Remnant-like Particle Cholesterol Research Articles

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.

Assessment of Remnant Lipoprotein Cholesterol and Oxidized Low density Lipoprotein Associated with Low-grade Inflammation in Coronary Heart Disease Subjects of Young South Indian Population.

Coronary heart disease (CHD) is a major disease entity responsible for significant mortality and morbidity in the Indian population. The prevalence of CHD is increasing day by day in India. The hardening of arteries is linked to oxidative variations in low-density lipoproteins (LDLs). Modification of LDL to oxidized LDL (ox-LDL) is a crucial step in the oxidation hypothesis of atherogenesis. Oxidized LDL and remnant lipoprotein cholesterol (RLP-C) stimulate the immune and inflammatory reactions and promote atherosclerosis. Because of its lesser size along with high cholesterol content, and increased residence period in blood the remnant lipoproteins are highly atherogenic. Remnant lipoproteins transport more cholesterol to macrophages compared to LDL particles. Remnant lipoproteins enter into the arterial wall easily and are taken up directly by macrophages. This leads to the formation of foam cells, thus initiating the lipid-laden plaque. High sensitive C-reactive protein acts as a nonspecific inflammatory marker. Oxidized LDL along with RLP-C and high-sensitivity C-reactive protein (hs-CRP) play crucial role in progression of CHD. The aim of the study is to assess ox-LDL and RLP-C associated with hs-CRP as potential biomarkers in the development of CHD. This cross-sectional study was conducted in Sri Ramaswamy Memorial Medical College Hospital and Research Centre on subjects appearing for master health check-up and medicine. This cross-sectional study was conducted on 273 subjects who were age and sex match in the age group of ≤45 years. 91 Non-Diabetic subjects with CHD, 91 Diabetic subjects with CHD, and 91 normal healthy subjects were selected as control. After overnight fasting, body fluid samples were collected for analysis for lipid profile, ox-LDL, and hs-CRP. Oxidized LDL and hs-CRP were measured by enzyme-linked immunosorbent assay (ELISA) method and lipid profile was measured using Auto Analyser AU480. Statistical analysis was done using Student's t-test and Pearson's correlation analysis for the comparison between two groups. The mean level of ox-LDL, RLP-C, and hs-CRP was significantly elevated in CHD group. A significantly positive correlation was observed between plasma ox-LDL, RLP-C, and hs-CRP. These results suggest that the link between high ox-LDL, RLP-C, and hs-CRP levels might be interrelated to atherogenesis in subjects with CHD. In addition to conventional parameters, ox-LDL, RLP-C, and hs-CRP can prove to be a valuable tool in risk assessment of CHD. Journal of the Association of Physicians of India (2022): 10.5005/japi-11001-0009.

Increased estimated remnant-like particle cholesterol is associated with impaired coronary collateralization in patients with coronary chronic total occlusions

AimsThis study intends to explore whether, or to what extent, the estimated remnant-like particle cholesterol was associated with coronary collateralization in patients with chronic total occlusion lesions.Methods792 patients with at least one coronary chronic total occlusion lesion were enrolled. Serum level of lipid profiles were determined and the estimated remnant-like particle cholesterol was calculated. The development of coronary collateralization was graded as low (Rentrop score 0–1) or high (Rentrop score 2–3) collateralization according to the Rentrop classification system and then the association between the estimated remnant-like particle cholesterol and collateralization was assessed.Results222 participants were classified into low collateralization group. The estimated remnant-like particle cholesterol level was significantly higher in low collateralization (P < 0.001) and type 2 diabetes mellitus (P = 0.009) group. To further explore the association between the estimated remnant-like particle cholesterol and the development of coronary collateralization, these patients were divided into 3 groups based on the estimated remnant-like particle cholesterol tertiles. The prevalence of low collateralization increased stepwise with the tertile groups (T1 12.5% vs. 27.1% vs. 45.3%, P < 0.001). Multivariate logistic regression analysis showed that the estimated remnant-like particle cholesterol was independently associated with the under-developed collateralization, with an OR and 95%CI of 2.34 (1.46–3.74) and 4.91 (3.01–8.02) in the T2 and T3 group, respectively. The following receiver-operating characteristic analysis indicated that the diagnostic value of estimated remnant-like particle cholesterol for the low collateralization was 0.696, with a cut-off value of 0.485, and its sensitivity was 82.88%. Besides, the addition of the estimated remnant-like particle cholesterol into the baseline model consisting of traditional risk factors could improve the incremental value of the discrimination of impaired collateralization only in overall and type 2 diabetes mellitus populations.ConclusionsThe increased estimated remnant-like particle cholesterol is independently associated with impaired collateralization in patients with coronary chronic total occlusion lesions. Therapies targeting at remnant-like particle cholesterol may be needed in advanced coronary artery disease patients with type 2 diabetes mellitus not suitable for vascular revascularization.

Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles.

We previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic risk factors. We analyzed serum metabolome from 1154 individuals with biopsy-proven NAFLD, and from four mouse models of NAFLD with impaired VLDL-triglyceride (TG) secretion, and one with normal VLDL-TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL-TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL-TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL-TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL-TG and VLDL-apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL5,6 , and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10-year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin-like phospholipase domain-containing protein 3 NAFLD risk allele were lower in subtype A. Metabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification.

Remnant lipoprotein cholesterol is associated with incident new onset diabetes after transplantation (NODAT) in renal transplant recipients: results of the TransplantLines Biobank and cohort Studies

BackgroundNew onset diabetes after transplantation (NODAT) is a frequent and serious complication of renal transplantation resulting in worse graft and patient outcomes. The pathophysiology of NODAT is incompletely understood, and no prospective biomarkers have been established to predict NODAT risk in renal transplant recipients (RTR). The present work aimed to determine whether remnant lipoprotein (RLP) cholesterol could serve as such a biomarker that would also provide a novel target for therapeutic intervention.MethodsThis longitudinal cohort study included 480 RTR free of diabetes at baseline. 53 patients (11%) were diagnosed with NODAT during a median [interquartile range, IQR] follow-up of 5.2 [4.1–5.8] years. RLP cholesterol was calculated by subtracting HDL and LDL cholesterol from total cholesterol values (all directly measured).ResultsBaseline remnant cholesterol values were significantly higher in RTR who subsequently developed NODAT (0.9 [0.5–1.2] mmol/L vs. 0.6 [0.4–0.9] mmol/L, p = 0.001). Kaplan-Meier analysis showed that higher RLP cholesterol values were associated with an increased risk of incident NODAT (log rank test, p < 0.001). Cox regression demonstrated a significant longitudinal association between baseline RLP cholesterol levels and NODAT (HR, 2.27 [1.64–3.14] per 1 SD increase, p < 0.001) that remained after adjusting for plasma glucose and HbA1c (p = 0.002), HDL and LDL cholesterol (p = 0.008) and use of immunosuppressive medication (p < 0.001), among others. Adding baseline remnant cholesterol to the Framingham Diabetes Risk Score significantly improved NODAT prediction (change in C-statistic, p = 0.01).ConclusionsThis study demonstrates that baseline RLP cholesterol levels strongly associate with incident NODAT independent of several other recognized risk factors.

Elevated Remnant Lipoprotein Related to Adverse Events in Patients with Chronic Limb-Threatening Ischemia after Endovascular Therapy for Below-the-Knee Lesions

The prognosis of patients with chronic limb-threatening ischemia (CLTI) is unacceptably poor, and risk factors are unknown. Serum remnant lipoprotein has been associated with cardiovascular events. The aim of our study was to test the hypothesis that remnant lipoprotein is associated with the prognosis of patients with CLTI. This retrospective study included 67 patients with CLTI who had received endovascular therapy (EVT) for de novo below-the-knee lesions. Patients were divided into 2 groups using fasting preoperative value of remnant-like particle cholesterol (RLP-C) with a cutoff value of 5.1mg/dL into LOW RLP-C (n=46) and HIGH RLP-C (n=21). We assessed the differences between the 2 groups in the prevalence of major adverse limb events (MALE), composed of target lesion revascularization and major amputation. At a median follow-up period of 12months, MALE had occurred in 11 LOW RLP-C patients (23.9%) and 11 HIGH RLP-C patients (52.4%; P=0.03). Kaplan-Meier analysis showed the prevalence of MALE was significantly higher in HIGH RLP-C than LOW RLP-C (log-rank χ2=5.2, P=0.02). Multivariate analysis found HIGH RLP-C to be an independent predictor for MALE (hazard ratio, 2.6; 95% confidence interval, 1.1-6.1; P=0.02) along with history of coronary artery disease. Preoperative remnant lipoprotein was associated with the prognosis of patients with CLTI who had received EVT for de novo below-the-knee lesions.

Lipoprotein subfractions in patients with sarcopenia and their relevance to skeletal muscle mass and function.

Loss of skeletal muscle mass is a characteristic of aging. Growing evidence suggests the role of fatty acids and their derived lipid intermediates in the regulation of skeletal muscle and function. However, the exact association between lipoprotein subfractions and sarcopenia in elderly individuals remains unclear. In this study, we aimed to investigate the levels of lipoprotein subfractions in sarcopenia patients and their relationship with skeletal muscle mass and function. A total of 84 elderly Chinese subjects aged ≥65years who did not have diseases that obviously affected lipid metabolism were included. Concentrations of lipoprotein subfractions, including total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), HDL2, HDL3, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), VLDL3, LDL-particle (LDL-P), lipoprotein(a) and remnant-like particle cholesterol (RLP-C), were determined by vertical auto profile. Triglyceride (TG) was measured by an enzymatic colorimetric assay. The skeletal muscle index (SMI) was assessed by bioelectrical impedance analysis. Handgrip strength was measured using a hand-held dynamometer. The levels of TC, TG, LDL-C, LDL-P, IDL, VLDL, VLDL3, RLP-C and C-reactive protein were significantly higher in sarcopenia patients than in controls (p<0.05). Pearson Product-Moment Correlation Coefficient analysis showed that the TC, TG, LDL-C, IDL, VLDL, VLDL3, and RLP-C levels were negatively associated with the SMI; The TG, IDL, VLDL, VLDL3, and RLP-C were negatively correlated with handgrip strength. In multivariate stepwise regression analysis, the VLDL and RLP-C levels were significantly correlated with the SMI. The sensitivity and specificity of the combined measurement of VLDL and RLP-C in predicting sarcopenia were 69.8% and 92.5% (AUC: 0.831; 95% CI:(0.739, 0.924); p<0.05). The occurrence of sarcopenia is associated with disorders of lipid metabolism, particularly VLDL and RLP-C.

Remnant Lipoprotein Cholesterol as a Factor Related to Adult Fatty Liver Disease

Dyslipidemia is related to fatty liver disease (FLD), whose relationship with remnant lipoprotein cholesterol (RLP-C), a component of blood lipids, remains unclear. To clarify the correlation between RLP-C and the occurrence and severity of FLD and establish an FLD discriminant model based on health check indicators. Retrospective study of participants who underwent health check-up in the First Affiliated Hospital of China Medical University (Shenyang, China) between January and December 2019. We categorized participants according to liver ultrasound results and analyzed the correlation between RLP-C and occurrence of FLD (n = 38 885) through logistic regression, restricted cubic spline, and receiver operating characteristic curve. We categorized the severity of FLD according to the control attenuation parameter and analyzed the correlation between RLP-C and FLD severity through multiple logistic regression; only males were included (n = 564). The adjusted OR (aOR) per SD between RLP-C and FLD was 2.33 (95% CI 2.21-2.46, P < .001), indicating a dose-response relationship (P < .0001). The optimal cut-off value of RLP-C was 0.45 mmol/L and the area under the curve (AUC) was 0.79. The AUC of the 8-variable model was 0.89 in both the training and the validation sets. FLD severity was related to the level of RLP-C (aOR per SD = 1.29, 95% CI 1.07-1.55, P = .008). RLP-C has a strong positive correlation with FLD occurrence and FLD severity. These results may help clinicians identify and implement interventions in individuals with high FLD risk and reduce FLD prevalence.

Abstract 9201: Association Between Remnant Cholesterol, High-Sensitivity C-reactive Protein, and Risk of Atherosclerotic Cardiovascular Disease Events in the Multi-ethnic Study of Atherosclerosis (MESA)

Background: Elevated remnant-like particle (RLP)-cholesterol (RLP-C) and high-sensitivity C-reactive protein (hsCRP) are each associated with atherosclerotic cardiovascular disease (ASCVD) individually. Whether a serum marker of systemic inflammation modifies RLP-C associated ASCVD risk is unknown. The purpose of this study was to evaluate the interplay of nuclear magnetic resonance (NMR)-derived RLP-C and hsCRP and their association with ASCVD risk in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: Lipoprotein particles were measured using NMR spectroscopic analysis among MESA participants. RLP-C includes very-low-density lipoprotein (VLDL)-cholesterol and intermediate-density lipoprotein (IDL)-cholesterol. Four groups were created as follows: Group 1: RLP-C ≤ median (≤29.14 mg/dL) and hsCRP &lt; 2 mg/dL; Group 2: RLP-C ≤ median (≤29.14 mg/dL) and hsCRP≥ 2 mg/dL; Group 3: RLP-C &gt; median (&gt;29.14 mg/dL) and hsCRP level &lt; 2 mg/dL; and Group 4: RLP-C &gt; median (&gt;29.14 mg/dL) and hsCRP level ≥ 2 mg/dL. 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. Results: A total of 6,720 MESA participants (mean age 62.2 y, SD 10.2, 53% female) who had baseline NMR-derived RLP-C and hsCRP measurements were included. At a median follow-up of 15.6 years, a total of 1,032 ASCVD events were observed. 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 24% (95%CI, 1.02 - 1.50), 22% (1.01 - 1.46), and 47% (1.22 - 1.77) increased risk of incident ASCVD events, respectively (p &lt;0.001). Conclusion: We found an independent association of NMR-derived RLP-C and hsCRP with incident ASCVD in an ethnically and geographically diverse population. Notably, the combination of increased RLP-C and hsCRP was associated with a markedly increased risk of future ASCVD events.

Abstract 12396: Association of Lipid Profiles With Presence of Aortic Stenosis in Older Adults: Atherosclerosis Risk in Communities Study

Introduction: Many risk factors for atherosclerosis are also risk factors for aortic stenosis. We sought to determine if novel and traditional lipid parameters are associated with aortic stenosis in a population-based study. Methods: We conducted a prospective analysis of participants without aortic stenosis at visit 4 (1996-98) of the ARIC Study. We used logistic regression to assess the association between lipoprotein (a) [Lp(a)], remnant-like particle cholesterol (RLP-C), low-density lipoprotein triglycerides (LDL-TG), small dense low-density lipoprotein-cholesterol (sdLDLc), non-high-density lipoprotein-cholesterol (non-HDLc), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) and incident aortic stenosis (defined as peak aortic valve velocity ≥2.0 m/s) on transthoracic echocardiogram (TTE) performed during visits 5 (2011-13) and 7 (2018-19). Results: Our study population included 11,587 individuals (mean age (SD): 76 (5) years, 56% women, 23% Black). 49% and 24.8% had TTE performed at visits 5 and 7 and the presence of aortic stenosis was 5% and 8%, respectively. In adjusted models, LDL-TG, RLP-C, sdLDLc, non-HDLc, TG, and LDLc at visit 4 were associated with aortic stenosis at visit 5. Lp(a) at visit 4 was predictive of aortic stenosis at visit 7 (table). Conclusions: Among persons who survived to old age, novel lipid parameters (including Lp(a), LDL-TG, RLP-C, and sdLDLc) in mid-life were associated with aortic stenosis in late-life. Further studies should determine if lipid-lowering therapies can prevent the development of aortic stenosis.

Discordantly Elevated Apolipoprotein B versus Low-Density Lipoprotein Cholesterol is Associated with Remnant Lipoproteins and Increased Cardiovascular Events

Abstract Atherosclerotic cardiovascular disease is a result of low-density lipoprotein (LDL) particles becoming trapped in arterial walls and forming plaques which ultimately restrict blood-flow. LDL cholesterol (LDL-C) and apolipoprotein B (apoB) are highly correlated measures of plaque-causing LDL particles. Both have been shown to predict major adverse cardiac events (MACE). ApoB is also carried on remnant lipoproteins (RLP). RLP-cholesterol (RLP-C) is increasingly appreciated as a MACE risk-factor. This study aimed to define discordances between apoB and LDL-C in a large data set from a clinical reference laboratory. We then applied this definition to evaluate which measure predicted the risk of MACE in a patient cohort referred for coronary angiography with &amp;gt;10 years follow-up. LDL-C was measured by beta-quantification and RLP-C was defined as total cholesterol – LDL-C – HDL-C. Apo B discordance relative to LDL-C was determined by linear regression in a discovery cohort (n=17,203) using beta quantification. Discordance was defined by quartiles of the residual-apoB (expected–actual); discordant-low (&amp;lt;25th percentile), concordant (25th to 75th percentile) and discordant-high (&amp;gt;75th percentile). Associations with prevalence and incident of MACE were evaluated by odds-ratio and logistic regression. Risk of MACE was calculated based on the apoB-discordance and reported MACE events by several years follow up in a separate cohort (n=501). In the discovery cohort, age ranged from 18-95 years, 51% were female and mean (±SD) lipid values were: ApoB: 100.4 ± 30.0mg/dl, LDL-C: 121.7 ± 47.9mg/dl, and RLP-C: 17.2 ± 26.9mg/dl. Expected-apoB was described by the formula: (LDL-c X 0.6278 + 24.07, R=0.88). Residual-apoB (discordance) ranged from -1037 to 581.2 with a mean 0.01±18.6, and notably increased with triglyceride concentration (rho=0.65) and with RLP-C (rho=0.64), but was minimally influenced by apoB (rho=0.35) and LDL-C (rho=0.009) (p&amp;lt;0.001 all cases). In the clinical follow-up cohort, age ranged from 26-77 years, 42% were female, 64% were current/former smokers, and 28% were on lipid-lowering therapy. Mean (±SD) lipids were: apoB: 97.8 ± 20.9mg/dl, LDL-C: 124.6 ± 36.6mg/dl, and RLP-C: 34.9 ± 25.6mg/dl. Serum triglycerides among subjects discordant-low apoB, concordant and discordant-high apoB were 148mg/dL, 157mg/dL and 238mg/dL, respectively; similarly for RLP-C. A total of 192 events occurred during a mean of 9 years follow-up. Subjects with discordantly elevated apoB had a significantly higher incidence of MACE compared to those with concordant values (47% vs. 36%, p=0.03). There was no difference in MACE for subjects with discordantly low apoB (35% vs. 36%). These data support previous reports of an association between apoB and LDL-C and the superior performance of apoB when discordantly elevated. Our data expand on previous studies by applying an externally defined threshold for discordant-apoB. Our data indicate that triglycerides, RLP-C are associated with discordances and MACE.

Contributions of small dense LDL and oxidized LDL on the formation of neoatherosclerosis in patients under statin treatment

Abstract Aim In-stent neoatherosclerosis (NA) has emerged as an important contributing factor to late stent failure and cardiovascular events. The aim of this study was to investigate whether lipid markers are associated with NA using optical coherence tomography (OCT) after percutaneous coronary intervention (PCI) in patients with coronary artery disease under well-controlled low density lipoprotein cholesterol (LDL-c) on statin treatment. Methods We enrolled consecutive 115 patients under statin treatment who underwent PCI with current-generation drug-eluting stent for acute and chronic coronary syndrome. OCT image and various lipid markers were obtained at 1-year for scheduled research assessment. NA was defined as a lipid laden neointima or calcified neointima. Both small dense LDL-c (sd-LDL-c) and remnant lipoprotein cholesterol (RL-c) were measured using direct homogenous assay. Results During an average follow-up of 13 months, NA was observed in 14 (13.6%) patients. Not LDL-c but sd-LDL-c, Malondialdehyde-modified LDL (MDA-LDL) as oxidized LDL and (RL-c) were significantly higher in patients with NA. The optimal threshold values of sd-LDL-c, MDA-LDL and RL-c for predicting NA according to receiver operating characteristics analysis were 32.3 mg/dl, 91.0 U/L, and 3.3 mg/dL, respectively. On multivariate logistic regression analysis, sd-LDL-c (≥32.3 mg/dL) and MDA (≥91.0 U/L) were significantly associated with NA (odds ratio [OR]:13.62, p=0.016, OR: 12.68, p=0.01, respectively). Conclusions In statin-treated patients, sd-LDL-c and MDA-LDL but not LDL-c might be useful biomarkers to identify the formation of NA at 1 years after PCI. Aggressive reduction of these atherogenic LDL may have a potential to prevent the formation of NA. Funding Acknowledgement Type of funding sources: None.

Abdominal and gluteofemoral fat depots show opposing associations with postprandial lipemia

High postprandial lipemia is associated with increased risk of cardiovascular disease, independently of fasting lipid concentrations. Abdominal and gluteofemoral fat depots handle lipoproteins differently, which could affect postprandial lipemia and contribute to the relation between abdominal fat distribution and cardiovascular disease risk. We aimed to study the influences of higher abdominal compared with gluteofemoral fat on postprandial lipemia after a high-fat meal in individuals with obesity. A total of 755 adults with obesity from a randomized controlled trial in 7 European countries consumed a liquid high-fat meal. Concentrations of triglycerides (TG), glycerol, free fatty acids, and the cholesterol component of remnant-like particles (RLP), LDL, and HDL were measured postprandially for 3 h. Associations of waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR) with changes in postprandial lipid concentrations, adjusted for fasting concentrations and BMI, were examined using linear regression models. To assess whether the association of WHR with postprandial lipemia could be causal, we performed instrumental variable analyses using a genetic score of 442 variants known to be associated with WHR adjusted for BMI in 2-stage least-squares regression models. WHR was associated with higher TG and RLP cholesterol concentrations, independent of fasting lipid concentrations and BMI. Instrumental variable analyses suggested that the associations of WHR with postprandial TG (β=0.038 μmol/L*min, SE=0.019 μmol/L*min, P=0.044) and RLP cholesterol concentrations (β=0.059 mmol/L, SE=0.025mmol/L, P=0.020) may be causal. WC and HC showed opposite effects: higher WC was associated with higher TG and RLP cholesterol concentrations whereas higher HC was associated with lower concentrations. Our results suggest that higher fat deposition abdominally versus gluteofemorally may be causally associated with elevated postprandial lipemia after a high-fat meal, independent of fasting lipid concentrations and BMI. Furthermore, higher abdominal and gluteofemoral fat depots show opposing effects on postprandial lipemia.This trial was registered at www.isrctn.com as ISRCTN25867281.

Correlation between estimated plasma remnant-like particle cholesterol and vegetable fat intake in Uku town, Japan

BackgroundRemnant-like particle cholesterol (RLP-C) is highly atherogenic, which is associated with atherosclerosis. However, RLP-C has not been routinely measured in the clinical practice. We estimated RLP-C levels using conventional lipid profiles and examined the association between estimated RLP-C and related factors including nutrient intake.MethodsThis study was performed in Uku town, Nagasaki prefecture, Japan in 2019. A total of 225 subjects were enrolled and directly measured RLP-C levels. Estimated RLP-C levels were defined as the following formula [total cholesterol − (LDL-cholesterol) − (HDL-cholesterol)]. Multivariate analyses were used to assess the relationship between estimated RLP-C and atherogenic factors. We calculated cut-off values on dichotomized RLP-C (< 7.5 mg/dL vs. ≥ 7.5 mg/dL) by receiver operating characteristic (ROC) curve.ResultsThe mean values of directly measured RLP-C levels and estimated RLP-C were 4.0 mg/dL and 16.4 mg/dL, respectively. In the multiple stepwise linear regression analysis, directly measured and estimated RLP-C levels were independently and commonly associated with apolipoprotein E, triglycerides, and vegetable fat intake (inversely). Using ROC curves, we found the cut-off value of estimated RLP-C was 22.0 mg/dL.ConclusionWe demonstrated that the estimated RLP-C levels using conventional lipid profiles may substitute for directly measured RLP-C and these levels were independently and inversely associated with vegetable fat intake in the community-dwelling Japanese population.

Does remnants-like particle cholesterol is elevated in FH?

Background and Aims: Familial hypercholesterolemia (FH) is often associated with mildly increased triglyceride levels, probably because remnant-like particles can also be catabolized by LDL receptor. Remnant-like particles cholesterol (RLP-C) has been associated with coronary artery disease in the general population. Few data exist regarding this issue in patients with FH. Aim: to evaluate RLP-C levels in severe hypercholesterolemic patients with clinical and genetic diagnosis for FH.

The Effects of Calculated Remnant-Like Particle Cholesterol on Incident Cardiovascular Disease: Insights from a General Chinese Population.

Background: Growing evidence suggests that remnant cholesterol (RC) contributes to residual atherosclerotic cardiovascular disease (ASCVD) risk. However, the cutoff points to treat RC for reducing ASCVD are still unknown. This study aimed to investigate the relationships between RC and combined cardiovascular diseases (CVDs) in a general China cohort, with 11,956 subjects aged ≥ 35 years. Methods: Baseline RC was estimated with the Friedewald formula for 8782 subjects. The outcome was the incidence of combined CVD, including fatal and nonfatal stroke and coronary heart disease (CHD). The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. The restricted cubic spline (RCS) model was used to evaluate the dose–response relationship between continuous RC and the natural log of HRs. Results: After a median follow-up of 4.66 years, 431 CVD events occurred. In the Cox proportional models, participants with a high level of categorial RC had a significantly higher risk for combined CVD (HR: 1.37; 95% CI: 1.07–1.74) and CHD (HR: 1.63; 95% CI: 1.06–2.53), compared to those with a medium level of RC. In the stratification analyses, a high level of RC significantly increased combined CVD risk for subgroups females, age < 65 years, noncurrent smokers, noncurrent drinkers, normal weight, renal dysfunction, and no hyperuricemia. The same trends were found for CHD among subgroups males, age < 65 years, overweight, renal dysfunction, and no hyperuricemia; stroke among subgroup females. In RCS models, a significant linear association between RC and combined CVD and a nonlinear association between RC and CHD resulted. The risk of outcomes was relatively flat until 0.84 mmol/L of RC and increased rapidly afterwards, with an HR of 1.308 (1.102 to 1.553) for combined CVD and 1.411 (1.061 to 1.876) for CHD. Stratified analyses showed a significant nonlinear association between RC and CVD outcomes in the subgroup aged < 65 years or the diabetes subgroup. Conclusions: In this large-scale and long-term follow-up cohort study, participants with higher RC levels had a significantly worse prognosis, especially for the subgroup aged 35–65 years or the diabetes mellitus subgroup.

Associations between remnant lipoprotein cholesterol and central systolic blood pressure in a Chinese community-based population: a cross-sectional study

BackgroundThe lipid profile is reportedly related to peripheral blood pressure or pulse wave velocity. However, no studies have investigated the associations between lipid parameters, especially remnant lipoprotein cholesterol (RLP-C), and central systolic blood pressure (cSBP).MethodsThis study used baseline data of a community-based cohort in Beijing, China. Participants who had been treated with anti-hypertensive or lipid-lowering agents were excluded. RLP-C is equal to total cholesterol (TC) minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). An Omron HEM-9000AI device was used to measure non-invasive cSBP. The associations between blood lipid profile and non-invasive cSBP were evaluated using multivariable regression models.ResultsThe 5173 included participants were 55.0 ± 8.5 years old; 35.7% (1845) of participants were men. Increased cSBP was significantly associated with increased TC, LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), triglyceride (TG), and RLP-C but with decreased HDL-C, even after adjusting for possible covariates. When simultaneously entering individual pairs of RLP-C and other blood lipid parameters into the multivariable regression model, RLP-C remained significantly associated with cSBP, even after adjusting for other lipids. Compared with participants who had RLP-C levels in the first quartile (Q1), cSBP for those with RLP-C in Q4 was increased to 4.57 (95% confidence interval [CI]: 3.08–6.06) mmHg after adjusting for LDL-C, 4.50 (95%CI: 2.98–6.02) mmHg after adjusting for TC, 3.91 (95%CI: 1.92–5.89) mmHg after adjusting for TG, 5.15 (95%CI: 3.67–6.63) mmHg after adjusting for HDL-C, and 4.10 (95%CI: 2.36–5.84) mmHg after adjusting for non-HDL-C.ConclusionsIncreased blood RLP-C level was significantly associated with higher cSBP in a Chinese population, independently of other lipids, which indicates its importance in individual cardiovascular risk assessment.

The Atherogenic Index of Plasma: A Powerful and Reliable Predictor for Coronary Artery Disease in Patients With Type 2 Diabetes.

We evaluated the predictive power of the atherogenic index of plasma (AIP) for coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). A total of 3278 patients who underwent coronary angiography were consecutively enrolled, including 2052 patients with CAD and 1226 patients with T2DM but without CAD. Patients in the CAD group had higher levels of triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, AIP and a lower level of high-density lipoprotein cholesterol (HDL-C). In correlation analyses, AIP correlated positively with body mass index, log (homeostasis model assessment of insulin resistance), TG, remnant lipoprotein cholesterol, non-HDL-C, but negatively with age and HDL-C. Multivariate logistic regression analyses demonstrated that AIP was an independent risk factor for CAD in diabetic patients and was validated by multiple models. Furthermore, the ORs for CAD risk were raised with increasing AIP quartiles; ORs of AIP quartiles Q2-Q4 compared with Q1 were 1.56, 1.70, and 2.22, respectively (Ps < .001), which suggested AIP was the lipid parameter that most strongly associated with incident CAD. In conclusion, AIP is a powerful and reliable biomarker for predicting CAD risk beyond individual lipid profiles in patients with T2DM.

Small Dense Low-Density Lipoprotein Cholesterol: A Residual Risk for Rapid Progression of Non-Culprit Coronary Lesion in Patients with Acute Coronary Syndrome.

Aim: This study investigated whether the small dense low-density lipoprotein cholesterol (sd-LDL-c) level is associated with the rapid progression (RP) of non-culprit coronary artery lesions and cardiovascular events (CE) after acute coronary syndrome (ACS). Methods: In 142 consecutive patients with ACS who underwent primary percutaneous coronary intervention for the culprit lesion, the sd-LDL-c level was measured using a direct homogeneous assay on admission for ACS and at the 10-month follow-up coronary angiography. RP was defined as a progression of any pre-existing coronary stenosis and/or stenosis development in the initially normal coronary artery. CEs were defined as cardiac death, myocardial infarction, stroke, or coronary revascularization. Results: Patients were divided into two groups based on the presence ( n =29) or absence ( n =113) of RP after 10 months. The LDL-c and sd-LDL-c levels at baseline were equivalent in both the groups. However, the sd-LDL-c, triglyceride, remnant lipoprotein cholesterol (RL-c), and apoC3 levels at follow-up were significantly higher in the RP group than in the non-RP group. The optimal threshold values of sd-LDL-c, triglyceride, RL-c, and apoC3 for predicting RP according to receiver operating characteristics analysis were 20.9, 113, 5.5, and 9.7 mg/dL, respectively. Only the sd-LDL-c level (≥ 20.9 mg/dL) was significantly associated with incident CEs at 31±17 months (log-rank: 4.123, p =0.043). Conclusions: The sd-LDL-c level on treatment was significantly associated with RP of non-culprit lesions, resulting in CEs in ACS patients. On-treatment sd-LDL-c is a residual risk and aggressive reduction of sd-LDL-c might be needed to prevent CEs.

Conventional and Novel Lipid Measures and Risk of Peripheral Artery Disease.

The aim of this study was to comprehensively assess the association of multiple lipid measures with incident peripheral artery disease (PAD). Approach and Results: We used Cox proportional hazards models to characterize the associations of each of the fasting lipid measures (total cholesterol, LDL-C [low-density lipoprotein cholesterol], HDL-C [high-density lipoprotein cholesterol], triglycerides, RLP-C [remnant lipoprotein cholesterol], LDL-TG [LDL-triglycerides], sdLDL-C [small dense LDL-C], and Apo-E-HDL [Apo-E-containing HDL-C]) with incident PAD identified by pertinent International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) hospital discharge codes (eg, 440.2) among 8330 Black and White ARIC (Atherosclerosis Risk in Communities) participants (mean age 62.8 [SD 5.6] years) free of PAD at baseline (1996-1998) through 2015. Since lipid traits are biologically correlated to each other, we also conducted principal component analysis to identify underlying components for PAD risk. There were 246 incident PAD cases with a median follow-up of 17 years. After accounting for potential confounders, the following lipid measures were significantly associated with PAD (hazard ratio per 1-SD increment [decrement for HDL-C and Apo-E-HDL]): triglycerides, 1.21 (95% CI, 1.08-1.36); RLP-C, 1.18 (1.08-1.29); LDL-TG, 1.18 (1.05-1.33); HDL-C, 1.39 (1.16-1.67); and Apo-E-HDL, 1.27 (1.07-1.51). The principal component analysis identified 3 components (1: mainly loaded by triglycerides, RLP-C, LDL-TG, and sdLDL-C; 2: by HDL-C and Apo-E-HDL; and 3: by LDL-C and RLP-C). Components 1 and 2 showed independent associations with incident PAD. Triglyceride-related and HDL-related lipids were independently associated with incident PAD, which has implications on preventive strategies for PAD. However, none of the novel lipid measures outperformed conventional ones. Graphic Abstract: A graphic abstract is available for this article.