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Primary objective: To determine if plasma levels of 24S-hydroxycholesterol, the primary catabolite of brain cholesterol, provide a measure of axonal damage in acute brain trauma. Research design: Determination of plasma 24S-hydroxycholesterol in a series of persons admitted to an intensive care unit for treatment of closed head injury. Methods and procedures: Levels of 24-S-hydroxycholesterol, 27-hydroxycholesterol, lathosterol and total cholesterol were measured in peripheral blood from 38 persons from 14-55 years of age treated by craniotomy and ventriculostomy for intractable intracerebral hypertension. Severity of brain injury was estimated by the Glasgow Coma Scale (range = 3-13, median = 6 points) and overall injury by the Injury Severity Scale (range = 10-48, median = 29). All subjects were intubated and anaesthetized with intravenous propofol. Plasma sterol levels were compared with those of age-matched control subjects. Outcomes and results: There was no significant increase in plasma 24-S-hydroxycholesterol in subjects with head injury, but measures of peripheral cholesterol synthesis were markedly reduced as compared with values for age-matched normal control subjects. Conclusion: Plasma 24S-hydroxycholesterol levels do not change with severe closed head injury. [ABSTRACT FROM AUTHOR]

Patients with combined hyperlipidemia (elevated triglyceride [TG] levels, elevated low-density lipoprotein [LDL] cholesterol, and multiple lipoprotein abnormalities) are at increased risk for coronary heart disease. We conducted a multicenter (in the United States), randomized, double-blind, active-controlled, 18-week study to determine if combination therapy with simvastatin plus fenofibrate is more effective in reducing elevated TG levels, thus improving the lipoprotein pattern in patients with combined hyperlipidemia compared with simvastatin monotherapy, and to evaluate safety and tolerability. Patients (aged 21 to 68 years) with a diagnosis of combined hyperlipidemia (fasting TG levels ≥150 and ≤500 mg/dl, and LDL cholesterol >130 mg/dl) received simvastatin monotherapy (20 mg/day, n = 207) or simvastatin 20 mg plus fenofibrate (160 mg/day) combination therapy (n = 411) for 12 weeks following a 6-week diet and placebo run-in period. From baseline to week 12, median TG levels decreased 43.0% (combination therapy) and 20.1% (simvastatin monotherapy [treatment difference −23.6%, p <0.001]). Mean LDL cholesterol levels decreased 31.2% and 25.8% (treatment difference −5.4%, p <0.001), and high-density lipoprotein cholesterol levels increased 18.6% and 9.7% (treatment difference 8.8%, p <0.001) in the combination therapy versus monotherapy groups, respectively. No drug-related serious adverse experiences were observed. No patient experienced clinical myopathy or severe abnormalities in liver function. Combination therapy with simvastatin 20 mg and fenofibrate 160 mg in patients with combined hyperlipidemia resulted in additional improvement in all lipoprotein parameters measured compared with simvastatin 20 mg monotherapy and was well tolerated. Thus, this combination therapy is a beneficial therapeutic option for managing combined hyperlipidemia. [Copyright &y& Elsevier]

Reports a cases in which a striking hypolipidemic response occured during treatment with crystalline nicotinic acid. Adverse effects of nicotinic acids; Medical history of the patients.

Abstract: Background: The metabolic syndrome is a constellation of risk factors including dyslipidemia, dysglycemia, hypertension, a pro‐inflammatory state, and a prothrombotic state. All of these factors are accentuated by obesity. However, obesity can be defined by body mass index (BMI), percent body fat, or by body fat distribution. The latter consists of upper body fat (subcutaneous and visceral fat) and lower body fat (gluteofemoral fat). Waist circumference is a common surrogate marker for upper body fat. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999‐2006 was examined for associations of metabolic risk factors with percent body fat, waist circumference, and BMI. Results: Associations between absolute measures of waist circumference and risk factors were similiar for men and women. The similarities of associations between waist circumference and risk factors suggests that greater visceral fat in men does not accentuate the influence of upper body fat on risk factors. Conclusions: Different waist concumference values should not be used to define abdominal obesity in men and women. [ABSTRACT FROM AUTHOR]

Background Registered dietitian nutritionists are trained to identify optimal food choices for clients based on medical state and lifestyle. Orthorexia nervosa (ON) is a proposed disorder related to obsessions about eating healthfully. Eating disorders (EDs) are serious mental illnesses with symptoms related to eating, body image, and self-esteem. Both ON and EDs are more common among RDNs than the general population. Objective This study examined the prevalence of ON and EDs in RDNs in the United States and, among this sample, assessed whether the presence of ON symptoms related to symptoms of EDs, including weight, shape, eating, and restraint. Design A cross-sectional design compared responses for participants after dividing into three groups: those scoring at-risk for ON, those with a current or past ED, and a comparison group. Participants A sample of 2,500 RDNs were invited to complete surveys electronically; 636 responses were received. Main outcome measures Scores on the Orthorexia Nervosa Questionnaire (ORTO-15) and Eating Disorder Examination Questionnaire (EDE-Q) determined prevalence of ON and EDs. Differences in these measures, and body mass index were compared among the three groups. Statistical analyses Analysis of variance and χ 2 analyses were used to compare the groups. Results For the entire sample, scores on the ORTO-15 suggested 49.5% were at risk for ON, and scores on the EDE-Q suggested 12.9% were at risk for an ED, with 8.2% of RDNs self-disclosing treatment for an ED. Both the group disclosing ED treatment and the group at risk for ON had a lower mean body mass index, lower scores on the ORTO-15, and higher scores on the EDE-Q and all its subscales than the comparison group. Conclusions Clarifying the relationship between ON and EDs is warranted because ON symptoms appear to be associated not only with disturbances in eating, but also with elevated shape and weight concerns. [ABSTRACT FROM AUTHOR]

African Americans often have normal high-density lipoprotein cholesterol (HDL-C) and low triglyceride levels despite insulin resistance and obesity. The higher than expected HDL-C levels are usually attributed to low levels of hepatic triglyceride lipase activity (HTGL). Factors that regulate HTGL in African Americans are not well delineated. In the current study, HTGL levels were examined in relation to body fat (body mass index (BMI) and waist circumference (WC)), insulin resistance indices (fasting plasma insulin and HOMA index) and adiponectin. Sixty-three African Americans (33 Men, 30 Women, median age 31 y, range 20-50 y, median BMI 28.6 kg/m², range 19.7-54.7 kg/m²) had anthropometry and measurement of post-heparin lipase activities (HTGL), plasma HDL-C, triglycerides and plasma adiponectin. HTGL correlated strongly with HDL-C (r =-0.52, P<0.0001) and adiponectin (r = -0.49, P<0.001). HTGL increased with BMI and WC (r =0.297, P=-0.018 and r =0.301, P=0.016, resp). Adiponectin correlated strongly with HDL-C (r =0.50, P<0.0001) and triglycerides (r = -0.493, P<0.001). Four multiple regression models predicted HTGL variability (P<0.001) in the study group: Model 1 with an adjusted R²=0.242 and a linear combination of adiponectin, BMI, and HOMA (log[sub e]); Model 2 (R²=0.229) with adiponectin + BMI + HOMA (log[sub e] + triglycerides (log[sub e]; Model 3 (R²=0.241) with adiponectin + age + BMI and Model 4 (R² =0.215) adiponectin + age + BMI + HOMA (logo + triglycerides (log[sub e]). It is apparent that about 23% of HTGL variability among African Americans can be explained by adiponectin levels in combination with markers of obesity and insulin resistance. In each model, the beta-coefficient for adiponectin with HTGL is in the range of 0.44 to 0.47 (P <0.002) rendering this parameter a major factor in HTGL variability. The data suggests that adiponectin is a strong determinant of HTGL levels and plasma triglyceride levels in African Americans. [ABSTRACT FROM AUTHOR]

Background: Currently, exogenous hormone replacement is used in many men with hypogonadism without clear organic cause. This study examines the contribution of modifiable health behaviors, i.e., physical activity and weight control, to the maintenance of testosterone levels with aging.Methods: In a cross-sectional study of 2994 healthy men aged 50-79 years examined at a preventive medicine clinic from January 2012 to March 2016, screening morning total testosterone levels were measured and categorized as low (<250 ng/dL), low normal (250-399 ng/dL), and normal (>400 ng/dL). Cardiorespiratory fitness (fitness) was estimated from a maximal exercise treadmill test. Multiple logistic regression models were used to test the associations between low testosterone levels and age, body mass index (BMI), and fitness.Findings: Mean testosterone levels were in the normal range for each age group (50-59, 60-69, and 70-79). There was a similar prevalence of low testosterone in each age group (11·3%, 10%, and 10·5%, respectively). The prevalence of low testosterone was positively associated with BMI and negatively associated with fitness but was not associated with age.Interpretation: This study found no evidence that low testosterone is an inevitable consequence of aging. Maintenance of healthy weight and fitness may help maintain normal testosterone levels. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to investigate the association between natriuretic peptides and body fat distribution in a multiethnic cohort. Background: Natriuretic peptides stimulate lipolysis, reduce weight gain, and promote adipocyte browning in animal models, but data are lacking in humans. Methods: A total of 2,619 participants without heart failure in the Dallas Heart Study underwent measurements of 1) B-type natriuretic peptide (BNP) and N-terminal pro–B-type natriuretic peptide (NT-proBNP); and 2) body fat distribution by dual energy x-ray absorptiometry and magnetic resonance imaging. Cross-sectional associations of natriuretic peptides with adiposity phenotypes were examined after adjustment for age, sex, race, comorbidities, and body mass index. Results: Median BNP and NT-proBNP levels in the study cohort (mean age 44 years; 56% women, 48% African Americans, 32% obese) were 3.0 and 28.1 pg/ml, respectively. Natriuretic peptide levels above the median were associated with a more favorable body fat profile and less insulin resistance, including lower visceral fat, liver fat, and homeostasis model assessment of insulin resistance index, and increased lower body fat and higher adiponectin (p < 0.05 for each). In multivariable analyses, NT-proBNP remained inversely associated with visceral fat (beta coefficient = −0.08; p < 0.0001) and liver fat (beta coefficient = −0.14; p < 0.0001) and positively associated with lower body fat (beta coefficient = 0.07; p < 0.0001) independent of age, sex, race, and obesity status; findings were similar with BNP. Adjustment for body composition, homeostasis model assessment of insulin resistance index, circulating androgens, and adipocytokines did not attenuate the associations. Conclusions: Higher natriuretic peptide levels were independently associated with a favorable adiposity profile, characterized by decreased visceral and liver fat and increased lower body fat, suggesting a link between the heart and adipose tissue distribution mediated through natriuretic peptides. [Copyright &y& Elsevier]

The article discusses the long term outcome of bariatric surgery. It reports that sustained weight loss, lower incidences of cardiovascular diseases, diabetes and cancer are some of the benefits from bariatric surgery. The study was conducted in obese controlled Swedish subjects. During a follow up of 20 years following the bariatric procedure, the surgery patients used a 54 mean cumulative hospital days against the 40 days of the control group at a confidence interval (C.I.) of 95 percent. However, the study highlights that the drug costs from the seventh year were lower for patients who underwent the surgery than control patients.

Periwal V, Chow CC, Bergman RN, Ricks M, Vega GL, Sumner AE. Evaluation of quantitative models of the effect of insulin on lipolysis and glucose disposal. Am J Physiol Regul Integr Comp Physiol 295: R1089-R1096, 2008. First published August 6, 2008; doi:l0.1152/ajpregu.90426.2008.-The effects of insulin on the suppression of lipolysis are neither fully understood nor quantified. We examined a variety of mathematical models analogous to the minimal model of glucose disposal (MMG) to quantify the combined influence of insulin on lipolysis and glucose disposal during an insulin-modified frequently sampled intravenous glucose tolerance test. The tested models, which include two previously published ones, consisted of separate compartments for plasma free fatty acids (FFA), glucose, and insulin. They differed in the number of compartments and in the action of insulin to suppress lipolysis that decreased the plasma FFA level. In one category of models, a single insulin compartment acted on both glucose and FFA simultaneously. In a second category, there were two insulin compartments, each acting on FFA and glucose independently. For each of these two categories, we tested 11 variations of how insulin suppressed lipolysis. We also tested a model with an additional glucose compartment that acted on FFA. These 23 models were fit to the plasma FFA and glucose concentrations of 102 subjects individually. Using Bayesian model comparison methods, we selected the model that best balanced fit and minimized model complexity. In the best model, insulin suppressed lipolysis via a Hill function through a remote compartment that acted on both glucose and FFA simultaneously, and glucose dynamics obeyed the classic MMG. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Higher C-reactive protein (CRP) levels in women compared with men may reflect sex differences in the relationship between obesity and inflammation. We evaluated how the adipokine leptin influenced these relationships. Methods and results: Dual energy X-ray absorptometry measurements of fat mass and plasma levels of leptin and CRP were measured in 1188 women and 1102 men from the Dallas Heart Study. Analyses were stratified by sex and a leptin/percent fat index was created to evaluate the association between leptin and CRP independent of fat mass. Women had higher body mass index, percent fat mass, and plasma levels of CRP and leptin. CRP levels correlated with leptin levels in both women (Spearman ρ =0.48, p <0.0001) and in men (ρ =0.27, p <0.0001). In multivariable models adjusting for confounders including total fat mass, leptin/percent fat index remained significantly associated with logCRP in women (p =0.005), but not in men (p =0.95). A significant interaction was observed between sex and leptin levels on CRP (p interaction =0.03). Conclusion: Leptin was associated with CRP independent of other measures of obesity in women, but not in men. These findings suggest that sex differences in CRP may reflect sex-related differences in the inflammatory responses to obesity, and may in part, be mediated by leptin. [Copyright &y& Elsevier]

Selected missense mutations in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) cause autosomal dominant hypercholesterolemia, whereas nonsense mutations in the same gene are associated with low plasma levels of low-density lipoprotein cholesterol (LDL-C). Here, DNA sequencing and chip-based oligonucleotide hybridization were used to determine whether other sequence variations in PCSK9 contribute to differences in LDLC levels. The coding regions of PCSK9 were sequenced in the blacks and whites from the Dallas Heart Study (n = 3,543 ) who had the lowest (<5th percentile) and highest (>95th percentile) plasma levels of LDL-C. Of the 17 missense variants identified, 3 (R46L, L253F, and A443T) were significantly and reproducibly associated with lower plasma levels of LDL-C (reductions ranging from 3.5% to 30%). None of the low-LDL-C variants were associated with increased hepatic triglyceride content, as measured by proton magnetic resonance spectroscopy. This finding is most consistent with the reduction in LDL-C being caused primarily by accelerating LDL clearance, rather than by reduced lipoprotein production. Association studies with 93 noncoding single-nucleotide polymorphisms (SNPs) at the PCSK9 locus identified 3 SNPs associated with modest differences in plasma LDL-C levels. Thus, a spectrum of sequence variations ranging in frequency (from 0.2% to 34%) and magnitude of effect (from a 3% increase to a 49% decrease) contribute to interindividual differences in LDL-C levels. These findings reveal that PCSK9 activity is a major determinant of plasma levels of LDL-C in humans and make it an attractive therapeutic target for LDL-C lowering. [ABSTRACT FROM AUTHOR]

An approach to understand quantitative traits was recently proposed based on the finding that nonsynonymous (NS) sequence variants in certain genes are preferentially enriched at one extreme of the population distribution. The NS variants, although individually rare, are cumulatively frequent and influence quantitative traits, such as plasma lipoprotein levels. Here, we use the NS variant technique to demonstrate that genetic variation in NPC1L1 contributes to variability in cholesterol absorption and plasma levels of low-density lipoproteins (LDLs). The ratio of plasma campesterol (a plant sterol) to lathosterol (a cholesterol precursor) was used to estimate relative cholesterol absorption in a population-based study. Nonsynonymous sequence variations in NPCIL1 were five times more common in low absorbers(n = 26 of 256) than in high absorbers (n = 5 of 256) (P < 0.001). The rare variants identified in low absorbers were found in 6% of 1,832 African-Americans and were associated with lower plasma levels of LDL cholesterol (LDL-C) (96 ± 36 mg/dl vs. 105 ± 36 mg/dl; P = 0.005). These data, together with prior findings, reveal a genetic architecture for LDL-C levels that does not conform to current models for quantitative traits and indicate that a significant fraction of genetic variance in LDL-C is due to multiple alleles with modest effects that are present at low frequencies in the population. [ABSTRACT FROM AUTHOR]

We sought to compare the prevalence of coronary atherosclerosis in a cohort of middle-age African American (black) and non-Hispanic Caucasian (white) men and women from a population-based probability sample.Blacks have a higher mortality from coronary heart disease (CHD) than whites, particularly among younger individuals, and yet several studies have reported that coronary atherosclerosis is less prevalent in blacks than in whites. Data from population-based samples comparing coronary atherosclerotic burden between blacks and whites are limited.The prevalence of coronary atherosclerosis in middle-aged blacks and whites was determined using coronary calcium measured by electron beam computed tomography in 1,289 men and women from a population-based probability sample from Dallas, Texas.The population estimates of the frequency of a positive scan for coronary artery calcium were not statistically different between black and white men (37% vs. 41%, p = 0.36) or between black and white women (29% vs. 23%, p = 0.21). Although the prevalence of most of the coronary risk factors varied significantly between blacks and whites, mean Framingham coronary risk factor scores were identical in black and white men (10 ± 4) but significantly higher in black women (13 ± 4) than in white women (12 ± 4).Blacks in the general population have a prevalence of coronary atherosclerosis similar to whites. Factors other than coronary atherosclerotic burden, which are not reflected in the Framingham risk score, contribute significantly to the higher CHD mortality rate in blacks. [Copyright &y& Elsevier]

Serum concentrations of cholesterol are positively correlated with exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) in humans. The associated change in cholesterol is small across a broad range of exposure to PFOA and PFOS. Animal studies generally have not indicated a mechanism that would account for the association in humans. The extent to which the relationship is causal is an open question. Nonetheless, the association is of particular importance because increased serum cholesterol has been considered as an endpoint to derive a point of departure in at least one recent risk assessment. To gain insight into potential mechanisms for the association, both causal and non-causal, an expert workshop was held Oct 31 and Nov 1, 2019 to discuss relevant data and propose new studies. In this report, we summarize the relevant background data, the discussion among the attendees, and their recommendations for further research. [ABSTRACT FROM AUTHOR]

The article discusses a study on the misperception of body size as an obstacle to effecting weight loss. Obese subjects from the Dallas Heart Study were examined with African Americans comprising 50% of the study cohort. It concludes that body size misperception is prevalent among obese adults particularly in ethnic minorities and suggests the need for multifaceted intervention to counter the effects of body size misperception. It recommends partnering between physicians and public health advocates to develop treatment programs in their communities.