Cholesterol

HDL, Atherosclerosis, and Emerging Therapies

Anouar Hafiane and Jacques Genest — Tue, 28 May 2013 08:38:48 +0000

This review aims to provide an overview on the properties of high-density lipoproteins (HDLs) and their cardioprotective effects. Emergent HDL therapies will be presented in the context of the current understanding of HDL function, metabolism, and protective antiatherosclerotic properties. The epidemiological association between levels of HDL-C or its major apolipoprotein (apoA-I) is strong, graded, and coherent across populations. HDL particles mediate cellular cholesterol efflux, have antioxidant properties, and modulate vascular inflammation and vasomotor function and thrombosis. A link of causality has been cast into doubt with Mendelian randomization data suggesting that genes causing HDL-C deficiency are not associated with increased cardiovascular risk, nor are genes associated with increased HDL-C, with a protective effect. Despite encouraging data from small studies, drugs that increase HDL-C levels have not shown an effect on major cardiovascular end-points in large-scale clinical trials. It is likely that the cholesterol mass within HDL particles is a poor biomarker of therapeutic efficacy. In the present review, we will focus on novel therapeutic avenues and potential biomarkers of HDL function. A better understanding of HDL antiatherogenic functions including reverse cholesterol transport, vascular protective and antioxidation effects will allow novel insight on novel, emergent therapies for cardiovascular prevention.

Cholesterol Metabolism and Weight Reduction in Subjects with Mild Obstructive Sleep Apnoea: A Randomised, Controlled Study

Thu, 16 May 2013 15:37:37 +0000

To evaluate whether parameters of obstructive sleep apnoea (OSA) associate with cholesterol metabolism before and after weight reduction, 42 middle-aged overweight subjects with mild OSA were randomised to intensive lifestyle intervention () or to control group () with routine lifestyle counselling only. Cholesterol metabolism was evaluated with serum noncholesterol sterol ratios to cholesterol, surrogate markers of cholesterol absorption (cholestanol and plant sterols) and synthesis (cholestenol, desmosterol, and lathosterol) at baseline and after 1-year intervention. At baseline, arterial oxygen saturation () was associated with serum campesterol () and inversely with desmosterol ratios () independently of gender, BMI, and homeostasis model assessment index of insulin resistance (HOMA-IR). Apnoea-hypopnoea index (AHI) was not associated with cholesterol metabolism. Weight reduction significantly increased and serum cholestanol and decreased AHI and serum cholestenol ratios. In the groups combined, the changes in AHI were inversely associated with changes of cholestanol and positively with cholestenol ratios independent of gender and the changes of BMI and HOMA-IR (). In conclusion, mild OSA seemed to be associated with cholesterol metabolism independent of BMI and HOMA-IR. Weight reduction increased the markers of cholesterol absorption and decreased those of cholesterol synthesis in the overweight subjects with mild OSA.

Leishmania major Self-Limited Infection Increases Blood Cholesterol and Promotes Atherosclerosis Development

Sun, 28 Apr 2013 08:35:29 +0000

Leishmania major infection of resistant mice causes a self-limited lesion characterized by macrophage activation and a Th1 proinflammatory response. Atherosclerosis is an inflammatory disease involving hypercholesterolemia and macrophage activation. In this study, we evaluated the influence of L. major infection on the development of atherosclerosis using atherosclerosis-susceptible apolipoprotein E-deficient (apoE KO) mice. After 6 weeks of infection, apoE KO mice exhibited reduced footpad swelling and parasitemia similar to C57BL/6 controls, confirming that both strains are resistant to infection with L. major. L. major-infected mice had increased plasma cholesterol levels and reduced triacylglycerols. With regard to atherosclerosis, noninfected mice developed only fatty streak lesions, while the infected mice presented with advanced lesions containing a necrotic core and an abundant inflammatory infiltrate. CD36 expression was increased in the aortic valve of the infected mice, indicating increased macrophage activation. In conclusion, L. major infection, although localized and self-limited in resistant apoE KO mice, has a detrimental effect on the blood lipid profile, increases the inflammatory cell migration to atherosclerotic lesions, and promotes atherogenesis. These effects are consequences of the stimulation of the immune system by L. major, which promotes the inflammatory components of atherosclerosis, which are primarily the parasite-activated macrophages.

Discordance of Non-HDL and Directly Measured LDL Cholesterol: Which Lipid Measure is Preferred When Calculated LDL Is Inaccurate?

Lawrence Baruch, Valerie J. Chiong, Sanjay Agarwal, and Bhanu Gupta — Tue, 23 Apr 2013 15:19:57 +0000

Objective. To determine if non-HDL cholesterol (N-HDL) and directly measured LDL cholesterol (D-LDL) are clinically equivalent measurements. Patients and Methods. Eighty-one subjects recruited for 2 cholesterol treatment studies had at least 1 complete fasting lipid panel and D-LDL performed simultaneously; 64 had a second assessment after 4 to 6 weeks, resulting in 145 triads of C-LDL, D-LDL, and N-HDL. To directly compare N-HDL to D-LDL and C-LDL, we normalized the N-HDL by subtracting 30 from the N-HDL (N-HDLA). Results. There was significant correlation between N-HDLA, D-LDL, and C-LDL. Correlation was significantly greater between N-HDLA and C-LDL than between N-HDLA and D-LDL. A greater than 20 mg/dL difference between measures was observed more commonly between N-HDLA and D-LDL, 29%, than between C-LDL and N-HDLA, 11% (), and C-LDL and D-LDL, 17% (). Clinical discordance was most common, and concordance was least common between N-HDL and D-LDL. Conclusions. Our findings suggest that N-HDL cholesterol and D-LDL cholesterol are not clinically equivalent and frequently discordant. As N-HDL may be superior to even C-LDL for predicting events in statin-treated patients, utilizing N-HDL to guide therapy would appear to be preferable to D-LDL when C-LDL is inaccurate.

Current Views on Genetics and Epigenetics of Cholesterol Gallstone Disease

Agostino Di Ciaula, David Q.-H. Wang, Leonilde Bonfrate, and Piero Portincasa — Sun, 14 Apr 2013 09:28:39 +0000

Cholesterol gallstone disease, one of the commonest digestive diseases in western countries, is induced by an imbalance in cholesterol metabolism, which involves intestinal absorption, hepatic biosynthesis, and biliary output of cholesterol, and its conversion to bile acids. Several components of the metabolic syndrome (e.g., obesity, type 2 diabetes, dyslipidemia, and hyperinsulinemia) are also well-known risk factors for gallstones, suggesting the existence of interplay between common pathophysiological pathways influenced by insulin resistance, genetic, epigenetic, and environmental factors. Cholesterol gallstones may be enhanced, at least in part, by the abnormal expression of a set of the genes that affect cholesterol homeostasis and lead to insulin resistance. Additionally, epigenetic mechanisms (mainly DNA methylation, histone acetylation/deacetylation, and noncoding microRNAs) may modify gene expression in the absence of an altered DNA sequence, in response to different lithogenic environmental stimuli, such as diet, lifestyle, pollutants, also occurring in utero before birth. In this review, we will comment on various steps of the pathogenesis of cholesterol gallstones and interaction between environmental and genetic factors. The epigenomic approach may offer new options for therapy of gallstones and better possibilities for primary prevention in subjects at risk.

Predictors of Metabolic Syndrome in the Iranian Population: Waist Circumference, Body Mass Index, or Waist to Hip Ratio?

Sun, 24 Mar 2013 13:20:25 +0000

This study aimed to investigate whether body mass index (BMI), waist circumference (WC), or waist to hip ratio (WHR) could be a better predictor of metabolic syndrome and, if so, what would be the cutoff points for these surrogates to appropriately differentiate metabolic syndrome in different age and sex subgroups. Methods. The present cross-sectional study was conducted on a sample of Isfahan Cohort Study (ICS). In total, 468 individuals (194 with and 274 subjects without metabolic syndrome) according to the National Cholesterol Education Program’s Adult Treatment Panel III (ATP-III) criteria were selected. Anthropometric indices were measured and plotted using receiver-operating characteristic (ROC) curves. Results. According to ROC curve analysis, WC and WHR parameters were better indicators of metabolic syndrome compared to BMI in women, whereas in men WHR had a lower discriminating value compared to the other two parameters. Among these three anthropometric parameters, BMI had a lower sensitivity and WC and WHR both had a higher sensitivity for predicting metabolic syndrome in women compared with in men. The cut points for WC were nearly equal in men and women, 90.3 versus 90.0, respectively. Women had higher cut points for BMI (28.5 kg/m2) compared to men (26.0 kg/m2). Our results showed the highest sensitivity and specificity for WC cut points specially in women. To predict metabolic syndrome, we looked into optimal age-specific cut points for BMI, WC, and WHR. The results indicated that WC had the highest discriminating value compared to other indicators in the different age subgroups. The optimal cut points for all three parameters gradually increased with age. Conclusion. Our results demonstrated that regardless of gender and age variables, WC could be a preferred parameter for predicting metabolic syndrome compared to BMI and WHR in Iranian population.

HDL-C Response Variability to Niacin ER in US Adults

Jennifer B. Christian, Eric J. Olson, Jeffery K. Allen, and Kimberly A. Lowe — Tue, 26 Feb 2013 09:35:58 +0000

Background. Niacin is the most effective treatment currently available for raising HDL-C levels. Objective. To evaluate if gender and baseline lipid levels have an effect on the HDL-C response of niacin ER and to identify factors that predict response to niacin ER at the 500 mg dose. Material and Methods. The change in HDL-C effect between baseline and follow-up levels was quantified in absolute change as well as dichotomized into high versus low response (high response was defined as an HDL-C effect of >15% increase and low response was HDL-C <5%) in a sample of 834 individuals. Results. Both males and females with low HDL-C levels at baseline exhibited a response to treatment in the multivariate model (males, HDL-C <40 mg/dL: , 95% CI: 2.36–11.39; females, HDL-C <50 mg/dL: , 95% CI: 1.84–15.79). There was also a significant difference in the mean HDL-C effect between baseline and follow-up HDL-C levels in the 500 mg niacin ER dose group for both males (mean HDL-C effect = 0.08, ) and females (mean HDL-C effect = 0.10, ). Conclusion. Baseline HDL-C levels are the biggest predictor of response to niacin ER treatment for both males and females among the factors evaluated.

Pediatric Metabolic Syndrome: From Prevention to Treatment

Sun, 11 Nov 2012 17:08:56 +0000

Effects of Diet, Aerobic Exercise, or Both on Non-HDL-C in Adults: A Meta-Analysis of Randomized Controlled Trials

George A. Kelley and Kristi S. Kelley — Thu, 08 Nov 2012 09:02:12 +0000

Purpose. To use the meta-analytic approach to examine the effects of diet (D), aerobic exercise (E), or both (DE) on non-high-density lipoprotein cholesterol (non-HDL-C) in adults. Methods. Randomized controlled trials in adults ≥18 years of age were included. A mixed-effect model was used to combine effect size (ES) results within each subgroup and to compare subgroups (). Heterogeneity was examined using the and statistics, and 95% confidence intervals (CI) were also calculated. Statistical significance was set at , while a trend for statistical significance was set between , and ≤0.10. Results. A statistically significant exercise minus control group decrease in non-HDL-C was found for DE (7 ESs, 389 participants, mg/dL, 95% to −0.6, , , , %), a trend for the D group (7 ESs, 402 participants, mg/dL, 95% to 1.6, , , , %), and no change for the E group (7 ESs, 387 participants, mg/dL, 95% to 13.1, , , , %). Overall, no statistically significant between-group differences were found (, ). Conclusions. Diet combined with aerobic exercise may reduce non-HDL-C among adults in some settings.

Cholesterol: Its Regulation and Role in Central Nervous System Disorders

Matthias Orth and Stefano Bellosta — Wed, 17 Oct 2012 11:12:28 +0000

Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer’s disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules). We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions.

Relationship of Lifestyle Medical Advice and Non-HDL Cholesterol Control of a Nationally Representative US Sample with Hypercholesterolemia by Race/Ethnicity

Joan Anne Vaccaro and Fatma G. Huffman — Mon, 15 Oct 2012 15:11:06 +0000

Objective. The main purpose of this study was to evaluate the associations of lifestyle medical advice and non-HDL cholesterol control of a nationally representative US sample of adults with hypercholesterolemia by race/ethnicity. Methods. Data were collected by appending sociodemographic, anthropometric, and laboratory data from two cycles of the National Health and Nutrition Survey (2007-2008 and 2009-2010). This study acquired data from male and female adults aged ≥ 20 years (N = 11,577), classified as either Mexican American (MA), (), other Hispanic (OH) (), Black non-Hispanic (BNH) (), or White non-Hispanic (WNH) (). Results. Minorities were more likely to report having received dietary, weight management, and exercise recommendations by healthcare professionals than WNH, adjusting for confounders. Approximately 80% of those receiving medical advice followed the recommendation, regardless of race/ethnicity. Of those who received medical advice, reporting “currently controlling or losing weight” was associated with lower non-HDL cholesterol. BNH who reported “currently controlling or losing weight” had higher non-HDL cholesterol than WNH who reported following the advice. Conclusion. The results suggest that current methods of communicating lifestyle advice may not be adequate across race/ethnicity and that a change in perspective and delivery of medical recommendations for persons with hypercholesterolemia is needed.

Improving Total-Cholesterol/HDL-Cholesterol Ratio Results in an Endothelial Dysfunction Recovery in Peripheral Artery Disease Patients

Tue, 25 Sep 2012 14:29:23 +0000

Aims. To evaluate the effects of variations of total-cholesterol/HDL-cholesterol ratio and the effects of the atorvastatin on endothelial function in peripheral artery disease (PAD). Material and Methods. A prospective, randomised controlled study was carried out in 150 PAD patients. Patients randomized to the control group () were treated with antiplatelet drugs, angiotensin-converting-enzyme inhibitors and cardiovascular-risk-factor control. Experimental group () also received treatment with atorvastatin for a month. It was determined baseline nitrite plasma levels and total-cholesterol/HDL-cholesterol ratio and after one month of treatment in both groups. It was also analysed the correlation between the gradient of nitrite levels and the differential of total-cholesterol/HDL ratio in treatment group. Results. After a month, a reduction in nitrite levels was detected in treatment group ( μM versus 5.7 ± 1.8 μM, ). It was shown a higher decrease in nitrite plasma levels in the atorvastatin group finding lower levels assessments (5.7 ± 1.8 μM versus 13.1 ± 9.1 μM, resp., ). A significant reduction in total-cholesterol/HDL-cholesterol ratio was observed in statin group after treatment (). A strong correlation was found between the gradient of nitrite levels and the differential of total-cholesterol/HDL-cholesterol ratio in atorvastatin group (; ). Conclusions. Improvement of nitrite levels are associated with decreased total cholesterol/HDL ratio values in PAD patients treated with atorvastatin.

Lipoprotein(a): Cellular Effects and Molecular Mechanisms

Kirsten Riches and Karen E. Porter — Thu, 06 Sep 2012 15:24:44 +0000

Lipoprotein(a) (Lp(a)) is an independent risk factor for the development of cardiovascular disease (CVD). Indeed, individuals with plasma concentrations >20 mg/dL carry a 2-fold increased risk of developing CVD, accounting for ~25% of the population. Circulating levels of Lp(a) are remarkably resistant to common lipid lowering therapies, and there are currently no robust treatments available for reduction of Lp(a) apart from plasma apheresis, which is costly and labour intensive. The Lp(a) molecule is composed of two parts, an LDL/apoB-100 core and a unique glycoprotein, apolipoprotein(a) (apo(a)), both of which can interact with components of the coagulation cascade, inflammatory pathways, and cells of the blood vessel wall (smooth muscle cells (SMC) and endothelial cells (EC)). Therefore, it is of key importance to determine the molecular pathways by which Lp(a) exerts its influence on the vascular system in order to design therapeutics to target its cellular effects. This paper will summarise the role of Lp(a) in modulating cell behaviour in all aspects of the vascular system including platelets, monocytes, SMC, and EC.

The Effects of Unripe Grape Juice on Lipid Profile Improvement

Wed, 29 Aug 2012 13:21:03 +0000

Introduction. Consumption of unripe grape juice (verjuice) has been portrayed by the traditional belief, as a means of combating dyslipidemia. We aimed to evaluate the effects of unripe grape juice consumption on lipid profile in healthy human volunteers. Methods. We asked 42 enrolled volunteers to drink 10 cc of verjuice within 30 minutes to 2 hours after lunch and 10 cc of it after dinner. After taking 120 doses of verjuice, another fasting lipid profile was obtained from each participant. The statistical analysis was performed by SPSS 13 software. Results. After analysis of the data, the mean ± standard deviation for all the variables was obtained. Among those improvement of HDL-C was significant after the trial (𝑃value<0.001). TG, TC, and LDL improvement were not significant. Conclusion. Our study declared that verjuice has a dramatic effect on improving HDL-C level of serum but no any other lipid improvement effect was obtained.

Immune Response to Lipoproteins in Atherosclerosis

Sonia Samson, Lakshmi Mundkur, and Vijay V. Kakkar — Thu, 23 Aug 2012 10:25:43 +0000

Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL) has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

MicroRNA Regulation of Cholesterol Metabolism

Noemi Rotllan and Carlos Fernández-Hernando — Sun, 05 Aug 2012 09:39:25 +0000

Disruption of cellular cholesterol balance results in pathologic processes including atherosclerosis, metabolic syndrome, type II diabetes and Alzheimer’s disease. Maintenance of cholesterol homeostasis requires constant metabolic adjustment, achieved partly through the fine regulation of the classical transcription factors (e.g., by SREBP and LXR), but also through members of a class of noncoding RNAs termed miRNAs. Some miRNAs have now been identified to be potent post-transcriptional regulators of lipid metabolism genes, including miR-122, miR-33, miR-758, and miR-106b. Different strategies have been developed to modulate miRNA effects for therapeutic purposes. The promise demonstrated by the use of anti-miRs in human preclinical studies, in the case of miR-122, raises the possibility that miR-33, miR-758, and miR-106b may become viable therapeutic targets in future. This review summarizes the evidence for a critical role of some miRNAs in regulating cholesterol metabolism and suggests novel ways to manage dyslipidemias and cardiovascular diseases.

Use of Lipid-Lowering Medications and the Likelihood of Achieving Optimal LDL-Cholesterol Goals in Coronary Artery Disease Patients

Dean G. Karalis, Brett Victor, Lilian Ahedor, and Longjian Liu — Wed, 25 Jul 2012 09:41:24 +0000

Background. In clinical practice, most coronary artery disease patients are not achieving their recommend LDL-cholesterol goal of <70 mg/dL. Methods. We conducted a retrospective analysis of outpatient electronic health records and the most recent lipid profile, lipid-lowering medications and doses were collected. Results. We identified 9950 coronary artery disease patients. Only 37% on a statin alone achieved an LDL-cholesterol of <70 mg/dL, and most were on moderate-to-high-potency statins. The intensity of statin therapy did not improve LDL-cholesterol goal attainment. Among patients on combination therapy, 41% on statin plus ezetimibe and 46% on statin plus niacin achieved an LDL-cholesterol of <70 mg/dL (𝑃=0.01 and <0.0001 versus statin alone). If patients were switched to a high-potency statin LDL-cholesterol goal attainment of <70 mg/dL would increase to 46% and would increase up to 72% with combination therapy. Conclusions. Most coronary artery disease patients in clinical practice do not attain an LDL-cholesterol of <70 mg/dL, even among patients on high potency statins. The combination of statin plus either ezetimibe or niacin is the most effective regimen to achieve an LDL-cholesterol of <70 mg/dL, however, these drug combinations are used infrequently in clinical practice.

Modulation of Lipoprotein Cholesterol Levels in Plasmodium berghei Malarial Infection by Crude Aqueous Extract of Ganoderma lucidum

Wed, 25 Jul 2012 08:52:58 +0000

In this study, attempt is made to establish changes in serum and liver lipoprotein cholesterols accompanying Plasmodium berghei malarial infection in mice treated with aqueous extract of Ganoderma lucidum at 100, 250, and 500 mg/kg body weight in comparison with 15 mg/kg chloroquine (CQ). Significant increases in all the lipoprotein fractions were observed in infected untreated mice compared with normal control mice. Treatment with 100 and 250 mg/kg G. lucidum extract produced significant reduction in serum total cholesterol (TC) and low-density cholesterol (LDL-C) contents compared with 500 mg/kg G. lucidum and CQ. Treatment with CQ, however, produced significant reduction in hepatic TC and LDL-C compared with the extract. A dose-dependent significant increase in serum high-density lipoprotein cholesterol (HDL-C) was observed in the G. lucidum treated mice compared with normal control but significantly lower compared with CQ-treated mice. Liver HDL-C level was significantly higher in CQ-treated mice compared with normal control and significantly lower compared with G. lucidum-treated and infected untreated mice. A dose-dependent effect of the extract was observed in both serum and liver very-low density lipoprotein cholesterol (VLDL-C). The implication of these results is discussed with respect to the parasite survival and proliferation in the serum and liver.

Determinants of Childhood Obesity in Representative Sample of Children in North East of Iran

Sun, 15 Jul 2012 13:33:51 +0000

Childhood obesity has become, a global public health problem, and epidemiological studies are important to identify its determinants in different populations. This study aimed to investigate factors associated with obesity in a representative sample of children in Neishabour, Iran. This study was conducted among 1500 randomly selected 6–12-year-old students from urban areas of Neishabour, northeast of Iran. Then, through a case-control study, 114 obese (BMI≥95th percentile of Iranian reference) children were selected as the case group and were compared with 102 controls (15th≤BMI<85th percentile). Factors suggested to be associated with weight status were investigated, for example, parental obesity, child physical activity levels, socio-economic status (SES), and so forth. The analysis was conducted using univariate and multivariate logistic regression (MLR) in SPSS version 16. In univariate logistic regression model, birth weight, birth order, family extension, TV watching, sleep duration, physical activity, parents’ job, parents’ education, parental obesity history, and SES were significantly associated with children’s obesity. After MLR analysis, physical activity and parental obesity history remained statistically significant in the model. Our findings showed that physical activity and parental obesity history are the most important determinants for childhood obesity in our population. This finding should be considered in implementation of preventive interventions.

The Prevalence of Dyslipidemia in Patients with Spinal Cord Lesion in Thailand

Tue, 10 Jul 2012 09:21:32 +0000

Objective. To assess the prevalence of dyslipidemia in 90 patients with spinal cord lesion (SCL) of duration greater than 2 years. The study was carried out from November 2007 to September 2008. Methods. Clinical history, physical examination, and lipid profiles were recorded and analyzed. Dyslipidemia was assessed using guidelines from the National Cholesterol Education Project Adult Treatment Panel III (ATP III). Results. The prevalence of dyslipidemia in at least one lipid parameter was 76.7%. The most frequent finding was low HDL-C (58.9%). Hypertriglyceridemia, hypercholesterolemia and high LDL-C were found in 28.9%, 26.7% and 21.1% of patients, respectively. The factors sex=male and age ≥45 years were associated with high LDL-C (𝑃<0.05 and 𝑃<0.01). Patients who exercised less than 30 minutes per day had associated hypercholesterolemia (𝑃<0.01), hypertriglyceridemia (𝑃<0.01), and higher LDL-C (𝑃<0.05). Patients with BMI ≥23 kg/m2 had associated hypercholesterolemia and high LDL-C. Age was a significant determinant of high LDL-C. BMI was the most powerful and significant determinant of hypercholesterolemia and high LDL-C. Conclusion. SCL patients should have a regular lipid checkup, especially those patients having the following risk factors: males, age ≥45 years, BMI ≥23 kg/m2 and exercise duration <30 minutes per day.

Trends of Components of the Metabolic Syndrome in German First Graders Throughout 10 Years: The PEP Family Heart Study

Gerda-Maria Haas, Thomas Bertsch, and Peter Schwandt — Thu, 05 Jul 2012 09:51:05 +0000

Although childhood overweight and obesity are increasing worldwide, some countries report trends for stabilization. However, the trend for the potentially atherogenic components of the metabolic syndrome (MetS) in children and adolescents is not well understood. Therefore, the purpose of this study was to analyze the trend of the five components of over 10 years in 2228 first graders aged 6 years. Waist circumference (WC) remained mainly unchanged between 1994 and 2003 whereas the other four components continuously decreased. In boys and girls mean values of triglycerides (−25.9% and −28.6%, resp.), HDL cholesterol (−19.8% and −23.4%, resp.), fasting glucose (−7.3% and −9%, resp.), systolic (−3.8% and −4.1%, resp.), and diastolic (−10.2% and −9.7%, resp.) blood pressure significantly decreased. Whereas the prevalence of abdominal adiposity was stable at baseline and after 10 years (−1% in boys and +2% in girls), the prevalence of hypertension, hypertriglyceridemia, low HDL-C, and glucose was very low without any trend.

Assessment of Metformin as an Additional Treatment to Therapeutic Lifestyle Changes in Pediatric Patients with Metabolic Syndrome

Rebecca M. Raub and Stanley J. Goldberg — Thu, 05 Jul 2012 09:43:57 +0000

Objective. To assess the effectiveness of metformin and therapeutic lifestyle changes (TLCs) in a clinical setting, compared to TLC alone in adolescents with metabolic syndrome (MS). Methodology. This study was a retrospective trial consisting of 60 patients, aged 8–18 years, who were treated for MS at an outpatient clinic. Two groups were formed: the metformin group (M group) and the control group (C group). The M group had been given metformin along with TLC, and the C group had been given TLC alone. Several outcome measures were obtained; the main outcome measure was measuring the change in percentile and z-score of weight and BMI. Results. There were no significant differences between the two groups at the conclusion of the study, except for height percentile (𝑃=0.02) and z-score (𝑃=0.03). Both groups showed promising significant intragroup decreases in weight z-score but BMI percentile and z-score were only significantly decreased in the M group. Conclusion. Metformin at an average dose of 1033 mg, when added to TLC, did not show any clinically important efficacy compared to TLC alone in a pediatric population with MS. However, both groups made significant changes in a positive direction, which may be solely due to TLC.

Comparison of Serum Apolipoprotein Levels of Diabetic Children and Healthy Children with or without Diabetic Parents

Mohammad Hashemi, Mohammad Saadat, Mohaddeseh Behjati, and Roya Kelishadi — Tue, 03 Jul 2012 17:05:28 +0000

Introduction. The association of diabetes and atherosclerosis with disorders of lipids and lipoproteins, notably high apolipoprotein B (apoB) and low apolipoprotein A1(apoA1) is well established. Because of the beginning of the atherosclerosis' process from early life, in this study, the plasma levels of apoA1 and apoB were compared in diabetic children with type I diabetes mellitus(DM), healthy children with diabetic parents (HDPs),and healthy children with nondiabetic parents (HNDPs). Methods. This case-control study was conducted among 90 children aged 9–18 years. Serum levels of apoA and apoB were compared among 30 diabetic children (DM), 30 healthy children with diabetic parents (HDPs), and 30 healthy children with nondiabetic parents (HNDP). Results. The mean serum apoA1 was higher in DM (153±69 mg/dL) followed by HNDPs (138±58 mg/dL) and HDPs (128±56 mg/dl), but the difference was not statistically significant. The mean apoB value in HNDPs was significantly lower than DM and HDPs (90±21 mg/dL versus 127±47 and 128±38 mg/dL, 𝑃<0.05, respectively). The mean apoB levels in DM (127±47 mg/dl) and HDP (128±38 mg/dL) were not statistically significantly different (𝑃>0.05). Conclusions. Diabetic children and healthy children with diabetic parent(s) are at higher risk of dyslipidemia and atherosclerosis. Thus for primordial and primary prevention of atherosclerosis, we suggest screening these children for low plasma apoA1 and high plasma apoB levels.

Are Dietary Cholesterol Intake and Serum Cholesterol Levels Related to Nonalcoholic Fatty Liver Disease in Obese Children?

Dimitrios Papandreou, Zaharoula Karabouta, and Israel Rousso — Tue, 03 Jul 2012 09:55:27 +0000

Background. Nonalcoholic fatty liver disease (NAFLD) in children has been recognized as a major health burden. Serum lipids as well as dietary cholesterol (DC) intake may positively relate to development of NAFLD. The purpose of this study was to investigate anthropometric, biochemical, and dietary intake parameters of obese Greek children with and without NAFLD. Materials and Methods. Eighty-five obese children aged 8–15 (45 boys/40 girls) participated in the study. NAFLD was diagnosed by ultrasonography (US) in all subjects. Liver indexes were measured in all children. A 3-day dietary was recorded for all subjects. Results. 38 out of 85 children (44.7%) were found to have fatty liver. Obese children with increased levels of TC (95% CI: 1.721–3.191), low density lipoprotein (LDL) (95% CI: 1.829–3.058), and increased dietary cholesterol intakes (95% CI: 1.511–2.719) were 2.541, 2.612, and 2.041 times more likely to develop NAFLD compared with the children without NAFLD. Conclusion. The present study showed that TC, LDL, and DC were the strongest risk factors of development of NAFLD. Reducing body weight and dietary cholesterol intakes as well as decreasing serum TC and LDL levels are urgently necessary in order to prevent NAFLD and possible other health implications later in life.

The Triglyceride to HDL Ratio and Its Relationship to Insulin Resistance in Pre- and Postpubertal Children: Observation from the Wausau SCHOOL Project

Karen Olson, Bryan Hendricks, and David K. Murdock — Thu, 28 Jun 2012 14:11:58 +0000

Insulin resistance (IR) is a risk factor for ischemic heart disease and diabetes and raises the triglyceride/high-density lipoprotein (TG/HDL) ratio in adults, but is not well defined in children. Purpose. To investigate the TG/HDL ratios in children as an IR marker. Methods. Wausau SCHOOL Project assessed 99 prepubertal and 118 postpubertal children. The TG/HDL ratio was correlated with numerous risk factors. Results. TG/HDL ratio was significantly correlated with QUICKI, HOMA-IR, zBMI, waist-to hip ratio, systolic and diastolic BP, LDL size and LDL number. A group of 32 IR children (HOMA-IR > 1 SD from the mean, i.e., >2.45) had significantly higher TG/HDL (3.11 ± 1.77) compared to non-IR children (1.86 ± 0.75). A TG/HDL ratio of ≥2.0 identified 32 of the 40 children deemed IR by HOMA-IR (>2.45) with a sensitivity of 0.80 and a specificity of 0.66. Children with TG/HDL ratio ≥3 were heavier and had higher BP, glucose, HOMA-IR, LDL number, and lower HDL level, QUICKI, and LDL size, regardless of pubertal status. Conclusion. The TG/HDL ratio is strongly associated with IR in children, and with higher BMI, waist hip ratio, BP, and more athrogenic lipid profile.

Macronutrient Intake Influences the Effect of 25-Hydroxy-Vitamin D Status on Metabolic Syndrome Outcomes in African American Girls

Tue, 26 Jun 2012 08:22:34 +0000

The objectives were to determine the effect of macronutrient modification on vitamin D status and if change in 25-hydroxy-vitamin D concentration influences components of metabolic syndrome in obese African American girls. Methods. Five-week intervention using reduced CHO (43% carbohydrate; 27% fat: SPEC) versus standard CHO (55% carbohydrate; 40% fat: STAN) eucaloric diet. Subjects were 28 obese African American females, aged 9–14 years. Dual energy X-ray absorptiometry and meal test were performed at baseline and five weeks. Results. Approximately 30% of girls had metabolic syndrome. Serum 25OHD increased in both groups at five weeks [STAN: 20.3 ± 1.1 to 22.4 ± 1.1 (𝑃<0.05) versus SPEC: 16.1±1.0 to 16.8±1.0 (𝑃=0.05)]. The STAN group, increased 25OHD concentration over five weeks (𝑃<0.05), which was positively related to triglycerides (𝑃<0.001) and inversely associated with total cholesterol (𝑃<0.001) and LDL (𝑃<0.001). The SPEC group, had increase in 25OHD (𝑃=0.05), which was positively related to fasting insulin (𝑃<0.001) and insulin sensitivity while inversely associated with fasting glucose (𝑃<0.05). The contribution of vitamin D status to metabolic syndrome parameters differs according to macronutrient intake. Improvement in 25OHD may improve fasting glucose, insulin sensitivity, and LDL; however, macronutrient intake warrants consideration.

Metabolic Risk Factors, Leisure Time Physical Activity, and Nutrition in German Children and Adolescents

Gerda-Maria Haas, Evelyn Liepold, and Peter Schwandt — Tue, 19 Jun 2012 09:02:58 +0000

Purpose. We assessed the five components of the metabolic syndrome (MetS) as defined by the International Diabetes Federation (IDF) in 6040 (3158 males) youths aged 6–16 years who participated in the Präventions-Erziehungs-Programm (PEP Family Heart Study) in Nuernberg between 2000 and 2007. The purpose of this cross-sectional study was to examine associations with lifestyle habits. Results and Discussion. The prevalence of MetS was low in children (1.6%) and adolescents (2.3%). High waist circumference (WC) and low HDL-C were slightly higher in females (9.5% and 7.5%, resp.) than in males (8.8% and 5.7%, resp.). Low leisure time physical activity (LTPA) was significantly associated with low HDL-C (odds ratio [OR] 2.4; 95% CI 1.2–5.0) and inversely associated with hypertension (𝑟=−0.146), hypertriglyceridemia (𝑟=−0.141), and central adiposity (𝑟=−0.258). The risk for low HDL-C (≤1.3 mmol/L) was 1.7-fold (CI 1.0–2.6) higher in youth with high (≥33%) saturated fat consumption. A low polyunsaturated/saturated fat ratio (P/S ratio) was significantly associated with fasting hyperglycemia (OR 1.4; 95% CI 1.0–1.2).

Ezetimibe and Simvastatin Reduce Cholesterol Levels in Zebrafish Larvae Fed a High-Cholesterol Diet

Ji Sun Baek, Longhou Fang, Andrew C. Li, and Yury I. Miller — Wed, 30 May 2012 16:07:18 +0000

Cholesterol-fed zebrafish is an emerging animal model to study metabolic, oxidative, and inflammatory vascular processes relevant to pathogenesis of human atherosclerosis. Zebrafish fed a high-cholesterol diet (HCD) develop hypercholesterolemia and are characterized by profound lipoprotein oxidation and vascular lipid accumulation. Using optically translucent zebrafish larvae has the advantage of monitoring vascular pathology and assessing the efficacy of drug candidates in live animals. Thus, we investigated whether simvastatin and ezetimibe, the principal drugs used in management of hypercholesterolemia in humans, would also reduce cholesterol levels in HCD-fed zebrafish larvae. We found that ezetimibe was well tolerated by zebrafish and effectively reduced cholesterol levels in HCD-fed larvae. In contrast, simvastatin added to water was poorly tolerated by zebrafish larvae and, when added to food, had little effect on cholesterol levels in HCD-fed larvae. Combination of low doses of ezetimibe and simvastatin had an additive effect in reducing cholesterol levels in zebrafish. These results suggest that ezetimibe exerts in zebrafish a therapeutic effect similar to that in humans and that the hypercholesterolemic zebrafish can be used as a low-cost and informative model for testing new drug candidates and for investigating mechanisms of action for existing drugs targeting dyslipidemia.

In Vivo Inflammation Does Not Impair ABCA1-Mediated Cholesterol Efflux Capacity of HDL

Tue, 24 Apr 2012 11:40:12 +0000

HDL provides atheroprotection by facilitating cholesterol efflex from lipid-laden macrophages in the vessel wall. In vitro studies have suggested impaired efflux capacity of HDL following inflammatory changes. We assessed the impact of acute severe sepsis and mild chronic inflammatory disease on the efflux capacity of HDL. We hypothesize that a more severe inflammatory state leads to stronger impaired cholesterol efflux capacity. Using lipid-laden THP1 cells and fibroblasts we were able to show that efflux capacity of HDL from both patients with severe sepsis or with Crohn's disease (active or in remission), either isolated using density gradient ultracentrifugation or using apoB precipitation, was not impaired. Yet plasma levels of HDL cholesterol and apoA-I were markedly lower in patients with sepsis. Based on the current observations we conclude that inflammatory disease does not interfere with the capacity of HDL to mediate cholesterol efflux. Our findings do not lend support to the biological relevance of HDL function changes in vitro.

Gender Differences Time Trends for Metabolic Syndrome and Its Components among Tehranian Children and Adolescents

Thu, 19 Apr 2012 10:16:36 +0000

Aims. To investigate the trend of metabolic syndrome and its components in Tehran children and adolescents during a median followup of 6.6 years. Methods. Data from 1999–2001 (phase I), 2002–2005 (phase II), and 2006–2008 (phase III) of the Tehran, Lipid and Glucose Study were analyzed (𝑛=5439; age 6–18 years) for the trend of metabolic syndrome (MetS) and its components. General estimation equation (GEE) models were used to analyze this correlated data. Results. The crude prevalence of MetS for boys at baseline was 13.2%, which increased to 16.4% in the third phase. In girls, the prevalence of Mets decreased from 11.8% at baseline to 6% during followup. The odd ratios (OR) of obesity over the whole study period were raised in both sexes. The OR of abdominal obesity increased significantly in boys, but no change was observed in girls. No significant OR was observed in boys, while OR for MetS was shown to have a decreasing trend in girls during the followup. In the three time points, the ORs of MetS decreased significantly in girls but no significant difference was observed in boys. Conclusion. Inspite of increasing trend for obesity in both sexes, the trend of MetS decreased in girls and was relatively stable in boys, in Tehranian children, and adolescents.