Remnant Cholesterol Research Articles

Associations of remnant cholesterol in early pregnancy with gestational diabetes mellitus risk: a prospective birth cohort study

BackgroundRemnant cholesterol (RC) reportedly contributes to the development of diabetes mellitus. However, evidence on the relationship between maternal RC and the risk of developing gestational diabetes mellitus (GDM) during pregnancy is limited. This study aimed to assess the relationship between maternal RC and GDM risk during early pregnancy, and explore the potential pathways involved in the relationship between RC levels and GDM risk.MethodsFrom 2018 to 2021, a prospective birth cohort study was designed and carried out in China. The associations of maternal RC and other lipid parameters with GDM risk were estimated using logistic regression models and restricted cubic splines. Subgroup analyses were performed stratified by prepregnancy body mass index (pre-BMI), maternal age and gravidity. Mediation analyses were conducted to explore the mediating effect of some related factors on the relationship between RC levels and the risk of GDM.ResultsA total of 33,018 pregnant women were included. The median RC level was 0.47 ± 0.20 mmol/L. The prevalence of GDM was 15.19%. As RC quartiles increased, the incidence of GDM increased substantially, reaching 19.24% for the highest quartile of RC (P < 0.001). Maternal RC in the first trimester was positively correlated with GDM risk (OR: 2.254, 95% CI: 1.943–2.615). Compared to the lowest RC quartile, higher RC quartiles were correlated with an increased risk of GDM, and the ORs (95% CIs) for Q3 and Q4 were 1.208 (1.101–1.325) and 1.489 (1.364–1.626), respectively. Moreover, a linear dose–response relationship was found for this association (P for all < 0.001, P for nonlinearity > 0.05) and was consistent across subgroups with different pre-BMIs, maternal ages and gravidities (all P values for interactions > 0.05). Furthermore, the correlation between RC level and GDM risk was partially mediated by pre-BMI (9.20%) and blood glucose level (-11.1%).ConclusionsHigher maternal RC levels in the early stage of pregnancy was positively associated with an increased risk of developing GDM. This association was partially mediated by pre- BMI and blood glucose levels.

Association of remnant cholesterol with coronary artery ectasia: a cross-sectional study

ObjectiveCoronary artery ectasia (CAE) is a condition characterized by the localized or widespread dilation of one or more coronary arteries. The majority of CAE patients do not present with clinical symptoms, and the exact cause of CAE remains unclear. Therefore, a retrospective analysis was conducted to explore the potential causes of CAE.MethodsThis study was a retrospective analysis of patients who underwent coronary angiography at Guangdong Provincial People’s Hospital between January 2017 and July 2022, of whom 679 patients were ultimately enrolled in the study. Among them, 260 patients were diagnosed with CAE, whereas 419 patients with normal coronary results composed the control group. Remnant cholesterol (RC) was calculated as total cholesterol (TC) minus high-density lipoprotein cholesterol (HDL-C) minus low-density lipoprotein cholesterol (LDL-C). The association between RC levels and the risk of CAE was assessed via multivariable logistic models.ResultsOut of the 679 patients who participated in this study, with an average age of 59.9 years, 38.3% were diagnosed with CAE. Patients with CAE had higher RC levels than did those without CAE (P = 0.001). A significant positive association was observed between RC levels and the risk of CAE, with a multivariable adjusted odds ratio (OR) of 1.950 (95% confidence interval [CI]: 1.163–3.270). There was a significant positive association between RC levels and the risk of CAE in both single-vessel and multivessel dilation cases, as well as in isolated CAE and dilation secondary to coronary atherosclerosis. According to the subgroup analyses, RC levels were positively associated with the risk of CAE in participants with hypertension (OR, 1.065; 95% CI, 1.034–1.098).ConclusionRC levels are positively correlated with CAE, implying that a focus on RC could be beneficial in CAE research.

Link between remnant cholesterol and the reversion to normoglycemia in Chinese adults with prediabetes: a 5-year cohort study

Despite the clear association between remnant cholesterol (RC)and diabetes risk, no study to date has examined the relationship between RC and reversal of prediabetes to normoglycemia. This retrospective cohort study included a total of 15,023 patients with prediabetes who underwent a physical examination between 2010 and 2016. The link between initial RC levels and the reversion from prediabetes to normoglycemia was analyzed using the Cox proportional-hazards regression model. Additionally, the study explored the possible relationship between RC and the probability of returning normoglycemia by applying Cox proportional hazards regression models with cubic spline functions. To address competing risks, a multivariate Cox regression analysis was undertaken, treating the onset of diabetes as a competing risk event for reversing prediabetes to normoglycemia. Additionally, the study incorporated extensive subgroup analyses alongside multiple sensitivity analyses, enhancing the reliability and robustness of the results. After adjusting for covariates, the findings indicated that RC was inversely associated with the likelihood of reverting to normoglycemia (per 5 mg/dL increase, HR = 0.918, 95% CI 0.909–0.927). The analysis also revealed a nonlinear relationship between RC and normoglycemia reversion, with an inflection point at 51.08 mg/dL. For RC values below this inflection point (RC < 50.08 mg/dL), the HR for the probability of returning to normoglycemia was 0.907 (95% CI 0.897–0.917 per 5 mg/dL). Additionally, the competing risks model demonstrated a negative relationship between RC and the reversal of prediabetes to normoglycemia (SHR = 0.92, 95% CI 0.91–0.93). Sensitivity analyses confirmed the robustness and stability of these results. This study demonstrated a negative and non-linear association between RC and the probability of reversion to normoglycemia in Chinese adults with prediabetes. By actively intervening to reduce RC levels, at least to below 51.08 mg/dL, further reduction of RC may significantly increase the probability of returning to normoglycemia from prediabetes.

Efficacy and Safety of Pemafibrate, a Novel Selective PPARα Modulator in Chinese Patients with Dyslipidemia: A Double-Masked, Randomized, Placebo- and Active-Controlled Comparison Trial.

Pemafibrate substantially lowers serum triglyceride (TG) levels and increases high-density lipoprotein cholesterol (HDL-C) levels primarily in Japan, but it has not been evaluated in China. We aimed to confirm the efficacy and safety of pemafibrate in Chinese patients with hypertriglyceridemia and low HDL-C levels by comparing placebo and fenofibrate. A multicenter, double-masked trial was conducted in China involving 344 patients with high TG and low HDL-C levels randomly assigned to one of four groups: pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, or placebo for 12 weeks. The primary endpoint was the percentage change in fasting TG levels. The percentage change in TG levels from baseline was -34.1%, -44.0%, -30.5%, and 6.5% in the pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, and placebo groups, respectively. Pemafibrate 0.4 mg/d significantly reduced TG levels compared with that in both placebo (p＜0.0001) and fenofibrate groups (p=0.0083). Significant improvements in HDL-C, remnant cholesterol, and apolipoprotein A1 levels were also observed with both doses of pemafibrate than with the placebo. Pemafibrate showed significantly smaller changes in alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels than those with fenofibrate. In Chinese patients, pemafibrate exhibited superior efficacy in improving TG levels and enhanced hepatic and renal safety compared to fenofibrate. Thus, pemafibrate may represent a promising therapeutic option for dyslipidemia in Chinese patients.

Discordant High Remnant Cholesterol With LDL-C Increases the Risk of Stroke: A Chinese Prospective Cohort Study.

Previous studies focusing on assessing the effects of remnant cholesterol (RC) and low-density lipoprotein cholesterol (LDL-C) on stroke may not consider their mutual influence. We aimed to explore the associations of RC and discordant high RC with LDL-C with stroke, ischemic stroke (IS), and hemorrhagic stroke. This prospective cohort study was conducted based on 3 cohorts of the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) project. RC was calculated as non-high-density lipoprotein cholesterol minus LDL-C estimated by Martin/Hopkins equations. Concordant/discordant categories for RC versus LDL-C were determined based on cut-points of 130 mg/dL for LDL-C and equivalent percentile (32.50 mg/dL) for RC. Cox models were used to estimate adjusted hazard ratios and 95% CIs for incident stroke. Among 113 448 participants recruited at baseline, a total of 98 967 participants were eligible for the final analysis (mean age of 51.44 years; 40.45% were men). During 728 776.87 person-years of follow-up, 2859 stroke cases, 1811 IS cases, and 849 hemorrhagic stroke cases were observed. RC was positively associated with stroke and IS, but not hemorrhagic stroke, with adjusted hazard ratios (95% CIs) of 1.06 (1.02-1.10), 1.09 (1.04-1.13), and 0.95 (0.88-1.03) for per SD increase in RC. Compared with low LDL-C/low RC group, low LDL-C/high RC group had higher risks of stroke (adjusted hazard ratio, 1.15 [95% CI, 1.02-1.30]) and IS (1.19, 1.03-1.38), while high LDL-C/low RC group had no increased risk of stroke (1.07 [0.95-1.20]) and IS (1.09 [0.94-1.25]). Higher RC was associated with increased risks of stroke and IS but not hemorrhagic stroke. Discordantly high RC, not discordantly high LDL-C, conferred higher risks of stroke and IS. Our findings support further lowering RC by interventions to reduce residual IS risk.

Remnant cholesterol is more positively related to diabetes, prediabetes, and insulin resistance than conventional lipid parameters and lipid ratios: A multicenter, large sample survey.

Not many large-sample investigations are available that compare the potency of the relationship of remnant cholesterol (RC) and other lipid parameters with diabetes and prediabetes. The goals of our study are to discover the relationship between RC and prediabetes, diabetes, and insulin resistance (IR) and to investigate RC, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C, which are the lipid parameters that are most positively related to diabetes, prediabetes, and IR. This research enrolled 36 684 subjects from China's eight provinces. We employed multiple logistic regression analysis for testing the relationship between lipid parameters and diabetes, prediabetes, and IR. After adjusting for potential confounders, and comparing the results with other lipid parameters, the positive relationship between RC and diabetes (odds ratio [OR] 1.417, 95% confidence interval [CI]: 1.345-1.492), prediabetes (OR 1.555, 95% CI: 1.438-1.628), and IR (OR 1.488, 95% CI: 1.404-1.577) was highest. RC was still related to diabetes, prediabetes, and IR even when TG <2.3 mmol/L (diabetes: OR 1.256, 95% CI: 1.135-1.390; prediabetes: OR 1.503, 95% CI: 1.342-1.684; and IR: OR 1.278, 95% CI: 1.140-1.433), LDL-C <2.6 mmol/L (diabetes: OR 1.306, 95% CI: 1.203-1.418; prediabetes: OR 1.597, 95% CI: 1.418-1.798; and IR: OR 1.552, 95% CI: 1.416-1.701), or HDL-C ≥1 mmol/L (diabetes: OR 1.456, 95% CI: 1.366-1.550; prediabetes: OR 1.553, 95% CI: 1.421-1.697; and IR: OR 1.490, 95% CI: 1.389-1.598). RC is more positively related to diabetes, prediabetes, and IR than conventional lipids and lipid ratios in the general population, the relationships between RC and diabetes, prediabetes, and IR are stable, even if HDL-C, LDL-C, or TG are at appropriate levels.

The Risk of Coronary Artery Calcification according to Different Lipid Parameters and Average Lipid Parameters.

We compared the association between the baseline and average lipid parameters over time and the coronary artery calcification (CAC) risk. Participants who underwent annual (biannual) health examinations and coronary artery computed tomography to measure CAC at least twice between March 2010 and December 2019, with a baseline CAC of 0, were included. The levels of apolipoprotein B (ApoB), Apolipoprotein A-I (ApoA1), ApoB/ApoA1, non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), TG/HDL-C, and TC/HDL-C were measured or calculated. The remnant cholesterol (RC) levels were calculated. The average lipid parameters before study entry were calculated using data from 2002 to 2010. The participants were divided into quartiles (Q) according to the parameter values. Cox proportional hazard modeling, adjusted for confounding factors, compared the CAC risk of the highest quartile to the lowest quartile. Among 29,278 participants (mean age, 39.19±5.21; men, 88.27%), 2,779 developed CAC ＞0. The highest quartile of ApoB showed a numerically strong association with CAC risk, compared with the lowest quartile of ApoB (Q1: reference; Q2: HR,1.41, 95% CI,1.25-1.59; Q3: HR,1.97, 95% CI,1.75-2.21; Q4: HR,2.72, 95% CI,2.41-3.07). RC showed a modest association with CAC risk (Q1: reference; Q2: HR,1.13, 95% CI,0.99-1.28; Q3: HR,1.3, 95% CI,1.15-1.47; Q4: HR,1.7, 95% CI,1.51-1.91). The strength of the association was comparable between the parameters at baseline and the average lipid parameters over time. A high ApoB level showed a strong association with CAC risk compared with the lowest ApoB quartile. The baseline lipid parameters can predict CAC development as effectively as the average of multiple measurements can.

Reduced Capacity of High-Density Lipoprotein to Acquire Free Cholesterol From Triglyceride-Rich Lipoproteins Is Associated With Elevated Postprandial Hypertriglyceridemia in Healthy Men.

The capacity of high-density lipoprotein cholesterol (HDL) to acquire free cholesterol (FC) from triglyceride-rich lipoproteins during lipoprotein lipase-dependent lipolysis in a process of reverse remnant cholesterol transport, has been proposed as a key biological function of HDL particles that underlies the U-shaped relationship between HDLcholesterol and cardiovascular diseases. Although reverse remnant cholesterol transport has been evaluated in a fasting state, it has never been explored under nonfasting conditions. FC transfer was evaluated in healthy men (n=78) before and throughout the postprandial phase up to 8 hours after consumption of a test meal. Postprandially, the capacity of HDL to acquire FC increased progressively, reaching a maximal mean value of 98.5%±22.5% 6 hours after meal intake (P<0.05). Analysis of the study population according to tertiles of postprandial variation of FC transfer identified subjects exhibiting reduced capacity of HDL to acquire FC (tertile 1), those for whom the capacity of HDL to acquire FC remained unchanged (tertile 2), and subjects characterized by an enhanced FC transfer during the postprandial phase (tertile 3). Across the tertiles, we found an inverse relationship between the maximal postprandial change in FC transfer to HDL and the degree of postprandial triglyceride response. Healthy individuals exhibiting exacerbated postprandial triglyceride response and reduced HDL cholesterol levels feature reduced FC transfer to HDL during the postprandial state. These data suggest that to normalize postprandial triglyceride response, 2 conditions need to be fulfilled: notably elevated FC transfer to HDL in the postprandial phase and increased levels of acceptor HDL particles.

The Relationship Between Remnant Cholesterol and Visceral Adipose Tissue: A National Cross-Sectional Study.

The aim of our study is to explore the relationship between remnant cholesterol (RC) levels and visceral adipose tissue (VAT) in the US adult population. This cross-sectional study utilized data from 5301 participants aged 20 to 59 years gathered by the National Health and Nutrition Examination Survey (NHANES). RC was determined by deducting both high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) from total cholesterol (TC), and VAT was measured using dual-energy X-ray absorptiometry. Visceral obesity is defined as a VAT area ≥ 100 cm2. With increasing quartiles of RC levels, the prevalence of visceral obesity rises (16.51% vs. 36.11% vs. 55.66% vs. 74.48%, p<0.001). After adjusting for confounders, RC levels positively correlate with visceral obesity risk (OR=1.039, 95% CI 1.031-1.048, p<0.001). Additionally, individuals with low LDL-c/high RC and those with high LDL-c/low RC showed 2.908-fold (95% CI 1.995-4.241) and 1.310-fold (95% CI 1.022-1.680) higher risk of visceral obesity, respectively, compared to those with low LDL-c/low RC. Receiver Operating Characteristic (ROC) and Decision Curve Analysis (DCA) show RC's superior predictive ability over other lipid markers. Subgroup analysis showed that the relationship between RC and visceral obesity was more ronounced in those with cardiovascular disease. Smooth curve fitting indicated a nonlinear relationship between RC levels and VAT area. Our study highlights that elevated levels of RC are associated with adverse accumulation of VAT. However, the causal relationship between RC and visceral obesity requires additional investigation.

Nonlinear association between visceral adipose tissue area and remnant cholesterol in US adults: a cross-sectional study

BackgroundExcessive visceral adipose tissue (VAT) is associated with a spectrum of diseases, including diabetes, cancer, and cardiovascular diseases. Remnant cholesterol (RC), denoting cholesterol within triglyceride-rich lipoproteins and their metabolic byproducts, has been identified as a key contributor to cardiovascular diseases and related mortality. However, the association between the VAT and RC remains unclear. In this study, the objective is to provide new evidence regarding the association between VAT and RC concentrations.Methods4727 individuals aged 18–59 were selected from the National Health and Nutrition Examination Survey conducted between 2011 and 2018 as study participants. This study utilized several weighted linear regression models and a restricted cubic spline (RCS) to explore the association and potential nonlinearities between VAT and RC. Subgroup analyses were performed to determine the consistency of findings.ResultsThe mean VAT value was 103.82 ± 1.42 cm2, and the median RC value was 18 mg/dl. VAT demonstrated a positive association with RC in a fully adjusted model, with a β and 95% confidence interval (CI) of 0.09 (0.08, 0.11) after adjustment for potential confounders. Analysis using RCS revealed a nonlinear association between the VAT area and RC (P < 0.001 for nonlinearity). Adjusted two-piecewise regression models demonstrated β coefficients of 0.13 (95%CI: 0.11 ~ 0.16, P < 0.001) for RC in individuals with VAT < 143 cm2, and 0.02 (95%CI: -0.01 ~ 0.06, P = 0.15) for those with VAT ≥ 143 cm2. Interactions were observed among the body mass index (BMI) subgroup; the β coefficients for RC were 0.14 (95%CI: 0.12 ~ 0.16) in those with BMI < 30 kg/m2 and 0.05 (95%CI:0.04 ~ 0.07) in those with BMI ≥ 30 kg/m2, with a P-value of < 0.001 for interaction.ConclusionsThis study identified a nonlinear association between VAT and RC in American adults. Reducing the VAT area may be beneficial in lowering RC concentration, particularly when VAT is < 143 cm2 and those with a BMI < 30 kg/m2.

Association of remnant cholesterol with risk of dementia: a nationwide population-based cohort study in South Korea

The association between remnant cholesterol (remnant-C) and cardiovascular disease risk is well established, but its association with dementia remains unclear. We aimed to examine this association using a large-scale population dataset. We did a nationwide, population-based cohort study in which we identified participants aged 40 years and older who underwent the national health examination in 2009 from South Korea's National Health Insurance Service. We excluded people who were younger than 40 years and those with a triglyceride concentration of 400 mg/dL or higher due to concerns regarding the accuracy of calculated low-density lipoprotein cholesterol concentration in individuals with extremely high triglyceride concentrations. People who were previously diagnosed with dementia before the index date, and those who had any missing variables were also excluded. To minimise the influence of possible reverse causation, we excluded individuals who had developed any type of dementia within 1 year of the baseline measurements. We calculated hazard ratios (HRs) for all-cause dementia, Alzheimer's disease, and vascular dementia in each quartile of remnant-C using the Cox proportional hazards model adjusted for age, sex, body-mass index, estimated glomerular filtration rate, income level, smoking status, alcohol consumption, regular exercise, diabetes, hypertension, statin and fibrate use, and total cholesterol concentrations. We also did subgroup analyses to investigate the association between remnant-C and the risk of dementia stratified by age, sex, obesity, glycaemic status (normoglycaemia, impaired fasting glucose, new-onset type 2 diabetes, type 2 diabetes with a duration of less than 5 years, and type 2 diabetes with a duration of 5 years or more), hypertension, chronic kidney disease, and dyslipidaemia, using likelihood ratio tests. 4 234 415 individuals who underwent the national health examination in 2009 were deemed eligible for inclusion. We excluded 1 612 819 individuals on the basis of age, triglyceride concentration, missing variables, or having dementia at baseline. We identified 2 621 596 participants aged 40 years and older (1 305 556 men and 1 316 040 women) who underwent the national health examination and followed them up until the date of any incident of dementia or the end of the study period of Dec 31, 2020. During a median follow-up of 10·3 years (IQR 10·1-10·6), 146 991 (5·6%) participants developed all-cause dementia, 117 739 (4·5%) developed Alzheimer's disease, and 14 536 (0·6%) developed vascular dementia. The risk of dementia increased progressively with higher remnant-C concentrations. Compared with the lowest quartile of remnant-C (quartile 1), HRs in the highest quartile (quartile 4) were 1·11 (95% CI 1·09-1·13) for all-cause dementia, 1·11 (1·08-1·13) for Alzheimer's disease, and 1·15 (1·09-1·21) for vascular dementia. Subgroup analyses revealed that the risk of dementia associated with high remnant-C concentrations was higher in middle-aged people aged 40-59 years than in older people. The risk of dementia associated with high concentrations of remnant-C was notably more pronounced in individuals with diabetes compared with those without diabetes, and the risk increased steeply with a longer duration of diabetes. Results showed that higher remnant-C concentrations were independently associated with increased risks of all-cause dementia, Alzheimer's disease, and vascular dementia. More research is needed to determine the mechanisms underlying this finding. Monitoring and managing higher concentrations of remnant-C might have important implications for reducing the risk of dementia. None.

More than simply leftovers: a new link between remnant cholesterol and dementia

More than simply leftovers: a new link between remnant cholesterol and dementia

Impact of Obesity on Target Organ Damage in Patients with Metabolic Syndrome.

Metabolic syndrome (MetSy) is characterized by the presence of obesity, hypertension, altered glucose metabolism, and/or increased non-HDL cholesterol. This study aimed at elucidating the association between obesity with subclinical target organ damage and biochemical parameters included in MetSy pathogenesis. This study included 130 apparently healthy subjects. Plasma levels of oxidized-LDL-cholesterol (ox-LDL-Chol), nitric oxide (NO) metabolites, inducible NO synthase (iNOS), and plasminogen activator inhibitor-1 (PAI-1) were measured. Non-invasive assessment of liver disease included fatty liver index (FLI) and nonalcoholic fatty liver disease (NAFLD) fibrosis score. Carotid artery plaques were assessed by color Doppler imaging. A total of 65 patients with MetSy were included in the MetSy group, while 65 without MetSy entered the control group. Ox-LDL-Chol levels were higher in the MetSy group compared to the control group, regardless of obesity. Levels of NO metabolites were similar in obese and non-obese patients with MetSy, but lower than in the control group. Obese patients with MetSy had higher iNOS values compared to non-obese ones, with similar PAI-1 levels. NAFLD was present in all obese patients with MetSy compared to 70% of non-obese subjects. Hypertension, higher values of waist-to-hip ratio, PAI-1, and remnant cholesterol were associated with NAFLD. Finding of asymptomatic carotid plaques was associated with patients' age, hypertension, and higher waist-to-hip ratio. MetSy and obesity significantly alter the levels of NO metabolites, iNOS, ox-LDL-Chol, and PAI-1. High prevalence of NAFLD in obese patients with MetSy requires active screening and treatment of potential risk factors.

Low Remnant Cholesterol and In-Hospital Bleeding Risk After Ischemic Stroke or Transient Ischemic Attack.

Bleeding risk brought by intensive lipid-lowering therapy and low low-density lipoprotein cholesterol is concerning, while evidence regarding the relationship between remnant cholesterol and bleeding is frightening. This study aimed to investigate the association between remnant cholesterol at admission and an in-hospital bleeding event after acute ischemic stroke or transient ischemic attack (TIA). A total of 3222 eligible patients admitted to Shanghai Huashan Hospital between 2015 and 2021 with complete lipid data were analyzed. Patients were classified into low (<20.0 mg/dL), moderate (20.0-29.9 mg/dL), and high (≥30 mg/dL) groups by remnant cholesterol. The mean age of patients was 63.0± 13.1 years, including 2301 (71.4%) men and 651 (20.2%) with TIA. The median (interquartile range) of remnant cholesterol was 18.6 (13.5-25.9) mg/dL. After adjustment for confounding variables, patients with low remnant cholesterol had a higher risk of bleeding events (odds ratio, 2.56 [95% CI, 1.12-6.67]) than those with moderate remnant cholesterol. The high remnant cholesterol group was not significantly associated with bleeding risk. Combined assessment of low-density lipoprotein cholesterol and remnant cholesterol further identified patients with the highest risk of bleeding events. Low remnant cholesterol levels were associated with bleeding events during the acute stage of ischemic stroke and TIA. The assessment of remnant cholesterol could inform the bleeding risk during hospitalization both for patients and physicians in clinical practice.

Remnant cholesterol and the risk of diabetic nephropathy progression to end-stage kidney disease in patients with type 2 diabetes mellitus: a longitudinal cohort study.

Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease (ESKD). Remnant cholesterol has been investigated as a predictor for the progression of DN in type 1 diabetes mellitus patients, as well as the incidence of DN in type 2 diabetes mellitus (T2DM) patients. This study aimed to evaluate the longitudinal relationship between baseline remnant cholesterol and kidney outcomes using a Chinese T2DM with biopsy-confirmed DN cohort. We included 334 patients with T2DM and biopsy-confirmed DN during 2010-2019 West China Hospital T2DM-DN cohort. Remnant cholesterol was defined by Martin-Hopkins equation. Patients were divided into four groups based on the median (IQR) remnant cholesterol concentration at the time of renal biopsy. The kidney outcome was defined as ESKD, which was defined as the need for chronic kidney replacement therapy or estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2. The relationship between remnant cholesterol and kidney outcome was analyzed using the Kaplan‒Meier method and Cox regression analysis. The mean age was 51.1 years, and 235 (70%) were men. During follow-up, a total of 121 (36.2%) patients reached ESKD. The Kaplan‒Meier analysis showed that patients in the highest quartile (quartile 4) group had lower cumulative renal survival (log-rank test, p = 0.033) and shorter median renal survival time [34.0 (26.4-41.6) vs. 55.0 (29.8-80.2) months] than patients in the lowest quartile (quartile 1) group. By univariate analysis, the high remnant cholesterol group was associated with a higher risk of progression to ESKD. Moreover, the risk of progression to ESKD in the highest quartile was still 2.857-fold (95% CI 1.305-6.257, p = 0.009) higher than that in the lowest quartile, and one-SD increase of remnant cholesterol was associated with a higher risk (HR = 1.424; 95% CI 1.075-1.886, p = 0.014) of progression to ESKD, after adjusted for confounding factors. High remnant cholesterol is independently associated with a higher risk of ESKD in patients with T2DM-DN, and it may be a new noninvasive marker of ESKD. Calculated remnant cholesterol has the advantages of being economical and clinically accessible. Moreover, to our knowledge, there are no longitudinal cohort studies for investigating the risk of progression of T2DM-DN to ESKD. In our study, higher remnant cholesterol was associated with a higher risk of ESKD in patients with T2DM-DN, and it may be a new noninvasive predictor of ESKD.

Long-term association of remnant cholesterol with all-cause and cardiovascular disease mortality: a nationally representative cohort study.

Despite reducing low-density lipoprotein cholesterol (LDL-C) to the normal range, residual cardiovascular risk remain. Remnant cholesterol (RC) exerts a potential residual risk for cardiovascular disease (CVD) prevention, and the long-term longitudinal association between RC and mortality has yet to be well elucidated. This study examined a nationally representative sample of 13,383 adults aged 20 years or older (mean age 45.7 and 52% women) who participated in the NHANES III (from1988 to1994). Causes of death were ascertained by linkage to death records through December 31, 2019. The relations of RC with all-cause and CVD mortality were tested using weighted Cox proportional hazard models. Through a median follow-up of 26.6 years, 5,044 deaths were reported, comprising 1,741 deaths of CVD [1,409 deaths of ischemic heart disease (IHD) and 332 deaths of stroke] and 1,126 of cancer. Compared to those with RC <14.26 mg/dl (lowest quartile), participants with RC ≥29.80 mg/dl (highest quartile) had multivariable-adjusted HRs of 1.23 (95% CI: 1.07-1.42) for all-cause mortality, 1.22 (95% CI: 0.97-1.53) for CVD mortality, and 1.32 (95% CI: 1.03-1.69) for IHD mortality, and 0.89 (95% CI: 0.55-1.43) for stroke mortality, and 1.17 (95% CI 0.90-1.52) for cancer mortality. We observed that elevated RC levels increased CVD risk and IHD mortality despite LDL-C being in the normal range. Elevated blood RC was associated with an increased long-term risk of all-cause, CVD, and IHD mortality. These associations were independent of socioeconomic factors, lifestyles, and history of diseases, and remained robust across the LDL-C stratum. Measuring RC levels might favor clinical assessment of early CVD risk. Further investigation is needed to elucidate the optimal range of RC levels for cardiovascular disease health in the general population.

A significant presence in atherosclerotic cardiovascular disease: Remnant cholesterol: A review.

The current first-line treatment for atherosclerotic cardiovascular disease (ASCVD) involves the reduction of a patient's low-density lipoprotein cholesterol (LDL-C) levels through the use of lipid-lowering drugs. However, even when other risk factors such as hypertension and diabetes are effectively managed, there remains a residual cardiovascular risk in these patients despite achieving target LDL-C levels with statins and new lipid-lowering medications. This risk was previously believed to be associated with lipid components other than LDL, such as triglycerides. However, recent studies have unveiled the crucial role of remnant cholesterol (RC) in atherosclerosis, not just triglycerides. The metabolized product of triglyceride-rich lipoproteins is referred to as triglyceride-rich remnant lipoprotein particles, and its cholesterol component is known as RC. Numerous pieces of evidence from epidemiological investigations and genetic studies demonstrate that RC plays a significant role in predicting the incidence of ASCVD. As a novel marker for atherosclerosis prediction, when LDL-C is appropriately controlled, RC should be prioritized for attention and intervention among individuals at high risk of ASCVD. Therefore, reducing RC levels through the use of various lipid-lowering drugs may yield long-term benefits. Nevertheless, routine testing of RC in clinical practice remains controversial, necessitating further research on the treatment of elevated RC levels to evaluate the advantages of reducing RC in patients at high risk of ASCVD.

Lipid levels in a cohort of healthy Danish schoolchildren ages 5 to 17 years

It is internationally recognized to use clinical decision limits (CDL) when interpreting the lipid levels in both adults and children, even though the evidence for children is scarce. The purpose of this study is to describe how lipid levels progress in healthy Danish children ages 5 to 17 years. This study is based on the Childhood Health, Activity, and Motor Performance School Study Denmark (CHAMPS-study DK) consisting of 1456 observations of schoolchildren aged 5 to 17 years. Participants have been tested for blood levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and remnant cholesterol levels are calculated. Finally, sex-specific percentile reference curves are presented. Percentile reference curves stratified by sex were generated for all cholesterols and showed that the total cholesterol level peaks at 4.32 mmol/l in 10-year-old boys and 4.46 mmol/l in nine-year-old girls. HDL levels in boys peak at 1.72 mmol/l in nine-year-old boys. HDL levels in girls and LDL levels in both sexes are nearly constant. Triglycerides kept rising to the age of 17 years in both sexes and remnant cholesterol decreased from age 5 to 17 years in both sexes. BMI z-score adjustment revealed no significant association with total cholesterol in both sexes but a significant association between HDL, LDL, triglycerides, and remnant cholesterol. This study is the first to generate percentile reference curves for blood levels of total cholesterol, LDL, HDL, triglycerides, and remnant cholesterol in a cohort of healthy Danish children aged 5 to 17 years.

Remnant cholesterol as a residual risk in atherosclerotic cardiovascular disease patients under statin-based lipid-lowering therapy: A post hoc analysis of the RACING trial

Remnant cholesterol as a residual risk in atherosclerotic cardiovascular disease patients under statin-based lipid-lowering therapy: A post hoc analysis of the RACING trial

Correlations of Remnant Cholesterol and Atherogenic Index of Plasma as Predictors of Cardiovascular Accidents in Obese and Overweight Individuals in Nigeria

Obesity is one of the indices of metabolic syndrome and has been implicated in cardiovascular incidents. Atherogenic index of plasma (AIP) has been associated as a biomarker in the predictor of cardiovascular diseases, with remnant cholesterol (RC) suggested as a link to the development of cardiovascular incidents irrespective of body mass index. Objective: The main aim of this current study was to investigate the correlation between AIP and RC among the participants. Materials: A total of 90 participants with average age of 36.05± for normal weight, 36.54±0.7 for overweight and 37.85±2.1 for obese, were enrolled into the study, the participants were categorized based on their BMI. AIP was calculated as Log10 (TG/HDLc), RC was calculated as (TC-HDLc-LDLc), fasting blood was collected for analysis of lipid profile, and fasting blood sugar by standard methods. Data obtained were analyzed using statistical packages for social sciences (SPSS) version 22.0. Results: The values of basic lipid profile and their mathematical derivatives except HDLc were significantly higher in obese and overweight subject when compared to the control (normal weight). In the regression analysis, we found out that subjects with higher AIP shows a tendency of increased risk for the development of obesity and its related complications (OR=2.74, &lt;P 0.001). AIP showed to be a better predictive value for obesity with AUC of 0.8, than other lipid components and derivatives. The Pearson correlation analysis indicates that AIP positively and significantly correlated with RC, BMI, Castelli index I and II, non-HDLc and VLDL and negatively correlated with HDLc across the group. In this study, the analyzed Cardiovascular risk indices were indicative of atherogenicity risk which might help in identifying individuals with abnormal lipid composition at risk of cardiovascular diseases. Our findings suggested that lipid profile derivatives such as Remnant Cholesterol (RC), Atherogenic Index of Plasma (AIP) and Castelli index, could serve as more sensitive cardiovascular risk predictors in the presence of normal value of basic lipid panel test.