Search Results (60)

Familial dysbetalipoproteinemia (FD) is a prevalent and highly atherogenic hyperlipoproteinemia associated with the ε2/ε2 APOE genotype or rare APOE variants. The contributions of additional genetic and clinical factors to the FD phenotype remain unclear. We investigated these factors in both autosomal recessive and autosomal dominant forms of FD. Targeted (n = 4666) and exome (n = 194) sequencing were used to identify the ε2/ε2 APOE genotype or rare FD-causative APOE variants. Twenty-four lipid-related genes and forty variants included in a polygenic risk score for hypertriglyceridemia (HTG) were analyzed. FD was defined by the presence of FD variants and triglycerides (TG) ≥ 1.5 mmol/L (main study group). The comparison group consisted of patients with FD variants but TG < 1.5 mmol/L. Univariable and multivariable regression analyses were performed. A total of 71 unrelated subjects were identified (45.1% male, median age 50 years). FD was diagnosed in 52 patients, while 19 had FD variants only. Age (p = 0.019), elevated polygenic risk for HTG (p = 0.001), and the presence of metabolic syndrome components (p = 0.014) were independently associated with the FD phenotype. TG levels were significantly associated with polygenic burden (0.05 mmol/L per percentile), the presence of additional rare lipid-related variants (7.0 mmol/L), and glucose metabolism disorders (3.62 mmol/L), together explaining 30% of TG variance in cross-validated model. These results highlight the interplay of genetic and metabolic factors in FD development and support the integration of HTG genetic risk scores and metabolic control into personalized FD management. Full article

Background: Evidence remains limited on the effects of dietary betaine intake and dyslipidemia. We aim to investigate the association between dietary betaine intake and dyslipidemia in Chinese children and adolescents and illustrate the differences in these associations stratified by different food sources. Methods: Based on a national cross-sectional study from the China National Nutrition and Health Surveillance of Children and Lactating Mothers, 11,452 individuals aged 6–17 years were enrolled between October 2016 and December 2018. Participants were divided into quartiles according to residual energy-adjusted dietary betaine intake. The associations of dietary betaine with dyslipidemia and lipid profiles were estimated using restricted cubic spline regression and logistic regression analysis. Results: Among the 11,452 participants, 2577 (22.5%) individuals were found to have dyslipidemia. The median (IQR) intake of dietary betaine was 56.35 (25.77, 207.66) mg/day. Negative dose-dependent associations were found between residual energy-adjusted dietary betaine intake and dyslipidemia. Compared with participants in the lowest quartile (Q1) of residual energy-adjusted betaine intake, participants in the fourth quartile (Q4) had lower odds of high total cholesterol (TC), high low-density lipoprotein cholesterol (LDL-C), high non-high-density lipoprotein cholesterol (non-HDL-C), high remnant cholesterol (RC), and dyslipidemia, with odds ratios (OR) and 95% confidence intervals (95% CI) of 0.56 (0.45, 0.70), 0.65 (0.48, 0.87), 0.53 (0.41, 0.68), 0.42 (0.28, 0.61), and 0.79 (0.69, 0.91), respectively. Furthermore, reduced odds of high TC, high LDL-C, high non-HDL-C, high RC, and dyslipidemia were observed in dietary betaine from plant-source foods but not in animal-source foods. Conclusions: High intake of dietary betaine (56.35–207.66 mg/day) was associated with reduced odds of dyslipidemia, including elevated TC, LDL-C, non-HDL-C, and RC, and dietary betaine from plant-source foods revealed significant benefits for dyslipidemia in Chinese children and adolescents. Full article

Background/Objectives: Previous studies have revealed the predictive potential of remnant cholesterol (RC) for acute coronary syndrome (ACS) occurrence in the general population. However, whether this association applies to patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), in which a lipid paradox exists, remains unclear. We investigated whether RC levels at diagnosis could predict ACS occurrence during follow-up in patients with AAV. Methods: This study included 139 patients with AAV. ACS was defined as ST-elevation myocardial infarction (STEMI), non-STEMI, or unstable angina occurring after AAV diagnosis. RC levels were calculated as (total cholesterol)–(low-density lipoprotein cholesterol)–(high-density lipoprotein cholesterol). Patients were categorised into three groups by RC tertiles: highest (≥26.2 mg/dL), middle (19.1−26.1 mg/dL), and lowest (≤19.0 mg/dL) tertile groups. Results: The median age of the 139 patients (male, 31.7%) was 58.0 years. During follow-up, six, two, and one patients were diagnosed with ACS in the highest, middle, and lowest tertile groups, respectively. Patients in the highest tertile group exhibited a significantly lower ACS-free survival rate than those in the lowest tertile (p = 0.030). In the multivariable Cox hazards model, male sex (hazard ratio [HR] 9.054, 95% confidence interval [CI] 1.786−45.910), Birmingham vasculitis activity score (HR 1.147, 95% CI 1.033−1.274), and the highest tertile of RC levels (HR 10.818, 95% CI 1.867–62.689) were significantly and independently associated with ACS occurrence during follow-up in patients with AAV. Conclusions: Our findings indicate that RC levels at diagnosis may predict ACS occurrence during follow-up in patients with AAV, regardless of the traditional cardiovascular risk factors. Full article

Background: Despite the widespread use of lipid-lowering agents, the risk of atherosclerotic cardiovascular disease (ASCVD) remains; this residual risk has been attributed to remnant cholesterol (RC) levels. However, the causal associations between RC levels and various atherosclerosis-related cardiometabolic and vascular risk factors for ASCVD remain unclear. Methods: Using genetic and biochemical data of 108,876 Taiwan Biobank study participants, follow-up data of 31,790 participants, and follow-up imaging data of 18,614 participants, we conducted a genome-wide association study, a Functional Mapping and Annotation analysis, and bidirectional Mendelian randomization analyses to identify the genetic determinants of RC levels and the causal associations between RC levels and various cardiometabolic and vascular risk factors. Results: We found that higher RC levels were associated with higher prevalence or incidence of the analyzed risk factors. The genome-wide association study unveiled 61 lead genetic variants determining RC levels. The Functional Mapping and Annotation analysis revealed 21 gene sets exhibiting strong enrichment signals associated with lipid metabolism. Standard Mendelian randomization models adjusted for nonlipid variables and low-density lipoprotein cholesterol levels unraveled forward causal associations of RC levels with the prevalence of diabetes mellitus, hypertension, microalbuminuria, and metabolic liver disease. Reverse Mendelian randomization analysis revealed the causal association of diabetes mellitus with RC levels. Conclusions: RC levels, mainly influenced by genes associated with lipid metabolism, exhibit causal associations with various cardiometabolic risk factors, including diabetes mellitus, hypertension, microalbuminuria, and metabolic liver disease. This study provides further insights into the role of RC levels in predicting the residual risk of ASCVD. Full article

Background/Objectives: Hormonal changes throughout a woman’s life cycle significantly affect serum lipid levels. Alterations in the serum lipid profile can increase the risk of cardiovascular diseases (CVDs). Additionally, nutrition and dietary habits are crucial for managing dyslipidemia. The current study evaluated the association between dietary habits and plasma lipid profiles among perimenopausal women in Latvia. Methods: The randomized clinical trial involved perimenopausal women (n = 61) aged 49 ± 3 years with moderately high low-density lipoprotein cholesterol (LDL-C) levels of 3.61 ± 0.30 mmol L⁻¹. A series of questionnaires were completed, including a questionnaire on the subject’s demographic, anthropometric, lifestyle, health, physical activity, and dietary factors, a 24 h food diary, a 72 h food diary, and a food-frequency questionnaire (FFQ). Blood testing was conducted for all participants, which included total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), alanine aminotransferase (ALAT), and glucose level analyses. Results: The consumption of refined sugar, honey, syrup, and jam demonstrated a strong positive association with higher levels of remnant cholesterol (β = 0.462, p ≤ 0.05) and non-high-density lipoprotein cholesterol (non-HDL-C) (β = 0.395, p ≤ 0.05). Similarly, the consumption of fruit juices is associated with increased LDL-C (β = 0.303, p ≤ 0.05) and non-HDL-C (β = 0.285, p ≤ 0.05). Conversely, higher meat and poultry consumption negatively correlates with TC levels (β = −0.290, p ≤ 0.05). Conclusions: This underscores the need for further examination to understand the impact of dietary habits on lipid profile. Full article

Background: The effectiveness of bariatric surgery in reducing remnant cholesterol (RC) levels, particularly when obesity is accompanied by elevated glycated hemoglobin (HbA1c), is insufficiently investigated. In this study, we aimed to examine the impacts of two common bariatric procedures, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), as regards their effects on RC and HbA1c levels. Methods: Adult morbidly obese subjects were included and assigned to receive either RYGB or SG. The levels of RC and HbA1c were determined 6 and 12 months after surgery and compared to preoperative levels to assess the efficacy of these surgical methods. In the statistical evaluation of covariations between RC and other biomarkers, previously determined C-reactive protein (CRP), triglycerides, apolipoprotein B, apolipoprotein A1, and low- and high-density lipoprotein cholesterol 6 and 12 months after surgery were included. A linear mixed regression model for repeated analyses was used. Results: The RC levels were markedly reduced both after RYGB and SG but without significant differences between the RYGB and the SG surgery. Furthermore, the RC values were strongly associated with the levels of CRP and HbA1c. Conclusions: A significant lowering of RC values after bariatric surgery appeared paralleled by concomitant reductions in HbA1c values and CRP levels. Together, these effects lead to a lower risk of cardiovascular disease. Full article

Background/Objectives: The relationship between lipid profiles, telomere length (TL), and cancer risk remains unclear. Methods: This study employed two-sample Mendelian randomization (MR) with mediation analysis to investigate their causal relationships, examining lipid profiles as exposure, TL as mediator, and nine cancer types as outcomes. We conducted our analysis using two-stage least squares (2SLS) regression integrated with inverse variance weighted (IVW) methods to address potential endogeneity and strengthen our causal inference. Results: we found that unfavorable lipid profiles were causally linked to increased TL (p < 0.05). TL showed positive causal associations with lung and hematologic cancers (OR > 1, p < 0.05). Direct associations were observed between total and low-density lipoprotein (LDL) cholesterol and gastric cancer (OR < 1, p < 0.05), and between remnant cholesterol and colorectal cancer (OR > 1, p < 0.05). Mediation analysis revealed TL as a significant mediator in the pathway from lipid profiles to cancer development (p < 0.05). No horizontal pleiotropy was detected. Conclusions: Our findings suggest that lipid metabolism disorders may influence cancer development through telomere regulation, particularly in lung and hematologic cancers. This emphasizes the importance of lipid management in cancer prevention and treatment, especially for these cancer types. Full article

Background/Objectives: Hypertriglyceridaemia and systemic inflammation are prevalent in patients with schizophrenia and contribute to an increased risk of cardiovascular disease. Although elevated triglycerides (TGs) and remnant cholesterol are linked to inflammation in the general population and individuals with metabolic syndrome, whether they are associated in patients with schizophrenia remains unclear. Methods: Fasting levels of TG, cholesterol (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and remnant cholesterol)), and markers of systemic inflammation including high-sensitivity C-reactive protein (hsCRP), leukocyte counts and their differentials (neutrophils, monocytes and lymphocytes) were determined in 147 patients diagnosed with schizophrenia on long-term antipsychotic regimens and compared with 56 age- and sex-matched healthy controls. Apolipoprotein B and glycosylation of acute phase reactant (GlycA) signatures were assessed by NMR. Circulating cytokine levels were measured by a cytokine/chemokine multiplex assay. Results: Patients with schizophrenia had markedly elevated TG and remnant cholesterol relative to controls and had evidence of systemic inflammation with increased circulating hsCRP, GlycA, leukocyte, neutrophil counts and neutrophil-to-lymphocyte ratio (NLR). Unexpectedly TG and remnant cholesterol did not correlate with systemic inflammatory markers in patients with schizophrenia, and differences in inflammatory markers between controls and patients persisted after adjusting for the lipid profile. Interleukin (IL)-10 levels were increased in patients with schizophrenia, suggesting an anti-inflammatory signature. Conclusions: The discordance between TG, remnant cholesterol and systemic inflammation in patients with schizophrenia suggests these are likely independent contributors to cardiovascular risk in this population. Full article

Familial dysbetalipoproteinemia (FD) is a highly atherogenic, prevalent genetically based lipid disorder. About 10% of FD patients have rare APOE variants associated with autosomal dominant FD. However, there are insufficient data on the relationship between rare APOE variants and FD. Genetic data from 4720 subjects were used to identify rare APOE variants and investigate their pathogenicity for autosomal dominant FD. We observed 24 variants in 86 unrelated probands. Most variants were unique (66.7%). Five identified APOE variants (p.Glu63ArgfsTer15, p.Gly145AlafsTer97, p.Lys164SerfsTer87, p.Arg154Cys, and p.Glu230Lys) are causal for autosomal dominant FD. One of them (p.Lys164SerfsTer87) was described for the first time. When we compared clinical data, it was found that carriers of pathogenic or likely pathogenic APOE variants had significantly higher triglyceride levels (median 5.01 mmol/L) than carriers of benign or likely benign variants (median 1.70 mmol/L, p = 0.034) and variants of uncertain significance (median 1.38 mmol/L, p = 0.036). For the first time, we estimated the expected prevalence of causal variants for autosomal dominant FD in the population sample: 0.27% (one in 619). Investigating the spectrum of APOE variants may advance our understanding of the genetic basis of FD and underscore the importance of APOE gene sequencing in patients with lipid metabolism disorders. Full article

Background: Remnant cholesterol (RC) is highly associated with several chronic diseases. However, the relationship between RC and Metabolic syndrome (MetS) remains unclear. The study’s objective is to illustrate the relationship of RC to MetS. Methods: The data were collected from the Chinese Nutrition and Health Surveillance (2015–2017), which included personal, household and dietary information. A total of 65,618 residents aged 20 years or older from 31 provinces in mainland China were included in this study. RC was calculated by the equation RC = TC − (LDL-C + HDL-C). The criteria for MetS were based on the 2020 Chinese Type 2 Diabetes Prevention and Treatment Guidelines. Logistic regression models were used to analyse the relationship between RC and MetS and every MetS component. The receiver operating characteristic (ROC) curve was established to evaluate the accuracy of RC in identifying MetS, and the area under the curve (AUC) and the best threshold were calculated. Results: The weighted RC level of Chinese residents aged 20 years or older was 0.48 mmol/L. Participants with high RC levels were likely to be elderly, have a higher prevalence of MetS, higher total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), hba1c, and lower high-density lipoprotein cholesterol (HDL-C). Sex, body mass index (BMI), education status, household yearly income per capita, marital status, area of the country, residence location, smoking status, fruit intake and sleep time had statistical differences in the RC group (p < 0.05). The OR of MetS gradually increased with an increase in the RC quartile (p < 0.01), and higher quartiles of RC (Q4) suggested the highest MetS risk. The prevalence of each MetS component gradually increased with an increase in the RC quartile. The ROC curve found that to identify MetS, the AUC and best threshold of RC were 0.71 and 0.52 mmol/L, respectively. Conclusions: RC had a positive association with MetS and each MetS component. The accuracy in identifying MetS was higher in RC than in other indexes. The current study could provide new scientific evidence for the early prevention and control of MetS. Full article

Over 50% of patients who take statins are still at risk of developing atherosclerotic cardiovascular disease (ASCVD) and do not achieve their goal LDL-C levels. This residual risk is largely dependent on triglyceride-rich lipoproteins (TRL) and their remnants. In essence, remnant cholesterol-rich chylomicron (CM) and very-low-density lipoprotein (VLDL) particles play a role in atherogenesis. These remnants increase when lipoprotein lipase (LPL) activity is inhibited. ApoCIII has been thoroughly studied as a chief inhibitor and therapeutic options to curb its effect are available. On top of apoCIII regulation of LPL activity, there is a more precise control of LPL in various tissues, which makes it easier to physiologically divide the TRL burden according to the body’s requirements. In general, oxidative tissues such as skeletal and cardiac muscle preferentially take up lipids during fasting. Conversely, LPL activity in adipocytes increases significantly after feeding, while its activity in oxidative tissues decreases concurrently. This perspective addresses the recent improvements in our understanding of circadian LPL regulations and their therapeutic implications. Three major tissue-specific lipolysis regulators have been identified: ANGPTL3, ANGPTL4, and ANGPTL8. Briefly, during the postprandial phase, liver ANGPTL8 acts on ANGPTL3 (which is released continuously from the liver) to inhibit LPL in the heart and muscle through an endocrine mechanism. On the other hand, when fasting, ANGPTL4, which is released by adipocytes, inhibits lipoprotein lipase in adipose tissue in a paracrine manner. ANGPTL3 inhibitors may play a therapeutic role in the treatment of hypertriglyceridemia. Several approaches are under development. We look forward to future studies to clarify (a) the nature of hormonal and nutritional factors that determine ANGPTL3, 4, and 8 activities, along with what long-term impacts may be expected if their regulation is impaired pharmacologically; (b) the understanding of the quantitative hierarchy and interaction of the regulatory actions of apoCIII, apoAV, and ANGPTL on LPL activity; (c) strategies for the safe and proper treatment of postprandial lipemia; and (d) the effect of fructose restriction on ANGPTL3, ANGPTL4, and ANGPTL8. Full article

Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a clinical situation characterized by evidence of acute myocardial infarction (AMI)—according to the Fourth Universal Definition of Myocardial Infarction—with normal or near-normal coronary arteries on angiographic study (stenosis < 50%). This condition is extremely variable in etiology, pathogenic mechanisms, clinical manifestations, prognosis and consequently therapeutic approach. Objective: The objective of the study was the evaluation of remnant cholesterol (RC), monocyte/high-density lipoprotein cholesterol ratio (MHR), platelet/lymphocyte ratio (PLR) and various lipoprotein ratios in patients with MINOCA in order to establish their validity as predictors of this event. Materials and Methods: We included 114 patients hospitalized in the Intensive Coronary Care Unit (ICCU) and Hospital Wards of our Hospital Center from 2015 to 2019 who received a diagnosis of MINOCA compared to a control group of 110 patients without previous cardiovascular events. RC was calculated with the following formula: RC = total cholesterol (TC) − HDL-C − LDL-C. MHR was calculated by dividing the monocyte count in peripheral blood by high-density lipoprotein cholesterol (HDL-C) levels; PLR was obtained by dividing platelet count by lymphocyte count. We also calculated various lipoprotein ratios, like total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C), triglycerides/high-density lipoprotein cholesterol (TG/HDL-C), and non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol (non-HDL-C/HDL-C) ratios. Results: The MINOCA group had higher mean levels of RC (21.3 ± 10.6 vs. 13.2 ± 7.7 mg/dL), MHR (23 ± 0.009 vs. 18.5± 8.3) and PLR (179.8 ± 246.1 vs. 135 ± 64.7) than the control group. Only the mean values of all calculated lipoprotein ratios were lower in MINOCA patients. Statistical significance was achieved only in the RC evaluation. Conclusions: Higher levels of RC and MHR were found in patients with MINOCA. We also observed higher levels of PLR than in the control group. Only various lipoprotein ratios were lower, but this could reflect the extreme heterogeneity underlying the pathogenic mechanisms of MINOCA. In patients who receive a diagnosis of MINOCA with a baseline alteration of the lipid profile and higher levels of cholesterol at admission as well, the evaluation of these parameters could play an important role, providing more detailed information about their cardiometabolic risk. Full article

Cardiovascular diseases represent the leading cause of death in the world and are subject to limitations in prevention strategies despite the use of very effective drugs. The concept of residual risk (RR) is intrinsically related to that of global risk of which it represents a very significant percentage. In the cardiovascular field, the term RR refers to the probability of incurring a major cardiovascular event, despite adequate control of the risk factors present in the individual patient. A significant portion of the RR in the cardiovascular field results from the underestimation of additional risk factors not subjected to adequate intervention such as, for example, triglyceride levels in patients treated for the presence of hypertension and/or hypercholesterolemia. The control of the RR therefore appears as an essential condition for the effective reduction of the global risk profile and is based on an integrated intervention that combines all the different prevention strategies derived from the available evidence and capable of interacting on the basis of a strengthening reciprocal between lifestyle and pharmacological and nutraceutical intervention methods. Full article

Sn-2 palmitate is widely used in infant formula. However, little is known about its effects on metabolism and body composition in middle-aged and elderly adults. In a double-blinded, randomized controlled trial, we enrolled Chinese adults aged 45–75 years with self-reported constipation. Individuals were randomly assigned in a 1:1 ratio to a 1,3-dioleoyl-2-palmitoyl-glycerol (OPO)-enriched oil (66% palmitic acid in the sn-2 position) or a control vegetable oil (24% palmitic acid in the sn-2 position) daily for 24 weeks. Skim milk powder was used as the carrier for both fats. Interviews and body composition were performed at baseline, week 4, week 12 and week 24. A fasting blood draw was taken except at week 4. This study was a secondary analysis and considered exploratory. A total of 111 adults (83 women and 28 men, mean age 64.2 ± 7.0 years) were enrolled, of whom 53 were assigned to the OPO group and 57 to the control group. During the intervention, blood glucose, triglyceride, the triglyceride-glucose index, total cholesterol, low-density lipoprotein cholesterol and remnant cholesterol remained stable, while high-density lipoprotein cholesterol decreased in both groups (p = 0.003). No differences in change were observed between the groups (all p > 0.05). From baseline to week 24, the level of visceral fat increased slightly (p = 0.017), while body weight, total body water, protein, soft lean mass, fat-free mass, skeletal muscle and skeletal muscle mass index (SMI) decreased in two groups (p < 0.01). At weeks 4, 12 and 24, the SMI decreased less in the OPO group than in the control group, with a trend towards significance (p = 0.090). A 24-week daily intake of sn-2-palmitate-enriched oil had no adverse impact on fasting blood glucose, lipids and body composition compared with the control vegetable oil in Chinese adults (funded by Chinese Nutrition Society National Nutrition Science Research Grant, National Key Research and Development Program of China and Wilmar (Shanghai) Biotechnology Research & Development Center Co., Ltd.; ChiCTR1900026480). Full article

ApoB is the main protein of triglyceride-rich lipoproteins and is further divided into ApoB48 in the intestine and ApoB100 in the liver. Very low-density lipoprotein (VLDL) is produced by the liver, contains ApoB100, and is metabolized into its remnants, intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL). ApoB100 has been suggested to play a crucial role in the formation of the atherogenic plaque. Apart from being a biomarker of atherosclerosis, ApoB100 seems to be implicated in the inflammatory process of atherosclerosis per se. In this review, we will focus on the structure, the metabolism, and the function of ApoB100, as well as its role as a predictor biomarker of cardiovascular risk. Moreover, we will elaborate upon the molecular mechanisms regarding the pathophysiology of atherosclerosis, and we will discuss the disorders associated with the APOB gene mutations, and the potential role of various drugs as therapeutic targets. Full article