levels of scavenger receptor class B type 1 (SR-B1) as a HDL-cholesterol receptor. d-Allulose enhanced hepatocyte uptake of HDL-cholesterol, with a concurrent increase in hepatic SR-B1 protein levels. The results suggest that d-allulose enhances HDL-cholesterol uptake into the liver by increasing SR-B1 expression. It is estimated that HDL-cholesterol levels decreased accordingly. Since SR-B1 overexpression would decrease HDL-cholesterol levels, reportedly preventing atherosclerosis development, d-allulose could be a useful sweetener for atherosclerosis prevention. [ABSTRACT FROM AUTHOR]

Background and objective: Within-subject variability of cardiovascular risk factors may influence the development of cardiovascular disease. We aimed to improve knowledge on HDL-cholesterol variability and its clinical significance in HIV-infected patients, a population at high risk of cardiovascular disease.Methods: This was a cohort study to quantify the variability of HDL-cholesterol between two consecutive visits and to determine factors associated with such variability, in a group of HIV-infected patients.Results: A total of 307 patients were included, mean ± standard deviation of their age was 45.1 ± 8.5 years, and 225 of them (73.3%) were male. The absolute difference (after squaring and root squaring) of serum HDL-cholesterol level between the first and the second visit was 12.1 ± 9.2 mg/dL. In 65 patients (21.2%) the absolute value of the difference between both serum HDL-cholesterol level results were 20 mg/dL or higher. In a multivariable analysis the number of cigarettes smoked per day showed a significant, negative, correlation with the absolute difference in serum HDL-cholesterol level between the two visits (P = 0,009).Conclusions: Within-subject variability of HDL-cholesterol was substantial among our HIV-infected patients. Smoking was inversely correlated with such variability. [ABSTRACT FROM AUTHOR]

Background We evaluated the qualitative characteristics of high-density lipoprotein (HDL) particles in metabolically healthy and unhealthy overweight and obese subjects. Methods The study involved 115 subject individuals classified as metabolically healthy and unhealthy, as in overweight and obese groups. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure oxidized HDL (OxHDL) and serum amyloid A (SAA) concentrations. Lipoprotein subfractions were separated using nondenaturing gradient gel electrophoresis. Results An independent association was shown between increased OxHDL/HDL-cholesterol ratio and the occurrence of metabolically unhealthy phenotype in the overweight and obese groups. The OxHDL/HDL-cholesterol ratio showed excellent and acceptable diagnostic accuracy in determination of metabolic health phenotypes (overweight group, AUC = 0.881; obese group, AUC = 0.765). Accumulation of smaller HDL particles in metabolically unhealthy subjects was verified by lipoprotein subfraction analysis. SAA concentrations did not differ significantly between phenotypes. Conclusions Increased OxHDL/HDL-cholesterol ratio may be a potential indicator of disturbed metabolic health in overweight and obese individuals. [ABSTRACT FROM AUTHOR]

Background: Fabry disease, an X-linked genetic condition, results from alpha-galactosidase deficiency and increased accumulation of glycosphingolipids in cardiovascular tissues. Clinical manifestation includes vasculature associated complications. Hyperlipidaemia is one of the cardiovascular risk factors however it has never been well defined in Fabry disease. Enzyme Replacement Therapy (ERT) is available but its effect on serum cholesterol is unknown. The aim of this project was to assess the influence of long-term ERT on lipid profile in a large cohort of adult patients with Fabry disease. Methods: This was a retrospective analysis of lipid profile results. Patients with Fabry disease were on ERT for 10 years, were not treated with statins and had no severe renal impairment. All patients had lipid profile measured before ERT was commenced and 6, 12, 24, 36, 48, 60, 120 months later. Statistical analysis included ANOVA, Student t-test and descriptive statistics. Results: Among 72 patients, 40 were females (median age 45; range 29–75), 32 males (median age 46; range 20–69). There was no significant difference in total cholesterol or HDL-cholesterol measured at baseline before ERT was commenced and 6, 12, 24, 36, 48, 60 and 120 months after ERT was commenced in 72 patients (ANOVA; P = 0.673 and P = 0.883, respectively). Female patients on ERT had higher mean HDL-cholesterol as compared to female patients with Fabry disease who were asymptomatic and not treated (P ≥ 0.05). Total cholesterol between treated and non-treated female patients was comparable. Female patients on ERT have higher total cholesterol and HDL-cholesterol when compared to lipid results in male patients on ERT. Total cholesterol/HDL-cholesterol ratio was low in female and male patients on ERT over 10 years. Conclusion: Adult patients with Fabry disease have remarkably elevated HDL-cholesterol and as a result, elevated total cholesterol. It is possible that elevated HDL-cholesterol has a cardioprotective effect in patients with this condition. Long term ERT does not have a significant impact on lipid profile in female and male population with Fabry disease.

Epidemiologically, high-density lipoprotein (HDL) cholesterol levels have been inversely associated to cardiovascular (CV) events, although a Mendelian Randomisation Study had failed to establish a clear causal role. Numerous atheroprotective mechanisms have been attributed to HDL, the main being the ability to promote cholesterol efflux from arterial walls; anti-inflammatory effects related to HDL ligands such as S1P (sphingosine-1-phosphate), resolvins and others have been recently identified. Experimental studies and early clinical investigations have indicated the potential of HDL to slow progression or induce regression of atherosclerosis. More recently, the availability of different HDL formulations, with different phospholipid moieties, has allowed to test other indications for HDL therapy. Positive reports have come from studies on coronary stent biocompatibility, where the use of HDL from different sources reduced arterial cell proliferation and thrombogenicity. The observation that low HDL-C levels may be associated with an enhanced risk of heart failure (HF) has also suggested that HDL therapy may be applied to this condition. HDL infusions or apoA-I gene transfer were able to reverse heart abnormalities, reduce diastolic resistance and improve cardiac metabolism. HDL therapy may be effective not only in atherosclerosis, but also in other conditions, of relevant impact on human health. High-density lipoproteins have as a major activity that of removing excess cholesterol from tissues (particularly arteries). Knowledge on the activity of high-density lipoproteins on health have however significantly widened. HDL-therapy may help to improve stent biocompatibility and to reduce peripheral arterial resistance in heart failure. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between osteocalcin levels and obesity, hypertension, type 2 diabetes and HDL cholesterol. Methods From January 2015 to December 2017 in our hospital, 82 subjects affected by both hypertension and type 2 diabetes from the Endocrinology Department, 129 cases who were overweight but unaffected by hypertension or type 2 diabetes, and 135 subjects affected by hypertension but not type 2 diabetes from the Physical Examination Center were selected as subjects. The basic data of all subjects were collected, and fasting blood samples were collected to measure the level of the osteocalcin, blood glucose and plasma lipids levels. Multiple linear regression was used to explore factors associated with osteocalcin level. Results The result of univariate linear regression showed that OC was positively correlated with BMI, waist circumference and HbA1 c, but negatively correlated with systolic blood pressure and HDL-C. Multiple linear regression result showed that OC level had independent positive association with BMI and HbA1 c, and independent negative association with systolic blood pressure and HDL-C. Conclusion The result of this study indicate that overweight and type 2 diabetes are independently and negatively correlated with OC levels, and systolic blood pressure and HDL-C are independently and positively correlated with OC levels. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is deeply related with risks of chronic disease and mortality. Furthermore, the metabolic syndrome disorder in childhood and adolescence usually tends to lead to a number of cardiovascular disease in the stage of adulthood. In this sense, metabolic syndrome needs to be investigated seriously. The purpose of this study is therefore to prove the relationship between dietary habits(high carbohydrate, high calorie) and metabolic syndrome among adolescents. We also aim to clarify the relationship between emotional factors perceived by adolescents and metabolic syndrome. Our empirical results based on KNHANES dataset significantly demonstrates that the HDL-cholesterol is a decisive factor for the diagnosis of metabolic syndrome disorder. Additionally, emotional experience factors such as stress also show significant effects in difference of adolescents' metabolic syndrome. [ABSTRACT FROM AUTHOR]

Increasing evidence has cast doubt over the HDL-cholesterol hypothesis. The complexity of the HDL particle and its proven susceptibility to remodel has paved the way for intense molecular investigation. This state-of-the-art review discusses the molecular changes in HDL particles that help to explain the failure of large clinical trials intending to interfere with HDL metabolism, and details the chemical modifications and compositional changes in HDL-forming components, as well as miRNA cargo, that render HDL particles ineffective. Finally, the paper discusses the challenges that need to be overcome to shed a light of hope on HDL-targeted approaches.

Plant-based foods rich in phenolic phytochemicals are among the promising strategies to counteract age-related changes in lipid profile. Aronia melanocarpa (AM) fruits are a rich source of phenolic compounds possessing lipid-modulating effects. The present study investigated the effect of 3-month supplementation of AM-based functional beverages on the lipid profile of healthy aging rats. Male Wistar rats (n = 40) were separated into five groups: (YC) young controls (2-month-old); (AC) adult controls (13-month-old); (A) adult animals supplemented with pure AM extract; (A + P) adult animals supplemented with pectin-enriched (1%) AM extract; (A + H) adult animals supplemented with AM extract enriched with a herbal mixture. Total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and atherogenic indices were investigated at the end of the study. Adult controls demonstrated age-related dyslipidemia resulting in decreased HDL-C, and increased TG and TC/HDL index. The supplemented groups showed a significant increase in HDL-C levels: A + P (1.49 mmol/L) and A + H (1.61 mmol/L), respectively, vs. AC (1.09 mmol/L), p < 0.05. The TC/HDL-C and LDL-C/HDL-C indices were decreased in the A + P and A + H groups in comparison to the AC group (p < 0.05). These results indicate that supplementation with polyphenol-rich AM beverages can successfully alter HDL-C levels and this effect is further potentiated by pectin and herbs.

Endothelial lipase (EL) is an enzyme capable of HDL phospholipids hydrolysis. Its action leads to a reduction in the serum high-density lipoprotein concentration, and thus, it exerts a pro-atherogenic effect. This study examines the impact of a single bout exercise on the gene and protein expression of the EL in skeletal muscles composed of different fiber types (the soleus—mainly type I, the red gastrocnemius—mostly IIA, and the white gastrocnemius—predominantly IIX fibers), as well as the diaphragm, and the heart. Wistar rats were subjected to a treadmill run: (1) t = 30 [min], V = 18 [m/min]; (2) t = 30 [min], V = 28 [m/min]; (3) t = 120 [min], V = 18 [m/min] (designated: M30, F30, and M120, respectively). We established EL expression in the total muscle homogenates in sedentary animals. Resting values could be ordered with the decreasing EL protein expression as follows: endothelium of left ventricle > diaphragm > red gastrocnemius > right ventricle > soleus > white gastrocnemius. Furthermore, we observed that even a single bout of exercise was capable of inducing changes in the mRNA and protein level of EL, with a clearer pattern observed for the former. After 30 min of running at either exercise intensity, the expression of EL transcript in all the cardiovascular components of muscles tested, except the soleus, was reduced in comparison to the respective sedentary control. The protein content of EL varied with the intensity and/or duration of the run in the studied whole tissue homogenates. The observed differences between EL expression in vascular beds of muscles may indicate the muscle-specific role of the lipase.

Abstract Background Although high-density lipoprotein-cholesterol (HDL) level is inversely correlated with cardiovascular events, HDL is also reported to be positively associated with hypertension, which is a known endothelial impairment factor. Since HDL mediates important protective actions on the vascular endothelium by increasing the number of circulating endothelial progenitor cells (CD34-positive cells), the level of circulating CD34-positive cells should influence the association between HDL and hypertension. Methods To investigate the association between HDL and hypertension in relation to the level of circulating CD34-positive cells, we conducted a cross-sectional study of 477 elderly men aged 60–69 years who participated in general health checkup. Results HDL was found to be significantly positively associated with hypertension in subjects with a high level of circulating CD34-positive cells, while no significant association was observed for subjects with low circulating CD34-positive cells. Known cardiovascular risk factors adjusted odds (ORs) and 95% confidence intervals (CIs) of hypertension for increments of one standard deviation (SD) in HDL (13.8 mg/dL) were 1.44 (1.06, 1.96) for subjects with a high level of circulating CD34-positive cells and 0.87 (0.63, 1.19) for subjects with low circulating CD34-positive cells. We also revealed a significant association between HDL level and CD34-positive cell level on hypertension, with fully adjusted p values for the effect of this interaction on hypertension at 0.022. Conclusions Independent of known cardiovascular risk factors, HDL was found to be positively associated with hypertension in subjects with a high level of circulating CD34-positive cells but not for subjects with low circulating CD34-positive cells.

Abstract Background Ketosis can be induced in humans and in animals by fasting or dietary interventions, such as ketogenic diets. However, the increasing interest on the ketogenic state has motivated the development of alternative approaches to rapidly increase ketonemia using less drastic interventions. Here, it was tested whether oral intake of a β-hydroxybutyrate (βHB) mineral salt mixture could increase ketonemia in Wistar rats without any other dietary changes, thereby being a useful model to study ketones effects alone on metabolism. Methods βHB salts were orally administered to provoke elevation in the ketonemia. Effects of this intervention were tested acutely (by gavage) and chronically (4 weeks in drinking water). Acutely, a concomitant glucose overload was used to suppress endogenous ketogenesis and verify whether βHB salts were really absorbed or not. Long-term administration allowed to weekly evaluate the impact on ketonemia, blood glucose and, after 4 weeks, on body weight, visceral fat mass, lipid blood profile, serum lipolysis products and adiponectinemia. Results βHB salts increased ketonemia in acute and long-term administrations, improved blood lipid profile by raising HDL-cholesterol concentration and decreasing LDL/HDL ratio, while reduced visceral adipocyte volume. Mean ketonemia correlated positively with HDLc and negatively with adipocyte volume and serum lipolysis products. Conclusions Oral βHB can rapidly increase ketonemia and, therefore, be used as an acute and long-term animal model of ketosis. Long-term treatment points to important beneficial effects of ketone bodies in serum lipid concentrations and visceral fat mass. These results may help to explain the metabolic adaptations following ketogenic diets, such as a better body fat control and a serum lipid profile improvement.

The distribution of adipose tissue is influenced by gender and by age, shifting from subcutaneous to visceral depots with longevity, increasing the development of several aging-related diseases and manifestations such as obesity, metabolic syndrome, and insulin resistance. Epigenetics might have an important role in aging processes. The aim of this research was to investigate the interactions between aging and epigenetic processes and the role of visceral adipose tissue, insulin resistance, and dyslipidaemia. Two different study samples of 366 and 269 adult participants were analyzed. Anthropometric, biochemical (including the triglycerides-glucose (TyG) index), and blood pressure measurements were assessed following standardized methods. Body composition measurements by Dual-energy X-ray absorptiometry (DXA) were also performed for the second sample. Methylation data were assessed by Infinium Human Methylation BeadChip (Illumina) in peripheral white blood cells. Epigenetic age acceleration was calculated using the methods DNAmAge (AgeAcc) and GrimAge (AgeAccGrim). Age acceleration (AgeAccGrim) showed better correlations than AgeAcc with most of the measured variables (waist circumference, glucose, HOMA-IR, HDL-cholesterol, triglycerides, and TyG index) for the first sample. In the second sample, all the previous correlations were confirmed, except for HOMA-IR. In addition, many of the anthropometrical measurements assessed by DXA and C-reactive protein (CRP) were also statistically associated with AgeAccGrim. Associations separated by sex showed statistically significant correlations between AgeAccGrim and HDL-cholesterol or CRP in women, whereas, in men, the association was with visceral adipose tissue mass DXA, triglycerides and TyG index. Linear regression models (model 1 included visceral adipose tissue mass DXA and TyG index and model 2 included HDL-cholesterol and CRP) showed a significant association for men concerning visceral adipose tissue mass DXA and TyG index, while HDL-cholesterol and CRP were associated in women. Moreover, structural equation modeling showed that the TyG index was mediating the majority of the visceral adipose tissue mass action on age acceleration. Collectively, these findings showed that there are different mechanisms affecting epigenetic age acceleration depending on sex. The identified relationships between epigenetic age acceleration and disease markers will contribute to the understanding of the development of age-related diseases.

Purpose: The triglyceride-to-high-density lipoprotein-cholesterol (TG/HDL-C) ratio is considered an alternative marker for insulin resistance. This longitudinal retrospective study investigated the relationship between TG/HDL-C ratio and the risk of progression to prediabetes., Methods: We investigated 24,604 Japanese participants (14,609 men and 9,995 women) who underwent annual medical health checkups in 2017 (baseline) and 2022. All participants had no diabetes and prediabetes at baseline. No lipid-lowering medications were taken during the follow-up period. Participants were divided into four groups according to the quartiles of TG/HDL-C ratio at baseline. Multivariable-adjusted Cox regression analysis was conducted to examine hazard ratios (HRs) of progression to prediabetes. Receiver operating characteristic curves were used to determine the optimal cutoff value of TG/HDL-C ratio for prediction of prediabetes., Results: Compared with the lowest TG/HDL-C ratio quartile (Q1) group, the adjusted HRs (95% confidence intervals (CI)) of progression to prediabetes in the Q2, Q3, and Q4 groups, respectively, were 1.17 (0.92-1.47), 1.26 (1.01-1.56), and 1.77 (1.41-2.23) for men and 1.07 (0.60-1.11), 1.19 (1.08-1.29), and 1.58 (1.18-2.31) for women. For every 1 unit increase in TG/HDL-C ratio, the adjusted HRs (95% CI) for progression to prediabetes was 1.09 (1.04-1.13) in men and 1.10 (1.04-1.15) in women. The optimal TG/HDL-C ratio cutoffs were 1.71 and 0.97 in men and women, respectively, but the area under the curve was > 0.70 in both sexes., Conclusion: High TG/HDL-C ratio is a risk factor for progression to prediabetes in Japanese men and women, but it had low discriminative ability in predicting prediabetes risk., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01329-8., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background The Hp (haptoglobin)2-2 phenotype (~40% of people) is associated with dysfunctional high-density lipoprotein (HDL) that is heavily oxidized in hyperglycemia, which may explain why raising HDL-cholesterol (HDL-C) does not reliably prevent coronary artery disease (CAD) in diabetes. Methods and Results In this observational study using longitudinal data from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) lipid trial, time-varying (achieved) HDL-C updated at 4, 8, and 12 months, and annually thereafter over a mean of 4.7 years, was analyzed in relation to risk of CAD and secondary outcomes using Cox proportional hazards regression with time-varying covariables among participants with (n=1781) and without (n=3191) the Hp2-2 phenotype. HDL-C did not differ between the phenotypes throughout the study. Having low HDL-C (<40 mg/dL for male participants and <50 mg/dL for female participants) was associated with a greater risk of CAD compared with non-low HDL-C among participants with the non-Hp2-2 phenotype (hazard ratio [HR], 1.48 [95% CI, 1.18-1.87]) but not among the Hp2-2 phenotype (HR, 0.97 [95% CI, 0.70-1.35]; P interaction=0.03). Similarly, an inverse relationship was observed between HDL-C quintiles and CAD risk among participants without the Hp2-2 phenotype, whereas no significant inverse relationship was observed among participants with the Hp2-2 phenotype ( P interaction=0.38). Among the Hp2-2 phenotype group, having low HDL-C was associated with higher risk of CVD mortality (HR, 2.09 [95% CI, 1.05-4.13]), and compared with the lowest HDL-C quintile, higher quintiles were associated with lower risk of CVD mortality and congestive heart failure. Conclusions Hp phenotype modified the association between HDL-C and risk of CAD in the ACCORD lipid study, suggesting that HDL dysfunction in the Hp2-2 phenotype may hinder CAD-protective properties of HDL-C.

Background: Many reports address the stability of biochemical analytes in serum. However, studies covering a wide range of storage temperatures are unavailable. Using equipment enabling precise temperature control, we investigated the effect of six different storage temperatures on serum analytes. Methods: Serum specimens from seven healthy volunteers were obtained and divided into multiple aliquots for storage at −30, −20, −10, 0, 4, and 25 °C. On days 1, 3, 7, 14, 28 and 56, the aliquots stored at each temperature were relocated to a deep freezer maintained at −80 °C. On day 60, all aliquots were measured collectively for 13 major chemistry analytes. Results: (1) At 25 °C, alanine aminotransferase (ALT), creatine kinase (CK), aspartate aminotransferase (AST) and total bilirubin (TBil) were very unstable especially on day 7 and later. (2) At ≤4 °C, alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), amylase (AMY), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG), TBil and complement component-4 (C4) were generally stable and were very stable at 25 °C until day 14. (3) Between −20 and 4 °C, especially at −10 °C, test results of ALT, AST and lactate dehydrogenase (LDH) showed prominent decreases, but their stability was greatly improved at −30 °C. (4) In contrast, the value of complement component-3 (C3) increased at ≥− 20 °C. (5) At −30 °C, test results of all analytes were generally very stable except for ALT and CK, which showed noticeable reductions in activity after 14 days. Conclusions: This is the first study to assess the stability of serum analytes at six graded temperatures simultaneously. Each analyte has a unique stability pattern for a range of temperatures. [ABSTRACT FROM AUTHOR]

Anxiety disorders (ADs) are chronic conditions that often have their onset in childhood and adolescence. Inflammation and oxidative stress markers have been associated with the vulnerability to ADs, however it is not known if ADs in childhood can influence these biomarkers levels longitudinally. This study aims to investigate a possible association between ADs and serum levels of IL-10, IL-6, IL-1β, TNF-α, BDNF, and protein carbonyl content, assessed after 5 years of follow-up. Moreover, we studied possible mediators for these associations, including physical activity, metabolic markers and childhood trauma. From 240 individuals evaluated at baseline, 73 were re-evaluated in the follow-up. Psychiatric diagnoses were assessed with the K-SADS or the MINI and child trauma questionnaire (CTQ) to evaluate presence of trauma. We searched serum levels of IL-10, IL-6, IL-1β and TNF-α (flow cytometry), BDNF (sandwich-ELISA) and carbonyl content in proteins (PCC method). We found a significant direct association between ADs at baseline and log IL-6 (B = 0.34, S.E. = 0.11, p = 0.002) and between AD and log BDNF (B = −0.10, S.E. = 0.05, p = 0.033) five years later. Searching for possible mediators of these association, we found that levels of HDL-cholesterol (ΔB = −0.148) partially mediated the association between ADs and IL-6. No significant mediators were found in the association between ADs and BDNF. Moreover, this association is no longer significant after controlling for the presence of depression. Our results demonstrated that previous AD diagnosis was associated with higher levels of IL-6 in the follow-up evaluation, suggesting that the presence of anxiety in childhood could influence altered inflammatory markers. [ABSTRACT FROM AUTHOR]

The distribution of adipose tissue is influenced by gender and by age, shifting from subcutaneous to visceral depots with longevity, increasing the development of several aging-related diseases and manifestations such as obesity, metabolic syndrome, and insulin resistance. Epigenetics might have an important role in aging processes. The aim of this research was to investigate the interactions between aging and epigenetic processes and the role of visceral adipose tissue, insulin resistance, and dyslipidaemia. Two different study samples of 366 and 269 adult participants were analyzed. Anthropometric, biochemical (including the triglycerides-glucose (TyG) index), and blood pressure measurements were assessed following standardized methods. Body composition measurements by Dual-energy X-ray absorptiometry (DXA) were also performed for the second sample. Methylation data were assessed by Infinium Human Methylation BeadChip (Illumina) in peripheral white blood cells. Epigenetic age acceleration was calculated using the methods DNAmAge (AgeAcc) and GrimAge (AgeAccGrim). Age acceleration (AgeAccGrim) showed better correlations than AgeAcc with most of the measured variables (waist circumference, glucose, HOMA-IR, HDL-cholesterol, triglycerides, and TyG index) for the first sample. In the second sample, all the previous correlations were confirmed, except for HOMA-IR. In addition, many of the anthropometrical measurements assessed by DXA and C-reactive protein (CRP) were also statistically associated with AgeAccGrim. Associations separated by sex showed statistically significant correlations between AgeAccGrim and HDL-cholesterol or CRP in women, whereas, in men, the association was with visceral adipose tissue mass DXA, triglycerides and TyG index. Linear regression models (model 1 included visceral adipose tissue mass DXA and TyG index and model 2 included HDL-cholesterol and CRP) showed a significant association for men concerning visceral adipose tissue mass DXA and TyG index, while HDL-cholesterol and CRP were associated in women. Moreover, structural equation modeling showed that the TyG index was mediating the majority of the visceral adipose tissue mass action on age acceleration. Collectively, these findings showed that there are different mechanisms affecting epigenetic age acceleration depending on sex. The identified relationships between epigenetic age acceleration and disease markers will contribute to the understanding of the development of age-related diseases. [ABSTRACT FROM AUTHOR]

Recent genome-wide association studies have identified various dyslipidemia-related genetic variants. However, most studies were conducted in a cross-sectional manner. We thus performed longitudinal exome-wide association studies of dyslipidemia in a Japanese population. We used ~244,000 genetic variants and clinical data of 6022 Japanese individuals who had undergone annual health checkups for several years. After quality control, the association of dyslipidemia-related phenotypes with 24,691 single nucleotide polymorphisms (SNPs) was tested using the generalized estimating equation model. In total, 82 SNPs were significantly (P < 2.03 × 10−6) associated with dyslipidemia phenotypes. Of these SNPs, four (rs74416240 of TCHP , rs925368 of GIT2 , rs7969300 of ATXN2 , and rs12231744 of NAA25) and two (rs34902660 of SLC17A3 and rs1042127 of CDSN) were identified as novel genetic determinants of hypo-HDL- and hyper-LDL-cholesterolemia, respectively. A replication study using the cross-sectional data of 8310 Japanese individuals showed the association of the six identified SNPs with dyslipidemia-related traits. • Two SNPs were identified as novel susceptibility loci for hyper-LDL-cholesterolemia. • Four SNPs were susceptibility loci for hypo-HDL-cholesterolemia. • Relations of six SNPs to dyslipidemia were determined in a replication cohort. [ABSTRACT FROM AUTHOR]

There is a growing evidence demonstrating an association between dyslipidemia and progression of chronic kidney disease (CKD), but results on the effects of high-density lipoprotein cholesterol (HDL-C) on renal outcome have been conflicting. In this study, the relationship between HDL-C variability and the risk for progression to end-stage renal disease (ESRD) was investigated. This study analyzed data of 4,283,318 subjects who were free of ESRD at the time of enrollment, received more than three medical examinations from 2009 to 2012, and were followed to the end of 2015, based on the Korean National Health Insurance Service database. HDL-C variability was measured using the standard deviation, coefficient of variation, average real variability and variability independent of the mean (VIM). A total of 2,095 new cases of ESRD were observed during a median follow up of 3.38 years. There was a graded association between higher HDL-C variability and incident ESRD. In the multivariable adjusted model, hazard ratio comparing the highest and lowest quartiles of VIM of HDL-C was 1.82 (95% confidence interval, 1.58–2.09). The results were consistent when the variability of HDL-C was modeled using standard deviation, coefficient of variation and average real variability and were independent of other confounding factors, including the presence of CKD. HDL-C variability independently predicted an increased risk for developing ESRD. Our findings suggest that identification of HDL-C variability may help improve risk stratification for the prevention of ESRD. Image 1 • Studies have demonstrated an association between dyslipidemia and progression of kidney disease. • Results on the effects of high-density lipoprotein cholesterol (HDL-C) on renal outcome have been conflicting. • Greater intra-individual variability in HDL-C is associated with higher incidence of end-stage renal disease. [ABSTRACT FROM AUTHOR]

Cholesteryl ester transfer protein (CETP) inhibitor-mediated induction of HDL-cholesterol has no effect on the protection from cardiovascular disease (CVD). However, the mechanism is still unknown. Data on the effects of this class of drugs on subclasses of HDL are either limited or insufficient. In this study, we investigated the effect of evacetrapib, a CETP inhibitor, on subclasses of HDL in patients with atherosclerotic cardiovascular disease or diabetes. Baseline and 3-month post-treatment samples from atorvastatin 40 mg plus evacetrapib 130 mg (n = 70) and atorvastatin 40 mg plus placebo (n = 30) arms were used for this purpose. Four subclasses of HDL (large HDL, medium HDL, small HDL, and preβ-1 HDL) were separated according to their size and quantified by densitometry using a recently developed native polyacrylamide gel electrophoresis (PAGE) system. Relative to placebo, while evacetrapib treatment dramatically increased large HDL and medium HDL subclasses, it significantly reduced small HDL (27%) as well as preβ-1 HDL (36%) particles. Evacetrapib treatment reduced total LDL, but also resulted in polydisperse LDL with LDL particles larger and smaller than the LDL subclasses of the placebo group. Evacetrapib reduced preβ-1 HDL and small HDL in patients with ASCVD or diabetes on statin. Preβ-1 HDL and medium HDL are negatively interrelated. The results could give a clue to understand the effect of CETP inhibitors on cardiovascular outcomes. Image 1 • Cholesteryl ester transfer protein (CETP) inhibitor, evacetrapib, significantly reduces preb1-HDL, which is involved in reverse cholesterol transport, while significantly induces larger HDLs and HDL-cholesterol. This could be one of reasons that the inhibitor has no effect on the protection of cardiovascular disease. • A simple and sensitive method for preb1-HDL measurement has been developed. The relationship between preb1-HDL and cardiovascular diseases should be re-evaluated, because the new method is focus on lipids and density, but not only on apoA-I. • Increasing preb1-HDL should be the focus of future study, in terms of anti-atherogenesis. [ABSTRACT FROM AUTHOR]

In this paper, the acute and subchronic toxicity and the effect of squalene isolated from heterotrophic marine microalga Schizochytrium mangrovei PQ6 on the serum levels of HDL-C were investigated using animal models. The results of acute toxicity study showed that by oral administration of the squalene on albino mice at the highest dose of 58.25 g/kg of whole body of mice/day, the LD50 was not determined. Squalene at doses of 400 mg/kg/day and 1,200 mg/kg/day for 60 consecutive days have allowed the normal behavior, body weight, hematological and biochemical parameters, liver and kidney functions, morphology of liver, kidney and spleen, total plasma cholesterol content, however, HDL-C level was higher in squalene treated mices compared to control group (p < 0.05). In addition, at doses of 600 and 1,200 mg/kg/day for 60 continuous days, squalene treated mice showed the increase in HDL-C level and HDL-C/total cholesterol ratio and the decrease in the contents of LDL-C and VLDL-C without affecting the body and liver weights and levels of total cholesterol and triglyceride. [ABSTRACT FROM AUTHOR]

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Objectives: Non-HDL-cholesterol (non-HDL-C) has been reported to be a better marker of cardiovascular risk than LDL-cholesterol (LDL-C) especially in individuals with high triglyceride values. Further, levels of remnant cholesterol have been suggested to in part explain residual risk not captured with LDL-C. The aim of the present study was to define reference values for non-HDL-C and remnant cholesterol based on data from the Nordic Reference Interval Project (NORIP).Methods: We analyzed the test results for total cholesterol, HDL-cholesterol and triglycerides from 1392 healthy females and 1236 healthy males. Non-HDL-C was calculated as measured total cholesterol minus measured HDL-cholesterol. Remnant cholesterol was calculated using the Friedewald equation for LDL-C: measured total cholesterol minus measured HDL-cholesterol and minus calculated LDL-cholesterol. The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values.Results: Age (18-<30, 30-49 and ≥50 years) and sex-specific reference intervals were calculated for non-HDL-cholesterol and remnant-cholesterol. Levels of non-HDL-C and remnant cholesterol differed between sex and age strata.Conclusions: Age- and sex-specific reference intervals should be used for the triglyceride rich lipid variables non-HDL-C and remnant cholesterol. Since these markers may add information on risk burden beyond LDL-C, our hope is that these reference intervals will aid the introduction of automatic reporting of non-HDL-C by hospital laboratories. [ABSTRACT FROM AUTHOR]

Introduction: Serum lipid management is important for patients with diabetes; however, it has not been examined in our specialized diabetes clinic.Aims: The aim of the study was to assess the percentage of patients who did not achieve management targets (MT) for low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG), and explore factors related to failure to achieve lipid MT in Japanese patients with type 1 (T1D) and type 2 diabetes (T2D).Methods: This cross-sectional study included 795 patients (35% men) with T1D and 4018 patients (60% men) with T2D attending our diabetes center. MTs for serum lipids were in accordance with the guidelines of the Japan Atherosclerosis Society. Logistic regression analysis was performed to identify factors related to failure to achieve MTs for serum lipids.Results: The percentages of men/women who did not achieve MT for LDL-C were 34.1/31.8% in T1D and 40.5/52.7% in T2D. The corresponding values for TG were 35.1/14.0% in T1D and 50.1/47.9% in T2D, and for HDL-C were 2.5/0% in T1D and 8.6/2.9% in T2D. Increase in body mass index (BMI) and glycated hemoglobin (HbA1c) were significantly and independently associated with failure to achieve lipid MT in patients with T1D and T2D for both sexes.Conclusions: The percentages of our patients who did not achieve serum lipid MT were relatively high in T1D and T2D, and higher HbA1c and BMI were associated with failure to achieve serum lipid MTs. More attention should be paid to lipid management in patients with diabetes especially who have higher HbA1c and BMI in our facility. [ABSTRACT FROM AUTHOR]

Abstract Amerindian ancestry appears to be a risk factor for metabolic diseases (MetD), making Mexicans an ideal population to better understand the genetic architecture of metabolic health. In this study, we determine the association of genetic variants previously reported with metabolic entities, in two Mexican populations, including the largest sample of Amerindians reported to date. We investigated the association of eigth single-nucleotide polymorphisms (SNPs) in AKT1 , GCKR , and SOCS3 genes with different metabolic traits in 1923 Mexican Amerindians (MAs) belonging to 57 ethnic groups, and 855 Mestizos (MEZs). The allele frequency of 7/8 SNPs showed significant differences between MAs and MEZs. Interestingly, some alleles were monomorphic in particular ethnic groups, and highly frequent in other ones. With the exception of GCKR rs1260326T, as expected, all SNP frequencies in the MEZ population had intermediate values between its two main ancestral populations (MAs and Iberian populations in Spain [IBS]). We detected ethnic differences in linkage disequilibrium patterns and haplotype structure between MAs and MEZs, possibly due to the high genetic heterogeneity in these populations. Remarkably, AKT1 was associated with hypertension in MEZs, but not in MAs. GCKR was associated with protection against type 2 diabetes (T2D) in MAs, and with hypertriglyceridemia and protection against low HDL Cholesterol (HDL-C) levels in MEZs. The CAT haplotype in SOCS3 was associated with metabolic syndrome (MetS) in MEZs, and correlated with protection against high blood pressure (HBP) and risk for high waist circumference and T2D in MAs. Our results show differential genetic associations with metabolic traits between MAs and MEZs, possibly due to the differences in genetic structure between these Mexican populations. Highlights • Differential genetic associations with metabolic traits between Mexican Amerindians and Mestizos. • Variants in AKT1 gene were associated with hypertension in Mestizo population. • GCKR polymorphisms were associated with protection against type 2 diabetes in Mexican Amerindians. • GCKR polymorphisms were associated with hypertriglyceridemia and protection against low HDL Cholesterol levels in Mestizos. • In Mexican Amerindians, only one polymorphism in SOCS3 gene was associated with protection against high blood pressure. • The CAT haplotype in SOCS3 was associated with metabolic syndrome in Mestizos. • The CAT haplotype in SOCS3 was associated with risk for high waist circumference and type 2 diabetes in Mexican Amerindians. [ABSTRACT FROM AUTHOR]

The REVEAL trial with anacetrapib, a CETP (cholesteryl ester transfer protein) inhibitor, has been one of the largest "lipid" studies conducted so far. Its aim was to confirm the hypothesis that an increase in high-density lipoprotein (HDL) cholesterol will reduce the cardiovascular risk. The CETP transporter glycoprotein transfers cholesterol esters and triglycerides from HDL to the liver and to atherogenic lipoproteins. The result is an increase in HDL cholesterol and a variable decrease in low-density lipoprotein (LDL) cholesterol. On the one hand, this effect is positive - i.e. a decreased concentration of cholesterol esters in atherogenic lipoproteins; on the other hand, there is a breaking of the cycle of cholesterol esters in the chain of macrophage-HDL-liver and VLDL/LDL. Previous studies with a number of other CETP inhibitors have failed to show a positive impact on the rates of atherothrombotic events or even demonstrated increased rates; therefore, the positive results of the secondary prevention REVEAL trial were surprising. The decrease in LDL cholesterol was high - in comparison with placebo, there was a documented decrease of more than 40% while the increase in HDL cholesterol was more than two-fold. The primary outcome measure, the rate of major coronary events, decreased statistically significantly - almost by a tenth. However, in absolute values, the decrease was small - only 1% for 4 years of treatment. The corresponding NNT (number needed to treat), i.e. the number of patients treated needed to prevent one bad outcome, was 400 patients a year. However, it needs to be emphasized that these were patients who had achieved optimal LDL cholesterol levels prior to treatment. Although the result of the trial was only of borderline significance from the clinical viewpoint, in terms of treatment strategy for dyslipidaemia the study has yielded a wealth of knowledge. First of all, it has shown that a decrease in LDL cholesterol is crucial. Given the fact that the study included patients with a mean baseline of 1.6 mmol/L under statin treatment, it has been shown that even a further decrease in LDL cholesterol is beneficial. Furthermore, it has been confirmed that increasing HDL cholesterol will not affect patient prognosis. In summary, the answer to the fundamental question "Is an increase in HDL cholesterol beneficial?" is negative. Nevertheless, the evidence that an LDL cholesterol decrease even below the strict target level of 1.6 mmol/L favourably affects atherothrombotic events is certainly beneficial. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Visit-to-visit variability in biological measures has been suggested as an independent predictor of cardiovascular disease (CVD). Although low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) are important risk factors of CVD, there are few studies investigating the effect of variability in LDL-C and HDL-C on cardiovascular outcomes. We investigated the association between visit-to-visit variability in LDL-C, HDL-C, and non-HDL-C and major adverse cardiovascular and cerebrovascular events (MACCE) in patients who underwent percutaneous coronary intervention (PCI). Methods Data from 1792 subjects who underwent PCI from January 2004 to December 2009 were analyzed. Visit-to-visit variability was calculated using various indices: standard deviation (SD), coefficient of variation, and corrected variability independent of mean (cVIM). MACCE comprised all-cause death, non-fatal myocardial infarction, and stroke. Results During a median follow-up period of 65 months, 114 subjects (6.4%) experienced MACCE: 68 (3.8%) all-cause death; 43 (2.4%) stroke, and 15 (0.8%) non-fatal myocardial infarction. Visit-to-visit variability in LDL-C, HDL-C, and non-HDL-C was significantly higher in the MACCE group compared to the non-MACCE group. In multiple regression analysis, all LDL-C, HDL-C, and non-HDL-C variability parameters were independent predictors for MACCE after adjusting for potential confounding factors. Each 1-SD increase of cVIM in LDL-C, HDL-C, and non-HDL-C increased the risk of MACCE by 34% (HR 1.34 [95% CI, 1.18–1.52]), 50% (HR 1.50 [95% CI 1.32–1.71]), and 37% (HR 1.37 [95% CI, 1.20–1.57]), respectively. These relationships were observed in various subgroups according to age, sex, and diabetes status. Conclusions Visit-to-visit variability in LDL-C, HDL-C, and non-HDL-C is associated with MACCE in subjects with previous PCI. Highlights • Higher visit-to-visit non-HDL-cholesterol variability in MACCE group. • Visit-to-visit LDL-, HDL-, and non-HDL-cholesterol variability can predict MACCE. • Important dynamic relationship between cholesterol levels and clinical outcomes. [ABSTRACT FROM AUTHOR]

High low-density-lipoprotein cholesterol (LDL-C) is routinely described as the main cause of cardiovascular disease (CVD) in familial hypercholesterolemia (FH). However, numerous observations are in conflict with Bradford Hill's criteria for causality: a) degree of atherosclerosis is not associated with LDL-C; b) on average the life span of people with FH is about the same as for other people; c) LDL-C of people with FH without CVD is almost as high as in FH patients of the same age with CVD; and d) questionable benefit or none at all have been achieved in the controlled, randomized cholesterol-lowering trials that have included FH individuals only. Obviously, those individuals with FH who suffer from CVD may have inherited other and more important risk factors of CVD than high LDL-C. In accordance, several studies of FH individuals have shown that various coagulation factors may cause CVD. Equally, some non-FH members of an FH kindred with early CVD, have been found to suffer from early CVD as well. Cholesterol-lowering has only been successful in an animal experiment by using probucol, which has anticoagulant effects as well. We conclude that systematic studies of all kinds of risk factors among FH individuals are urgently required, because today millions of people with FH are treated with statins, the benefit of which in FH is unproven, and which have many serious side effects. We predict that treatment of FH individuals with elevated coagulation factors with anticoagulative drugs is more effective than statin treatment alone. [ABSTRACT FROM AUTHOR]

The aim of the present study was to find out the effects of 12 weeks of competitive phase specific training on basal levels of selected biochemical and haematological variables in male Taekwondo players. A total of 15 Indian male Taekwondo players (Age: 16.9 ± 1.4 years; Height: 173.5 ± 0.81 cm; Weight: 60.92 ± 11.79 kg, BMI: 20.04 ± 2.44 kg/m2) were volunteered for this study. Twelve weeks of competitive phase specific Taekwondo training was given to the participants for the perfection of technical skills and for the improvement of general physical conditioning abilities. Blood samples were collected from antecubital vein in the morning after overnight fasting and 24 hours of rest, both before and after training. The samples were analyzed for the selected biochemical and haematological parameters such as Lipid profile, Iron Profile, Creatine phosphokinase (CPK) Lactate dehydrogenase (LDH) and Complete Blood Picture (CBP). Data were analyzed by paired-t test by using SPSS software. A significant increase (P < 0.05) of Serum Iron, Total cholesterol, HDL-cholesterol, Hematocrit, and Mean Corpuscular Volume were observed after training. Also a significant reduction (P < 0.05) in total cholesterol/HDL-cholesterol Ratio, Lactate Dehydrogenase and Mean Corpuscular Hemoglobin Concentration (MCHC) were noted after the training. From this study it is concluded that the competitive phase specific Taekwondo training is effective for improving lipid profile and some of the biochemical parameters in national level male Taekwondo players and biochemical monitoring will be helpful for the evaluation of training effects and training related adaptations at molecular level. [ABSTRACT FROM AUTHOR]

Summary Background & aims Melatonin supplementation may be associated with blood lipids improvement; however, the current evidence from randomized controlled trials (RCTs) is inconsistent. The present study aimed to systematically review and analyze RCTs assessing the effects of melatonin supplementation on blood lipids. Methods A comprehensive literature search in several database was performed up to January 2017. Quantitative data synthesis was performed using a fixed or random-effects model, with weight mean difference (WMD) and 95% confidence intervals (CI). Standard methods were used for assessment of heterogeneity, meta-regression, sensitivity analysis and publication bias. Results A total of 8 RCTs were eligible. Meta-analysis suggested a significant association between melatonin supplementation and a reduction in triglycerides (WMD: −31.54 mg/dL, 95% CI: −50.71, −12.38, p = 0.001), and total cholesterol levels (WMD: −18.48 mg/dL, 95% CI: −35.33, −1.63, p = 0.032), while no significant effect on LDL-C (WMD: −2.37 mg/dL, 95% CI: −11.61, −6.86, p = 0.615) and HDL-C (WMD: 1.28 mg/dL, 95% CI: −0.66, 3.23, p = 0.197) was found. In sub-group analysis, a significant decrease in triglycerides was found at doses ≥8 mg/d and when trials last ≥8 weeks. In addition, a significant decrease of total cholesterol was found at doses ≥8 mg/d and when total cholesterol baseline levels were ≥200 mg/dL. Conclusions Melatonin supplementation has significant effects on triglycerides and total cholesterol levels, which was more evident in higher dose and longer duration and also in a higher concentration of cholesterol levels. Further studies are required to determine the benefits of melatonin on lipid profile. [ABSTRACT FROM AUTHOR]

Background& Aims: The association of low-carbohydrate diet with weight loss and the risk of cardiovascular diseases has recently been the focus of increasing research attention. However, studies on low-carbohydrate diet in the Asian population are limited. The present study was aimed to examine the association between low-carbohydrate diet and metabolic syndrome among Korean adults.Methods and Results: A total of 16,349 participants aged 30 years or older who participated in a 24-h dietary recall survey of the fifth and sixth Korea National Health and Nutrition Examination Survey were included in this study. Low-carbohydrate diet was evaluated using the low-carbohydrate-diet score, which was calculated based on the percentage of energy from carbohydrate, protein, and fat by sex. The association between the low-carbohydrate-diet score and metabolic syndrome was analyzed using multiple logistic regression analysis. A low-carbohydrate diet was not associated with metabolic syndrome and its components such as waist circumference, blood pressure, and triglyceride levels. However, women in the highest decile of the animal- or plant-based low-carbohydrate-diet score showed a decreased risk of reduced high-density lipoprotein (HDL)-cholesterol levels, and men in the highest decile of the animal-based low-carbohydrate-diet score showed a decreased risk of reduced HDL-cholesterol levels than those in the lowest decile of the low-carbohydrate-diet score.Conclusion: These findings indicate that, in Korea, a low-carbohydrate diet did not increase the risk of metabolic syndrome among adults who typically consume a high-carbohydrate low-fat diet. However, it may moderately decrease the risk of reduced HDL-cholesterol levels. [ABSTRACT FROM AUTHOR]

Background: The plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) is a simple way to estimate insulin resistance. We aimed to evaluate the TG/HDL-C ratio as a simple clinical way to identify apparently healthy individuals with insulin resistance and enhanced risk of future cardiovascular disease (CVD). Methods: One thousand seven hundred twenty men, aged 50 years, free from diabetes and CVD when evaluated at baseline in 1970–1974 were followed for 40 years regarding incident CVD (myocardial infarction and/or ischemic stroke, n = 576). Results: Participants with a high TG/HDL-C ratio (highest quartile >1.8) at baseline were more insulin resistant, with a significantly more adverse cardiometabolic risk profile (P < 0.001) at baseline, compared with those with a lower ratio. This group also showed an increased risk of CVD [hazard ratio, HR 1.47 (95% confidence interval 1.26–1.93) P < 0.001]. Fourteen percent of subjects with metabolic syndrome, in whom insulin resistance is increased, were also at enhanced CVD risk [HR 1.75 (1.42–2.16) P < 0.001]. Conclusions: Twenty-five percent of apparently healthy 50-year-old men with the highest TG/HDL-C plasma concentration ratio had a significantly more adverse cardiometabolic profile at baseline, and developed more CVD over the next 40 years, compared with those not meeting this cut point. Determining the TG/HDL-C ratio in middle-aged men provided a simple and potentially clinically useful way to identify increased risk of developing CVD in persons free of diabetes or manifest CVD. [ABSTRACT FROM AUTHOR]

Dyslipidemia is characterized by elevation of plasma cholesterol, triglycerides (TGs) or both, or a low high-density lipoprotein-cholesterol (HDL-C) level that contributes to the development of insulin resistance, Diabetes mellitus type 2 (DM2) and atherosclerosis. Dietary fat and cholesterol, genetics and other risk factors are responsible for producing variations in the lipids. The cholesterol plays a major function in the body, cholesterol homeostasis mechanism is regulated by the sterol regulatory-element binding proteins (SREBPs) and firstly introduced by Brown and Goldstein. The SREBP transcription factors act coordinately with their intronic microRNAs (miRNA-33a / miRNA-33b) to regulate both fatty acid and cholesterol homeostasis. Recently, multiple studies described microRNA-33a and SREBP2 cooperation for cholesterogenic transcription to improve intracellular cholesterol levels; suggesting that therapeutic approach of miR-33 targeting antisense would imperative for reverse cholesterol transport from atherogenic macrophages, as a result reduce atherosclerosis.

Ex vivo human peripheral blood mononuclear cell (PBMC) systems offer the possibility to test transcriptomic effects of food bioactive compounds with potential health effects. We investigated all-trans retinoic acid (ATRA) effect on mRNA expression of key lipid metabolism and inflammatory genes in PBMCs from normal-weight (NW) and overweight-obese (OW-OB) men with different metabolic syndrome-related features. PBMCs were incubated with 10 µM ATRA and mRNA levels of selected genes were analyzed using real-time RT-qPCR. Human ex vivo PBMCs responded to ATRA treatment, but the response for some genes was dependent on body mass index (BMI), with a lower response in PBMC from OW-OB than from NW donors. Moreover, gene expression response was affected by circulating high-density lipoprotein (HDL)-cholesterol levels. Particularly, the response to ATRA of CPT1A, previously reported as a sensitive metabolic risk predictive biomarker, was dependent on HDL levels and not on BMI, being impaired in those individuals with lower HDL levels, specifically in OW-OB. Thus, PBMCs’ insensitivity to ATRA, which can be considered as indicative of impaired metabolism, was observed in individuals with higher metabolic risk (OW-OB with low HDL levels). In conclusion, an ex vivo human PBMC system indicates that ATRA response could be influenced by metabolic syndrome features. Moreover, our study reinforces the role of CPT1A as a marker of metabolic risk and points to plasmatic HDL-cholesterol levels as a parameter to take into consideration when the effects of nutritional factors and/or dietary interventions on humans are under study. Further studies including women are required to detect potential gender differences in the observed effects.

Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvención con DIeta MEDiterranea-Plus) study. The polyphenol content of foods was estimated from the Phenol-Explorer 3.6 database. The mean of total polyphenol intake was 846 ± 318 mg/day. Except for stilbenes, women had higher polyphenol intake than men. Total polyphenol intake was higher in older participants (>70 years of age) compared to their younger counterparts. Participants with body mass index (BMI) >35 kg/m2 reported lower total polyphenol, flavonoid, and stilbene intake than those with lower BMI. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. To conclude, in participants with MetS, higher intake of several polyphenol subclasses was associated with a better profile of MetS components, especially HDL-c.

The aim of this study was to examine the independent association between flavonoid intake and hypo-high-density lipoprotein (HDL)-cholesterolemia and the potential modifying effect of polyunsaturated fatty acid (PUFA) intake on this association among Korean adults. This cross-sectional analysis used data from 10,326 subjects who participated in the 2013−2016 Korean National Health and Nutrition Examination Survey. Multiple logistic regression analyses were used to assess the associations of flavonoid and PUFA intakes with hypo-HDL-cholesterolemia prevalence. Proanthocyanidins intake showed an inverse relationship with hypo-HDL-cholesterolemia only in men (Tertile (T) 3 vs. T1: odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.59−0.92, p-trend = 0.0330). Total flavonoid and PUFA intakes were not associated with hypo-HDL-cholesterolemia in both men and women. However, when stratified by PUFA intake, there was an inverse relationship between total flavonoid intake and hypo-HDL-cholesterolemia prevalence in men with a high n-3 PUFA intake (total flavonoid intakes T3 vs. T1: OR = 0.59, 95% CI = 0.42−0.82, p-trend = 0.0004) or a low n-6/n-3 PUFA intake ratio (T3 vs. T1: OR = 0.67, 95% CI = 0.48−0.93, p-trend = 0.0053), but not in those with a low n-3 PUFA intake (p-interaction = 0.0038) or a high n-6/n-3 PUFA intake ratio (p-interaction = 0.1772). In women, no association was found between total flavonoid intake and hypo-HDL-cholesterolemia, regardless of PUFA intake. These results imply that the intake of proanthocyanidins might have beneficial effects on the HDL-cholesterol level in Korean men. In addition, n-3 PUFA intake might modify the association of total flavonoid intake with the hypo-HDL-cholesterolemia among Korean men.