Remnant-like Particle Cholesterol Research Articles

Association between the ZJU index and risk of new-onset non-alcoholic fatty liver disease in non-obese participants: a Chinese longitudinal prospective cohort study.

Non-alcoholic fatty liver disease (NAFLD) is increasingly observed in non-obese individuals. The ZJU (Zhejiang University) index has been established as a new and efficient tool for detecting NAFLD, but the relationship between the ZJU index and NAFLD within non-obese individuals still remains unclear. A post-hoc evaluation was undertaken using data from a health assessment database by the Wenzhou Medical Center. The participants were divided into four groups based on the quartile of the ZJU Index. Cox proportional hazards regression, Kaplan-Meier analysis and tests for linear trends were used to evaluate the relationship between the ZJU index and NAFLD incidence. Subgroup analysis was conducted to test the consistency of the correlation between ZJU and NAFLD in subsgroups. Receiver operative characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the ZJU index, compared with the Atherogenic index of plasma (AIP) and Remnant lipoprotein cholesterol (RLP-C) index. A total of 12,127 were included in this study, and 2,147 participants (17.7%) developed NAFLD in 5 years follow-up. Participants in higher ZJU quartiles tended to be female and have higher liver enzymes (including ALP, GGT, ALT, AST), GLU, TC, TG, LDL and higher NAFLD risk. Hazard Ratios (HR) and 95% confidence intervals (CI) for new-onset NAFLD in Q2, Q3, and Q4 were 3.67(2.43 to 5.55), 9.82(6.67 to 14.45), and 21.67(14.82 to 31.69) respectively in the fully adjusted model 3. With increased ZJU index, the cumulative new-onset NAFLD gradually increased. Significant linear associations were observed between the ZJU index and new-onset NAFLD (p for trend all<0.001). In the subgroup analysis, we noted a significant interaction in sex, with HRs of 3.27 (2.81, 3.80) in female and 2.41 (2.21, 2.63) in male (P for interaction<0.01). The ZJU index outperformed other indices with an area under the curve (AUC) of 0.823, followed by AIP (AUC=0.747) and RLP-C (AUC=0.668). The ZJU index emerges as a promising tool for predicting NAFLD risk in non-obese individuals, outperforming other existing parameters including AIP and RLP-C. This could potentially aid in early detection and intervention in this specific demographic.

Optimization of the MACE endpoint composition to increase power in studies of lipid-lowering therapies-a model-based meta-analysis.

To develop a model-informed methodology for the optimization of the Major Adverse Cardiac Events (MACE) composite endpoint, based on a model-based meta-analysis across anti-hypercholesterolemia trials of statin and anti-PCSK9 drugs. Mixed-effects meta-regression modeling of stand-alone MACE outcomes was performed, with therapy type, population demographics, baseline and change over time in lipid biomarkers as predictors. Randomized clinical trials up to June 28, 2022, of either statins or anti-PCSK9 therapies were identified through a systematic review process in PubMed and ClinicalTrials.gov databases. In total, 54 studies (270,471 patients) were collected, reporting 15 different single cardiovascular events. Treatment-mediated decrease in low density lipoprotein cholesterol, baseline levels of remnant and high-density lipoprotein cholesterol as well as non-lipid population characteristics and type of therapy were identified as significant covariates for 10 of the 15 outcomes. The required sample size per composite 3- and 4-point MACE endpoint was calculated based on the estimated treatment effects in a population and frequencies of the incorporated events in the control group, trial duration, and uncertainty in model parameters. A quantitative tool was developed and used to benchmark different compositions of 3- and 4-point MACE for statins and anti-PCSK9 therapies, based on the minimum population size required to achieve statistical significance in relative risk reduction, following meta-regression modeling of the single MACE components. The approach we developed may be applied towards the optimization of the design of future trials in dyslipidemia disorders as well as in other therapeutic areas.

The effects of endurance physical exercise with fat-free milk intake as a therapy for metabolic syndrome and/or sarcopenia

Background: Nutrition and exercise are important factors for addressing metabolic syndrome and sarcopenia as they are related to insulin secretion. Proteins, particularly branched-chain amino acids (BCAAs), have insulinotropic effects, while exercise reduces insulin secretion. It is thus important to investigate the effects of protein intake and exercise alone and in combination to determine suitable dietary and exercise therapies for treating metabolic syndrome and sarcopenia. Methods: Eight healthy young adult female volunteers participated in a crossover trial consisting of two 5-day experiments. Days 1 and 2 comprised a body-weight-maintained adjustment period during which the participants consumed control diets (energy, 2,010 kcal; protein, 51.9 g). Days 3 to 5 comprised the treatment period during which the participants consumed experimental diets (energy, 2,010 kcal; protein 82.3 g) containing 402 kcal of fat-free milk, and either performed only normal daily activities (non-Ex) or performed normal daily activities and exercised on a bicycle with an ergometer at a target intensity of about 50% of the maximal oxygen intake, expending 402 kcal of additional energy (Ex). Total urine samples were collected during the daytime (6:45 to 18:45) and nighttime (18:45 to 6:45 the next morning). Fasting blood samples were collected early in the morning before and after the treatment period. Results: Plasma valine, leucine, and BCAA levels were significantly elevated after both the non-Ex and Ex periods. Serum insulin levels were significantly elevated only after the non-Ex period. Urinary C-peptide immunoreactivity excretion levels increased significantly during the non-Ex period, but they decreased significantly during the Ex period. After the Ex period, the serum triglyceride and remnant lipoprotein-cholesterol (RLP-C) levels were significantly decreased. Homeostatic model assessment for insulin resistance (HOMA-IR) and atherosclerosis index (AI) values were slightly, yet significantly, increased after the non-Ex period, but were unchanged after the Ex period. The degree of change (Δ) in the RLP-C level significantly and positively correlated with the Δ HOMA-IR and Δ AI.

Predictive value of remnant-like particle cholesterol in the prediction of long-term AF recurrence after radiofrequency catheter ablation

Predictive value of remnant-like particle cholesterol in the prediction of long-term AF recurrence after radiofrequency catheter ablation

Abstract 17244: Association of Remnant Lipoprotein Cholesterol, Type 2 Diabetes Mellitus, and Major Adverse Cardiovascular Events: Insights From the UK Biobank

Background: Remnant lipoprotein-cholesterol (RLP-C) has emerged as a potential contributor to adverse cardiovascular events. While the association of low-density lipoprotein- cholesterol and atherosclerotic cardiovascular disease is well-established, the joint association of RLP-C and type 2 diabetes mellitus (T2DM) in driving major adverse cardiovascular events (MACE) remains less explored. Methods: We included a total of 118,004 participants from the UK Biobank with nuclear magnetic resonance-measured RLP-C. Participants were categorized into four groups based on their RLP-C levels and T2DM status: Group 1 (RLP-C below the median and no T2DM), Group 2 (RLP-C above the median and no T2DM), Group 3 (RLP-C below the median and T2DM), and Group 4 (RLP-C above the median and T2DM). Cox proportional hazards regression was employed to assess the association of these four categories with the time to incident MACE. The model was adjusted for age, sex, race, BMI, smoking, systolic blood pressure, anti-hypertensive and lipid-lowering therapy, and physical activity. Results: Our analysis revealed significant associations between RLP-C levels, T2DM, and the risk of MACE. Compared to the reference group (Group 1), Groups 2-4 had hazard ratio for the MACE outcome of 1.27 (95% CI: 1.18-1.37, p &lt; .0001), 1.43 (95% CI: 1.29-1.59, p &lt; .0001), and 2.04 (95% CI: 1.78-2.32, p &lt; .0001), respectively (see Figure). Conclusion: This analysis from individuals in UK Biobank free from cardiovascular disease at baseline demonstrated a significant joint association between elevated RLP-C levels and T2DM, with the risk of major adverse cardiovascular events. Keywords: remnant lipoprotein cholesterol, type 2 diabetes mellitus, major adverse cardiovascular events, UK Biobank, nuclear magnetic resonance

Abstract 13940: Remnant Lipoprotein Particles and Cholesterol Contribute to Proatherogenic Phenotype and Subclinical Inflammation in Youth-Onset Type 2 Diabetes

Introduction: Youth-onset type 2 diabetes (YT2D) is a rapidly progressive disease characterized by severe insulin resistance (IR), elevated triglyceride concentrations, and low HDL-cholesterol (-C). However, the contribution of triglyceride-rich remnant lipoproteins (TRLp) and remnant-C to overall atherogenic risk in YT2D is unknown, especially in the absence of clinically relevant elevations in LDL-C. Hypothesis: We hypothesized that YT2D would have higher remnant TRLp, remnant-C, and greater subclinical inflammation and IR compared to healthy peers with obesity. Methods: We measured fasting lipoprotein particle size and number, GlycA (a composite marker of inflammation), and lipoprotein IR index (LPIR) using NMR LipoProfile® in 61 YT2D (age 17.2 ±2.9 y, mean±SD, BMI 39.1 ±8.4 kg/m2) and 25 healthy peers (age 17.9 ± 5.1 y, BMI 35.8 ±5.7 kg/m2). Remnant Lp (small TRLp plus very small TRLp) and remnant-C (total-C minus HDL-C minus LDL-C) were calculated and the relationship with GlycA and LPIR determined by spearman correlations. Results: YT2D had higher HemoglobinA1c (7.6 ± 2.0 vs 5.8 ± 0.8%), GlycA (427 [388, 474] vs 376 [332, 406] nmol/L, median[25th,75th]), LPIR (53.7 ± 23.6 vs 29.6 ± 16.5). YT2D had higher remnant TRLp and remnant-C (Figure 1) and a more proatherogenic lipid and lipoprotein profile: LDL-C: 89 ± 23 vs 74 ± 20 mg/dL; total LDLp: 1392 ±368 vs 1075 ±289 nmol/L; small LDLp: 890 ±450 vs 519 ±232 nmol/L, all P&lt;0.01. LPIR was associated with remnant-C (r=0.6, P&lt;0.001) but not with LDL-C (r=0.1, P=0.6). GlycA was associated with remnant-C, remnant TRLp, and small LDLp (all r≥0.3, P&lt;0.01). Conclusion: The proatherogenic profile in YT2D is characterized by higher small LDLp, remnant TRLp, and remnant-C and is related to IR and subclinical inflammation compared to healthy peers with obesity. Future research is needed to determine whether reducing all proatherogenic lipoproteins and inflammation will reduce ASCVD risk.

Postprandial Hyperlipidemia: Its Pathophysiology, Diagnosis, Atherogenesis, and Treatments.

Postprandial hyperlipidemia showing postprandial increases in serum triglyceride (TG) is associated with the development of atherosclerotic cardiovascular disease (ASCVD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed; however, this test is very time-consuming and is difficult to perform. Elevated serum TG levels reflect an increase in TG-rich lipoproteins (TRLs), such as chylomicrons (CM), very low-density lipoproteins (VLDL), and their remnants (CM remnants [CMRs] and VLDL remnants [VLDLRs]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurement of apo B48, which is a constituent of CM and CMR; non-fasting TG, which includes TG content in all lipoproteins including CM and CMR; non-high-density lipoprotein cholesterol (non-HDL-C), which includes TRLs and low-density lipoprotein; and remnant cholesterol are useful to reveal the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an inducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with postprandial hyperlipidemia have various atherogenic properties such as induction of inflammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss, and exercise positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, fenofibrate, bezafibrate, ezetimibe, and eicosapentaenoic acid have been shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide 1 analogues have been shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments. However, there are some problems with the diagnosis for postprandial hyperlipidemia. Postprandial hyperlipidemia cannot be specifically defined by measures such as TG levels 2 h after a meal. To study interventions for postprandial hyperlipidemia with the outcome of preventing the onset of ASCVD, it is necessary to define postprandial hyperlipidemia using reference values such as IGT.

Association between serum leptin concentrations and homeostasis model assessment-insulin resistance of 2.5 and higher in normal weight Japanese women

Normal weight insulin resistant phenotype was characterized in 251 Japanese female university students using homeostasis model assessment-insulin resistance. Birth weight, body composition at age 20, cardiometabolic traits and dietary intake were compared cross-sectionally between insulin sensitive (< 1.6, n = 194) and insulin resistant (2.5 and higher, n = 16) women. BMI averaged < 21 kg/m2 and waist < 72 cm and did not differ between two groups. The percentage of macrosomia and serum absolute and fat-mass corrected leptin concentrations were higher in insulin resistant women although there was no difference in birth weight, fat mass index, trunk/leg fat ratio and serum adiponectin. In addition, resting pulse rate, serum concentrations of free fatty acids, triglycerides and remnant-like particle cholesterol were higher in insulin resistant women although HDL cholesterol and blood pressure did not differ. In multivariate logistic regression analyses, serum leptin (odds ratio:1.68, 95% confidential interval:1.08–2.63, p = 0.02) was associated with normal weight insulin resistance independently of macrosomia, free fatty acids, triglycerides, remnant-like particle cholesterol and resting pulse rate. In conclusion, normal weight IR phenotype may be associated with increased plasma leptin concentrations and leptin to fat mass ratio in young Japanese women, suggesting higher leptin production by body fat unit.

Beneficial effects of luseogliflozin on lipid profile and liver function in patients with type 2 diabetes mellitus (BLUE trial): a single-center, single-arm, open-label prospective study

BackgroundArteriosclerosis and non-alcoholic fatty liver disease are major complications of diabetes mellitus. Hyperglycemia, insulin resistance, obesity, and metabolic syndrome are associated with the progression of these complications. Sodium-glucose transporter 2 inhibitors such as luseogliflozin are oral hypoglycemic agents that reduce glucose levels, induce loss of weight or body fat, and improve liver function. However, the effects of these agents on lipid profiles are unclear. Therefore, this study aimed to investigate these effects and their relationship with arteriosclerosis and non-alcoholic fatty liver disease.MethodsThis single-center, single-arm, open-labeled prospective study enrolled 25 outpatients with type 2 diabetes mellitus who visited Minami Osaka Hospital. Laboratory tests and body measurements were performed at weeks 0 and 24. Luseogliflozin was started at 2.5 mg/day after breakfast, and data from weeks 0 and 24 were evaluated. There were no changes in the doses of other antidiabetic and dyslipidemia drugs a month prior to or during the study.ResultsThe patients showed significant reductions in the levels of triglycerides, remnant-like particle cholesterol, and triglyceride/high-density lipoprotein cholesterol ratio, along with significant increases in the levels of high-density lipoprotein cholesterol and apolipoprotein A-1. Alanine aminotransferase, γ-glutamyl transpeptidase, and the fatty liver index were significantly reduced.ConclusionsLuseogliflozin-induced changes in the lipid profile were related to the suppression or improvement of arteriosclerosis and liver function, respectively. Patients who received this drug also showed improvements in the levels of liver enzymes and reductions in the fatty liver index. Earlier use of luseogliflozin might prevent diabetic complications.Trial registration This study was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN 000043595) on April 6th, 2021

Elevated postprandial triglyceride-rich lipoproteins in patients with diabetes and stable coronary artery disease correlated with early renal damage and systemic inflammation

BackgroundDyslipidaemia is key in the development of coronary heart disease (CHD) in patients with diabetes mellitus (DM). Accumulated evidence supports that diabetic nephropathy increases the mortality risk of patients with CHD, while the influence of diabetic dyslipidaemia on renal damage in patients with DM and CHD remains unknown. Moreover, recent data indicate that postprandial dyslipidaemia has predictive value in terms of CHD prognosis, especially in patients with DM. The study aimed to determine the relationship of triglyceride-rich lipoproteins (TRLs) after daily Chinese breakfast on systemic inflammation and early renal damage in Chinese patients with DM and SCAD.MethodsPatients with DM diagnosed with SCAD while in the Department of Cardiology of Shengjing Hospital from September 2016 to February 2017 were enrolled in this study. Fasting and 4-h postprandial blood lipids, fasting blood glucose, glycated haemoglobin, urinary albumin-to-creatinine ratio (UACR), serum interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) concentrations, and other parameters were measured. Fasting and postprandial blood lipid profiles and inflammatory cytokines were analysed using a paired t-test. The association between variables was analysed using Pearson or Spearman bivariate analysis. P < 0.05 was considered to be statistically significant.ResultsThe study enrolled 44 patients in total. Compared with fasting state, postprandial total cholesterol high-density lipoprotein-cholesterol (HDL-C),low-density lipoprotein-cholesterol (LDL-C) and non-high-density lipoprotein-cholesterol (non-HDL-C) all showed no significant change. Postprandial serum triglyceride (TG) concentration increased significantly compared with that at fasting (1.40 ± 0.40 vs. 2.10 ± 0.94 mmol/L, P < 0.001), as did serum remnant lipoprotein-cholesterol (RLP-C) (0.54 ± 0.18 mmol/L vs. 0.64 ± 0.25 mmol/L). Pearson analysis revealed that serum TG and RLP-C positively correlated before and after breakfast. Moreover, during fasting, positive correlations were observed between TG and serum IL-6, TNF-α, and UACR. Positive correlations were observed between RLP-C and IL-6, UACR under fasting condition, while both TG and RLP-C were positively correlated with postprandial serum IL-6, TNF-α, and UACR concentrations. Finally, positive correlations were observed between UACR and IL-6 and TNF-α concentration under both fasting and postprandial conditions.ConclusionsAn increase in postprandial TRLs was observed in Chinese patients with DM and SCAD after daily breakfast, and this increase may be related to early renal injury via the induction of systemic inflammation.

Association between remnant lipoprotein cholesterol levels and risk of non-alcoholic fatty liver disease in non-obese populations: a Chinese longitudinal prospective cohort study

ObjectivesThe association between remnant lipoprotein cholesterol (RLP-C) levels and the incidence of non-alcoholic fatty liver disease (NAFLD) is unclear, especially in non-obese populations.SettingWe used data from a health assessment database....

Association of Remnant-like Particle Cholesterol with Major Adverse Cardiovascular Events in Subjects with Different Levels of Proprotein Convertase Subtilisin/Kexin 9: A 9.5-year Follow-up Study in a Beijing Community Population

Objective: The purpose of this study was to determine the relationship between remnant-like particle cholesterol (RLP-C) and major adverse cardiovascular events (MACEs) in patients with different levels of proprotein convertase subtilisin/kexin 9 (PCSK9). Methods: From September 2007 to January 2009, 1,859 subjects in Pingguoyuan communities in Beijing were initially screened. After excluding those with bedridden status, mental illness, severe systemic diseases, and missing data, 1,680 subjects were recruited for follow up. All recruited subjects were followed up from February 2013 to September 2013 (181 subjects were lost to follow-up) and from June 2017 to September 2018 (174 subjects were lost to follow up). Finally, 1,325 subjects were included in the study. General demographic characteristics, lifestyle and behaviors, disease history and use of medication was collected. Levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fast blood glucose, RLP-C, low-density lipoprotein triglycerides and PCSK9 were measured. The levels of RLP-C (low: RLP-C ≤ 157 mg/L; high: RLP-C &gt; 157 mg/L) and PCSK9 (low: PCSK9 ≤ 135.87 μg/L; high: PCSK9 &gt; 135.87 μg/L) were represented using quartiles. Subjects were categorized into 4 groups according to their RLP-C and PCSK9 levels: Q4, high levels of RLP-C with high levels of PCSK9; Q3, high levels of RLP-C with low levels of PCSK9; Q2, low levels of RLP-C with high levels of PCSK9; and Q1, low levels of RLP-C with low levels of PCSK9. The association of RLP-C with MACEs in subjects with different PCSK9 levels was evaluated. Results: After a median follow-up of 9.5 years, 1,325 subjects were included in the study and a total of 191 MACEs had occurred. The incidence of MACEs was higher in the RLP-C &gt; 157 mg/L group than the RLP-C ≤ 157 mg/L group (18.40% vs. 10.42%). Cox proportional hazards regression model analysis showed that increased RLP-C levels were associated with an increased risk of MACEs (hazard ratio: 1.405; 95% confidence interval: 1.005–1.964; P &lt; 0.005). The incidence of MACEs was higher in the high RLP-C/PCSK9 group vs. the low RLP-C/PCSK9 group (20.68% vs. 8.76%). Cox proportional hazards regression model analysis showed that RLP-C was associated with an increased risk of MACEs in subjects with high PCSK9 levels independent of traditional risk factors (hazard ratio: 1.791; 95% confidence interval: 1.168–2.825; P = 0.001), but not in those with low PCSK9 levels. Conclusions: RLP-C was identified as a risk factor for MACEs, particularly in subjects with high PCSK9 levels. Lowering PCSK9 levels may reduce residual risk in subjects with elevated plasma RLP-C levels.

Significance of Circulating Remnant Lipoprotein Cholesterol Levels Measured by Homogeneous Assay in Patients with Type 2 Diabetes

Remnant lipoproteins (RLs), which are typically present at high concentrations in patients with type 2 diabetes mellitus (T2DM), are associated with cardiovascular disease (CVD). Although an RL cholesterol homogeneous assay (RemL-C) is available for the measurement of RL concentrations, there have been no studies of the relationship between RemL-C and clinical parameters in T2DM. Therefore, we evaluated the relationships between RemL-C and CVD-related parameters in patients with T2DM. We performed a cross-sectional study of 169 patients with T2DM who were hospitalized at Kumamoto University Hospital. Compared with those with low RemL-C, those with higher RemL-C had higher fasting plasma glucose, homeostasis model assessment for insulin resistance (HOMA-R), total cholesterol, triglyceride, small dense low-density lipoprotein cholesterol (sdLDL-C), and urinary albumin-creatinine ratio; and lower high-density lipoprotein cholesterol, adiponectin, and ankle brachial pressure index (ABI). Multivariate logistic regression analysis showed that sdLDL-C and ABI were significantly and independently associated with high RemL-C. Although LDL-C was lower in participants with CVD, there was no difference in RemL-C between participants with or without CVD. Thus, RemL-C may represent a useful index of lipid and glucose metabolism, and that may be a marker of peripheral atherosclerotic disease (PAD) in male patients with T2DM.

Abstract P555: Variants of Neurocan, a Nonalcoholic Fatty Liver Disease Risk Allele, Are Associated With Plaque Development in the Carotid Artery Over 5 Years

Introduction: Nonalcoholic fatty liver disease (NAFLD) genetic risk alleles are associated with lipid metabolism. However, the association between those variants and atherosclerosis has not yet been fully evaluated. Hypothesis: We hypothesized that NAFLD risk alleles are associated with the progression of atherosclerosis. Methods: A total of 1,050 Japanese men and women (median age 55 years and median body mass index 22.9 kg/m2) free of cardiovascular disease, dyslipidemia, hypertension, and diabetes were studied. . Among NAFLD risk SNPs, variants of patatin-like phospholipase domain containing 3 ( PNPLA3 ), transmembrane 6 superfamily member 2 ( TM6SF2 ), glucokinase regulator ( GCKR ), and neurocan ( NCAN ) were assessed. Plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL-C, LDL-triglycerides, high-density lipoprotein cholesterol (HDL-C), HDL3-C, triglycerides, remnant-like particle cholesterol, lipoprotein(a), and adiponectin were also measured. At both baseline and after a five-year follow-up, carotid intima-media thickness (cIMT) was assessed. Atherosclerosis was defined as cIMT ≥ 1.1mm or the presence of a plaque. Univariate and multivariate analyses and chi-square and Fisher’s exact tests were performed to examine the associations between NAFLD risk SNPs, lipoproteins, and progression of atherosclerosis. Results: Both median and maximum cIMT of total participants did not differ between baseline and after a five-year follow-up. Among participants without atherosclerosis at baseline, the rate of plaque development was 13.8% (121/880) with the major allele (CC) of NCAN being significantly higher than other alleles. Variants of NCAN were associated with the development of plaque ( P = 0.04, Fisher’s exact test). Participants with the CT allele of NCAN had significantly lower RLP cholesterol at baseline than those with the CC allele (7.6 mg/dl vs. 10.5 mg/dl, P = 0.02). Variants of PNPLA3 , TM6SF2 , GCKR , and NCAN were not associated with changes in lipoproteins. Conclusions: A NCAN variant, one of the NAFLD risk SNPs, was associated with the development of plaque independent of lipoprotein alterations among healthy Japanese participants.

Remnant Indices for Estimating Postprandial Lipidemia in Young Women

Postprandial hyperglycemia is well established as a major risk factor for prediabetes and type 2 diabetes. However, for postprandial hyperlipidemia, no definitive criteria exist, and fasting values of lipids and lipoproteins had limited efficacy for estimating postprandial lipidemia. In the present study, we performed a fat-ingestion test and aimed to propose indices for estimating postprandial lipoprotein metabolism. Methods: Healthy young Japanese women (n=54, age 21.1 ± 1.0 y) with apolipoprotein E phenotype 3/3 were enrolled. They ingested fat cream (OFTT cream™, Jomo, Japan; 1 g/kg as cream, 0.35 g/kg as fat). Venous blood samples were taken before (0 h) and at 0.5, 1, 2, 4, and 6 h after ingestion. Results: The serum triglyceride (TG) level peaked at 2 h and returned to below baseline at 6 h. The remnant-like particle-TG (RP-TG) level increased at 1 h, peaked at 2 h, and returned to baseline at 6 h. The remnant lipoprotein-cholesterol (RLP-C) level increased at 2 h, peaked at 4 h, and returned to baseline at 6 h. The apolipoprotein B48 level increased at 1 h, peaked at 4 h, and did not return to baseline at 6 h. The apolipoprotein B100 concentration slightly decreased at 2 h and increased at 6 h. TG−RP-TG did not change during 6 h, but RP-TG/TG rose at 2–6 h compared to the fasting value. RP-TG/RLP-C increased at 2–4 h and returned to baseline at 6 h. Conclusion: After fat ingestion, while the concentration of non-remnant TG was stable, remnant TG increased. The content of TG per remnant particle increased up to 2 h and decreased from 2 h to 6 h, and the size became smaller. The remnant indices, RP-TG/TG and RP-TG/RLP-C, may be useful for estimating postprandial lipidemia.

The effects of pemafibrate and omega-3 fatty acid ethyl on apoB-48 in dyslipidemic patients treated with statin: A prospective, multicenter, open-label, randomized, parallel group trial in Japan (PROUD48 study).

We compared the lowering effects of pemafibrate and omega-3 fatty acid ethyl on fasting apolipoprotein (apo) B-48 (apoB-48), a marker that reflects postprandial hypertriglyceridemia, which is one of the residual risks for atherosclerotic cardiovascular disease (ASCVD) with statin treatment. This prospective, multicenter, open-label, randomized, parallel group trial was conducted at 4 medical institutions between April 2020 and May 2022. A total of 126 ambulatory patients with dyslipidemia receiving statin treatment for more than 4 weeks, aged 20-79 years with fasting triglyceride (TG) levels of ≥177 mg/dl were randomly assigned to 16-week pemafibrate 0.4 mg per day treatment group (PEMA, n = 63) or omega-3 fatty acid ethyl 4 g per day treatment group (OMEGA-3, n = 63). The primary endpoint was the percentage change in fasting apoB-48 from baseline to week 16. The percentage changes in fasting apoB-48 in PEMA and OMEGA-3 were -50.8% (interquartile range -62.9 to -30.3%) and -17.5% (-38.3 to 15.3%) (P < 0.001), respectively. As the secondary endpoints, the changes in fasting apoB-48 in PEMA and OMEGA-3 were -3.10 μg/ml (-5.63 to -1.87) and -0.90 μg/ml (-2.95 to 0.65) (P < 0.001), respectively. Greater decreases with significant differences in the percentage changes in TG, remnant lipoprotein cholesterol, apoC-III, fasting plasma glucose, alanine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase were observed in PEMA, compared with OMEGA-3. Greater increases with significant differences in those in high-density lipoprotein (HDL) cholesterol, apoA-I, and apoA-II were observed in PEMA, compared with OMEGA-3. PEMA showed anti-atherosclerotic lipoprotein profiles in gel-permeation high-performance liquid chromatography analyses, compared with OMEGA-3. Although adverse events occurred in 9 of 63 (14.3%) patients in PEMA and 3 of 63 (4.8%) patients in OMEGA-3, no serious adverse events associated with drug were observed in either group. This is the first randomized trial to compare the lowering effects of pemafibrate and omega-3 fatty acid ethyl on fasting apoB-48. We concluded that pemafibrate was superior to omega-3 fatty acid ethyl in lowering effect of fasting apoB-48. Pemafibrate is expected to reduce the residual risk for ASCVD with statin treatment. https://rctportal.niph.go.jp/en, identifier jRCTs071200011.

Remnant-Like Particle Cholesterol and the Risk of Major Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis.

Background: The remnant-like particle cholesterol (RLP-C) has been demonstrated to be associated with residual cardiovascular risk. The meta-analysis aimed to evaluate the impact of baseline RLP-C on the incidence of major cardiovascular adverse events (MACEs) in patients with coronary artery disease (CAD). Methods: A systematic literature search was performed in PubMed and Embase electronic databases from the inception of the databases through 1 October 2022. Studies evaluating the association between baseline RLP-C and the risk of MACEs in patients with CAD were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled by a random-effect method (RLP-C analyzed as a categorical variable) and a fixed-effects model (RLP-C analyzed as a continuous variable). Results: Ten studies including 18,053 subjects were finally included in this meta-analysis. In our pooled analysis, compared to CAD patients with the lowest RLP-C category, the CAD patients with the highest RLP-C category had a significantly higher risk of future MACEs during follow-up (HR 1.79, 95% CI, 1.42−2.26, I2 = 60.31%, p < 0.01), which was consistent with outcomes of meta-analysis with the RLP-C analyzed as a continuous variable (HR 1.40, 95% CI, 1.28−1.53, I2 = 38.20%, p < 0.01). The sensitivity analysis confirmed the robustness of the results, and no significant publication bias was identified. Conclusion: The present meta-analysis suggests that the RLP-C was associated with an increased risk of long-term MACEs in patients with CAD at baseline. It is necessary to conduct randomized controlled trials to explore whether reducing the RLP-C level is conducive to reducing residual cardiovascular risk, even coronary plaque regression.

Abstract 11228: Association Between Nonalcoholic Fatty Liver Disease Risk Alleles and Atherosclerosis

Introduction: Nonalcoholic fatty liver disease (NAFLD) risk alleles are associated with lipid metabolisms. However, the association between those variants and atherosclerosis has not yet been fully evaluated. Hypothesis: We hypothesized that NAFLD genetic risk alleles are associated with the progression of atherosclerosis. Methods: A total of 1,050 Japanese men and women (median age 55 years and median body mass index 22.9 kg/m2) free of cardiovascular disease, dyslipidemia, hypertension, and diabetes were studied. Among NAFLD risk SNPs, variants of patatin-like phospholipase domain containing 3 ( PNPLA3 ), transmembrane 6 superfamily member 2 ( TM6SF2 ), glucokinase regulator ( GCKR ), and neurocan ( NCAN ) were assessed. Plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL-C, LDL-triglycerides, high-density lipoprotein cholesterol (HDL-C), HDL3-C, triglycerides, remnant-like particle cholesterol, lipoprotein(a), and adiponectin were also measured. At both baseline and after a five-year follow-up, carotid intima-media thickness (cIMT) was assessed. Atherosclerosis was defined as cIMT more than 1.1mm or the presence of a plaque. Univariate and multivariate analyses and chi-square and Fisher’s exact tests were performed to examine the associations between NAFLD risk SNPs, lipoproteins, and progression of atherosclerosis. Results: Both median and maximum cIMT of total participants did not differ between baseline and after a five-year follow-up. Among participants without atherosclerosis at baseline, the rate of plaque development was 13.8% (121/880) with the major allele (CC) of NCAN being significantly higher than other alleles. Variants of NCAN were associated with the development of plaque ( P = 0.04, Fisher’s exact test). Variants of PNPLA3 , TM6SF2 , GCKR , and NCAN were not associated with changes in lipoproteins. Conclusions: A NCAN variant, one of the NAFLD risk SNPs, was associated with the development of plaque independent of lipoproteins alterations among healthy Japanese participants.

Sugar-Sweetened Beverage Consumption and Plasma Lipoprotein Cholesterol, Apolipoprotein, and Lipoprotein Particle Size Concentrations in US Adults

Prospective cohort studies have found a relation between sugar-sweetened beverage (SSB) consumption (sodas and fruit drinks) and dyslipidemia. There is limited evidence linking SSB consumption to emerging features of dyslipidemia, which can be characterized by variation in lipoprotein particle size, remnant-like particle (RLP), and apolipoprotein concentrations. To examine the association between SSB consumption and plasma lipoprotein cholesterol, apolipoprotein, and lipoprotein particle size concentrations among US adults. We examined participants from the Framingham Offspring Study (FOS; 1987-1995, n = 3047) and the Women's Health Study (1992, n = 26,218). Concentrations of plasma LDL cholesterol, apolipoprotein B (apoB), HDL cholesterol, apolipoprotein A1 (apoA1), triglyceride (TG), and non-HDL cholesterol, as well as total cholesterol:HDL cholesterol ratio and apoB:apoA1 ratio, were quantified in both cohorts; concentrations of apolipoprotein E, apolipoprotein C3, RLP-TG, and RLP cholesterol (RLP-C) were measured in the FOS only. Lipoprotein particle sizes were calculated from nuclear magnetic resonance signals for lipoprotein particle subclass concentrations (TG-rich lipoprotein particles [TRL-Ps]: very large, large, medium, small, and very small; LDL particles [LDL-Ps]: large, medium, and small; HDL particles [HDL-Ps]: large, medium, and small). SSB consumption was estimated from food frequency questionnaire data. We examined the associations between SSB consumption and all lipoprotein and apoprotein measures in linear regression models, adjusting for confounding factors such as lifestyle, diet, and traditional lipoprotein risk factors. SSB consumption was positively associated with LDL cholesterol, apoB, TG, RLP-TG, RLP-C, and non-HDL cholesterol concentrations and total cholesterol:HDL cholesterol and apoB:apoA1 ratios; and negatively associated with HDL cholesterol and apoA1 concentrations (P-trend range: <0.0001 to 0.008). After adjustment for traditional lipoprotein risk factors, SSB consumers had smaller LDL-P and HDL-P sizes; lower concentrations of large LDL-Ps and medium HDL-Ps; and higher concentrations of small LDL-Ps, small HDL-Ps, and large TRL-Ps (P-trend range: <0.0001 to 0.001). Higher SSB consumption was associated with multiple emerging features of dyslipidemia that have been linked to higher cardiometabolic risk in US adults.

Association between remnant lipoprotein cholesterol, high-sensitivity C-reactive protein, and risk of atherosclerotic cardiovascular disease events in the Multi-Ethnic Study of Atherosclerosis (MESA)

Elevated remnant-lipoprotein (RLP)-cholesterol (RLP-C) and high-sensitivity C-reactive protein (hsCRP) are each individually associated with atherosclerotic cardiovascular disease (ASCVD). To evaluate the interplay of nuclear magnetic resonance (NMR)-derived RLP-C and hsCRP and their association with ASCVD in the Multi-Ethnic Study of Atherosclerosis (MESA). Lipoprotein particles were measured using NMR spectroscopic analysis at baseline. RLP-C includes very-low-density lipoprotein cholesterol and intermediate-density lipoprotein cholesterol. Four groups were created as follows: Group 1: RLP-C ≤ median (≤29.14 mg/dL) and hsCRP < 2 mg/L; Group 2: RLP-C ≤ median and hsCRP≥ 2 mg/L; Group 3: RLP-C > median and hsCRP level < 2 mg/L; and Group 4: RLP-C > median and hsCRP level ≥ 2 mg/L. Kaplan-Meier survival curves and multivariable-adjusted Cox proportional hazard models were used to examine the relationship between RLP-C and hsCRP with incident ASCVD. A total of 6,720 MESA participants (mean age 62.2 y, 53% female) with a median follow-up of 15.6 years were included. In the fully adjusted model, compared to those in the reference group (Group 1), participants in Group 2, Group 3, and Group 4 demonstrated a 20% (95% CI, -2%-48%), 18% (-4%-44%), and 43% (18%-76%) increased risk of incident ASCVD events, respectively (p<0.01). An additive and multiplicative interaction between RLP-C and hsCRP was not statistically significant. NMR-derived RLP-C and hsCRP showed a similar independent association with incident ASCVD. Notably, the combination of increased RLP-C and hsCRP was associated with an increased risk of future ASCVD events.