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Context Cottonseed oil (CSO) is higher in polyunsaturated fatty acids (PUFA) and saturated fatty acids (SFAs) than many liquid plant oils. Objectives To conduct a systematic review of randomized controlled trials (RCTs) examining effects of CSO on markers of lipid metabolism and evaluate lipid and lipoprotein effects of incorporating CSO into a healthy dietary pattern using regression equations. Data Sources A systematic search was conducted for RCTs comparing CSO with a non-CSO comparator in any population. Data Analyses The Katan regression equation was used to predict lipid/lipoprotein changes when incorporating CSO into a US-style healthy eating pattern at 25 to 100% of the total oil allowance (ie, 27 g/2000 kcal) compared with average American intake (NHANES 2017 to 2020 pre-COVID pandemic). Results In total, 3 eligible publications (n = 2 trials), with 58 participants that provided 44% and 30% of total energy as CSO, were included. Fasting low-density lipoprotein cholesterol (LDL-C; ≈ –7.7 mg/dL) and triglycerides (≈ –7.5 mg/dL) were lower after 5 days of a CSO-enriched diet vs olive oil (OO). In a 56-day trial, CSO lowered total cholesterol (TC; ≈ –14.8 mg/dL), LDL-C (≈ –14.0 mg/dL), and non–high-density lipoprotein cholesterol (≈ –14.2 mg/dL) vs OO. Postprandially, angiopoietin-like protein-3, -4, and -8 concentrations decreased with CSO and increased with OO intake. Compared with average American intake, a healthy eating pattern with 27 g of CSO was estimated to lower TC (–8.1 mg/dL) and LDL-C (–7.3 mg/dL) levels, with minimal reduction in high-density lipoprotein cholesterol (–1.1 mg/dL). Compared with the healthy eating pattern, incorporating 27 g of CSO was predicted to increase TC and LDL-C levels by 2.4 mg/dL. Conclusion Limited high-quality research suggests CSO may improve lipid/lipoprotein levels compared with OO. Cholesterol predictive equations suggest CSO can be incorporated into a healthy dietary pattern without significantly affecting lipids/lipoproteins. [ABSTRACT FROM AUTHOR]

Objective Low-density lipoprotein cholesterol (LDL-C) has been commonly calculated by equations, but their performance has not been entirely satisfactory. This study aimed to develop a more accurate LDL-C prediction model using machine learning methods. Methods The study involved predicting directly measured LDL-C, using individual characteristics, lipid profiles, and other laboratory results as predictors. The models applied to predict LDL-C values were multiple regression, penalized regression, random forest, and XGBoost. Additionally, a novel 2-step prediction model was developed and introduced. The machine learning methods were evaluated against the Friedewald, Martin, and Sampson equations. Results The Friedewald, Martin, and Sampson equations had root mean squared error (RMSE) values of 12.112, 8.084, and 8.492, respectively, whereas the 2-step prediction model showed the highest accuracy, with an RMSE of 7.015. The LDL-C levels were also classified as a categorical variable according to the diagnostic criteria of the dyslipidemia treatment guideline, and concordance rates were calculated between the predictive values obtained from each method and the directly measured ones. The 2-step prediction model had the highest concordance rate (85.1%). Conclusion The machine learning method can calculate LDL-C more accurately than existing equations. The proposed 2-step prediction model, in particular, outperformed the other machine learning methods. [ABSTRACT FROM AUTHOR]

The goal of this narrative review is to summarize the effects of prolonged fasting on various metabolic health measures, including body weight, blood pressure, plasma lipids, and glycemic control. Prolonged fasting is characterized by consciously eating little to no food or caloric beverages for several days to weeks. Results reveal that prolonged fasting for 5–20 days produces potent increases in circulating ketones, and mild to moderate weight loss of 2–10%. Approximately two-thirds of the weight lost is lean mass, and one-third is fat mass. The excessive lean mass loss suggests that prolonged fasting may increase the breakdown of muscle proteins, which is a concern. Systolic and diastolic blood pressure consistently decreased with prolonged fasting. However, the impact of these protocols on plasma lipids is less clear. While some trials demonstrate decreases in LDL cholesterol and triglycerides, others show no benefit. With regard to glycemic control, reductions in fasting glucose, fasting insulin, insulin resistance, and glycated hemoglobin (HbA1c) were noted in adults with normoglycemia. In contrast, these glucoregulatory factors remained unchanged in patients with type 1 or type 2 diabetes. The effects of refeeding were also examined in a few trials. It was shown that 3–4 months after the fast was completed, all metabolic benefits were no longer observed, even when weight loss was maintained. With regard to adverse events, metabolic acidosis, headaches, insomnia, and hunger were observed in some studies. In summary, prolonged fasting appears to be a moderately safe diet therapy that can produce clinically significant weight loss (>5%) over a few days or weeks. However, the ability of these protocols to produce sustained improvements in metabolic markers warrants further investigation. [ABSTRACT FROM AUTHOR]

Background Lower skeletal muscle mitochondrial function is associated with future cognitive impairment and mobility decline, but the biological underpinnings for these associations are unclear. We examined metabolomic markers underlying skeletal muscle mitochondrial function, cognition and motor function. Methods We analysed data from 560 participants from the Baltimore Longitudinal Study of Aging (mean age: 68.4 years, 56% women, 28% Black) who had data on skeletal muscle oxidative capacity (post-exercise recovery rate of phosphocreatine, kPCr) via 31P magnetic resonance spectroscopy and targeted plasma metabolomics using LASSO model. We then examined which kPCr-related markers were also associated with cognition and motor function in a larger sample (n = 918, mean age: 69.4, 55% women, 27% Black). Results The LASSO model revealed 24 metabolites significantly predicting kPCr, with the top 5 being asymmetric dimethylarginine, lactic acid, lysophosphatidylcholine a C18:1, indoleacetic acid and triacylglyceride (17:1_34:3), also significant in multivariable linear regression. The kPCr metabolite score was associated with cognitive or motor function, with 2.5-minute usual gait speed showing the strongest association (r = 0.182). Five lipids (lysophosphatidylcholine a C18:1, phosphatidylcholine ae C42:3, cholesteryl ester 18:1, sphingomyelin C26:0, octadecenoic acid) and 2 amino acids (leucine, cystine) were associated with both cognitive and motor function measures. Conclusion Our findings add evidence to the hypothesis that mitochondrial function is implicated in the pathogenesis of cognitive and physical decline with aging and suggest that targeting specific metabolites may prevent cognitive and mobility decline through their effects on mitochondria. Future omics studies are warranted to confirm these findings and explore mechanisms underlying mitochondrial dysfunction in aging phenotypes. [ABSTRACT FROM AUTHOR]

Background Childhood cancer survivors have increased risk of dyslipidemia and atherosclerotic cardiovascular disease (CVD). The aim of this study was to evaluate the prevalence and associated cardiovascular risks of specific lipid abnormalities among childhood cancer survivors. Methods Comprehensive lipid panel measurements were obtained from 4115 5-year survivors, with 3406 (mean age at evaluation = 35.2 years, SD = 10.4 years) not having previous dyslipidemia diagnosis, as well as 624 age, sex, and race and ethnicity matched community controls. Results Previously undiagnosed dyslipidemia with abnormal low-density lipoprotein (LDL) cholesterol (>160 mg/dL), non–high density lipoprotein (HDL) cholesterol (>190 mg/dL), HDL cholesterol (<40 mg/dL for men, <50 mg/dL for women), and triglycerides (>150 mg/dL) were identified in 4%, 6%, 30%, and 17%, respectively. Survivors without previous dyslipidemia diagnosis had higher LDL cholesterol and non-HDL cholesterol and lower HDL cholesterol than community controls. Cranial radiotherapy (relative risk [RR] = 2.2, 95% confidence interval [CI] = 1.6 to 3.0 for non-HDL cholesterol) and total body irradiation for hematopoietic cell transplantation (RR = 6.7, 95% CI = 3.5 to 13.0 for non-HDL cholesterol; RR = 9.9, 95% CI = 6.0 to 16.3 for triglycerides) were associated with greater risk of dyslipidemia. Diagnoses of low HDL cholesterol (hazard ratio [HR] = 2.9, 95% CI = 1.8 to 4.7) and elevated triglycerides (HR = 3.1, 95% CI = 1.9 to 5.1) were associated with increased risk for myocardial infarction, and diagnoses of high LDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), high non-HDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), low HDL cholesterol (HR = 3.9, 95% CI = 2.8 to 5.4), and elevated triglycerides (HR = 3.8, 95% CI = 2.7 to 5.5) were associated with increased risk for cardiomyopathy. Conclusions Previously undiagnosed dyslipidemia among childhood cancer survivors was associated with increased risk for myocardial infarction and cardiomyopathy. Comprehensive dyslipidemia evaluation and treatment are needed to reduce cardiovascular morbidity in this population. [ABSTRACT FROM AUTHOR]

Background Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed. Materials and Methods We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoproteins [LDL], high-density lipoproteins [HDL]) of patients with consecutive solid cancer treated with ICIs, and we investigated their role in predicting clinical outcomes. Results At a median follow-up of 32.9 months, among 430 enrolled patients, those with TC ≥ 200 mg/dl showed longer median progression-free survival (mPFS; 6.6 vs. 4.7 months, P  = .4), although not reaching statistical significance, and significantly longer median overall survival (mOS; 19.4 vs. 10.8 months, P  = .02) compared to those with TC < 200 mg/dl. Conversely, patients with TG ≥150 mg/dl displayed shorter PFS (3.4 vs. 5.1 months, P  = .02) and OS (7.1 vs. 12.9 months, P  = .009) compared to those with TG <150 mg/dl. TC and TG were then combined in a "LIPID score" identifying three subgroups: good-risk (GR) (TC ≥200 mg/dl and TG <150 mg/dl), intermediate-risk (IR) (TC <200 mg/dl and TG <150 mg/dl or TC ≥200 mg/dl and TG ≥150 mg/dl) and poor-risk (PR) (TC <200 mg/dl and TG ≥150 mg/dl). The mPFS of GR, IR, and PR groups was 7.8, 4.3, and 2.5 months, respectively (P  = .005); mOS of GR, IR, and PR was 20.4, 12.4, and 5.3 months, respectively (P  < .001). At multivariable analysis, the PR profile represented an independent poor prognostic factor for both PFS and OS. Conclusions We developed a lipid score that defined subgroups of patients with cancer who differently benefit from ICIs. Further mechanistic insights are warranted to clarify the prognostic and predictive role of lipid profile components in patients treated with ICIs. [ABSTRACT FROM AUTHOR]

Context Nonalcoholic fatty liver disease (NAFLD) is prevalent in 25–30% of British and European populations, representing a potential global public health crisis. Marine omega-3 (n-3) polyunsaturated fatty acids offer well-evidenced benefits to NAFLD biomarkers; however, the effect of plant-based n-3 has not been evaluated with a systematic review and meta-analysis. Objective The review aimed to systematically evaluate the effect of plant-based n-3 supplementation on NAFLD surrogate biomarkers and parameters. Data Sources Medline (EBSCO), PubMed, CINAHL (EBSCO), Cochrane Central Register of Controlled Trials, the International Clinical Trials Registry Platform, and Google Scholar databases were searched to identify randomized controlled trials published between January 1970 and March 2022 evaluating the impact of plant-based n-3 interventions on diagnosed NAFLD. The review followed the PRISMA checklist and is PROSPERO registered (CRD42021251980). Data Extraction A random-effects model and generic inverse variance methods synthesized quantitative data, followed by a leave-one-out method for sensitivity analysis. We identified 986 articles; after the application of selection criteria, six studies remained with 362 patients with NAFLD. Results The meta-analysis showed that plant-based n-3 fatty acid supplementation significantly reduced alanine aminotransferase (ALT) (mean difference: 8.04 IU/L; 95% confidence interval: 14.70, 1.38; I2 = 48.61%) and plasma/serum triglycerides (44.51 mg/dL; 95% confidence interval: –76.93, –12.08; I2 = 69.93%), alongside body-composition markers in patients with NAFLD (P < 0.05). Conclusion Plant-based n-3 fatty acid supplementation improves ALT enzyme biomarkers, triglycerides, body mass index, waist circumference, and weight loss when combined with lifestyle interventions to increase physical activity and a calorie-controlled diet. Further research is needed to identify the most effective plant-based n-3 sources in larger numbers of patients with NAFLD over longer study durations. Systematic Review Registration PROSPERO registration no. CRD42021251980. [ABSTRACT FROM AUTHOR]

Context Cardiovascular disease is the leading cause of death worldwide. Low-calorie, low-fat therapeutic diets (TDs) developed by the US National Cholesterol Education Program, ie, the Step I and II diets and the therapeutic lifestyle changes diet, are approximately similar and are the initial therapeutic interventional approaches for lifestyle modification. Objective This systematic review with meta-analysis was undertaken to evaluate the effects of TDs diet on blood lipids, apolipoprotein A-1, apolipoprotein B, blood pressure, fasting blood glucose, and insulin. Data Sources A comprehensive search of the PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar databases until October 2022 was performed to identify clinical trials investigating the effects of TDs on the aforementioned parameters. Data Extraction One investigator screened the records and extracted data, and another reviewed the extracted data. Data Analysis A total of 910 records were retrieved. After records were screened for eligibility, 34 clinical trials met the inclusion criteria. The pooled analysis from the random-effects model revealed a significant reduction in total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-1, and apolipoprotein B in the TD intervention group vs the control group. The overall effects of TDs on fasting blood glucose, insulin, and blood pressure were not significant, but the results of subgroup analysis revealed a significant reduction in fasting blood glucose with the Step II diet and an intervention duration of more than 24 weeks. For blood pressure, the Step I diet and an intervention duration of more than 24 weeks resulted in significant reduction. There was no evidence of publication bias, but strong heterogeneity was observed. Conclusion Therapeutic diets have promising effects on lipid profile parameters, glycemic indexes, and blood pressure, which can promote cardiovascular health. Systematic Review Registration PROSPERO registration no. CRD42021259355. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of death in women and men globally, with most due to atherosclerotic cardiovascular disease (ASCVD). Despite progress during the last 30 years, ASCVD mortality is now increasing, with the fastest relative increase in middle-aged women. Missed or delayed diagnosis and undertreatment do not fully explain this burden of disease. Sex-specific factors, such as hypertensive disorders of pregnancy, premature menopause (especially primary ovarian insufficiency), and polycystic ovary syndrome are also relevant, with good evidence that these are associated with greater cardiovascular risk. This position statement from the European Atherosclerosis Society focuses on these factors, as well as sex-specific effects on lipids, including lipoprotein(a), over the life course in women which impact ASCVD risk. Women are also disproportionately impacted (in relative terms) by diabetes, chronic kidney disease, and auto-immune inflammatory disease. All these effects are compounded by sociocultural components related to gender. This panel stresses the need to identify and treat modifiable cardiovascular risk factors earlier in women, especially for those at risk due to sex-specific conditions, to reduce the unacceptably high burden of ASCVD in women. [ABSTRACT FROM AUTHOR]

Aims It is unclear whether higher triglyceride metabolism per se contributes to mortality separate from elevated triglyceride-rich lipoproteins and body mass index. This study tested the hypotheses that higher triglyceride metabolism, measured as higher plasma glycerol and β-hydroxybutyrate, is associated with increased all-cause, cardiovascular, cancer, and other mortality. Methods and results This study included 30 000 individuals nested within 109 751 individuals from the Copenhagen General Population Study. During a median follow-up of 10.7 years, 9897 individuals died (2204 from cardiovascular, 3366 from cancer, and 2745 from other causes), while none were lost to follow-up. In individuals with glycerol >80 µ mol/L (highest fourth) vs. individuals with glycerol <52 µ mol/L (lowest fourth), the multivariable adjusted hazard ratio for all-cause mortality was 1.31 (95% confidence interval 1.22–1.40). In individuals with β-hydroxybutyrate >154 µ mol/L (highest fourth) vs. individuals with β-hydroxybutyrate <91 µ mol/L (lowest fourth), the multivariable adjusted hazard ratio for all-cause mortality was 1.18 (1.11–1.26). Corresponding values for higher plasma glycerol and β-hydroxybutyrate were 1.37 (1.18–1.59) and 1.18 (1.03–1.35) for cardiovascular mortality, 1.24 (1.11–1.39) and 1.16 (1.05–1.29) for cancer mortality, and 1.45 (1.28–1.66) and 1.23 (1.09–1.39) for other mortality, respectively. Results were robust to exclusion of first years of follow-up, to stratification for covariates including plasma triglycerides and body mass index, and to further adjustments. Conclusion This study observed an increased risk of all-cause, cardiovascular, cancer, and other mortality with higher triglyceride metabolism. This was not explained by higher plasma triglycerides and body mass index. The hypothesis studied in the present paper should be further validated by isotope flux studies. [ABSTRACT FROM AUTHOR]

Context A recent US national survey of the health status of the male transgender population has raised awareness about the little-studied relationship between testosterone hormone therapy in transgender men and cardiovascular outcomes. Objective The aim of this systematic review was to assess the relationship between cross-sex hormone therapy in transgender men and lipid profiles and cardiovascular risk. Data Sources The PubMed, SciELO, SpringerLink, and EBSCOhost databases were searched up to March 2021 for studies assessing the association between cross-sex hormone therapy and the incidence of outcomes related to cardiovascular disease in transgender men over 18 years of age. Data Extraction Data extracted were sorted into clinical data (systolic, diastolic, and mean blood pressure), anthropometric data (body mass index, weight, waist circumference, fat mass, and lean mass), and biochemical data (triglycerides, total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], very low-density lipoprotein cholesterol [VLDL-C], and the HDL-C to LDL-C ratio). Data Analysis Study quality was appraised independently by two reviewers using the Cochrane tools for assessment of methodological quality or risk of bias in nonrandomized studies, and the Newcastle-Ottawa Scale was applied. Of 735 studies identified, 11 were included in the review. Most studies reported no change in cholesterol or triglyceride levels after hormone treatment. A reduction in HDL-C levels was observed in 7 of 11 studies, although this alone cannot be considered a cardiovascular risk factor. Likewise, clinical and anthropometric findings showed no changes predictive of cardiovascular risk. Conclusions Although these findings suggest that hormone therapy may lead to a decrease in HDL-C levels and an increase in LDL-C levels, they are insufficient to establish a relationship with cardiovascular disease. Furthermore, no significant effects on metabolic and anthropometric values were found. Further studies with higher quality and longer follow-up periods are needed to establish cardiovascular risk. Systematic Review Registration PROSPERO registration number CRD 42020212560. [ABSTRACT FROM AUTHOR]

Variability in sleep duration and cardiovascular health have been infrequently investigated, particularly among reproductive-age women. We examined these associations across the menstrual cycle among a cohort of 250 healthy premenopausal women, aged 18-44 years. The BioCycle study (New York, 2005–2007) collected cardiovascular biomarkers (serum high- and low-density lipoprotein (HDL, LDL), total cholesterol, triglycerides, and C-reactive protein (CRP)) at key time points along the menstrual cycle (follicular, ovulatory, and luteal phases). Women also recorded sleep duration in daily diaries. From these data, we computed L-moments, robust versions of location, dispersion, skewness, and kurtosis. We fitted linear mixed models with random intercepts and inverse probability weighting to estimate associations between sleep variability and cardiovascular biomarkers, accounting for demographic, lifestyle, health, and reproductive factors. Sleep dispersion (any deviation from mean duration) was associated with lower mean LDL for nonshift workers and non-White women. Skewed sleep duration was associated with higher mean CRP and lower mean total cholesterol. Sleep durations with extreme short and long bouts (kurtosis) were associated with a lower mean HDL, but not mean CRP, LDL, or triglycerides. Sleep duration modified associations between sleep dispersion and LDL, HDL, and total cholesterol. Even in young and healthy women, sleep duration variability could influence cardiovascular health. [ABSTRACT FROM AUTHOR]

Objectives Emerging evidence demonstrates that aPS-PT associate with thrombotic events. Genetic predisposition, including HLA-DRB1 alleles, is known to contribute to the occurrence of conventional aPL [anti-β2glycoprotein-I (anti-β2GPI) and aCL]. We investigated associations between aPS-PT and HLA-DRB1 * alleles and thrombosis in SLE. Conventional aPL were included for comparison. Methods We included 341 consecutive SLE patients, with information on general cardiovascular risk factors, including blood lipids, LA and thrombotic events. aPS/PT, anti-β2GPI and aCL of IgA/G/M isotypes and LA were quantified. Results aPS/PT antibodies associated positively with HLA-DRB1 *13 [odds ratio (OR) 2.7, P  = 0.002], whereas anti-β2GPI and aCL antibodies associated primarily with HLA-DRB1*04 (OR 2.5, P  = 0.0005). These associations remained after adjustment for age, gender and other HLA-DRB1 * alleles. HLA-DRB1*13 , but not DRB1*04 , remained as an independent risk factor for thrombosis and APS after adjustment for aPL and cardiovascular risk factors. The association between DRB1*13 and thrombosis was mediated by aPS-PT positivity. HLA-DRB1*03 , on the other hand, associated negatively with thrombotic events as well as all aPL using both uni- and multivariate analyses. HLA-DRB1*03 had a thrombo-protective effect in aPL-positive patients. Additionally, HLA-DRB1*03 was associated with a favourable lipid profile regarding high-density lipoprotein and triglycerides. Conclusions HLA-DRB1*13 confers risk for both aPS-PT and thrombotic events in lupus. The association between HLA-DRB1*13 and thrombosis is largely, but not totally, mediated through aPS-PT. HLA-DRB1*03 was negatively associated with aPL and positively with favourable lipid levels. Thus, HLA-DRB1*03 seems to identify a subgroup of SLE patients with reduced vascular risk. [ABSTRACT FROM AUTHOR]

Aims: Psychological stress has been linked to lipid dysregulation with noticeable gender differences, but it remains unclear whether women are more susceptible to non-optimal lipid levels than men, when experiencing stressful life events. This study aims to examine the association between stressful life events and non-optimal lipid levels among persons with hyperlipidaemia and whether the association differs between men and women. Methods and results: A nested case–control study was performed using data from the Wisconsin Sleep Cohort (WSC) Study from 2011 to 2015, including 224 participants with hyperlipidaemia and without a history of myocardial infarction or heart failure. Among them, 63 participants with non-optimal LDL cholesterol or triglyceride levels were identified as cases, and 161 participants with optimal LDL cholesterol and triglyceride levels were identified as controls. Cases and controls were traced back to their self-reported life events collected through the Retirement and Sleep Trajectories study during 2010–11. The association between stressful life events and non-optimal lipid levels was examined using multivariable logistic regression; confounding effects were addressed using propensity score weighting and Mahalanobis distance matching; gender differences were examined using subgroup analysis. Results showed that a higher number of stressful life events during 2010–11 was associated with greater odds of non-optimal lipid levels during 2011–15 (odds ratio = 1.45, P = 0.03) among women with hyperlipidaemia, whereas the association was not significant among men with hyperlipidaemia (P = 0.910). Conclusion: Future studies are needed to examine the underlying mechanisms that explain gender differences in the association between stressful life events and non-optimal lipid levels. Registration: ClinicalTrials.gov NCT00005557 Graphical Abstract [ABSTRACT FROM AUTHOR]

Background the effects regarding n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on sarcopenia have been explored by several clinical trials. Nonetheless, the use of n-3 PUFA for improving body composition, muscle strength and physical performance in older people is conflicting. Objectives our aim was to perform a randomised, double-blind, controlled trial to evaluate the effects of 6-month n-3 PUFA supplementation on body composition, muscle strength and physical performance in older Chinese people. Methods in this double-blind, placebo-controlled trial, 200 eligible subjects were randomly assigned to receive 4 g/day fish oil capsules (1.34 g eicosapentaenoic [EPA] + 1.07 docosahexaenoic [DHA]) or 4 g/day corn oil capsules (EPA + DHA <0.05 g) for 6 months. The primary outcomes were the changes of body composition, muscle strength (hand grip strength) and physical performance (Timed Up and Go time). Secondary outcomes were the changes in serum lipid profiles. Results compared with control group, fish oil-derived n-3 PUFA supplementation resulted in significant increases in thigh circumference (interaction time × group effect P  < 0.001), total skeletal muscle mass (interaction time × group effect P  < 0.001) and appendicular skeletal muscle mass (interaction time × group effect P  < 0.001); the differences were still significant even after height correction. Muscle strength and physical performance including hand grip strength (interaction time × group effect P  < 0.001) and Timed Up and Go time (interaction time × group effect P  < 0.001) were also improved after a 6-month fish oil-derived n-3 PUFA intervention. In terms of serum lipid profiles, fish oil-derived n-3 PUFA supplementation could significantly reduce serum level of triglyceride (interaction time × group effect P  = 0.012) and increase high density lipoprotein cholesterol (interaction time × group effect P  < 0.001); while no significant improvement was found in serum concentrations of total cholesterol (interaction time × group effect P  = 0.413) and low density lipoprotein cholesterol (interaction time × group effect P  = 0.089). Conclusions our present trial demonstrated that a 6-month fish oil-derived n-3 PUFA supplementation could beneficially affect the body composition, muscle strength, physical performance and serum lipid profiles in older people, which could be into considerations when making strategies aiming to the primary prevention of sarcopenia. [ABSTRACT FROM AUTHOR]

Many genetic risk factors for Parkinson's disease have lipid-related functions and lipid-modulating drugs such as statins may be protective against Parkinson's disease. Moreover, the hallmark Parkinson's disease pathological protein, α-synuclein, has lipid membrane function and pathways dysregulated in Parkinson's disease such as the endosome-lysosome system and synaptic signalling rely heavily on lipid dynamics. Despite the potential role for lipids in Parkinson's disease, most research to date has been protein-centric, with large-scale, untargeted serum and CSF lipidomic comparisons between genetic and idiopathic Parkinson's disease and neurotypical controls limited. In particular, the extent to which lipid dysregulation occurs in mutation carriers of one of the most common Parkinson's disease risk genes, LRRK2, is unclear. Further, the functional lipid pathways potentially dysregulated in idiopathic and LRRK2 mutation Parkinson's disease are underexplored. To better determine the extent of lipid dysregulation in Parkinson's disease, untargeted high-performance liquid chromatography-tandem mass spectrometry was performed on serum (n = 221) and CSF (n = 88) obtained from a multi-ethnic population from the Michael J. Fox Foundation LRRK2 Clinical Cohort Consortium. The cohort consisted of controls, asymptomatic LRRK2 G2019S carriers, LRRK2 G2019S carriers with Parkinson's disease and Parkinson's disease patients without a LRRK2 mutation. Age and sex were adjusted for in analyses where appropriate. Approximately 1000 serum lipid species per participant were analysed. The main serum lipids that distinguished both Parkinson's disease patients and LRRK2 mutation carriers from controls included species of ceramide, triacylglycerol, sphingomyelin, acylcarnitine, phosphatidylcholine and lysophosphatidylethanolamine. Significant alterations in sphingolipids and glycerolipids were also reflected in Parkinson's disease and LRRK2 mutation carrier CSF, although no correlations were observed between lipids identified in both serum and CSF. Pathway analysis of altered lipid species indicated that sphingolipid metabolism, insulin signalling and mitochondrial function were the major metabolic pathways dysregulated in Parkinson's disease. Importantly, these pathways were also found to be dysregulated in serum samples from a second Parkinson's disease cohort (n = 315). Results from this study demonstrate that dysregulated lipids in Parkinson's disease generally, and in LRRK2 mutation carriers, are from functionally and metabolically related pathways. These findings provide new insight into the extent of lipid dysfunction in Parkinson's disease and therapeutics manipulating these pathways may be beneficial for Parkinson's disease patients. Moreover, serum lipid profiles may be novel biomarkers for both genetic and idiopathic Parkinson's disease. [ABSTRACT FROM AUTHOR]

Growth in early infancy is hypothesized to affect chronic disease risk factors later in life. To date, most reports draw on European-ancestry cohorts with few repeated observations in early infancy. We investigated the association between infant growth before 6 months and lipid levels in adolescents in a Hispanic/Latino cohort. We characterized infant growth from birth to 5 months in male (n  = 311) and female (n  = 285) infants from the Santiago Longitudinal Study (1991–1996) using 3 metrics: weight (kg), length (cm), and weight-for-length (g/cm). Superimposition by translation and rotation (SITAR) and latent growth mixture models (LGMMs) were used to estimate the association between infant growth characteristics and lipid levels at age 17 years. We found a positive relationship between the SITAR length velocity parameter before 6 months of age and high-density lipoprotein cholesterol levels in adolescence (11.5, 95% confidence interval; 3.4, 19.5), indicating higher high-density lipoprotein cholesterol levels occurring with faster length growth. The strongest associations from the LGMMs were between higher low-density lipoprotein cholesterol and slower weight-for-length growth, following a pattern of associations between slower growth and adverse lipid profiles. Further research in this window of time can confirm the association between early infant growth as an exposure and adolescent cardiovascular disease risk factors. [ABSTRACT FROM AUTHOR]

Lipid disorders involving derangements in serum cholesterol, triglycerides, or both are commonly encountered in clinical practice and often have implications for cardiovascular risk and overall health. Recent advances in knowledge, recommendations, and treatment options have necessitated an updated approach to these disorders. Older classification schemes have outlived their usefulness, yielding to an approach based on the primary lipid disturbance identified on a routine lipid panel as a practical starting point. Although monogenic dyslipidemias exist and are important to identify, most individuals with lipid disorders have polygenic predisposition, often in the context of secondary factors such as obesity and type 2 diabetes. With regard to cardiovascular disease, elevated low-density lipoprotein cholesterol is essentially causal, and clinical practice guidelines worldwide have recommended treatment thresholds and targets for this variable. Furthermore, recent studies have established elevated triglycerides as a cardiovascular risk factor, whereas depressed high-density lipoprotein cholesterol now appears less contributory than was previously believed. An updated approach to diagnosis and risk assessment may include measurement of secondary lipid variables such as apolipoprotein B and lipoprotein(a), together with selective use of genetic testing to diagnose rare monogenic dyslipidemias such as familial hypercholesterolemia or familial chylomicronemia syndrome. The ongoing development of new agents—especially antisense RNA and monoclonal antibodies—targeting dyslipidemias will provide additional management options, which in turn motivates discussion on how best to incorporate them into current treatment algorithms. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to characterize the systemic lipid profile of patients with asymptomatic hyperuricemia (HUA) and gout using lipidomics, and to find potential underlying pathological mechanisms therefrom. Methods Sera were collected from Affiliated Hospital of Nanjing University of Chinese Medicine as centre 1 (discovery and internal validation sets) and Suzhou Hospital of Traditional Chinese Medicine as centre 2 (external validation set), including 88 normal subjects, 157 HUA and 183 gout patients. Lipidomics was performed by ultra high performance liquid chromatography plus Q-Exactive mass spectrometry (UHPLC-Q Exactive MS). Differential metabolites were identifed by both variable importance in the projection ≥1 in orthogonal partial least-squares discriminant analysis mode and false discovery rate adjusted P ≤ 0.05. Biomarkers were found by logistic regression and receiver operating characteristic (ROC) analysis. Results In the discovery set, a total of 245 and 150 metabolites, respectively, were found for normal subjects vs HUA and normal subjects vs gout. The disturbed metabolites included diacylglycerol, triacylglycerol (TAG), phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, etc. We also found 116 differential metabolites for HUA vs gout. Among them, the biomarker panel of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 could differentiate well between HUA and gout. The area under the receiver operating characteristic ROC curve was 0.8288, the sensitivity was 82% and the specificity was 78%, at a 95% CI 0.747, 0.9106. In the internal validation set, the predictive accuracy of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 panel for differentiation of HUA and gout reached 74.38%, while it was 84.03% in external validation set. Conclusion We identified serum biomarkers panel that have the potential to predict and diagnose HUA and gout patients. [ABSTRACT FROM AUTHOR]

Background Blood lipids and glucose levels dysregulation represent potential mechanisms intermediating the adverse cardiovascular effects of ambient particulate matter (PM) exposure. This study aims to estimate the effect of long-term PM10 exposure on blood lipids and glucose levels and to assess the potential mediation and/or modification action of abdominal obesity (AO) (waist-to-height ratio). Methods Our study was based on 2,390 participants of the first Portuguese Health Examination Survey (INSEF, 2015) with available data on blood lipids and glucose parameters and living within a 30-km radius of an air quality monitoring station with available PM10 measurements. PM10 concentrations were acquired from the air quality monitoring network of the Portuguese Environment Agency. Generalized linear models were used to assess the effect of 1-year PM10 exposure on blood lipids and glucose levels. An interaction term was introduced in the models to test the modification action of AO. Results We found an association between PM10 and non-fasting blood triglycerides (TG) after adjustment for age, sex, education, occupation, lifestyles-related variables and temperature but only in participants with AO. Per each 1 µg/m3 PM10 increment, there was a 1.84% (95% confidence interval: 0.02–3.69) increase in TG. For the remaining blood lipid and glucose parameters, no associations were found. Conclusions Our study demonstrates that even at low levels of exposure, long-term PM10 exposure interacts with AO to increase blood TG. Our findings suggest that reducing both AO prevalence and PM10 below current standards would result in additional health benefits for the population. [ABSTRACT FROM AUTHOR]

Context There is renewed interest in using very low-carbohydrate ketogenic (VLCK) diets to manage diabetes. Many clinical trials have been published, often with mixed results. Objective This meta-analysis compares the effect of a VLCK diet on glycemic control, body weight, lipid profile, medication use, and dropouts with that of recommended diets for 12 weeks or longer in people with type 2 diabetes. Data Sources Ovid MEDLINE, Ovid Embase, CENTRAL, and CINAHL databases were searched (January 1980 through September 2019). Study Selection Two authors independently reviewed search results to select randomized controlled trials (RCTs) comparing a VLCK diet (carbohydrate intake < 50 g/d or < 10% of total energy) with any recommended diet for type 2 diabetes in adults. Discrepancies were resolved after consulting with the third author. Data Extraction Eight RCTs with 648 participants were identified. Results Compared with control diets, the VLCK diet resulted in a greater decrease in hemoglobin A1c after 3 months (weighted mean difference[WMD]: −6.7 mmol/mol; 95%CI, −9.0 to −4.4) (WMD: −0.61%; 95%CI, −0.82 to −0.40; P  < 0.001; moderate-certainty evidence) and after 6 months (WMD: −6.3 mmol/mol; 95%CI, −9.3 to −3.5) (WMD: −0.58%; 95%CI, −0.85 to −0.32; low-certainty evidence). There was a significantly greater weight loss with the VLCK diet after 3 months (WMD: −2.91 kg; 95%CI, −4.88 to −0.95; low-certainty evidence) and after 6 months (WMD: −2.84 kg; 95%CI, −5.29 to −0.39; low-certainty evidence). The VLCK diet was not better than a control diet after 12 months. It was superior in decreasing triglyceride levels, increasing high-density lipoprotein cholesterol levels, and reducing the use of antidiabetic medications for up to 12 months. Conclusion The VLCK diet appears to control glycemia and decrease body weight for up to 6 months in people with obesity and diabetes. Beneficial changes in serum triglycerides and high-density lipoprotein cholesterol, along with reductions in antidiabetic medications, continued in the VLCK group until 12 months. However, the quality of currently available evidence is not sufficient to recommend VLCK diets. A major limitation of the VLCK diet is patients' lack of adherence to carbohydrate restriction. Systematic Review Registration PROSPERO registration number CRD42020154700 [ABSTRACT FROM AUTHOR]

Context Consumption of lean fish and fish-derived proteins were effective for improving lipid profiles in published studies; however, evidence remains inconclusive. Objective To evaluate the effectiveness of lean fish or fish-derived protein on serum/plasma lipid and lipoprotein levels by conducting a systematic review of the literature and meta-analysis of available randomized controlled trials (RCTs). Data sources Medline (Ovid), Scopus, CINAHL, and Food and Nutritional Sciences databases were searched from the start date of each database to September 2019 to identify RCTs determining the effect of lean fish on lipid profile. Study selection Included RCTs investigated lean fish and fish-derived proteins intake and determined at least 1 major lipid or lipoprotein measurement. Data extraction Two reviewers independently evaluated 1217 studies against the inclusion and exclusion criteria. Relevant studies were assessed for risks of bias, and random-effects meta-analysis was conducted to generate average estimates of effect. Results A total of 24 studies met the inclusion criteria. Meta-analysis of data from 18 to 21 eligible crossover and parallel-design RCTs with a total of 1392 to 1456 participants found triacylglycerol-lowering effects for lean fish compared with no fish consumption. Lean fish intake showed no significant differences related to total cholesterol or lipoprotein levels. Subanalysis showed that parallel-group RCTs tended to find greater reduction effects on circulating triacylglycerol than did crossover RCTs. Conclusion Additional better-designed, longer, and larger RCTs, particularly crossover RCTs, are needed to clarify the impact of lean fish and fish proteins on the serum/plasma lipid profile. Findings from such studies would enable practitioners to provide their patients evidence-based recommendations to meet the American Heart Association guidelines for fish consumption to reduce cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

Context Dyslipidemia is highly prevalent in youth with type 2 diabetes (T2D), yet the pathogenic components of dyslipidemia in youth with T2D are poorly understood. Objective To evaluate the genetic determinants of lipid traits in youth with T2D through a genome-wide association study. Design, Participants, and Main Outcome Measures We genotyped 206 928 variants and imputed 17 642 824 variants in 1076 youth (mean age 15.0 ± 2.48 years) with T2D from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) and SEARCH for Diabetes in Youth (SEARCH) studies as part of the Progress in Diabetes Genetics in Youth (ProDiGY) consortium. We performed association testing for triglyceride and low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (HDL-c) concentrations adjusted for the genetic relationship matrix within each substudy followed by meta-analyses for each trait. Results We identified a novel association between a deletion on chromosome 3 (3:67817380_AT/A_Deletion:RP11-81N13.1) and triglyceride levels at genome-wide level of significance (P = 2.3 × 10−8) with each risk allele increasing triglycerides by 20%. We also identified a genome-wide significant signal at rs247617 (P = 5.1 × 10−9) between HERFUD1 and CETP associated with HDL-c, with carriers of 1 copy of the risk allele having twice higher HDL-c. Conclusions Our genetic analyses of lipid traits in youth with T2D have identified 1 novel and 1 previously known locus. Additional studies are needed to further characterize the genetic architecture of dyslipidemia in youth with T2D. [ABSTRACT FROM AUTHOR]

Background: The causal nature of the observed associations between serum lipids and apolipoproteins and kidney function are unclear.Methods: Using two-sample and multivariable Mendelian randomization (MR), we examined the causal effects of serum lipids and apolipoproteins on kidney function, indicated by the glomerular-filtration rate estimated using creatinine (eGFRcrea) or cystatin C (eGFRcys) and the urinary albumin-to-creatinine ratio (UACR). We obtained lipid- and apolipoprotein-associated genetic variants from the Global Lipids Genetics Consortium (n = 331 368) and UK Biobank (n = 441 016), respectively, and kidney-function markers from the Trøndelag Health Study (HUNT; n = 69 736) and UK Biobank (n = 464 207). The reverse causal direction was examined using variants associated with kidney-function markers selected from recent genome-wide association studies.Results: There were no strong associations between genetically predicted lipid and apolipoprotein levels with kidney-function markers. Some, but inconsistent, evidence suggested a weak association of higher genetically predicted atherogenic lipid levels [indicated by low-density lipoprotein cholesterol (LDL-C), triglycerides and apolipoprotein B] with increased eGFR and UACR. For high-density lipoprotein cholesterol (HDL-C), results differed between eGFRcrea and eGFRcys, but neither analysis suggested substantial effects. We found no clear evidence of a reverse causal effect of eGFR on lipid or apolipoprotein traits, but higher UACR was associated with higher LDL-C, triglyceride and apolipoprotein B levels.Conclusion: Our MR estimates suggest that serum lipid and apolipoprotein levels do not cause substantial changes in kidney function. A possible weak effect of higher atherogenic lipids on increased eGFR and UACR warrants further investigation. Processes leading to higher UACR may lead to more atherogenic lipid levels. [ABSTRACT FROM AUTHOR]

Context: Maternal lipids during pregnancy and placental growth factors are associated with excess fetal growth. However, how these factors interact to increase the risk of delivering large-for-gestational-age (LGA) neonates remains unclear. In this study, we investigated the relationship between maternal plasma triglycerides (TGs) and free fatty acids (FFAs) during pregnancy, cord blood insulin-like growth factors (IGF), and LGA.Objective: In a cell model, we studied the effect of different FAs on placental IGF-1 secretion.Methods: This cohort study included pregnant women with term pregnancy and without diabetes or hypertensive disorders in pregnancy. Maternal fasting plasma TGs and FFAs were measured in the second trimester. Cord blood IGF-1, IGF-2, and IGF binding protein-1 and protein-3 were measured at the time of delivery. A human trophoblast cell line, 3A-sub-E, was used to evaluate the effect of different FFAs on placental IGF-1 secretion.Results: We recruited 598 pregnant women-neonate pairs. Maternal plasma TG (180 mg/dL [152.5-185.5 mg/dL] vs 166 mg/dL [133-206 mg/dL], P = .04) and cord blood IGF-1 concentrations (72.7 ± 23.0 vs 54.1 ± 22.8 ng/mL, P < .001) were higher in the LGA group and were significantly associated with birth weight z score. Maternal plasma free palmitic acid (PA) and stearic acid (SA), but not oleic acid (OA) or linoleic acid (LA), were significantly associated with cord blood IGF-1 concentrations. In 3A-sub-E cells, treatment with PA, SA, and LA, but not OA, induced IGF-1 expression and secretion.Conclusion: Certain FFAs can induce placental IGF-1 secretion, which suggests a potential pathophysiology linking maternal plasma lipids and LGA. [ABSTRACT FROM AUTHOR]

Context Women with polycystic ovary syndrome (PCOS) have increased incidence of atherogenic dyslipidemia and cardiovascular disease (CVD). Interventions targeting atherogenic dyslipidemia to reduce CVD risk are limited in women with PCOS. Objective This pilot study was conducted to determine the effect of 12 weeks of high dose fish oil (FO), metformin, and FO as an adjunct to metformin (FO-metformin) therapy on fasting and nonfasting plasma lipids and ApoB-remnants in young women with the metabolic syndrome (MetS) and PCOS. Methods In this open-label parallel pilot trial, women with MetS and PCOS (18-30 years of age) were randomized into 1 of 3 interventions: (1) FO; (2) metformin; and (3) FO-metformin. Plasma lipids and ApoB (48 and 100)-lipoproteins and triglycerides (TG) were measured in the fasted and postprandial state following a high-fat meal at baseline and postintervention. Results FO-metformin significantly lowered fasting plasma TG by >40% compared with FO and metformin treatments. Fasting plasma apoB48 was lowered 40% in FO-metformin and 15% in the FO groups from baseline to postintervention. ApoB48 area under the curve (ApoB48AUC), ApoB48 incremental AUC (ApoB48iAUC), ApoB100AUC, and ApoB100iAUC decreased in all groups from baseline to postintervention; however, these findings did not reach statistical significance. Conclusion The findings of this pilot trial show that high dose FO and FO-metformin combination therapy tend to lower fasting and postprandial plasma TG and ApoB-lipoprotein remnants compared with metformin; however, the study is limited by small sample size. These results may be clinically significant in individuals with PCOS for management of atherogenic dyslipidemia. [ABSTRACT FROM AUTHOR]

Aims Recent studies have emphasized that metabolic syndrome (MetS) was the most important modifiable risk factor for cardiovascular and cerebrovascular diseases in the institutionalized elderly. In addition, the occurrence of MetS was higher in those with longer age-adjusted institutionalization time. The present study was conducted to assess predictive value of markers of adipose tissue dysfunction for the early screening of MetS in this population. Methods and results Two hundred and eleven institutionalized older adults (132 women, aged 74.3 ± 7.3 years; 79 men, aged 71.5 ± 7.3 years) were enrolled in the current cross-sectional study. Lipid accumulation product (LAP), visceral adiposity index (VAI), body adiposity index (BAI), and triglycerides (TG)/high-density lipoprotein (HDL)-cholesterol ratio were determined. The receiver operating characteristic curve was calculated to compare the area under the curve of each index. The total prevalence of MetS was 23.8%. In female group, VAI and TG/HDL ratio presented moderate--high sensitivity (77.78% and 78.38%, respectively) and specificity (77.62% and 73.49%, respectively). In males group, LAP presented moderate--high sensitivity (75%) and specificity (76.9%). Conclusion Gender played a key role on the prediction of MetS by adipose dysfunction markers in institutionalized elderly. Accordingly, VAI and TG/HDL-cholesterol ratio showed the highest predictive value for MetS in female elderly. LAP was the strongest predictor of MetS in male elderly. [ABSTRACT FROM AUTHOR]

Aims Previous studies suggested that neck circumference (NC) as a new, simple, and valuable tool for the measuring obesity. However, the results of studies regarding the relationship between blood lipids and neck circumference were inconsistent. Therefore, we aimed to perform a systematic review and meta-analysis to summarize the association between NC and lipid profiles in adults. Methods and results PubMed and Scopus electronic databases were searched until 30 June 2018 to find articles that reported the association between NC and blood lipids. Mean serum lipids and variables contributed to heterogeneity were extracted. Sources of inter-study heterogeneity were determined by subgroup analysis. Of 2490 publications identi- fied, 33 studies were included in the qualitative and quantitative synthesis. We found an inverse correlation between NC and high-density lipoprotein cholesterol [HDL-C; overall Fisher's Z = -0.18; 95% confidence interval (CI): -0.21, -0.15]. Furthermore, we found positive associations between NC and total cholesterol (TC; overall Fisher's Z = 0.11; 95% CI = 0.06, 0.16), low-density lipoprotein cholesterol (LDL-C; overall Fisher's Z = 0.1; 95% CI = -0.04, 0.16), and triglyceride (TG; overall Fisher's Z = 0.21; 95% CI = 0.17, 0.25) in men. Neck circumference was directly correlated to TC (overall Fisher's Z = 0.1; 95% CI = 0.01, 0.19) and LDL-C (overall Fisher's Z = 0.16; 95% CI = 0.12, 0.20) in healthy and unhealthy women, respectively. There was no correlation between NC and serum concentration of TC (overall Fisher's Z = 0.01; 95% CI = -0.02, 0.03) and LDL-C (overall Fisher's Z = 0.09; 95% CI = 0.02, 0.16) in unhealthy and healthy women, respectively. Conclusion Higher NC in unhealthy men was strongly indirectly associated with HDL-C, and directly related to LDL-C, TG, and TC. In unhealthy women, higher NC was inversely associated with HDL and directly related to LDL-C. [ABSTRACT FROM AUTHOR]

Objective The relationship between serum lipid variations in SS and healthy controls was investigated to identify potential predictive lipid biomarkers. Methods Serum samples from 230 SS patients and 240 healthy controls were collected. The samples were analysed by ultrahigh-performance liquid chromatography coupled with Q Exactive™ spectrometry. Potential lipid biomarkers were screened through orthogonal projection to latent structures discriminant analysis and further evaluated by receiver operating characteristic analysis. Results A panel of three metabolites [phosphatidylcholine (18:0/22:5), triglyceride (16:0/18:0/18:1) and acylcarnitine (12:0)] was identified as a specific biomarker of SS. The receiver operating characteristic analysis showed that the panel had a sensitivity of 84.3% with a specificity of 74.8% in discriminating patients with SS from healthy controls. Conclusion Our approach successfully identified serum biomarkers associated with SS patients. The potential lipid biomarkers indicated that SS metabolic disturbance might be associated with oxidized lipids, fatty acid oxidation and energy metabolism. [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (AMD) is a leading cause of vision loss. Whereas lipids have been studied extensively to understand their effects on cardiovascular diseases, their relationship with AMD remains unclear.Methods: Two-sample Mendelian randomization (MR) analyses were performed to systematically evaluate the causal relationships between eight serum lipid biomarkers, consisting of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], triglycerides (TG) and non-HDL cholesterol (non-HDL-C), and the risk of different AMD stages and subtypes. We derived 64-407 genetic instruments for eight serum lipid biomarkers in 419 649 participants of European descent from the UK Biobank cohort. We conducted genome-wide association studies (GWAS) for 12 711 advanced AMD cases [8544 choroidal neovascularization (CNV) and 2656 geographic atrophy (GA) specific AMD subtypes] and 5336 intermediate AMD cases with 14 590 controls of European descent from the International AMD Genomics Consortium.Results: Higher genetically predicted HDL-C and ApoA1 levels increased the risk of all AMD subtypes. LDL-C, ApoB, CHOL and non-HDL-C levels were associated with decreased risk of intermediate and GA AMD but not with CNV. Genetically predicted TG levels were associated with decreased risk of different AMD subtypes. Sensitivity analyses revealed no evidence for directional pleiotropy effects. In our multivariable MR analyses, adjusting for the effects of correlated lipid biomarkers yielded similar results.Conclusion: These results suggest the role of lipid metabolism in drusen formation and particularly in AMD development at the early and intermediate stages. Mechanistic studies are warranted to investigate the utility of lipid pathways for therapeutic treatment in preventing AMD. [ABSTRACT FROM AUTHOR]

Patients with schizophrenia have a lower than average life span, largely due to the increased prevalence of cardiometabolic comorbidities. There is an unmet public health need to identify individuals with psychotic disorders who have a high risk of rapid weight gain and who are at risk of developing metabolic complications. Here, we applied mass spectrometry-based lipidomics in a prospective study comprising 48 healthy controls (CTR), 44 first-episode psychosis (FEP) patients, and 22 individuals at clinical high risk (CHR) for psychosis, from 2 study centers (Turku, Finland and London, UK). Baseline serum samples were analyzed using lipidomics, and body mass index (BMI) was assessed at baseline and after 12 months. We found that baseline triacylglycerols (TGs) with low double-bond counts and carbon numbers were positively associated with the change in BMI at follow-up. In addition, a molecular signature comprised of 2 TGs (TG[48:0] and TG[45:0]) was predictive of weight gain in individuals with a psychotic disorder, with an area under the receiver operating characteristic curve (AUROC) of 0.74 (95% CI: 0.60–0.85). When independently tested in the CHR group, this molecular signature predicted said weight change with AUROC = 0.73 (95% CI: 0.61–0.83). We conclude that molecular lipids may serve as a predictor of weight gain in psychotic disorders in at-risk individuals and may thus provide a useful marker for identifying individuals who are most prone to developing cardiometabolic comorbidities. [ABSTRACT FROM AUTHOR]

Objective: This guideline will provide the practicing endocrinologist with an approach to the assessment and treatment of dyslipidemia in patients with endocrine diseases, with the objective of preventing cardiovascular (CV) events and triglyceride-induced pancreatitis. The guideline reviews data on dyslipidemia and atherosclerotic cardiovascular disease (ASCVD) risk in patients with endocrine disorders and discusses the evidence for the correction of dyslipidemia by treatment of the endocrine disease. The guideline also addresses whether treatment of the endocrine disease reduces ASCVD risk.Conclusion: This guideline focuses on lipid and lipoprotein abnormalities associated with endocrine diseases, including diabetes mellitus, and whether treatment of the endocrine disorder improves not only the lipid abnormalities, but also CV outcomes. Based on the available evidence, recommendations are made for the assessment and management of dyslipidemia in patients with endocrine diseases. [ABSTRACT FROM AUTHOR]

Context: Hyperthyroidism is associated with low levels of cholesterol and triglycerides, and hypothyroidism is associated with hypercholesterolemia and hypertriglyceridemia.Objective: The aim of this systematic review was to investigate the impact of therapy for overt and subclinical hyper- and hypothyroidism on serum lipids.Data Sources: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus from 1970 through April 5, 2018.Study Selection: Pairs of independent reviewers selected randomized and observational studies evaluating lipid parameters in patients undergoing treatment for hyper- or hypothyroidism.Data Extraction: Pairs of independent reviewers extracted data and appraised studies.Data Synthesis: Treatment of overt hyperthyroidism showed a significant increase in total cholesterol (TC) by 44.50 mg/dL (95% confidence interval [CI]: 37.99, 51.02), low-density lipoprotein cholesterol (LDL-C) by 31.13 mg/dL (95% CI: 24.33, 37.93), high-density lipoprotein cholesterol (HDL-C) by 5.52 mg/dL (95% CI: 1.48, 9.56), apolipoprotein A (Apo A) by 15.6 mg/dL (95% CI: 10.38, 20.81), apolipoprotein B (apo B) by 26.12 mg/dL (95% CI: 22.67, 29.57), and lipoprotein (Lp[a]) by 4.18 mg/dL (95% CI: 1.65, 6.71). There was no significant change in triglyceride (TG) levels. Treatment of subclinical hyperthyroidism did not change any lipid parameters significantly. Levothyroxine therapy in overt hypothyroidism showed a statistically significant decrease in TC by -58.4 mg/dL (95% CI: -64.70, -52.09), LDL-C by -41.11 mg/dL (95% CI: -46.53, -35.69), HDL-C by -4.14 mg/dL (95% CI: -5.67, -2.61), TGs by -7.25 mg/dL (95% CI: -36.63, 17.87), apo A by -12.59 mg/dL (95% CI: -17.98, -7.19), apo B by -33.96 mg/dL (95% CI: 41.14, -26.77), and Lp(a) by -5.6 mg/dL (95% CI: -9.06, -2.14). Levothyroxine therapy in subclinical hypothyroidism showed similar changes but with a smaller magnitude. The studies contained varied population characteristics, severity of thyroid dysfunction, and follow-up duration.Conclusions: Treatment of overt but not subclinical hyperthyroidism is associated with worsening of the lipid profile. Levothyroxine therapy in both overt and subclinical hypothyroidism leads to improvement in the lipid profile, with a smaller magnitude of improvement in subclinical hypothyroidism. [ABSTRACT FROM AUTHOR]

Context Cardiovascular disease is a major public health problem and represents a significant burden of disease globally. Lifestyle interventions have their limitations and an intervention that will effectively address cardiovascular risk factors to help reduce this growing burden of disease is required. Objective Carnosine and other histidine-containing dipeptides (HCDs) have exerted positive effects on cardiovascular risk factors and diseases in animal and human studies. The authors conducted a systematic review and meta-analysis examining the effects of HCDs on cardiovascular outcomes in line with the PRISMA guidelines. Data Sources The Medline, Medline in process, Embase, Cumulative Index of Nursing and Allied Health, and All EBM databases were searched from inception until January 25, 2019, for randomized controlled trials (RCTs) examining the effects of HCDs on cardiovascular outcomes, compared with placebo or controls. Data Extraction Basic characteristics of the study and populations, interventions, and study results were extracted. The grading of recommendations assessment, development, and evaluation approach was used to assess the quality of evidence for each outcome. Data Analysis A total of 21 studies were included. Of these, 18 were pooled for meta-analysis (n  = 913). In low risk of bias studies, HCD-supplemented groups had lower total cholesterol (n = 6 RCTs; n = 401; weighted mean difference [WMD], −0.32 mmol/L [95%CI, −0.57 to −0.07], P  = 0.01) and triglyceride levels (n = 6 RCTs; n = 401; WMD, −0.14 mmol/L [95%CI, −0.20 to −0.08], P  < 0.001) compared with controls. In studies using carnosine, triglycerides levels were also lower in the intervention group vs controls (n = 5 RCTS; n = 309; P  < 0.001). There were no significant differences in blood pressure, heart rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C) or the total cholesterol to HDL-C ratio between groups. Conclusions Carnosine and other HCDs may have a role in improving lipid profiles. Larger studies with sufficient follow-up are necessary to confirm these findings and explore the use of HCDs in the prevention of cardiovascular diseases. Systemic Review Registration PROSPERO registration no.: CRD42017075354 [ABSTRACT FROM AUTHOR]

Prevailing strategies in genome-wide association studies (GWAS) mostly rely on principles of medical genetics emphasizing one gene, one function, one phenotype concept. Here, we performed GWAS of blood lipids leveraging a new systemic concept emphasizing complexity of genetic predisposition to such phenotypes. We focused on total cholesterol, low- and high-density lipoprotein cholesterols, and triglycerides available for 29,902 individuals of European ancestry from seven independent studies, men and women combined. To implement the new concept, we leveraged the inherent heterogeneity in genetic predisposition to such complex phenotypes and emphasized a new counter intuitive phenomenon of antagonistic genetic heterogeneity, which is characterized by misalignment of the directions of genetic effects and the phenotype correlation. This analysis identified 37 loci associated with blood lipids but only one locus, FBXO33, was not reported in previous top GWAS. We, however, found strong effect of antagonistic heterogeneity that leaded to profound (quantitative and qualitative) changes in the associations with blood lipids in most, 25 of 37 or 68%, loci. These changes suggested new roles for some genes, which functions were considered as well established such as GCKR, SIK3 (APOA1 locus), LIPC, LIPG, among the others. The antagonistic heterogeneity highlighted a new class of genetic associations emphasizing beneficial and adverse trade-offs in predisposition to lipids. Our results argue that rigorous analyses dissecting heterogeneity in genetic predisposition to complex traits such as lipids beyond those implemented in current GWAS are required to facilitate translation of genetic discoveries into health care. [ABSTRACT FROM AUTHOR]

Aims The 2019 vs. 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) dyslipidaemia guidelines contains new recommendations for primary prevention with statins; however, the potential impact of these changes is unclear. We compared the 2019 and 2016 guidelines regarding statin eligibility and potential impact on prevention of atherosclerotic cardiovascular disease (ASCVD) in the general population. Methods and results We examined 45 750 individuals aged 40–75 from the Copenhagen General Population Study, all free of ASCVD and statin use at baseline. During the 9.2-year follow-up, 3337 experienced ASCVD (myocardial infarction, stroke, and cardiovascular death). For Class I/A recommendations, 32.3% (95% confidence interval: 31.8–32.7) and 15.4% (15.1–15.7) of individuals were statin eligible according to the 2019 and 2016 guidelines. The increased statin eligibility by the 2019 guidelines was explained by lower low-density lipoprotein cholesterol (LDL-C) thresholds alone (explaining 33.2%), older age range alone (49.4%), older age range in combination with lower LDL-C thresholds (14.7%), and updated SCORE risk algorithm (2.8%). If fully implemented, the estimated percentage of ASCVD events that can be prevented by using high-intensity statins for 10 years were 25% and 11% with the 2019 and 2016 guidelines. Mainly because of older age range in the 2019 guidelines, the corresponding estimated numbers needed to treat (NNT) to prevent one ASCVD event were 19 and 20. Conclusion Due to lower LDL-C threshold and older age range, the 2019 vs. 2016 ESC/EAS guidelines doubles the number of individuals eligible for primary prevention with statins. This considerably improves the potential for ASCVD prevention in the general population, with similar NNT to prevent one event. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Background: Conventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four genetically predicted lipid traits.Methods: Previous genome-wide association studies (GWAS) have identified 164 discrete variants associated with high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides and total cholesterol. We used 162 of these unique variants to construct weighted genetic scores (wGSs) for a total of 101 424 breast cancer cases and 80 253 controls of European ancestry from the Breast Cancer Association Consortium (BCAC). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between per standard deviation increase in genetically predicted lipid traits and breast cancer risk. Additional Mendelian randomization analysis approaches and sensitivity analyses were conducted to assess pleiotropy and instrument validity.Results: Corresponding to approximately 15 mg/dL, one standard deviation increase in genetically predicted HDL-C was associated with a 12% increased breast cancer risk (OR: 1.12, 95% CI: 1.08-1.16). Findings were consistent after adjustment for breast cancer risk factors and were robust in several sensitivity analyses. Associations with genetically predicted triglycerides and total cholesterol were inconsistent, and no association for genetically predicted LDL-C was observed.Conclusions: This study provides strong evidence that circulating HDL-C may be associated with an increased risk of breast cancer, whereas LDL-C may not be related to breast cancer risk. [ABSTRACT FROM AUTHOR]

Context Clinical trials examining the cardiovascular protective effects of quercetin in humans have reported conflicting results. Objective The aim of this systematic review was to summarize evidence of the effects of quercetin supplementation on plasma lipid profiles, blood pressure (BP), and glucose levels in humans by performing a meta-analysis of randomized controlled trials. Data Sources MEDLINE, Embase, and Scopus databases were searched electronically from their inception to July 2018 to identify randomized controlled trials that assessed the impact of quercetin on lipid profiles, BP, and glucose levels. Study Selection Randomized controlled trials assessing the effects of quercetin or a standardized quercetin-enriched extract on plasma lipid profiles, BP, and glucose levels in humans were eligible for inclusion. Data Extraction A random-effects model was used for data analysis. Continuous variables were expressed as weighted mean differences (WMDs) and 95%CIs. Subgroup analyses were conducted to explore possible influences of study characteristics. Sensitivity analyses were also performed, as were analyses of publication bias. Results Seventeen trials (n = 896 participants total) were included in the overall analysis. Pooled results showed that quercetin significantly lowered both systolic BP (WMD, −3.09 mmHg; 95%CI, −4.59 to −1.59; P = 0.0001) and diastolic BP (WMD, −2.86 mmHg; 95%CI, −5.09 to −0.63; P = 0.01). Neither lipid profiles nor glucose concentrations changed significantly. In subgroup analyses, significant changes in high-density lipoprotein cholesterol and triglycerides were observed in trials with a parallel design and in which participants consumed quercetin for 8 weeks or more. Conclusion Quercetin intake resulted in significantly decreased BP in humans. Moreover, participants who consumed quercetin for 8 weeks or more showed significantly changed levels of high-density lipoprotein cholesterol and triglycerides in trials with a parallel design. [ABSTRACT FROM AUTHOR]

Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and non-HDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries.Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group.Results: Since ∼1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at ∼0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as ∼0.7 per decade in Swiss men (equivalent to ∼26% decline in coronary heart disease risk per decade). The ratio increased in China.Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol. [ABSTRACT FROM AUTHOR]

Objective The aim was to evaluate whether T cell subsets and the lipid profile could be linked to the cardioprotective effect of IgM anti-phosphorylcholine (PC) antibodies in SLE. Methods Anti-PC antibodies were quantified by ELISA in 197 patients and 99 controls and analysed in relationship to clinical features, treatments and serum lipids. Carotid atheromatosis was evaluated by ultrasonography; Th1, Th17, Treg and CD4+CD28null cells by flow cytometry; and cytokine serum levels by immunoassays, in a subgroup of 120 SLE patients and 33 controls. Results IgM anti-PC serum levels were reduced in SLE patients compared with controls (P < 0.001) and were associated with age (β= −0.252; P = 0.002), high-density lipoprotein (HDL; β = 0.271; P = 0.001), low-density lipoprotein (LDL; β= −0.192; P = 0.017) and glucocorticoid treatment (β= −0.201; P = 0.012), whereas the IgG-to-IgM anti-PC ratio was increased (P = 0.007) and associated with age (β = 0.194; P = 0.028) and SLEDAI (β = 0.250; P = 0.005). Also, patients with clinical or subclinical cardiovascular disease exhibited reduced IgM anti-PC levels compared with their cardiovascular disease-free counterparts, regardless of glucocorticoid usage (P = 0.001). CD4+CD28null and Th17 cells were increased in SLE patients compared with controls (P < 0.01) and correlated inversely with IgM anti-PC levels. These associations were observed in patients displaying high triglyceride or low HDL levels, even after adjusting for clinical parameters and treatments (CD4+CD28null: β = −0.455, P = 0.001; Th17: β= −0.280, P = 0.035), but not in those with a normal lipid profile. High triglyceride and low HDL profiles were related to low IgM anti-PC and Treg levels, respectively, whereas both lipid profiles were associated with inflammatory markers and cytokines. Conclusion The present study provides evidence for an association of IgM anti-PC antibodies with pro-atherogenic T cell subsets in SLE, with a high triglyceride/low HDL lipid profile playing a facilitating major role. [ABSTRACT FROM AUTHOR]

Blood lipids are causally involved in the pathogenesis of atherosclerosis, but their role in cerebral small vessel disease remains largely elusive. Here, we explored associations of genetic determinants of blood lipid levels, lipoprotein particle components, and targets for lipid-modifying drugs with small vessel disease phenotypes. We selected genetic instruments for blood levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides, for cholesterol and triglycerides components of size-defined lipoprotein particles, and for lipid-modifying drug targets based on published genome-wide association studies (up to 617 303 individuals). Applying two-sample Mendelian randomization approaches we investigated associations with ischaemic and haemorrhagic manifestations of small vessel disease [small vessel stroke: 11 710 cases, 287 067 controls; white matter hyperintensities (WMH): 10 597 individuals; intracerebral haemorrhage: 1545 cases, 1481 controls]. We applied the inverse-variance weighted method and multivariable Mendelian randomization as our main analytical approaches. Genetic predisposition to higher HDL-C levels was associated with lower risk of small vessel stroke [odds ratio (OR) per standard deviation = 0.85, 95% confidence interval (CI) = 0.78-0.92] and lower WMH volume (β = -0.07, 95% CI = -0.12 to -0.02), which in multivariable Mendelian randomization remained stable after adjustments for LDL-C and triglycerides. In analyses of lipoprotein particle components by size, we found these effects to be specific for cholesterol concentration in medium-sized high-density lipoprotein, and not large or extra-large high-density lipoprotein particles. Association estimates for intracerebral haemorrhage were negatively correlated with those for small vessel stroke and WMH volume across all lipid traits and lipoprotein particle components. HDL-C raising genetic variants in the gene locus of the target of CETP inhibitors were associated with lower risk of small vessel stroke (OR: 0.82, 95% CI = 0.75-0.89) and lower WMH volume (β = -0.08, 95% CI = -0.13 to -0.02), but a higher risk of intracerebral haemorrhage (OR: 1.64, 95% CI = 1.26-2.13). Genetic predisposition to higher HDL-C, specifically to cholesterol in medium-sized high-density lipoprotein particles, is associated with both a lower risk of small vessel stroke and lower WMH volume. These analyses indicate that HDL-C raising strategies could be considered for the prevention of ischaemic small vessel disease but the net benefit of such an approach would need to be tested in a randomized controlled trial. [ABSTRACT FROM AUTHOR]

Context Vitamin D deficiency is highly prevalent across the world. The existing evidence suggests vitamin D may have beneficial effects on serum lipid profiles and thus cardiovascular health. Objective The objective of this systematic review and meta-analysis was to examine the effect of vitamin D supplementation on serum lipid profiles. Data Source Original randomized controlled trials (RCTs) examining the effect of vitamin D supplementation on serum lipid profiles and published before July 2018 were identified by searching online databases, including PubMed, Google Scholar, and ScienceDirect, using a combination of relevant keywords. Data Extraction Data on study characteristics, effect size, measure of variation, type of vitamin D supplementation, and duration of follow-up were extracted by the author. Data Analysis PRISMA guidelines for systematic reviews were followed. Random effects (DerSimonian and Laird [D-V)] models were used to pool standardized mean differences in total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides between the active and the placebo arms of RCT studies. Between-study heterogeneities were assessed using Cochrane Q and I2, and publication bias was assessed using Begg's test, Egger's test, and funnel plot. Results A total of 41 RCTs comprising 3434 participants (n = 1699 in the vitamin D supplementation arm and n = 1735 in the placebo arm) were identified and included in the meta-analysis. Approximately 63.4% of study participants were women, with 14 studies conducted entirely among women. Approximately 24% of the trials had follow-up duration >6 months, whereas the remaining 76% had follow-up duration of < 6 months. The standardized mean differences (SMDs) and 95% confidence intervals (CIs) for comparing the change from baseline to follow-up between the vitamin D supplementation arm and the placebo (control) arm were as follows: total cholesterol = –0.17 (–0.28 to –0.06); LDL cholesterol = –0.12 (–0.23 to –0.01); triglycerides = –0.12 (–0.25 to 0.01); and HDL cholesterol = –0.19 (–0.44 to 0.06). After removing a trial that was an outlier based on the magnitude of the effect size, the SMD for triglycerides was –0.15 (–0.24 to –0.06) and that for HDL cholesterol was –0.10 (–0.28 to 0.09). The improvements in total cholesterol and triglycerides were more pronounced in participants with baseline vitamin D deficiency. Conclusions Vitamin D supplementation appeared to have a beneficial effect on reducing serum total cholesterol, LDL cholesterol, and triglyceride levels but not HDL cholesterol levels. Vitamin D supplementation may be useful in hypercholesterolemia patients with vitamin D insufficiency who are at high risk of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: The intrauterine environment is critical for fetal growth and development. However, observational associations between maternal gestational lipid concentrations and offspring birth weight (BW) have been inconsistent and ascertaining causality is challenging.Methods: We used a novel two-sample Mendelian randomization (MR) approach to estimate the causal effect of maternal gestational high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride concentrations on offspring BW. Single nucleotide polymorphisms (SNPs) associated with serum HDL-C, LDL-C and triglyceride concentrations identified in the Global Lipids Genetics Consortium genome-wide association study meta-analysis (n = 188 577 European-ancestry individuals; sample 1) were selected as instrumental variables. The effects of these SNPs on offspring BW were estimated using a structural equation model in the UK Biobank and Early Growth Genetics consortium (n = 230 069 European-ancestry individuals; sample 2) that enabled partitioning of the genetic associations into maternal- (intrauterine) and fetal-specific effects.Results: We found no evidence for a causal effect of maternal gestational HDL-C, LDL-C or triglyceride concentrations on offspring BW [standard deviation change in BW per standard deviation higher in HDL-C = -0.005 (95% confidence interval: -0.039, 0.029), LDL-C = 0.014 (-0.017, 0.045), and triglycerides = 0.014 (-0.025, 0.052)].Conclusions: Our findings suggest that maternal gestational HDL-C, LDL-C and triglyceride concentrations play a limited role in determining offspring BW. However, we cannot comment on the impact of these and other lipid fractions on fetal development more generally. Our study illustrates the power and flexibility of two-sample MR in assessing the causal effect of maternal environmental exposures on offspring outcomes. [ABSTRACT FROM AUTHOR]

Motivation Functional enrichment testing methods can reduce data comprising hundreds of altered biomolecules to smaller sets of altered biological 'concepts' that help generate testable hypotheses. This study leveraged differential network enrichment analysis methodology to identify and validate lipid subnetworks that potentially differentiate chronic kidney disease (CKD) by severity or progression. Results We built a partial correlation interaction network, identified highly connected network components, applied network-based gene-set analysis to identify differentially enriched subnetworks, and compared the subnetworks in patients with early-stage versus late-stage CKD. We identified two subnetworks 'triacylglycerols' and 'cardiolipins-phosphatidylethanolamines (CL-PE)' characterized by lower connectivity, and a higher abundance of longer polyunsaturated triacylglycerols in patients with severe CKD (stage ≥4) from the Clinical Phenotyping Resource and Biobank Core. These finding were replicated in an independent cohort, the Chronic Renal Insufficiency Cohort. Using an innovative method for elucidating biological alterations in lipid networks, we demonstrated alterations in triacylglycerols and cardiolipins-phosphatidylethanolamines that precede the clinical outcome of end-stage kidney disease by several years. Availability and implementation A complete list of NetGSA results in HTML format can be found at http://metscape.ncibi.org/netgsa/12345-022118/cric%5fcprobe/022118/results%5fcric%5fcprobe/main.html. The DNEA is freely available at https://github.com/wiggie/DNEA. Java wrapper leveraging the cytoscape.js framework is available at http://js.cytoscape.org. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014–November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2–degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10−6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10−8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models. [ABSTRACT FROM AUTHOR]

Context Carbohydrate-restricted diets may increase low-density lipoprotein cholesterol and thereby cardiovascular risk. Objective A systematic review and meta-analyses were conducted to compare the effects of very low, low, and moderate carbohydrate, higher fat diets versus high-carbohydrate, low-fat diets on low-density lipoprotein cholesterol and other lipid markers in overweight/obese adults. Data Sources Medline, PubMed, Cochrane Central, and CINAHL Plus were searched to identify large randomized controlled trials (n > 100) with duration ≥ 6 months. Data Extraction Eight randomized controlled trials (n = 1633; 818 carbohydrate-restricted diet, 815 low-fat diet) were included. Data Analysis Quality assessment and risk of bias, a random effects model, and sensitivity and subgroup analyses based on the degree of carbohydrate restriction were performed using Cochrane Review Manager. Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol. Results Carbohydrate-restricted diets showed no significant difference in low-density lipoprotein cholesterol after 6, 12, and 24 months. Although an overall pooled analysis statistically favored low-fat diets (0.07 mmol/L; 95% confidence interval [CI], 0.02–0.13; P = 0.009], this was clinically insignificant. High-density lipoprotein cholesterol and plasma triglycerides at 6 and 12 months favored carbohydrate-restricted diets (0.08 mmol/L; 95%CI, 0.06–0.11; P < 1 × 10−5 and −0.13 mmol/L; 95%CI, −0.19 to −0.08; P < 1 × 10−5, respectively). These favorable changes were more marked in the subgroup with very-low carbohydrate content (< 50 g/d; 0.12 mmol/L; 95%CI, 0.10–0.14; P < 1 × 10−5 and −0.19 mmol/L; 95%CI, −0.26 to −0.12; P = 0.02, respectively). Conclusions Large randomized controlled trials of at least 6 months duration with carbohydrate restriction appear superior in improving lipid markers when compared with low-fat diets. Dietary guidelines should consider carbohydrate restriction as an alternative dietary strategy for the prevention/management of dyslipidemia for populations with cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Objectives: To analyse lipid changes and tolerability in a cohort of HIV-infected patients who switched their antiretroviral regimens to rilpivirine/emtricitabine/tenofovir (RPV/FTC/TDF) in a real-world setting.Methods: PRO-STR is a 48 week prospective observational post-authorization study in 25 hospitals. Patients with a viral load <1000 copies/mL, receiving at least 12 months of combination ART (cART), with constant posology for at least the prior 3 months, were categorized according to previous treatment [NNRTI or ritonavir-boosted PI (PI/r)]. Analytical tests were performed at the baseline visit, between week 16 and week 32, and at week 48.Results: A total of 303 patients were included (mean age 46.6 years; male 74.0%; previous treatment 74.7% NNRTI and 25.3% PI/r). Both groups exhibited significantly reduced lipid profiles, except for HDL cholesterol, for which a non-significant increase was observed. [NNRTI patients: total cholesterol (baseline: 195.5 ± 38.4 mg/dL; week 48: 171.0 ± 35.5 mg/dL), total cholesterol/HDL ratio (baseline: 4.2 ± 1.2; week 48: 4.0 ± 1.2), HDL (baseline: 49.1 ± 12.0 mg/dL; week 48: 49.2 ± 45.8 mg/dL), LDL (baseline: 119.2 ± 30.2 mg/dL; week 48: 114.2 ± 110.7 mg/dL), and triglycerides (baseline: 136.6 ± 86.8 mg/dL; week 48: 113.4 ± 67.8 mg/dL); PI/r patients: total cholesterol (baseline: 203.2 ± 48.8 mg/dL; week 48: 173.4 ± 36.9 mg/dL), total cholesterol/HDL ratio (baseline: 4.7 ± 1.6; week 48: 4.0 ± 1.2), HDL (baseline: 46.4 ± 12.5 mg/dL; week 48: 52.1 ± 54.4 mg/dL), LDL (baseline: 127.0 ± 36.3 mg/dL; week 48: 111.4 ± 35.8 mg/dL), and triglycerides (baseline: 167.6 ± 107.7 mg/dL; week 48: 122.7 ± 72.1 mg/dL)]. The most common intolerances were neuropsychiatric in the NNRTI patients and gastrointestinal and metabolic in the PI/r patients, and these intolerances were significantly reduced in both groups at week 48 [NNRTI: neuropsychiatric (baseline: 81.3%; week 48: 0.0%); PI/r: gastrointestinal (baseline: 48.7%; week 48: 0.0%) and metabolic (baseline: 42.1%; week 48: 0.0%)].Conclusions: RPV/FTC/TDF improved the lipid profiles and reduced the intolerances after switching from NNRTI or PI-based regimens, in a cohort of HIV-infected patients. [ABSTRACT FROM AUTHOR]

Background. Prior research in sub-Saharan Africa reports dyslipidemia in perinatally human immunodeficiency virus (HIV)- infected children receiving ritonavir-boosted lopinavir (LPV/r) compared with efavirenz; however, interpretation of findings is limited by lack of comparison data from HIV-uninfected children. Methods. We conducted a cross-sectional analysis of lipid profiles and growth within a larger longitudinal cohort study of perinatally HIV-infected and HIV-uninfected children aged 4-9 years in Johannesburg, South Africa. At enrollment, anthropometrics, viral load, CD4, total cholesterol (TC), high-density lipoprotein, low-density lipoprotein (LDL), and triglycerides were measured. Weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ), and body mass index-for-age Z-score (BAZ) were calculated. United States pediatric thresholds for dyslipidemia were used. Results. Five hundred fifty-three HIV-infected and 300 HIV-uninfected children (median age 6.9 years) of similar demographic characteristics were enrolled. Of the HIV-infected children, 94.8% were on combination antiretroviral therapy (cART) (65.4% on LPV/r- and 28.6% on efavirenz-based regimens). Among the treated, 94.3% had a viral load <200 copies/mL. Median CD4% was 34.4. The HIV-infected children had lower mean WAZ (-0.7 vs -0.3, P < .01) and HAZ (-1.1 vs -0.7, P < .01) compared with HIV-uninfected children. A lower proportion of HIV-infected children were overweight (BAZ >1) compared with HIV-uninfected children (14.4% vs 21.7%, P = .04). Whether on LPV/r or efavirenz, a higher proportion of HIV-infected children had borderline/ elevated TC or abnormal triglycerides than HIV-uninfected children, although a higher proportion of those on LPV/r had borderline/ elevated TC, borderline/elevated LDL, or abnormal triglycerides than those on efavirenz. Conclusions. In a South African cohort of HIV-infected children and population-appropriate HIV-uninfected children, unfavorable alterations in lipid profiles were detected in HIV-infected children regardless of treatment regimen compared with HIV-uninfected children. The HIV-infected children were of smaller size than HIV-uninfected children, but there was a high prevalence of overweight in both groups. Strategies for optimizing growth and early life management of lipid alterations may be warranted. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids.Methods: Participants from the GLACIER Study (Nmax = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms; replication, fine-mapping regions and wildcard SNPs for lipid traits) were extracted for association tests with 10-year change in total cholesterol (ΔTC) and triglycerides (ΔTG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; Nmax = 8263 participants) were used for replication. We conducted an in silico look-up for association with coronary artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAMplusC4D) Consortium (N ∼ 190 000) and functional annotation for the top ranking variants.Results: In total, 956 variants were associated (P < 0.01) with either ΔTC or ΔTG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with ΔTG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5 × 10-8), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 × 10-6). The rs7412 variant at APOE was associated with ΔTC in GLACIER (P < 1.7 × 10-6). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with ΔTC and for ΔTG, respectively (P < 10-3). Of these, a variant at CAPN3 (P = 1.2 × 10-4), multiple variants at HPR (Pmin = 1.5 × 10-6) and a variant at SIX5 (P = 1.9 × 10-4) showed evidence for association with CAD.Conclusions: We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk. [ABSTRACT FROM AUTHOR]

The ability to transform Camelina sativa easily with biosynthetic enzymes derived from other plants has made this oil seed crop an ideal platform for the production of unusual lipids valuable for different applications. However, in addition to expressing transgenic enzymes, the suppression of endogenous enzyme activity to reduce competition for common substrates or cofactors is also required to enhance the production of target compounds. As camelina possesses a relatively undifferentiated hexaploid genome, up to three gene homeologs can code for any particular enzymatic activity, complicating efforts to alter endogenous biosynthetic pathways. New genome editing technologies, such as that offered by the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein) system, offer the capability to introduce mutations into specifically targeted genomic sites. Here, by using a carefully designed guide RNA identical to all three homeologs, we demonstrate the ability of the CRISPR/Cas genome editing system to introduce mutations in all three CsDGAT1 or CsPDAT1 homeologous genes important for triacylglycerol (TAG) synthesis in developing seeds. Sequence analysis from transgenic T1 plants revealed that each CsDGAT1 or each CsPDAT1 homeolog was altered by multiple mutations, resulting in a genetic mosaic in the plants. Interestingly, seed harvested from both CsDGAT1- and CsPDAT1-targeted lines was often shrunken and wrinkled. Further, lipid analysis revealed that many lines produced seed with reduced oil content and altered fatty acid composition, consistent with the role of the targeted genes in seed oil biosynthesis. The CRISPR/Cas system therefore represents a useful method to alter endogenous biosynthetic pathways efficiently in polyploid species such as camelina. [ABSTRACT FROM AUTHOR]