Atherogenic Lipid Profile Research Articles

Lorcaserin treatment decreases body weight and reduces cardiometabolic risk factors in obese adults: A six-month, randomized, placebo-controlled, double-blind clinical trial.

Lorcaserin is a serotonin 2c receptor agonist that promotes weight loss while contributing to the prevention and improvement of type 2 diabetes and improvement of atherogenic lipid profiles, without higher rates of major cardiovascular events. The full spectrum of possible lorcaserin-induced improvements in cardiometabolic health remains to be clarified. Thus, we investigated the way in which lorcaserin treatment may alter cardiovascular disease risk, either independently or through changes in body weight. We measured, for the first time, lipid particle quantification, lipid peroxidation, appetite-regulating hormones and mRNA expression of the 5-hydroxytryptamine 2c receptor (5-HT2c receptor). A total of 48 obese participants were enrolled in this six-month, randomized (1:1), placebo-controlled, double-blinded clinical trial. Lorcaserin treatment reduced fat mass (P < 0.001), the fatty liver index (P < 0.0001) and energy intake (P < 0.03) without affecting energy expenditure or lean mass. Total low-density lipoprotein (LDL) (P < 0.04) and small LDL particles (P < 0.03) decreased, while total high-density lipoprotein (HDL) P < 0.02) increased and heart rate significantly decreased with lorcaserin treatment. No mRNA expression of the 5-HT2c receptor was observed in peripheral organs. These data suggest that lorcaserin treatment for six months improves cardiometabolic health in obese individuals, acting mainly through the brain.

Atherogenic lipid profile and health behaviours in women post-menopause working in agriculture

There is a significantly higher risk of lipid disorders occurrence, including atherogenic dyslipidemia in women after menopause than it is in general population. The aim of the work was to investigate the correlation between health behaviours and the occurrence of lipid disorders in women after menopause working in agriculture. The study was conducted in years 2015-2016 and included 843 post-menopausal women working in agriculture. The following were used: a questionnaire including socio-demographic data, laboratory lipid tests, inventory of health behaviours. The following were estimated: logistic regression models for serum lipids concentration versus frequency of health behaviours in the examined women. Adverse lipid profile was found in over a half of post-menopausal women working in agriculture, whereas the frequency of health behaviours were estimated at the average level, although the frequency of correct eating habits and health practices was significantly lower than preventive behaviours and positive psychological attitudes. A correlation was found between the frequency of health behaviours and the occurrence of lipid disorders in women after menopause working in agriculture: more frequent health practices co-existed with the lower concentration of total cholesterol and a higher concentration of HDL-cholesterol, more frequent preventive behaviours co-existed with lower concentration of LDL-cholesterol. Women with higher concentration of triglycerides undertook pro-health practices relatively more often. The study revealed a high prevalence of lipid disorders in postmenopausal women working in agriculture. More effective health education programmes are necessary in the area of reduction the risk factors of CVD in the population of women working in agriculture.

Gestational Diabetes But Not Prepregnancy Overweight Predicts for Cardiometabolic Markers in Offspring Twenty Years Later.

Maternal gestational diabetes mellitus (GDM) and prepregnancy overweight/obesity [body mass index (BMI) ≥25 kg/m2] might adversely affect offspring cardiometabolic health. To assess the associations between maternal GDM and prepregnancy overweight/obesity with adult offspring cardiometabolic risk factors. Longitudinal cohort study (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study). Province of Uusimaa and Northern Finland. At a mean age of 24.1 ± 1.3 years, we classified offspring as offspring of mothers with GDM regardless of the prepregnancy BMI (OGDM; n = 193); normoglycemic mothers with prepregnancy overweight/obesity (ONO; n = 157); and normoglycemic mothers with prepregnancy BMI <25 kg/m2 (controls; n = 556). We assessed the cardiometabolic biomarkers from blood and measured the blood pressure at rest and heart rate. Compared with the controls, the OGDM and ONO groups had greater fasting glucose (1.6%; 95% CI, 0.1% to 3.1%; and 2.3%; 95% CI, 0.5% to 4.3%, respectively) and insulin (12.7%; 95% CI, 4.4% to 21.9%; and 8.7%; 95% CI, 0.2% to 17.8%). These differences attenuated to nonsignificance when adjusted for confounders and/or current offspring characteristics, including BMI or body fat percentage. The OGDM group had lower SHBG (men, -12.4%; 95% CI, -20.2% to -3.9%; women, -33.2%; 95% CI, -46.3% to -16.8%), high-density lipoprotein (-6.6%; 95% CI, -10.9% to -2.2%), and apolipoprotein A1 (-4.5%; 95% CI, -7.5% to -1.4%). These differences survived the adjustments. The heart rate and other biomarkers were similar among the groups. Adult offspring of mothers with GDM have increased markers of insulin resistance and a more atherogenic lipid profile. These were only partly explained by confounders or current offspring adiposity. Maternal prepregnancy overweight/obesity was associated with impaired offspring glucose regulation, which was explained by confounders and/or current adiposity.

Abstract P203: Lipoprotein Particle Number and Particle Size Profile in Impaired Fasting Glucose or Impaired Glucose Tolerance Are Similar to Those With Diabetes: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Introduction: Although studies have evaluated the association between the lipid profile measured by nuclear magnetic resonance (NMR) and the diagnosis of diabetes, scarce data are available addressing the association of lipoprotein particles and lipoprotein size among people with impaired fasting glucose and impaired glucose tolerance. Hypothesis: People with impaired fasting glucose and impaired glucose tolerance have a more atherogenic lipid profile measured by lipoprotein particle concentration and size compared to subjects without glucose homeostasis alterations and with a similar pattern of to people with diabetes. Methods: We tested this hypothesis among 5060 men and women aged 35 to 74 years-old enrolled in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We measured lipids and lipoproteins subfractions using NMR spectroscopy (LabCorp): 5 triglyceride-rich lipoprotein particles (TRL-P, from very large to very small), 3 LDL-P and 3 HDL-P (large, medium, small) subclasses. Diabetes was defined: fasting plasma glucose ≥126 mg/dl, 2h post-load glucose ≥200 mg/ dl, HbA1c ≥6.5 % or treatment for diabetes; impaired fasting glucose as fasting plasma glucose &lt;126 and &gt;110 mg/dl; impaired glucose tolerance as 2h post-load 75g-glucose between 140-199 mg/dl. Pre-diabetes was defined when one condition impaired fasting glucose or impaired glucose tolerance was identified. We used generalized linear regression models adjusted by sociodemographic/cardiovascular risk factors and lipids measured by enzymatic methods to compare the mean values of each lipoprotein variable. Results: Of the 4,095 subjects (mean age 50± 8.7years-old; 53% women), 706 subjects were diagnosed with diabetes, 365 with impaired fasting glucose, 904 with impaired glucose tolerance, and 2,120 had no glucose homeostasis change (reference group for all comparisons). People with pre-diabetes and diabetes had higher levels of large triglyceride-rich particles (P&lt;0.0001 for all). Subjects with diabetes had lower levels of medium TRL-P; and people with diabetes and impaired glucose tolerance had lower levels of small TRL-P (respectively, P&lt;0.0001, P=0.02). All groups had higher levels of both total LDL-P (P&lt;0.0001 for all) small LDL-P (P&lt;0.0001 for all). HDL particles (total and small) were lower only among subjects with diabetes. Compared with the participants without glucose homeostasis change, the participants with diabetes and pre-diabetes had higher TRL-P sizes (P&lt;0.0001 for all), lower HDL-P sizes (P&lt;0.04 for all), but lower LDL-P sizes were observed for persons with diabetes and impaired glucose tolerance. (P&lt;0.009 for all). Conclusions: Our results suggest that people with impaired fasting glucose or impaired glucose tolerance had a proatherogenic profile of lipoprotein particles compared to people with normal glucose homeostasis and similar to subjects with diabetes.

Increased ApoB/ApoA1 ratio is associated with excess weight, body adiposity, and altered lipid profile in children

ObjectiveTo investigate ApoB/ApoA1 ratio and its association with cardiovascular risk factors in children. MethodsCross‐sectional study with 258 children aged 8 and 9 years old, enrolled in all urban schools in the city of Viçosa‐MG. Anthropometric and body composition assessment, as well as biochemical profile of the children was performed. Socioeconomic variables and sedentary lifestyle were evaluated through a semi‐structured questionnaire. ResultsMany children had excess weight (35.2%), abdominal adiposity (10.5%), and body fat (15.6%), as well as increased ApoB/ApoA1 ratio (14.7%), total cholesterol (51.8%), and triglycerides (19.8%). Children with excess weight and total and central fat had a higher prevalence of having a higher ApoB/ApoA1 ratio, as well as those with atherogenic lipid profile (increased LDL‐c and triglycerides and low HDL‐c). A direct association was found between the number of cardiovascular risk factors and the ApoB/ApoA1 ratio (p=0.001), regardless of age and income. ConclusionThe increased ApoB/ApoA1 ratio was associated with excess weight, body adiposity (total and central), and altered lipid profile in children. Children with a higher number of cardiovascular risk factors had higher ApoB/ApoA1 ratio, in both genders.

Nutraceutical approach for the management of cardiovascular risk \u2013 a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study

BackgroundProbiotics incorporated into dairy products have been shown to reduce total (TC) and LDL cholesterolemia (LDL-C) in subjects with moderate hypercholesterolemia. More specifically, probiotics with high biliary salt hydrolase activity, e.g. Bifidobacterium longum BB536, may decrease TC and LDL-C by lowering intestinal cholesterol reabsorption and, combined with other nutraceuticals, may be useful to manage hypercholesterolemia in subjects with low cardiovascular (CV) risk. This study was conducted to evaluate the efficacy and safety of a nutraceutical combination containing Bifidobacterium longum BB536, red yeast rice (RYR) extract (10 mg/day monacolin K), niacin, coenzyme Q10 (Lactoflorene Colesterolo®). The end-points were changes of lipid CV risk markers (LDL-C, TC, non-HDL-cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (ApoB), HDL-C, apolipoprotein AI (ApoAI), lipoprotein(a) (Lp(a), proprotein convertase subtilisin/kexin type 9 (PCSK9)), and of markers of cholesterol synthesis/absorption.MethodsA 12-week randomized, parallel, double-blind, placebo-controlled study. Thirty-three subjects (18–70 years) in primary CV prevention and low CV risk (SCORE: 0–1% in 24 and 2–4% in 9 subjects; LDL-C: 130–200 mg/dL) were randomly allocated to either nutraceutical (N = 16) or placebo (N = 17).ResultsTwelve-week treatment with the nutraceutical combination, compared to placebo, significantly reduced TC (− 16.7%), LDL-C (− 25.7%), non-HDL-C (− 24%) (all p < 0.0001), apoB (− 17%, p = 0.003). TG, HDL-C, apoAI, Lp(a), PCSK9 were unchanged. Lathosterol:TC ratio was significantly reduced by the nutraceutical combination, while campesterol:TC ratio and sitosterol:TC ratio did not change, suggesting reduction of synthesis without increased absorption of cholesterol. No adverse effects and a 97% compliance were observed.ConclusionsA 12-week treatment with a nutraceutical combination containing the probiotic Bifidobacterium longum BB536 and RYR extract significantly improved the atherogenic lipid profile and was well tolerated by low CV risk subjects.Trial registrationNCT02689934.

Relation between sexual dysfunction and metabolic syndrome

The prevalence of the metabolic syndrome, type 2 diabetes mellitus, cardiovascular diseases, obesity and depression have increased during the recent years. As the sexual dysfunction is also frequent, we aimed to search for the associations between sexual dysfunction and the metabolic syndrome and its components, respectively, by reviewing the literature. The clinical and biochemical components of the metabolic syndrome included cardiovascular disease, type 2 diabetes mellitus, visceral obesity and depression, furthermore, insulin resistance, atherogenic lipid profile, hypogonadism, chronic systemic inflammation and endothelial dysfunction were all demonstrated to affect adversely the sexual function. The dysfunction of the sexual arousal response shows a strong association in men and a milder one in women with the cardiovascular diseases and depression. Sexual function in diabetes mellitus is mostly impaired by microvascular injury, polyneuropathy and autonomic neuropathy. Erectile dysfunction and disorder of the female sexual arousal response and the orgasm, respectively, are associated with insulin resistance, atherogenic lipid profile and systemic inflammatory condition in overweight or obese patients. Sexual dysfunction particularly in men can be an early sign of the severe complications of metabolic syndrome. The pathogenetic link between the metabolic syndrome and the sexual dysfunction seems to be the insulin resistance. Both metabolic syndrome and sexual dysfunction can be restored by altering the lifestyle. Orv Hetil. 2019; 160(3): 98-103.

Atherogenic ratios and serum lipid levels in patients with end-stage renal disease on continuous ambulatory peritoneal dialysis

Background: Patients with end-stage renal disease (ESRD) on continuous ambulatory peritoneal dialysis (CAPD) often have an atherogenic lipid profile. Lipid disturbances that have been observed in patients with ESRD on CAPD include hypercholesterolemia, hypertriglyceridemia, and decreased high-density lipoprotein cholesterol (HDL-c). Aim and Objectives: To study the atherogenic ratios and serum lipid levels in patients with ESRD on CAPD and compare with healthy controls. Materials and Methods: This study included 30 patients with ESRD before and after the initiation of continuous ambulatory peritoneal dialysis and 30 healthy controls. Thirty patients with ESRD after the start of peritoneal dialysis were regularly followed up for 3rd, 6th, 9th, 12th, and 15th months. The biochemical parameters were measured in baseline and follow-up samples. Results: The concentrations of (TC), serum triglycerides (TGs), very low-density lipoprotein cholesterol (VLDL-c), and atherogenic ratios were increased and levels of serum TC, low-density lipoprotein cholesterol (LDL-c), and HDL-c were decreased significantly during 3rd and 6th months. However, after 1 year of CAPD, the serum TGs, VLDL-c, TC, and LDL-c levels were significantly higher than the baseline values and HDL-c was significantly lower than the baseline values. Conclusion: The present study findings conclude that the continuous peritoneal absorption of glucose during CAPD contributes to alteration in serum lipids. However, the changes are fluctuating as an adaptation to the peritoneal absorption of glucose.

Role of 11β HSD 1, rs12086634, and rs846910 single-nucleotide polymorphisms in metabolic-related skin diseases: a clinical, biochemical, and genetic study.

Background11β HSD1 generates cortisol from cortisone. 11β HSD1 single-nucleotide polymorphism (SNP) was associated with metabolic syndrome (MeTS). Although the relation of acne vulgaris (AV) and skin tags (STs) with MeTS has been reported, the relationship between 11β HSD 1 SNP and cortisol activity in those patients has not studied till now.AimsTo investigate, two 11β-HSD1 SNPs (rs846910 and rs12086634), serum lipid profile and cortisol levels in patients with AV and STs in an Egyptian population.Patients and methodsThis case–control study was performed on 50 patients having STs and 50 complaining of AV and 50 sex- and age-matched controls. We searched for serum lipid profile, cortisol levels, and 11β-HSD1 rs846910 and rs12086634 SNPs using real time-PCR.ResultsCompared to controls,11β-HSD1 rs846910 GA genotype carriers had significantly higher risks for developing AV and STs by 3.4- and 4.9-fold, respectively, and its A allele increases these risks by 3.1 and 4.4 times, respectively. Also, 11β-HSD1 rs12086634 TG genotype increases the risk of AV by 3.2-fold, as well as STs by 3.5-fold, and its G allele increases the risk of AV by 3.2-fold and STs by 7-fold. In AV and ST patients, rs846910 GA genotype demonstrated significant associations with elevated body mass index (BMI), and cholesterol, low density lipoprotein (LDL), cortisol, and decreased high density lipoprotein serum levels, respectively. However, rs12086634 GG genotype was significantly associated with increased BMI, cholesterol, and LDL serum levels in patients with AV and STs, in addition to the number of STs and serum cortisol levels in ST patients.Conclusion11β-HSD1 rs846910 and rs12086634 gene polymorphisms may contribute to AV and STs pathogenesis, that may be mediated through enhancing the enzymatic activity (increasing cortisol levels). AV and STs are associated with obesity and atherogenic lipid profile. Diagnosis of AV and STs may play a role in early detection of the MeTS.

Fructose Consumption and Lipid Metabolism in Obese Children and Adolescents.

Inappropriate dietary habits influence the development of excessive body weight. The role of added sugars, including fructose, notably is significant in this process. It is estimated that fructose intake has increased many times over the past two centuries. The aim of the study was to define the effect of fructose consumption on anthropometric indices and lipid metabolism in obese (body mass index (BMI) >30kg/m2) children and adolescents. The study included 84 patients (47 girls and 37 boys) aged 7-18years, divided into prepubertal, pubertal, and post-pubertal age groups. Aside from BMI, the assessment comprised waist circumference, body composition estimated with bioelectrical impedance (BIA), plasma lipid profile, fructose intake consumption based on a 3-day menu analysis, and a number of calculated atherogenic indices. The major findings were that total daily fructose intake was high, on average, ranging from 19 to 26g, with no appreciable relation to age. A higher fructose intake from beverages is significantly associated with the percentage of body fat, waist circumference, waist-to-height ratio, and also with the content of total cholesterol, triglycerides, and the level of atherogenic indices. In conclusion, fructose appears a particularly unfavorable component in children's diet as it is conducive to visceral obesity and atherogenic lipid profile. However, inadequate proportions of other macronutrients may also be at play in the development of metabolic diet-related disorders.

Association of Skin Tag with Metabolic Syndrome and its Components: A Case-control Study from Eastern India.

Background:Skin tags are benign polyps, usually found in the natural folds of the skin. Some studies have found an association of skin tags with obesity, diabetes, hypertension, and atherogenic lipid profile. Metabolic syndrome refers to co-occurrence of these cardiovascular risk factors such as insulin resistance, obesity, dyslipidemia, and hypertension.Aims and Objectives:To find out any possible association of skin tags with metabolic syndrome and its components.Materials and Methods:A case–control study was conducted including 140 participants. Seventy patients with skin tags were considered cases, and 70 age- and sex-matched patients without skin tags were considered as controls. Various anthropometric and biochemical parameters were compared and analyzed between the two groups.Results:Univariate analysis revealed significantly higher waist circumference, high triglyceride, and low high-density lipoproteins (HDLs) in cases compared to controls. The prevalence of diabetes, hypertension, and metabolic syndrome was significantly higher in patients with skin tags, and risk of developing metabolic syndrome was 11.13 times higher in cases compared to controls (P < 0.05). Multivariate logistic regression analysis revealed high waist circumference and low serum HDL had significant association with skin tags.Conclusion:Risk of development of metabolic syndrome is significantly higher in patients with skin tags. Among the various components of metabolic syndrome, only high waist circumference and low serum HDLs are significantly associated with skin tags.

Elevated Triglycerides (≥150 mg/dL) and High Triglycerides (200–499 mg/dL) Are Significant Predictors of Hospitalization for New-Onset Kidney Disease: A Real-World Analysis of High-Risk Statin-Treated Patients

Background: Dyslipidemia in kidney disease (KD) involves increased levels of triglycerides (TG) and TG-rich lipoproteins, with only minor changes in low-density lipoprotein cholesterol. The increasing prevalence of diabetic KD and the shared atherogenic lipid profile between KD and diabetes underscore the importance of understanding dyslipidemia in these patients. Previous studies suggest an association between elevated TG and new-onset KD. Additional data are needed to better define the relationship between hypertriglyceridemia and new-onset KD. Objective: To evaluate the real-world impact of elevated and high TG on risk of KD in high-risk statin-treated patients. Methods: This retrospective administrative claims analysis of the Optum Research Database included statin-treated patients (age ≥45 years) with diabetes and/or atherosclerotic cardiovascular disease who were followed for ≥6 months. Cohorts included patients with elevated TG (≥150 mg/dL; n = 27,471) or high TG (200–499 mg/dL; subgroup of elevated TG cohort; n = 13,411), and a comparator cohort (TG <150 mg/dL and high-density lipoprotein cholesterol >40 mg/dL; n = 32,506). The probability of hospitalization for new-onset KD was calculated post hoc from multivariate analyses controlled for patient characteristics and comorbidities using a Cox proportional hazards model. Results: The rate of hospitalization for new-onset KD was 31% higher in the elevated-TG cohort (hazard ratio [HR], 1.311; 95% confidence interval [CI], 1.228–1.401; p < 0.001) and 45% higher in the high-TG cohort (HR, 1.451; 95% CI, 1.339–1.572; p < 0.001) compared with the respective comparator cohorts. Conclusions: In a real-world analysis of statin-treated patients with high cardiovascular risk, both elevated TG (≥150 mg/dL) and high TG (200–499 mg/dL) were significant predictors of hospitalization for new-onset KD, identifying hypertriglyceridemia as a potential KD risk factor.

Serum TSH level in obese children and its correlations with atherogenic lipid indicators and carotid intima media thickness.

Objective: Moderately elevated level of thyroid-stimulating hormone accompanied by normal serum concentrations of free thyroxine, suggesting subclinical hypothyroidism, is the most common hormonal abnormality in obese children. Controversy remains, whether a thyroid dysfunction related to obesity has an influence on the cardiovascular risk factors. The aim of the study was to assess correlation between thyroid-stimulating hormone and free thyroxine and chosen atherogenic lipid indicators, and carotid intima media thickness in obese children and adolescents. Methods: A study group consisted of 110 obese children (11.5 ± 2.9 years) and 38 healthy children (13.4 ± 2.6 years). Obesity was defined using International Obesity Task Force criteria. In each patient anthropometric measurements, thyroid-stimulating hormone, free thyroxine, a lipid profile were evaluated. Carotid intima-media thickness was measured in 74 obese children and 28 lean children. The resulting data were used to calculate indicators of atherogenesis: total cholesterol to HDL cholesterol ratio; triglycerides to HDL cholesterol ratio and LDL cholesterol to HDL cholesterol ratio. Results: Obese children had higher mean serum thyroid-stimulating hormone levels compared to their lean peers and an adverse atherogenic lipid profile. Serum free thyroxine concentrations were comparable between the groups. Serum thyroid-stimulating hormone values correlated with total cholesterol to HDL cholesterol ratio; triglycerides to HDL cholesterol ratio, LDL cholesterol to HDL cholesterol ratio, and intima-media thickness. In a multivariate regression analysis, thyroid-stimulating hormone weakly correlated only with intima-media thickness after adjustment for age, gender and Body Mass Index (β = 0.249, p = 0.04). This relationship weakened after considering a lipid profile (β = 0.242, p = 0.058). No relationship was found for free thyroxine. Conclusion: Serum level of thyroid-stimulating hormone in obese children did not seem to impact atherogenic lipid indicators and carotid intima-media thickness. Therefore, an adverse lipid profile should still be considered the main risk factor for development of cardiovascular diseases in obese children.

Higher hemoglobin A1C and atherogenic lipoprotein profiles in children and adolescents with type 2 diabetes mellitus

AimSignificant knowledge gaps exist regarding lipoprotein profiles in children with type 2 diabetes mellitus (T2DM). The primary objective was to analyze the type and nature of lipoprotein abnormalities present in children with T2DM and to identify determinants of adverse lipoprotein profiles. The secondary objective was to assess associations with elevated glycated hemoglobin (HbA1C), i.e., <8% vs. ≥8.0% and pediatric dyslipidemias in the setting of T2DM. MethodsThis retrospective chart review included children with T2DM who had undergone lipoprotein analysis and were not on lipid lowering medications (n = 93). ResultsThe participants (mean age 15.2 ± 2.7y) were 71% female and 78% African American (AA). Adjusted for age, sex, and race, BMI z-score was positively associated with LDL-pattern B (pro-atherogenic profile with small dense LDL particles) (P = 0.01), and negatively associated with total HDL-C (P = 0.0003). HbA1C was robustly positively associated with the LDL-C, apoB and LDL pattern B (all P < 0.001). Patients with an HbA1C >8% had significantly higher total cholesterol (191.4 vs. 158.1 mg/dL, P = 0.0004), LDL-C (117.77 vs. 92.3 mg/dL, P = 0.002), apoB (99.5 vs. 80.9 mg/dL, P = 0.002), non-HDL-C (141.5 vs. 112.5, P = 0.002), and frequency of LDL pattern B (57% vs. 20%, P = 0.0008). ConclusionHbA1C and BMI were associated with adverse lipoprotein profiles, and may represent two major modifiable cardiovascular risk factors in the pediatric T2DM population. Patients with an HbA1C higher than 8.0% had significantly worse atherogenic lipid profile, i.e., higher LDL-C, non-HDL-C, apoB and LDL pattern B, suggesting adequate glycemia may improve adverse lipoprotein profiles.

Obesity, altered oxidative stress, and clinical correlates in chronic schizophrenia patients

Antipsychotic pharmacotherapy is strongly obesogenic and is associated with increased oxidative stress in patients with schizophrenia. However, whether these changes reflect psychopathology, antipsychotic efficacy, or some other factor is not known. Our study aims to investigate the degree of oxidative stress in different BMI categories and to identify clinical symptomatology that may be paired with increased oxidative stress in a schizophrenia population. To this end, we performed a cross-sectional study and recruited 89 long-term inpatients with schizophrenia and collected the following variables: plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), routine biochemical analysis, and psychopathology through the Positive and Negative Syndrome Scale (PANSS). The results indicate that the levels of the lipid peroxidation product, MDA, were significantly higher in the high BMI group than the low (normal) BMI group. As expected, high BMI was associated with an atherogenic lipid profile; however, it was also associated with fewer psychopathological symptoms. Multiple regression analysis found that MDA levels, the PANSS general psychopathology subscore, and triglyceride levels (all p < 0.05) were independent contributors to the BMI in patients. These results suggested that oxidative stress may play an important role in antipsychotic-induced weight gain. Further investigations using the longitudinal design in first-episode schizophrenia patients are needed to explore the beneficial effect of antioxidants on the abnormal lipid metabolism mediated by antipsychotic treatment.

Malprogramming of Hepatic Lipid Metabolism due to Excessive Early Cholesterol Exposure in Adult Progeny.

The programming of hepatic lipid dysfunction in response to early cholesterol exposure and the influencing effects of postnatal diet is evaluated in apoE-/- mice. In two separate studies, female mice are assigned to a standard chow (S) or a cholesterol-enriched chow (C) diet during gestation and lactation. Male offspring from each dam are weaned on a postnatal S or a hypercaloric western (W) diet resulting in four experimental groups: S-S and C-S (Experiment 1) and S-W and C-W (Experiment 2). At weaning, litters from hypercholesterolemic mothers weighed less (p<0.05) and pups had higher blood lipids, glucose, and hepatic cholesterol compared with pups from S-fed mothers. Adult C-S offspring demonstrate an atherogenic lipid profile and increased (p<0.05) hepatic cholesterol and triglyceride content with altered lipid regulatory mRNA expression and protein content compared with S-S offspring. Alternatively, no difference (p>0.05) is observed between S-W and C-W in serum and hepatic lipid profiles; however, serum AST and ALT are higher (p<0.05) in C-W versus S-W offspring. The degree of hepatic lipid deposition observed in adult offspring exposed to excessive early cholesterol is influenced by the postnatal diet.

Immunosuppression and HIV Viremia Associated with More Atherogenic Lipid Profile in Older People with HIV.

To explore reasons for the disproportionate metabolic and cardiovascular disease burdens among older HIV-infected persons, we investigated whether associations of CD4 count and HIV viral load (VL) with non-high-density lipoprotein cholesterol (non-HDL-C) and high-density lipoprotein cholesterol [HDL-C] differed by age. Longitudinal clinical and laboratory data were collected between 2011 and 2016 for HIV-infected outpatients in the DC Cohort study. Using data for patients aged ≥21 years with ≥1 cholesterol result and contemporaneous CD4/VL results, we created multivariable linear regression models with generalized estimating equations. Among 3,912 patients, the median age was 50 years, 78% were male, 76% were non-Hispanic black, 93% were using antiretroviral therapy, 8% had a CD4 count <200 cells/μL, and 18% had an HIV VL ≥200 copies/mL. Overall, CD4 count <200 (vs. >500) cells/μL and VL ≥200 copies/mL were associated with lower non-HDL-C concentrations (p < .01), but associations were more positive with increasing age (CD4-age/VL-age interactions, p < .01). CD4 count <200 cells/μL was associated with lower non-HDL-C among patients aged <50 years [β = -7.8 mg/dL (95% confidence interval, CI: -13.2 to -2.4)] but higher non-HDL-C among patients aged 60-69 years [β = +8.1 mg/dL (95% CI: 0.02-16.2)]. VL ≥200 copies/mL was associated with lower non-HDL-C among patients aged <50 years [β = -3.3 mg/dL (95% CI: -6.7 to 0.1)] but higher non-HDL-C among patients aged ≥70 years [β = +16.0 mg/dL (95% CI: -1.4 to 33.3)], although precision was reduced in age-stratified analyses. Although no age differences were detected for HDL-C, VL ≥200 copies/mL was more strongly associated with lower HDL-C concentrations when CD4 count was <200 cells/μL [β = -7.0 mg/dL (95% CI: -9.7 to -4.3)] versus 200-500 cells/μL [β = -4.2 (95% CI: -5.9 to -2.6)] or >500 cells/μL [β = -2.2 (95% CI: -3.7 to -0.8)] (CD4-VL interaction, p < .01). We detected a novel age-modified relationship between immunosuppression and viremia and atherogenic cholesterol patterns. These findings may contribute to our understanding of the high risk of dyslipidemia observed among persons aging with HIV.

Cardiometabolic risk factors in preschool children with abdominal obesity from Medellín, Colombia.

Background Abdominal obesity (AO) is linked to inflammation and insulin resistance (IR). However, there is limited information on whether preschoolers with AO present these risk factors. We evaluated the association between AO and cardiovascular risk factors in preschoolers. Methods We enrolled 232 children (2-5 years), of whom 50% had AO. Serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), high-density lipoprotein-cholesterol (HDL-c), triglycerides (TG), apolipoprotein B (Apo-B) and apolipoprotein A-1 (Apo-A1), glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, monocyte chemoattractant protein (MCP-1/CCL2), leptin, adiponectin, vascular cell adhesion molecule (VCAM-1/CD106) and intercellular adhesion molecule (ICAM-1/CD54) were measured. The homeostatic model assessment of IR (HOMA-IR) was calculated. We analyzed these variables according to the presence of AO and other metabolic syndrome (MetS) components. Results A total of 75.8% of children with AO had one or more risk factors for MetS. Children with AO had significantly higher body mass indexes (BMIs), insulin, HOMA-IR, TG, very low-density lipoprotein-cholesterol (VLDL-c) and TC/HDL-c ratio and lower HDL-c, compared to children without AO; but there were no differences in inflammatory markers. After adjusting for BMI, sex and age, the differences between groups were not significant for any variable. Waist circumference (WC) was correlated with insulin (r=0.547; p<0.001), TG (r=0.207; p=0.001), ICAM-1 (r=0.213; p=0.039), hs-CRP (r=0.189; p=0.015) and glucose (r=0.187; p=0.004). After adjusting for BMI, age and sex, AO plus one MetS component contributed to individual variation in glucose, insulin, HOMA-IR and TG. Conclusions AO in preschool children is associated with greater IR and atherogenic lipid profiles, although these findings seem to be more related to general obesity than just central obesity. In addition, our data suggest that IR may precede the elevation of systemic cytokines in obese children, unlike findings in adults. More studies in pediatric populations are needed to elucidate these associations.

Moderate weight loss attenuates chronic endoplasmic reticulum stress and mitochondrial dysfunction in human obesity

ObjectiveIn obese patients undergoing caloric restriction, there are several potential mechanisms involved in the improvement of metabolic outcomes. The present study further explores whether caloric restriction can modulate endoplasmic reticulum (ER) stress and mitochondrial function, as both are known to be mechanisms underlying inflammation and insulin resistance (IR) during obesity. MethodsA total of 64 obese patients with BMI ≥35 kg/m2 underwent a dietary program consisting of 6 weeks of a very-low-calorie diet followed by 18 weeks of low-calorie diet. We evaluated changes in the metabolic and inflammatory markers -TNFα, hsCRP, complement component 3 (C3c), and retinol binding protein 4 (RBP4)-, in the ER stress markers and modulators -eIF2α-P, sXBP1, ATF6, JNK-P, CHOP, GRP78, and SIRT1-, and in mitochondrial function parameters -mitochondrial reactive oxygen species (mROS), glutathione peroxidase 1 (GPX1), cytosolic Ca2+, and mitochondrial membrane potential. ResultsThe dietary intervention produced an 8.85% weight loss associated with enhanced insulin sensitivity, a less marked atherogenic lipid profile, and a decrease in systemic inflammation (TNFα, hsCRP) and adipokine levels (RBP4 and C3c). Chronic ER stress was significantly reduced (ATF6-CHOP, JNK-P) and expression levels of SIRT1 and GRP78 – a Ca2+-dependent chaperone – were increased and accompanied by the restoration of Ca2+ depots. Furthermore, mROS production and mitochondrial membrane potential improvement were associated with the up-regulation of the antioxidant enzyme GPX1. ConclusionsOur data provide evidence that moderate weight loss attenuates systemic inflammation and IR and promotes the amelioration of ER stress and mitochondrial dysfunction, increasing the expression of chaperones, SIRT1 and antioxidant GPX1.

30. Maternal lipid profile in early pregnancy and the link with blood pressure and pregnancy complications

Introduction An atherogenic lipid profile is a risk factor for atherosclerosis and consequently for stroke and cardiovascular disease (CVD). An atherogenic lipid profile can cause endothelial dysfunction and consequently higher blood pressure (BP). Placentas of women with a gestational hypertensive disorder (GHD) are histologically comparable to an early stage of atherosclerosis. Objective To determine the association between maternal lipid profile in early pregnancy, GHD and BP throughout pregnancy and six and nine years after pregnancy. Methods We included 5692 women from The Generation R Study; an ongoing population-based prospective birth cohort. 218 (4.1%) women developed gestational hypertension (GH) and 139 (2.6%) women developed pre-eclampsia (PE). Maternal lipid levels included total-cholesterol, triglycerides and HDL-c, and were measured in early pregnancy (median 13.4 weeks of gestation). LDL-c, remnant cholesterol and non-HDL-c were calculated. Systolic and diastolic BP were measured in early, mid- and late pregnancy, and six and nine years after pregnancy. Results In the total population, total-cholesterol, triglycerides, LDL-c, remnant cholesterol and non-HDL-c were positively associated with BP in early, mid- and late pregnancy, six and nine years after pregnancy. Women with PE had higher levels of triglycerides and remnant cholesterol in early pregnancy compared to those with a normotensive pregnancy. Maternal lipid levels in early pregnancy were not associated with GH. Discussion An atherogenic lipid profile in pregnancy is positively associated with BP throughout pregnancy, and six and nine years after pregnancy. In particular triglycerides are important for the risk for PE. Lipid levels in early pregnancy might help to identify women at risk for not only PE, but also future hypertension and consequently initiate early prevention of future CVD.