Lower HDL-cholesterol Concentrations Research Articles

Point: The Relationship between Cholesteryl Ester Transfer Protein and Cardiovascular Risk

There is overwhelming epidemiologic evidence that increased concentrations of LDL cholesterol (LDL-C)2) and low concentrations of HDL cholesterol (HDL-C) are independently associated with increased cardiovascular risk. Furthermore, the risk associated with low HDL-C concentrations persists even when LDL-C has been reduced to concentrations <1.8 mmol/L (<70 mg/dL) by treatment with statins (1). It is logical, therefore, to investigate strategies designed to redistribute cholesterol away from atherogenic LDL particles in favor of potentially protective HDL particles. One such approach is to inhibit the cholesteryl ester transfer protein (CETP), a protein in human plasma that transfers cholesterol from the HDL to non-HDL fractions (2). CETP activity is prominent in humans, nonhuman primates, and rabbits (2). In contrast, there is little or no CETP activity in the plasma of most other species, including rodents (2). In general, species with CETP activity in plasma are susceptible to the development of atherosclerosis, whereas those lacking the protein tend to be naturally resistant. Furthermore, inhibiting CETP in rabbits markedly reduces the development of atherosclerosis, regardless of whether the CETP inhibition is achieved by genetic manipulation (3), by vaccination against CETP (4), or by chemical inhibitors of CETP (5). ### CETP POLYMORPHISMS AND SUSCEPTIBILITY TO ATHEROSCLEROSIS IN HUMANS Several polymorphisms of the human CETP (cholesteryl ester transfer protein, plasma) gene have been reported (2). Although many of these studies have demonstrated associations between CETP single-nucleotide polymorphisms and small changes in plasma CETP and HDL concentrations, the relationship between these polymorphisms and susceptibility to atherosclerosis is variable (2). A recent metaanalysis of 92 studies involving 113 833 participants (6) concluded, however, that those CETP genotypes associated with inhibition of CETP activity show an inverse association with coronary risk and that the magnitude of the reduction of coronary events was consistent with the reductions in risk for equivalent increases in HDL-C concentration as predicted from …

Ethnic differences in blood lipids and dietary intake between UK children of black African, black Caribbean, South Asian, and white European origin: the Child Heart and Health Study in England (CHASE)

Ischemic heart disease (IHD) rates are lower in UK black Africans and black Caribbeans and higher in South Asians when compared with white Europeans. Ethnic differences in lipid concentrations may play a part in these differences. The objective was to investigate blood lipid and dietary patterns in UK children from different ethnic groups. This was a cross-sectional study in 2026 UK children (including 285 black Africans, 188 black Caribbeans, 534 South Asians, and 512 white Europeans) attending primary schools in London, Birmingham, and Leicester. We measured fasting blood lipid concentrations and collected 24-h dietary recalls. In comparison with white Europeans, black African children had lower total cholesterol (-0.14 mmol/L; 95% CI: -0.25, -0.04 mmol/L), LDL-cholesterol (-0.10 mmol/L; 95% CI: -0.20, -0.01 mmol/L), and triglyceride concentrations (proportional difference: -0.11 mmol/L; 95% CI: -0.16, -0.06 mmol/L); HDL-cholesterol concentrations were similar. Lower saturated fat intakes (-1.4%; 95% CI: -1.9%, -0.9%) explained the differences between total and LDL cholesterol. Black Caribbean children had total, LDL-cholesterol, HDL-cholesterol, and triglyceride concentrations similar to those for white Europeans, with slightly lower saturated fat intakes. South Asian children had total and LDL-cholesterol concentrations similar to those for white Europeans, lower HDL-cholesterol concentrations (-0.7 mmol/L; 95% CI: -0.11, -0.03 mmol/L), and elevated triglyceride concentrations (proportional difference: 0.14 mmol/L; 95% CI: 0.09, 0.20 mmol/L); higher polyunsaturated and monounsaturated fat intakes did not explain these lipid differences. Only black African children had a blood lipid profile and associated dietary pattern likely to protect against future IHD. The loss of historically lower LDL-cholesterol concentrations among UK black Caribbeans and South Asians may have important adverse consequences for future IHD risk in these groups.

Metabolic syndrome in Iran

Metabolic Syndrome (MS) also known as syndrome X, the Dysmetabolic Syndrome and Insulin resistance syndrome, refers to a cluster of cardiovascular risk factors including hypertension, glucose intolerance, triglyceridemia and low HDL cholesterol concentrations in blood. This syndrome consists of multiple metabolic risk factors. The significance of MS is that MS and its components seem to be underlying factors for the development of atherosclerotic cardiovascular disease and diabetes type 2. The current article reviews the literature on the prevalence of MS in Iran. According to global statistics, a quarter of the adult population suffers from metabolic syndrome. The prevalence of MS in United States is 24% and 44% of adults over 50 years old suffer from MS. In contrast to this high prevalence of MS in United States of America, its prevalence in some countries such as South Korea is less than 14.2% in men. However, its prevalence in two neighbor country of Iran including Saudi (39.3%) and Turkish (33%) populations is relatively high compared to other countries. We know that 30% of adults in Tehran (Capital city of Iran) suffer from MS and more than 45% of adults older than 20 years old in the Khorasan province (in north east Iran) have MS. This statistics reveal that the prevalence of MS in Iran is even higher than the developed countries and the relation between MS and Coronary Artery disease suggests that we need to continue research on MS, its components, and the association between MS and Coronary Artery Disease.Key words: Metabolic syndrome, Coronary artery disease, Risk factor

Levels of high-density lipoprotein cholesterol (HDL-C) among children with steady-state sickle cell disease.

BackgroundThe search for sickle cell disease (SCD) prognosis biomarkers is a challenge. These markers identification can help to establish further therapy, later severe clinical complications and with patients follow-up. We attempted to study a possible involvement of levels of high-density lipoprotein cholesterol (HDL-C) in steady-state children with SCD, once that this lipid marker has been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities, important aspects to be considered in sickle cell disease pathogenesis.MethodsWe prospectively analyzed biochemical, inflammatory and hematological biomarkers of 152 steady-state infants with SCD and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records.ResultsOf the 152 infants investigated had a significant positive association of high-density lipoprotein cholesterol with hemoglobin (P < 0.001), hematocrit (P < 0.001) and total cholesterol (P < 0.001) and a negative significant association with reticulocytes (P = 0.046), leukocytes (P = 0.015), monocytes (P = 0.004) and platelets (P = 0.005), bilirubins [total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and indirect bilirubin (P < 0.001], iron (P < 0.001), aminotransferases [aspartate aminotransferase (P = 0.004), alanine aminotransferase (P = 0.035)], lactate dehydrogenase (P < 0.001), urea (P = 0.030), alpha 1-antitrypsin (P < 0.001), very low-density lipoprotein cholesterol (P = 0.003), triglycerides (P = 0.005) and hemoglobin S (P = 0.002). Low high-density lipoprotein cholesterol concentration was associated with the history of cardiac abnormalities (P = 0.025), pneumonia (P = 0.033) and blood transfusion use (P = 0.025). Lipids and inflammatory markers were associated with the presence of cholelithiasis.ConclusionsWe hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by low HDL-C with hypertriglyceridemia and high VLDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. Additional studies are warranted to test this hypothesis and the probably mechanisms involved in this complex network of markers and their role in SCD pathogenesis.

Role of insulin resistance in non-obese adolescents.

Insulin resistance in the obese is closely related with cardiovascular diseases and their risk factors not only in adults but also in children and adolescents. We aimed to elucidate whether insulin resistance in non-obese adolescents is related with these conditions. A total of 74 non-obese high-school students (38 boys and 36 girls) were recruited. Anthropometry, blood pressure, fasting serum chemistry and insulin activity were measured. Subjects with a homeostasis model assessment-insulin resistance (HOMA-IR) level greater than the 75th percentile (> 2.25 for boys and > 2.89 for girls) were defined as insulin resistant. Non-obese boys with impaired insulin sensitivity had higher systolic blood pressure, lower HDL-cholesterol concentration, and fewer hours of vigorous exercise during weekdays, while non-obese girls with impaired insulin sensitivity had higher systolic blood pressure than their peers with normal insulin sensitivity. By multiple stepwise regression analysis, systolic blood pressure (p < 0.001) and the hours of vigorous exercise during weekdays (p < 0.03) were independently associated with HOMA-IR in boys, while systolic blood pressure (p < 0.0001) and serum concentrations of HDL-cholesterol (p < 0.01) were found in girls. In nonobese adolescents, insulin sensitivity is related with cardiovascular risk factors.

Síntesis y purificación de apolipoproteína apo A-I Zaragoza (L144R) recombinante

Introduction Apolipoprotein A-I Zaragoza (apo A-I Z, L144R mutation) is an apolipoprotein A-I variant whose carriers have low HDL-cholesterol (HDL-c) concentrations but, paradoxically, no atherosclerotic symptoms despite the presence of additional atherogenic risks. In vivo metabolic studies performed on heterozygous carriers of this apo A-I variant revealed a two-fold increased fractional catabolic rate compared to the wild type protein, suggesting an enhanced effect on the overall reverse cholesterol transport process. Objectives To establish an expression and purification system of recombinant wild type apo A-I and apo A-I Z with high yield and purity in order to compare their properties related to reverse cholesterol transport as well as other anti-atherogenic characteristics. Methods A cDNA clone of wild type apo A-I was used as a PCR template to amplify the mature peptide sequence. Specially designed primers allowed the cloning of the sequence into an inducible expression pET-45 plasmid adding a Histidine tag in the N-terminal expressed peptide. Site directed mutagenesis was used to produce the L144R mutation in the apo A-I sequence to be expressed in the same system. E. coli BL21(DE3) were transformed with the prepared plasmids, peptide expression was induced and purification was performed in non-denaturing conditions by nickel affinity chromatography. Results Expression and purification of both proteins was achieved and verified by SDS-PAGE and immunochemical procedures. Actual yields were over 30 mg of purified protein per litre of culture and a 94% purity grade for the wild type protein and 93% for the mutant protein were obtained. Conclusions A system for the expression and purification of wild type apo A-I and apo A-I Z with high yield and purity grade has been set up. This will be the basis for future structural and functional characterization of the L144R apo A-I mutant allowing the study of its anti-atherogenic properties.

The effect of fenofibrate on HDL cholesterol and HDL particle concentration in postmenopausal women on tibolone therapy

Low high-density lipoprotein (HDL) cholesterol and particle concentration are risk factors for coronary heart disease in women. Tibolone lowers HDL cholesterol and HDL particle concentration, an effect that could be reversed by the peroxisome proliferator-activator receptor-α agonist fenofibrate. To assess the effects of fenofibrate on plasma HDL particles in postmenopausal women taking tibolone therapy. Randomized crossover study conducted in a women's health clinic. Fourteen postmenopausal women taking tibolone 2.5 mg daily for menopausal symptoms were randomized to either fenofibrate 160 mg daily or no treatment for 8 weeks, followed by a 3-week wash-out for fenofibrate and then crossed over to alternate therapy for another 8 weeks. The main outcome measure was changes in plasma HDL cholesterol concentration, apoA-I and apoA-II, LpA-I and LpA-I-A-II. After 8 weeks of fenofibrate therapy, there was no change in HDL cholesterol, 1.13 ± 0.06 v 1.16 ± 0.06 mmol/l (P = 0.47) or apoA-I, 1.19 ± 0.05 v 1.20 ± 0.05 g/l (P = 0.23). LpA-I fell significantly 0.35 ± 0.03 v 0.29 ± 0.02 (P = 0.02) but there was a rise in apoA-II, 0.35 ± 0.01 v 0.39 ± 0.01 g/l (P = 0.01). There was a significant fall in total cholesterol, triglycerides, low-density lipoprotein cholesterol and apoB. In women taking tibolone, fenofibrate increases plasma apoA-II concentration and effects a redistribution of HDL subfractions but does not correct tibolone-induced changes in HDL cholesterol or HDL particle concentration. The mechanism and significance of this require further investigation.

Obesity and metabolic syndrome in 7-9 years-old Portuguese schoolchildren

BackgroundBody fat is related to changes in lipid profile, blood pressure and metabolism of insulin and glucose, known as the metabolic syndrome (MS). The aim of this study was to estimate the prevalence of metabolic syndrome (MS) and its components among overweight and obese Portuguese schoolchildren, and to identify associated clinical and biochemical characteristics.MethodsA total of 82 children (14 overweight and 68 obese; 40 boys and 42 girls) aged 7-9 years, underwent anthropometric measurements. A blood sample was obtained to assess biochemical parameters. Insulin resistance (IR) was determined by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). MS was defined by the National Cholesterol Education Program Adult Treatment Panel III criteria modified by Cook.ResultsThe prevalence of MS was 15.8%. Abdominal obesity was present in all children. Frequency of elevated blood pressure, low HDL-cholesterol and elevated triglyceride concentrations were 62.6%, 13.4% and 11.0%, respectively. None of the children presented impaired fasting glucose, however hyperinsulinemia (7.3%) and IR (8.5%) were observed. The number of components of MS was higher in children with higher z-BMI (ρ = 0.411; p < 0.001). MS was associated with higher leptin concentrations. No association was found with adiponectin or ghrelin levels. Leptin correlated positively with obesity, glucose metabolism, lipid profile, hepatic function and C-reactive protein, and negatively with HDL and Apolipoprotein A-I/B ratio.ConclusionsThis study shows a significant prevalence of MS among obese schoolchildren. Abdominal obesity and elevated blood pressure were the most frequent components of this syndrome. Dyslipidemia, IR and high levels of leptin were also associated with MS in this young group.

Nut Consumption and Blood Lipid Levels

Epidemiological studies have consistently associated nut consumption with reduced risk for coronary heart disease. Subsequently, many dietary intervention trials investigated the effects of nut consumption on blood lipid levels. The objectives of this study were to estimate the effects of nut consumption on blood lipid levels and to examine whether different factors modify the effects. We pooled individual primary data from 25 nut consumption trials conducted in 7 countries among 583 men and women with normolipidemia and hypercholesterolemia who were not taking lipid-lowering medications. In a pooled analysis, we used mixed linear models to assess the effects of nut consumption and the potential interactions. With a mean daily consumption of 67 g of nuts, the following estimated mean reductions were achieved: total cholesterol concentration (10.9 mg/dL [5.1% change]), low-density lipoprotein cholesterol concentration (LDL-C) (10.2 mg/dL [7.4% change]), ratio of LDL-C to high-density lipoprotein cholesterol concentration (HDL-C) (0.22 [8.3% change]), and ratio of total cholesterol concentration to HDL-C (0.24 [5.6% change]) (P < .001 for all) (to convert all cholesterol concentrations to millimoles per liter, multiply by 0.0259). Triglyceride levels were reduced by 20.6 mg/dL (10.2%) in subjects with blood triglyceride levels of at least 150 mg/dL (P < .05) but not in those with lower levels (to convert triglyceride level to millimoles per liter, multiply by 0.0113). The effects of nut consumption were dose related, and different types of nuts had similar effects on blood lipid levels. The effects of nut consumption were significantly modified by LDL-C, body mass index, and diet type: the lipid-lowering effects of nut consumption were greatest among subjects with high baseline LDL-C and with low body mass index and among those consuming Western diets. Nut consumption improves blood lipid levels in a dose-related manner, particularly among subjects with higher LDL-C or with lower BMI.

High-Density Lipoprotein at the Interface of Type 2 Diabetes Mellitus And Cardiovascular Disorders

Type 2 diabetes mellitus is associated with low high-density lipoprotein (HDL) cholesterol levels, which is an independent cardiovascular risk factor. Low HDL cholesterol concentrations reflect a dysregulation in HDL metabolism, which is determined by the concerted action of different proteins, including cholesterol ester transfer protein, lecithin: cholesterol acyltransferase, endothelial and lipoprotein lipase, phospholipid transfer protein, and hepatic lipase, as well as different receptors, including the scavenger receptor class B type I and ATP-binding cassette transporter A1 and G1. Type 2 diabetes mellitus is besides a dysregulation in HDL metabolism, also associated with dysfunctional HDL: HDL-mediated reverse cholesterol transport as well as the anti-oxidative and endothelial-protective features of HDL are impaired in type 2 diabetes mellitus. The first part of the present review gives an overview of how type 2 diabetes mellitus affects the expression and/or activity of receptors and proteins involved in HDL metabolism and how different diabetes-associated factors influence the functionality of HDL. The second part of the review focuses on describing the newest insights in the impact of HDL on glucose metabolism and on diabetes-associated cardiovascular complications.

Association of Apolipoprotein B with Incident Type 2 Diabetes in an Aboriginal Canadian Population1

Expanding evidence indicates that apolipoprotein B (apo B) is superior to LDL cholesterol as a marker of vascular disease. Although traditional lipid measures are known to predict type 2 diabetes, limited data are available regarding apo B. We assessed the association of apo B with incident type 2 diabetes and compared it with traditional lipid variables as a risk predictor in aboriginal Canadians. Of an initial cohort of 606 individuals without diabetes in 1993-1995, 540 were contacted for the 10-year follow-up evaluation in 2003-2005. Fasting and 2-h postload glucose concentrations were obtained at baseline and follow-up to determine incident type 2 diabetes. Baseline fasting serum lipids were measured with standard laboratory procedures. The cumulative 10-year incidence of type 2 diabetes was 17.5%. High concentrations of apo B, triglycerides, and LDL cholesterol, and low concentrations of HDL cholesterol were individually associated with incident type 2 diabetes in univariate analyses. Comparing C statistics of univariate models showed apo B to be a superior determinant of incident diabetes compared with LDL (P = 0.026) or HDL (P = 0.004) cholesterol. With multivariate adjustment including waist circumference, apo B (odds ratio, 1.50; 95% CI, 1.11-2.02) and triglycerides (odds ratio, 1.49; 95% CI, 1.12-1.98) remained associated with incident diabetes, whereas LDL and HDL cholesterol became nonsignificant. The association of plasma apo B with incident type 2 diabetes and its better prediction of risk compared with LDL or HDL cholesterol suggest the potential for the use of apo B in type 2 diabetes risk communication and prevention.

Lipoproteína de alta densidad como marcador de riesgo residual en pacientes tratados con estatinas: prevalencia y trascendencia clínica

Statin treatment reduces the relative risk of a coronary event by approximately 30% and consequently a high residual risk persists. Data from epidemiological, angiographic and intervention studies suggest that this residual risk could be reduced by increasing highdensity lipoprotein cholesterol (HDL-c). Approximately one out of every four patients with chronic ischemic heart disease has low HDL-c concentrations, independently of the use of statins. In this population low HDL-c levels are most frequent in women, patients with diabetes and those with criteria of metabolic syndrome. Therefore, a high percentage of patients with chronic ischemic heart disease could benefit from interventions aimed at increasing HDL-c levels.

Relation of Oxidative Stress and Impaired Fibrinolysis with HDL Biogenesis in Indonesian Men with Metabolic Syndrome

BACKGROUND: Biogenesis of HDL involves factors that regulate the synthesis, intravascular remodeling, and catabolism of HDL. Disturbance of these factors can lead to low concentration of HDL-C. Metabolic syndrome (MetS) is characterized by low concentration of high-density lipoprotein cholesterol (HDL-C). In MetS occur several pathological conditions including oxidative stress and impaired fibrinolysis, which contribute to the risk of atherosclerosis process. The correlation between oxidative stress and impaired fibrinolysis with HDL biogenesis dysfunction and its correlation with low concentration of HDL-C has not been well understood and therefore needs to be further investigated.METHODS: This study was an observational study with crosssectional design, involving 163 adult men, aged 25-60 years with metabolic syndrome. Concentration of apoA-1, prebeta-1 HDL, CETP, F2-isoprostan, PAI-1, and HDL-C were measured. The apo A1/HDL ratio indicated HDL maturation, whereas the CETP/HDL-C and CETP/TG ratios indicated HDL catabolism.RESULTS: The study showed that there were a positive correlation between PAI-1 with apoA1/HDL-C ratios (r=0.226, p=0.005) and a negative correlation with the CETP/TG ratios (r=-0.215, p=0.007), whereas F2-isoprostan did not have correlation with HDL biogenesis factors.CONCLUSIONS: We concluded that there was correlation between impaired fibrinolysis with decreased HDL maturation and there was increased HDL catabolism leading to low HDL-C concentration in men with metabolic syndrome.KEYWORDS: F2-isoprostan, PAI-1, apoA-1, prebeta-1 HDL, CETP, metabolic syndrome

Correlation Between Visfatin, Insulin Resistance (Homeostasis Model Assesment of Insulin Resistance), Inflammation (High Sensitivity C-Reactive Protein) and HDL Cholesterol Concentration in Individuals with Visceral Obesity

BACKGROUND: Visfatin is a novel adipokine secreted from visceral adipose tissue and has insulinomimetic properties. Visceral obesity is a risk factor for metabolic syndrome. Insulin resistance and inflammation are linked to visceral obesity and metabolic syndrome. Dysregulation of visfatin as an adipokine could play an important role in metabolic syndrome through insulin resistance and inflammation, or lower HDL cholesterol concentration. However, this need more evidence.METHOD: This was a crossectional study in 40 Indonesian obese men and 40 Indonesian obese women. Age: 30-60 years in men and 50-60 years for women, from February to March 2008 in Jakarta.RESULTS: No correlation between visfatin and hs-CRP as a marker of inflammation (r=0.190, p=0,101), or HOMA-IR as a marker of insulin resistance (r=-0.020, p=0.246). Suprisingly visfatin concentration is correlated with HDL Cholesterol (r=0.416, p=0.000).CONCLUSIONS: Visfatin plays an important role in metabolic syndrome through lipid metabolism. Positive correlation between visfatin and HDL cholesterol, was assumed that visfatin had a protective effect. Visfatin also known as as nicotinamide phosphoribosyltransferase (NAMPT) links Nicotinamide Adenine Dinucleotide (NAD) metabolism and raising of HDL Cholesterol. But the exact mechanisms need to be further studied.KEYWORDS: visceral obesity, metabolic syndrome, NAMPT, visfatin, HDL

Lipoproteínas de alta densidad y riesgo cardiovascular: revisión de las evidencias y de las dudas

High-density lipoproteins (HDL) transport cholesterol from the periphery to the liver. Cross-sectional studies relating low HDL-cholesterol (HDL-c) concentrations to a higher prevalence of cardiovascular disease (CVD) date back to the 1950s. Subsequent populationbased studies established that low HDL-c levels are an independent predictor of CVD, a finding that is recognized in clinical guidelines for cardiovascular prevention. Many publications, although not all, have established an inverse correlation between the incidence of ischemic stroke, whether fatal or non-fatal, and HDL-c. Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglyceride (for cholesteryl ester) from very low density lipoprotein (VLDL) particles to HDL particles. Some families with genetic CETP alterations have high HDL-c concentrations and a lower incidence of CVD. Some observational studies, but not all, have shown that persons with functional CETP anomalies have high HDL-c levels and a lower incidence of CVD. This observation has prompted interest in CETP inhibition as an intervention to reduce coronary heart disease.

Metabolic Syndrome Prevalence, Dietary Intake, and Cardiovascular Risk Profile Among Overweight and Obese Adults 18–50 Years Old From the United Arab Emirates

The prevalence of diabetes mellitus is among the highest worldwide, and metabolic syndrome predisposes to diabetes. We recruited 227 overweight/obese Emirati adults living in the city of Al-Ain, Emirati of Abu Dhabi to screen for the metabolic syndrome and to assess for the most relevant criteria for the metabolic syndrome in this population. We identified subjects as having the metabolic syndrome if they had three of the following characteristics: Waist circumference (WC) >88 cm in women and >102 cm in men; plasma glucose >5.5 mmol/L; blood pressure >130/85 mmHg, triglycerides (TG) >1.7 mmol/L, and high-density lipoprotein cholesterol (HDL-C) <1.0 mmol/L in men and <1.3 mmol/L in women. In addition to features of metabolic syndrome, lipoprotein subfractions and 24-hour dietary recalls were assessed in a random sample of participants. A total of 92 subjects (40.5%) were classified as having metabolic syndrome. The most relevant clinical criteria associated with metabolic syndrome were large WC, high blood pressure, and low HDL-C. Only 7% of subjects had TG >1.7 mmol/L, whereas 95% had plasma LDL-C >2.6 mmol/L. In addition, subjects presented low concentrations of medium very-low-density lipoprotein (VLDL) and small HDL subfractions in agreement with low concentrations of HDL-C and TG. Dietary analysis revealed high-energy consumption, with diets high in total carbohydrates, fat, and simple sugars. In addition, subjects were sedentary with only 14% of the population engaged in physical activity. The high prevalence of metabolic syndrome among overweight/obese Emirati adults predisposes this population to increased risk for developing diabetes and cardiovascular disease. Public health involvement targeting poor dietary habits and exercise programs among Emirati citizens is urgently needed.

Negative impact of imflammation and insulin resistance on the biogenesis of HDL-c in Indonesian men with metabolic syndrome

Aim To find out the relationship between inflammation and insulin resistance with impaired HDL biogenesis that cause low HDL-c concentrationMethods Using a cross-sectional design, this study involved 163 adult men, aged 25-60 years old with metabolic syndrome (IDF criteria, 2005), without liver and kidney dysfunction. This study was undertaken in Jakarta in the year 2007-2009. Measured indicators were serum apolipoprotein A-1 (apoA-1), prebeta-1 HDL, cholesteryl ester transfer protein (CETP), HDL cholesterol (HDL-c), body weight, height, waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and triglyceride. The apoA-1/HDL-c ratios were taken as indicator of HDL maturation, whereas CETP/HDL-c and CETP/TG ratios were indicated HDL catabolism. high-sensitivity CRP (hsCRP) and HOMA-IR were taken as indicator of inflammation and insulin resistance, respectively. Data were analyzed by using univariate, bivariate, and multivariate analysis.Results Positive correlations were found between hsCRP and CETP (rs= 0.200, p= 0.042), and CETP/HDL-c ratios (rs= 0.188, p= 0.013). HOMA-IR positively correlated with apoA-1/HDL-c ratios (rs= 0.190, p= 0.016) and negatively correlated with the CETP/TG ratios (rs= -0.162, p= 0.04). Results of general linear model analysis showed that serum hsCRP concentration had the highest contribution to CETP/HDL-c ratios, apoA-1, dan CETP (p= 0.009; 0.016; 0.054, respectively).Conclusions Inflammation and insulin resistance related to dysfunction of HDL biogenesis in men with metabolic syndrome. The inflammation correlated with increased HDL catabolism, whereas the insulin resistance correlated with decreased HDL maturation and increased HDL catabolism. These may lead to low HDL-c concentration. Inflammation had higher contribution to HDL biogenesis factors than insulin resistance. (Med J Indones 2010; 19:36-45)Keywords: hsCRP, HOMA-IR, apoA-1, prebeta-1 HDL, CETP, HDL-c and metabolic syndrome

Mulling over the odds of CETP inhibition

Both elevated plasma concentrations of LDL cholesterol and low concentrations of HDL cholesterol are important risk factors of coronary heart disease.1 In randomized controlled trials of >100 000 individuals, lowering of LDL cholesterol with statins was found to be safe and effective in reducing cardiovascular morbidity and mortality by 20–40%.2 As the flip side of the coin, 60–80% of cardiovascular events are not prevented by statin treatment. Therefore, and because low HDL cholesterol explains some of the residual risk of patients with well controlled LDL cholesterol levels, both lower treatment goals for LDL cholesterol ( 1.05 mmol/L) are propagated.3 The clinical validity of this concept is currently evaluated in ongoing randomized clinical endpoint trials of statin combination therapies with ezitimibe, fenofibrate, nicotinic acid, or the cholesteryl ester transfer protein (CETP) inhibitor dalcetrapib. CETP exchanges cholesteryl esters of HDL with triglycerides of apolipoprotein B (apoB)-containing lipoproteins ( Figure 1 ).4 This has two important consequences in lipoprotein metabolism. First, notably large HDL2 particles lose their cholesteryl esters which have accumulated there as the result of efflux of phospholipids and unesterified cholesterol from hepatocytes, enterocytes, macrophages, and other cells, as well as subsequent esterification by the enzyme lecithin:cholesterol acyltransferase (LCAT). The HDL2 particles shrink in size and liberate lipid-free apoA-I that undergoes either lipidation for regeneration of HDL or glomerular filtration for renal elimination. Secondly, CETP supports the transformation of the triglyceride-rich very low density lipoproteins (VLDLs) into cholesteryl-ester rich LDLs by enhancing the otherwise mainly lipolytic removal of triglycerides and by inducing the accumulation of cholesteryl esters ( Figure 1 ).4 The physiological importance of CETP for the regulation of VLDL/LDL and HDL metabolism originally emerged from the observation of high HDL cholesterol and … *Corresponding author. Tel: +41 44 255 2260, Fax: +41 44 255 4590, Email: arnold.voneckardstein{at}usz.ch

Substantial Proportion of Apparently Healthy, Urban South Indian Young Adults Has Insulin Resistance Associated with Other Cardiovascular Risk Factors

Objective: To study the prevalence and correlation of cardiovascular disease (CVD) risk factors in apparently healthy, urban south Indian young adults. Research Design and Methods: Eighty-five apparently healthy men and women volunteers aged twenty to thirty years with no smoking habit were recruited as study subjects. Anthropometric measurements, blood pressure, plasma zinc, adiponectin, resistin, blood glucose, insulin concentration and lipid levels were measured. Results: A significant proportion (43.8%) of the study subjects had poor insulin sensitivity as judged by homeostasis model assessment (HOMA) ≥3.16 and a proportion of 36.3% had body mass index (BMI) ≥23.0. Total cholesterol (TC) and triglyceride (TG) concentrations were higher than the normal values in 7.1% and 8.2% respectively while HDL cholesterol (HDL-C) was less than the normal value in 58.8% of the subjects. 7.2% of the subjects had Zinc deficiency. Significantly higher proportions of males had higher BMI and higher HOMA compared to females (P<0.05). Mean zinc values were higher in females compared to males. BMI was directly associated with HOMA (P<0.05), while zinc was inversely associated with HOMA (P<0.05). Of the two adipokines tested, resistin was not associated with any of the parameters studied, but adiponectin was associated both with BMI (p<0.05) and HOMA (p<0.06). Conclusion: Poor insulin sensitivity and low HDL-C concentration, which are important risk factors for CVD are commonly prevalent in young adults. Adiponectin was inversely associated with insulin sensitivity. The finding that zinc levels are lower in males compared to females indicates a likelihood for zinc having a role in insulin sensitivity and a male predisposition to develop insulin resistance and higher BMI.

Effect of a dietary intervention and n–3 fatty acid supplementation on measures of serum lipid and insulin sensitivity in persons with HIV

BackgroundElevated serum triglyceride and low HDL-cholesterol concentrations have been reported in persons with HIV. ObjectiveThe effect of a dietary intervention plus n–3 (ω−3) fatty acid supplementation on serum triglycerides and markers of insulin sensitivity was investigated. DesignFifty-four persons with HIV and elevated serum triglycerides (>150 mg/dL) and/or abnormal Quantitative Insulin Sensitivity Check Index values (<0.35 but >0.30) were recruited for a dietary intervention in which total fat, type of fat, fiber, and glycemic load were controlled along with supplementation with n–3 fatty acids to achieve an intake of 6 g/d. The subjects were randomly assigned to an intervention or control group, and serum lipids, markers of insulin sensitivity, and serum phospholipid fatty acids were measured in both groups at baseline, 3 wk, and 13 wk. ResultsTriglycerides in the intervention group decreased from a median of 180 mg/dL (interquartile range: 141, 396) to 114 mg/dL (interquartile range: 84, 169) from baseline to 3 wk, whereas they remained stable in the control group (P = 0.003). Serum phospholipid fatty acids indicated a decrease in de novo lipogenesis and a decrease in arachidonic acid (% nmol; P ≤ 0.001) in the intervention group. At 3 wk, the insulin area under the curve decreased but not significantly. ConclusionsDiet and n–3 fatty acid supplementation dramatically reduced serum triglycerides, decreased arachidonic acid in the phospholipids fraction, and appeared to decrease the de novo lipogenesis associated with the metabolic syndrome in the intervention group.