Remnant-like Particle Cholesterol Research Articles

Evaluation of atherogenic lipoprotein-cholesterol to HDL cholesterol ratio as a prognostic test for ST-segment elevation myocardial infarction.

Background: The detectable component of triglyceride-rich lipoproteins (TGRLs), remnant lipoprotein cholesterol (RLP-c), has been proven being correlated with the progression of atherosclerosis and myocardial infarction. However, when taken as a risk predictor, the prognostic and diagnostic potential of RLP-c remains controversial in studies. In this study, we evaluated the hypothesis that atherogenic lipoprotein-cholesterol (AL-c), representing the sum of RLP-c and the sd-LDL-c, to the HDL-c ratio, could represent a better predictive indicator than RLP-c alone in ST-segment elevation myocardial infarction (STEMI).Methods: The 316 consecutive patients suffering from persistent chest discomfort admitted to the Shanghai General Hospital between January 2018 and June 2018 were enrolled. 149 STEMI patients (62% men, mean age 69.6 ± 13.3 years) were included as the study cohort. The AL-c/HDL-c ratio was calculated on admission in a cohort of electrocardiogram-confirmed STEMI patients and compared to other lipid profiles as a predictive indicator.Results: The AL-c/HDL-c ratio was significantly increased in STEMI patients compared with apparently healthy adults (0.93; IQR [0.71-1.18] vs 0.70; IQR [0.45-1.04]; p < 0.001). Gender dependency existed, and the male and female patients had median AL-c/HDL-c ratios of 1.01 and 0.79, respectively (p < 0.001). Compared to RLP-c, the AL-c/HDL-c ratio had a better prognostic value to predict STEMI risk in both sexes (AUC of 0.672 with a sensitivity of 0.794 in males and 0.613 with a sensitivity of 0.684 in females).Conclusions: The AL-c/HDL-c ratio could represent a convenient and sensitive biomarker for screening and predicting STEMI risk.

Simultaneous Evaluation of Postchallenge Glycemia and Lipidemia in Young Women

<i>Aim:</i> To determine the effects of simultaneously ingesting glucose and fat on postchallenge glycemia and lipidemia in 12 healthy young Japanese women. <i>Methods:</i> Three test trials were administered in a randomized crossover design: glucose (1 g/kg, G trial); fat cream (0.35 g/kg as fat; F trial); glucose + fat cream (GF trial). Blood samples were taken before and at 0.5, 1, 2, 4, and 6 h post-ingestion. <i>Results:</i> The GF trial's serum glucose peak value was lower than the G trial's, and its remnant lipoprotein-cholesterol (RLP-C) increase was less than the F trial's. The GF trial's apolipoprotein (Apo) B48 increase happened faster than the F trial's. The G and GF trials' insulinogenic index (I/G30) values were negatively correlated with the area under the curve (AUC) of glucose for 2 h. Fasting insulin level and HOMA-IR were positively (and QUICKI and I/G30 were negatively) correlated with the AUC of insulin for 2 h. The F and GF trials' fasting TG, RLP-C, ApoB48, and ApoC-III levels were positively correlated with the AUC of TG and RLP-C for 6 h. The fasting ApoB48 level predicted the AUC of ApoB48 for 6 h. <i>Conclusion:</i> The glucose peak was ameliorated by co-ingesting fat. I/G30 predicted an early postchallenge (0–2 h) glucose rise. The fasting insulin level, HOMA-IR, QUICKI, and I/G30 predicted an insulin rise. The RLP-C rise by fat ingestion was ameliorated by co-ingesting glucose. Fasting TG, RLP-C, ApoB48, and ApoC-III levels predicted postchallenge TG and RLP-C rises. The fasting ApoB48 level predicted postchallenge apoB48, i.e., a rise in intestinal lipoprotein.

Efficacy and Safety of Low-Dose Pemafibrate Therapy for Hypertriglyceridemia in Patients with Type 2 Diabetes.

Introduction: Pemafibrate is a potent selective peroxisome proliferator-activated receptor α (PPARα) modulator that may be safer than conventional PPARα agonists in the treatment of dyslipidemia. This study was designed to investigate the efficacy of low-dose pemafibrate (0.1 mg/day) therapy for hypertriglyceridemia in 31 patients with type 2 diabetes and high triglyceride (TG) levels at the Manda Memorial Hospital. Methods: TG, remnant lipoprotein cholesterol (RLP-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI, Apo AII, Apo B, Apo CII, Apo CIII, and Apo E levels were evaluated. Liver, kidney, and muscle toxicity tests were also performed. Pemafibrate (0.1 mg) was administered once daily. Results: This treatment significantly decreased TG, RLP-C, Apo CII, Apo CIII, and Apo E levels while significantly increasing HDL-C, Apo AI, and Apo AII levels. No significant changes were observed in LDL-C and Apo B levels. There were no significant liver-, kidney-, or muscle-related adverse events. Conclusions: The results of this study show that low-dose pemafibrate administration improves the lipid profile in Japanese patients with hypertriglyceridemia and type 2 diabetes.

Effect of Remnant Lipoprotein Cholesterol and Nitric Oxide in Young Coronary Heart Disease Subjects

Effect of Remnant Lipoprotein Cholesterol and Nitric Oxide in Young Coronary Heart Disease Subjects

Measurement of Oxidized LDL and Remnant Lipoprotein Cholesterol Associated with High‑Sensitive C‑Reactive Protein in Coronary Heart Disease

Measurement of Oxidized LDL and Remnant Lipoprotein Cholesterol Associated with High‑Sensitive C‑Reactive Protein in Coronary Heart Disease

Atherogenic lipoproteins and atherosclerotic cardiovascular disease in the Framingham offspring study

Background and Aims: Elevated low-density lipoprotein cholesterol (LDL-C), small-dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), triglycerides, remnant-lipoprotein cholesterol (RLP-C), triglyceride-rich lipoprotein-C (TRL-C), very low-density lipoprotein cholesterol (VLDL-C), and lipoprotein(a) [Lp(a)] levels have been associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. We assessed the hypothesis that these atherogenic lipoprotein parameters add significant information for ASCVD risk prediction in the Framingham Offspring Study.

Autologous adipose mesenchymal stem cell administration in arteriosclerosis and potential for anti-aging application: a retrospective cohort study

ObjectiveArteriosclerosis is an age-related disease and a leading cause of cardiovascular disease. In animal experiments, mesenchymal stem cells and its culture-conditioned medium have been shown to be promising tools for prevention or treatment of arteriosclerosis. On the basis of these evidences, we aimed to assess whether administration of autologous adipose-derived mesenchymal stem cells (Ad-MSC) is safe and effective for treatment of arteriosclerosis.MethodsWe retrospectively reviewed clinical records of patients with arteriosclerosis who had received autologous Ad-MSC administration at our clinic. Patients’ characteristics were recorded and data on lipid profile, intimal-media thickness (IMT), cardio-ankle vascular index (CAVI), and ankle-brachial index (ABI) before and after Ad-MSC administration were collected and compared.ResultsTreatment with Ad-MSC significantly improved HDL, LDL, and remnant-like particle (RLP) cholesterol levels. No adverse effect or toxicity was observed in relation to the treatment. Of the patients with abnormal HDL values before treatment, the vast majority showed improvement in the values. Overall, the measurements after treatment were significantly increased compared with those before treatment (p < 0.01). In addition, decreases in LDL cholesterol and RLP levels were observed after treatment in patients who had abnormal LDL cholesterol or RLP levels before treatment. The majority of patients with pre-treatment abnormal CAVI values had improved values after treatment. In patients with available IMT values, a significant decrease in the IMT values was found after therapy (p < 0.01). All patients with borderline arteriosclerosis disease had improved laboratory findings after treatment. In general, post-treatment values were significantly decreased as compared with pre-treatment values. Of the patients with normal ABI values before treatment at the same time as CAVI, the vast majority remained normal after treatment.ConclusionsThese findings suggest that Ad-MSC administration is safe and effective in patients developing arteriosclerosis, thereby providing an attractive tool for anti-aging application.

Abstract 15567: Residual Cholesterol and Cardiovascular Events in Patients With Coronary Artery Disease Under Different Glucose Metabolism Status

Introduction: The atherogenicity of residual cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). Hypothesis: This study aimed to examine the prognostic value of plasma RC, clinically presented as triglyceride-rich lipoprotein-cholesterol (TRL-C) or remnant-like lipoprotein particles-cholesterol (RLP-C), in CAD patients with different glucose metabolism status. Methods: Fasting plasma TRL-C and RLP-C levels were directly calculated or measured in 4331 patients with CAD. Patients were followed for incident MACEs for up to 8.6 years and categorized according to both glucose metabolism status [DM, pre-DM, normal glycaemia regulation (NGR)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Results: During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NGR groups (p&gt;0.05). When stratified by status of glucose metabolism and RC levels, highest levels of RLP-C, calculated and measured TRL-C were significant and independent predictors of developing MACEs in pre-DM (HR: 2.10, 1.98, 1.92, respectively; all p&lt;0.05) and DM (HR: 2.25, 2.00, 2.16, respectively; all p&lt;0.05). Conclusions: In this large cohort study with long-term follow-up, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting RC might be a target for patients with impaired glucose metabolism.

Abstract 13902: Gender Differences in Lipoprotein Parameters in Cardiovascular Disease Risk; The Framingham Offspring Study

Introduction: Elevated serum lipoprotein cholesterol levels have been considered as atherosclerosis cardiovascular disease (ASCVD) risk factors. However, gender differences among these lipoproteins have not become clear. Hypothesis: Our hypothesis was that gender differences exist with regard to serum lipoprotein cholesterol levels and the risk of ASCVD risk in the prospective Framingham Offspring Study. Methods: A total of 1300 men and 1676 women, none of whom had ASCVD at baseline, were followed for a median time of 16 years for new onset fatal or non fatal myocardial infarction or stroke, coronary angioplasty or bypass, or carotid or peripheral vascular surgery (302 of 1300 or 23.2% of men and 226 of 1676 or 13.5% of women developed). At baseline, standard risk factors including fasting total and high density lipoprotein (HDL) cholesterol, and triglycerides were assessed, as were direct, small dense, and large low density lipoprotein (LDL) cholesterol and LDL triglyceride (LDL-TG), remnant lipoprotein cholesterol and lipoprotein(a) were measured. Univariate and multivariate analyses were carried out to assess relationships to disease risk. Results: All parameters were associated with ASCVD risk on univariate analysis. On multivariate analysis after controlling for all standard risk factors (age, hypertension, use of anti-hypertensive medication, diabetes, smoking, total cholesterol, HDL cholesterol, and use of cholesterol lowering medication), only lipoprotein(a) was significant in men with a 1.26 hazard ratio (P = 0.009), while small dense LDL cholesterol and LDL-TG, but not lipoprotein(a), were significant risk factors in women (hazard ratios 1.65 and 1.35, P = 0.007 and 0.015, respectively). Using the pooled cohort equation, only lipoprotein(a) added significant risk information in men and only small dense LDL cholesterol and LDL-TG added significant risk information in women. Conclusions: Our data indicate that men are at significantly higher disease risk then women, and that elevated lipoprotein(a) is a significant independent ASCVD risk factor in men, while small dense LDL cholesterol and LDL-TG are significant independent ASCVD risk factors in women after controlling for all other standard cardiovascular disease risk factors.

Prognostic utility of triglyceride-rich lipoprotein-related markers in patients with coronary artery disease

TG-rich lipoprotein (TRL)-related biomarkers, including TRL-cholesterol (TRL-C), remnant-like lipoprotein particle-cholesterol (RLP-C), and apoC-III have been associated with atherosclerosis. However, their prognostic values have not been fully determined, especially in patients with previous CAD. This study aimed to examine the associations of TRL-C, RLP-C, and apoC-III with incident cardiovascular events (CVEs) in the setting of secondary prevention of CAD. Plasma TRL-C, RLP-C, and total apoC-III were directly measured. A total of 4,355 participants with angiographically confirmed CAD were followed up for the occurrence of CVEs. During a median follow-up period of 5.1 years (interquartile range: 3.9-6.4 years), 543 (12.5%) events occurred. Patients with incident CVEs had significantly higher levels of TRL-C, RLP-C, and apoC-III than those without events. Multivariable Cox analysis indicated that a log unit increase in TRL-C, RLP-C, and apoC-III increased the risk of CVEs by 49% (95% CI: 1.16-1.93), 21% (95% CI: 1.09-1.35), and 40% (95% CI: 1.11-1.77), respectively. High TRL-C, RLP-C, and apoC-III were also independent predictors of CVEs in individuals with LDL-C levels ≤1.8 mmol/l (n = 1,068). The addition of RLP-C level to a prediction model resulted in a significant increase in discrimination, and all three TRL biomarkers improved risk reclassification. Thus, TRL-C, RLP-C, and apoC-III levels were independently associated with incident CVEs in Chinese CAD patients undergoing statin therapy.

Changes in serum levels of angiopoietin-like protein-8 and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 after ezetimibe therapy in patients with dyslipidemia

Changes in serum levels of angiopoietin-like protein-8 (ANGPTL8) and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) in patients with dyslipidemia after ezetimibe therapy remain to be elucidated. Thirty-eight patients who initially received ezetimibe and were followed for 16 weeks were enrolled. Various parameters were investigated before and after 16 weeks of ezetimibe treatment in all patients. In addition, the patients were also divided into metabolic syndrome (MetS) (n = 22) and Non-MetS (n = 16) groups, and various parameters were compared between these groups. ANGPTL8 was significantly positively correlated with triglyceride (TG) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) before treatment in all patients and in the MetS group. After treatment, TC and LDL-C were significantly decreased in all patients, and in both the MetS and Non-MetS groups, whereas there were no changes in TG or HDL-C. Serum levels of remnant-like particle cholesterol (RLP-C) significantly decreased in all patients and in the MetS group. The ANGPTL8 level before treatment was significantly positively associated with TG and negatively correlated with HDL-C in all patients and in the MetS group. ANGPTL8 and GPIHBP1were significantly decreased after treatment in all patients. GPIHBP1 was also significantly decreased after treatment in both groups. In conclusion, this is the first report to support the possibility of a new effect of ezetimibe therapy. Ezetimibe significantly decreased the serum level of LDL-C, but not TG or HDL-C, while reducing ANGPTL8 and GPIHBP1 in all patients with dyslipidemia. In addition, ezetimibe significantly decreased RLP-C levels in the MetS group.

Comparison of low-density lipoprotein cholesterol level calculated using the modified Martin/Hopkins estimation or the Friedewald formula with direct homogeneous assay measured low-density lipoprotein cholesterol.

IntroductionLow-density lipoprotein cholesterol (LDL-C) represents the primary lipoprotein target for reducing cardiovascular risk (CV). The aim of our study is to compare the direct and the calculated LDL-C levels in the range below 1.8 mmol/l and 2.6 mmol/l depending on triglycerides, and to evaluate the variation in remnant lipoprotein cholesterol.Material and methodsWe investigated 14 906 lipid profiles from fasting blood samples of Hungarian individuals with triglycerides < 4.5 mmol/l. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and direct LDL-C were measured by the enzymatic assay. We calculated LDL-C by Friedewald’s formula (F-LDL-C) and by using the new Martin/Hopkins estimation (MH-LDL-C).ResultsFor F-LDL-C below 1.8 mmol/l, MH-LDL-C was 58% between 1.8 and 2.59 mmol/l when TG was in the range 2.3–4.5 mmol/l. For F-LDL-C below 2.6 mmol/l, the MH-LDL-C concordance was 73% in the same TG range (2.3–4.5 mmol/l. If MH-LDL-C was less than 1.8 mmol/l or between 1.8 and 2.59 mmol/l, the difference between non-HDL-C (TC – HDL-C = AC: atherogenic cholesterol) and (MH)LDL-C was less than 0.8 mmol/l in the TG range below 2.3 mmol/l. The remnant lipoprotein cholesterol values were on average 0.5 mmol/l lower by the Martin/Hopkins estimation compared to the Friedewald’s calculation if the TG was above 2.3 mmol/l.ConclusionsThe Friedewald equation tends to underestimate LDL-C levels in very high and high-risk settings. Our analysis supports the conclusion that in Hungarian patients, LDL-C estimation using the Martin/Hopkins formula, which is validated by the beta-quantification method, yields a more accurate LDL-C value than that calculated by the Friedewald formula.

Prognostic impact of estimated remnant-like particle cholesterol in patients with differing glycometabolic status: an observational cohort study from China

BackgroundIt is uncertain whether estimated remnant-like particle cholesterol (RLP-C) could predict residual risk in patients with different glycometabolic status. This study aimed to evaluate the relationship between estimated RLP-C and adverse prognosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) treated with percutaneous coronary intervention (PCI) and to identify the potential impact of glycometabolism on the predictive value of estimated RLP-C.MethodsThe study assessed 2419 participants with NSTE-ACS undergoing PCI at Beijing Anzhen Hospital from January to December 2015. Estimated RLP-C was calculated as follows: total cholesterol (TC) minus low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The adverse events included all-cause death, non-fatal myocardial infarction (MI), and ischemia-driven revascularization.ResultsEstimated RLP-C was prominently associated with adverse prognosis in the total population [hazard ratio (HR) 1.291 per 1-SD increase, 95% confidence interval (CI) 1.119–1.490, P < 0.001], independent of confounding risk factors. However, subgroup analysis showed that increasing estimated RLP-C was related to a higher risk of adverse events in the diabetic population only [HR 1.385 per 1-SD increase, 95% CI 1.183–1.620, P < 0.001]. Estimated RLP-C failed to be a significant determinant of adverse prognosis in non-diabetic and pre-diabetic subgroups. The addition of estimated RLP-C to a baseline model including traditional risk factors enhanced the predictive performance both in total and diabetic populations.ConclusionsHigh estimated RLP-C level is a significant predictor for recurrent adverse events in patients with diabetes and NSTE-ACS treated with PCI.

Association between remnant lipoprotein cholesterol levels and non-alcoholic fatty liver disease in adolescents

Background & AimsRemnant lipoprotein cholesterol (RLP-C) is an atherogenic lipid profile associated with non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). With increased rates of CVD seen in adults with NAFLD, RLP-C has the potential to identify individuals with NAFLD who are at increased risk of CVD. This study examined in adolescents sex-different associations among RLP-C, NAFLD, and cardiometabolic risk factors, and whether RLP-C is associated with NAFLD beyond traditional cardiometabolic risk factors.MethodsAdolescents in the Raine Study had anthropometry, clinical, biochemistry and arterial stiffness measurements recorded at 17 years of age. Fatty liver, subcutaneous and visceral adipose thickness were assessed using abdominal ultrasound. Relationships among RLP-C, NAFLD, liver biochemistry, insulin resistance, adipokines, adiposity and arterial stiffness were assessed.ResultsNAFLD was diagnosed in 15.1% (19.6% females and 10.7% males) of adolescents. Increasing RLP-C levels were associated with increasing severity of hepatic steatosis and metabolic syndrome. Adolescents with NAFLD and serum RLP-C levels in the highest quartile compared with the lowest quartile, had higher serum leptin, homeostatic model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein, low-density-lipoprotein cholesterol, triglycerides, BMI, subcutaneous and visceral adipose thickness, systolic blood pressure and arterial stiffness, but lower adiponectin and high-density-lipoprotein cholesterol. Using multivariable logistic regression, RLP-C in the lowest quartile compared with the highest quartile was associated with 85% lower odds of NAFLD in males and 55% in females, after adjusting for waist circumference, leptin, ALT, adiponectin and HOMA-IR.ConclusionsThere is an association between RLP-C and NAFLD beyond traditional risk factors of adiposity and insulin resistance in adolescents. Although raised serum RLP-C levels were associated with the severity of hepatic steatosis and markers of cardiometabolic risk, lower serum RLP-C might reflect reduced cardiovascular risk.Lay summaryRemnant lipoprotein cholesterol (RLP-C) is a part of the blood cholesterol that is linked with heart disease and non-alcoholic fatty liver disease (NAFLD) in adults. In the Raine Study, teenagers with high RLP-C levels had more severe fat accumulation in their liver. Thus, RLP-C might be the hidden link between NAFLD and future risk of heart disease.

Atherogenic postprandial remnant lipoproteins—a causal lipoproteins for the initiation of obesity and atherosclerosis

: Oxidized low density lipoprotein (Ox-LDL) and chylomicron (CM) remnants were proposed previously as the most atherogenic lipoproteins which initiate and progress the coronary atherosclerosis as the causal lipoproteins. However, there are still controversies on these hypothesizes. Therefore, we propose a new hypothesis on postprandial remnant lipoproteins (RLP) which contain hepatic origin apoB100 and intestinal origin apoB48 in VLDL fraction. Plasma RLP-cholesterol (RLP-C) and RLP-triglyceride (RLP-TG) increased significantly after fat load associated with the increase of TG. Approximately above 80% of the increased TG after fat load is composed of TG in RLP. Postprandial RLP contained significantly greater apoB100 lipoprotein particles than apoB48 particles. Also most LPL in non-heparin plasma was found in RLP as RLP-LPL complex and found in circulation and incorporated in peripheral issues primarily for energy delivery as a ligand for VLDL receptor. Plasma LPL concentration and activity don’t increase in plasma after fat intake, therefore it may cause the insufficient hydrolysis of RLP. As the results, we observed the significant increase of RLP-TG concentration with large particle size as mostly VLDL remnants in postprandial plasma. Therefore, LPL concentration was inversely correlated with RLP-C and RLP-TG concentration in postprandial plasma. Increased postprandial TG associated with increased RLP having striking similarity with Ox-LDL has been shown as the risk of cardiovascular disease by large epidemiological studies. We have shown that VLDL remnants, not CM remnants, are the major atherogenic lipoproteins increased in postprandial plasma associated with insufficient LPL activity as the possible causal factor for the initiation of atherosclerosis. Therefore, overproduced RLP in postprandial plasma should be the initial target to be controlled as the initiator of atherosclerosis by choosing the kind of food intake and appropriate exercise, without using therapeutic drugs.

Non-HDL Cholesterol or apoB: Which to Prefer as a Target for the Prevention of Atherosclerotic Cardiovascular Disease?

Guidelines propose using non-HDL cholesterol or apolipoprotein (apo) B as a secondary treatment target to reduce residual cardiovascular risk of LDL-targeted therapies. This review summarizes the strengths, weaknesses, opportunities, and threats (SWOT) of using apoB compared with non-HDL cholesterol. Non-HDL cholesterol, calculated as total-HDL cholesterol, includes the assessment of remnant lipoprotein cholesterol, an additional risk factor independent of LDL cholesterol. ApoB is a direct measure of circulating numbers of atherogenic lipoproteins, and its measurement can be standardized across laboratories worldwide. Discordance analysis of non-HDL cholesterol versus apoB demonstrates that apoB is the more accurate marker of cardiovascular risk. Baseline and on-treatment apoB can identify elevated numbers of small cholesterol-depleted LDL particles that are not reflected by LDL and non-HDL cholesterol. ApoB is superior to non-HDL cholesterol as a secondary target in patients with mild-to-moderate hypertriglyceridemia (175-880mg/dL), diabetes, obesity or metabolic syndrome, or very low LDL cholesterol < 70mg/dL. When apoB is not available, non-HDL cholesterol should be used to supplement LDLC.

Comparison of calculated remnant lipoprotein cholesterol levels with levels directly measured by nuclear magnetic resonance

BackgroundRemnant cholesterol (RC) can partly explain the residual risk in atherosclerotic cardiovascular disease (ASCVD). A consensus method of measuring RC levels has not been established yet. In clinical practice, RC levels are usually calculated from the standard lipid profile, which are not true RC. Nuclear magnetic resonance (NMR) can measure RC levels directly. This study aimed to characterize RC at fasting and non-fasting states in more details and establish the performance of calculated RC and NMR-measured RC.MethodsBlood samples at fasting state and at 2 h and 4 h postprandial states were collected in 98 subjects. Lipid parameters including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), subfractions 3, 4, and 5 of very low-density lipoprotein cholesterol (VLDL3-C, VLDL4-C, and VLDL5-C, respectively), and intermediate-density lipoprotein cholesterol (IDL-C) were measured by enzymatic method and NMR. RC levels calculated from the standard lipid profile or measured by NMR were referred here as RCe or RCn.ResultsThe RCe and RCn levels were different, but both of them increased after a meal (P < 0.05), especially at 4 h postprandial state. Low correlations were found between RCe and RCn in the 1st, 2nd, and 3rd quartiles of TG, but RCn showed great correlation with RCe in the highest quartile regardless of the fasting or non-fasting state (R = 0.611, 0.536, and 0.535 for 0 h, 2 h, and 4 h, respectively). However, across the 2nd and 3rd quartiles, RCe levels were nearly close to RCn levels. RCe levels tended to overestimate RCn levels in the 1st quartile of TGe levels with median differences of 0.23(− 0.13, 0.63) and underestimate RCn levels with median differences of − 0.23(− 0.33, 0.07) in the highest quartile of TGe levels.ConclusionsRC calculated from the standard lipid profile as TC minus LDL-C minus HDL-C is different from the NMR-measured RC. According to different TG levels, RC could overestimate or underestimate the actual RC level. Developing a consensus clinical method to measure RC levels is necessary, so that results from different studies and platforms can be more directly compared.Trial registrationChinese Clinical Trial Registry, ChiCTR1900020873. Registered in 21 January 2019 - Retrospectively registered.

Omarigliptin decreases inflammation and insulin resistance in a pleiotropic manner in patients with type 2 diabetes

BackgroundOmarigliptin is a potent, selective, oral dipeptidyl peptidase 4 (DPP4) inhibitor with a half-life that allows weekly dosing. Inflammation or insulin resistance might be pathological mediators of cardiovascular events in patients with type 2 diabetes.MethodsWhether omarigliptin has anti-inflammatory effects that result in decreased levels of high-sensitivity C-reactive protein (hsCRP) and anti-insulin resistance effects that decrease levels of homeostatic model assessment of insulin resistance (HOMA-IR) were investigated. Patients were allocated to continue with daily DPP4 inhibitors (control, n = 28) or to switch from daily DPP4 inhibitors to weekly omarigliptin (omarigliptin, n = 56). Fasting blood and urine samples were collected before, and every 3 months after intervention for 1 year.ResultsOmarigliptin tended to elicit reductions in fasting blood glucose (FBG), LDL-cholesterol, triglyceride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), the urinary albumin-to-creatinine ratio (ACR) with logarithmic transformation (log ACR), and systolic and diastolic blood pressure, but the differences did not reach statistical significance compared with control. Values for HDL-cholesterol tended to increase, but also did not reach statistical significance compared with control. Omarigliptin significantly decreased HOMA-IR, remnant-like particle cholesterol (RLP-C), and hsCRP with logarithmic transformation (log hsCRP) compared with control. However, omarigliptin did not affect hemoglobin A1c (HbA1c), body mass index (BMI), and estimated glomerular filtration rates (eGFR).ConclusionOmarigliptin decreased inflammation and insulin resistance without affecting HbA1c or BMI. Although how DPP4 inhibitors affect cardiovascular (CV) outcomes remains uncertain, omarigliptin might confer CV benefits at least in part, via pleiotropic anti-inflammatory or anti-insulin resistance effects.Trial registration UMIN Clinical Registry (UMIN000029288). Registered 22 September, 2017, https://upload.umin.ac.jp/UMIN000029288

Could remnant-like particle cholesterol become a risk factor in diabetic menopausal women with coronary artery disease? A cross-sectional study of single academic center in China

Background and aimsIt has been confirmed that remnant-like particle cholesterol (RLP-C) mediates the progression of coronary artery disease (CAD). Currently there is limited information on RLP-C in menopausal women. With the special status of diabetes mellitus (DM) combined with the special body changes of the menopausal women, the RLP-C is particularly important when studying the changes that occurred in response to CAD and its associated risk factors. This study discussed whether RLP-C could be an independent risk factor for menopausal women with CAD and DM.MethodsThe cohort consisted of 4753 menopausal women who had undergone coronary angiography. Subjects were separated into CAD and non-CAD groups, and univariate and multivariate logistic regression analysis of CAD risk factors were performed. All patients with a history of DM were divided into DM subgroups. Then, the univariate and multivariate logistic regression analysis of the risk factors of CAD and the comparison among age groups in the DM subgroup were performed. After age stratification of the DM group, the Kruskal-Wallis test was used to analyze the differences of various lipid indexes among age groups.ResultsThe multivariate logistic regression showed that RLP-C was an independent risk factor for CAD in menopausal women (OR 1.232, 95%CI 1.070–1.419). In the DM subgroup, it was also found that RLP-C was an independent risk factor for CAD (OR 1.366, 95%CI 1.043–1.791). Kruskal-Wallis test analysis found that RLP-C had no significant difference among three groups (P > 0.05).ConclusionsRLP-C was proved to be an independent risk factor for menopausal women with CAD and DM.

Effects of a Fiber-Rich Nutritional Supplement on Postprandial Glycemic Response and Lipid Parameters in Overweight Adults with and without Impaired Fasting Glucose in India

Objectives: This study evaluated the effects of a fiber-rich nutritional supplement on postprandial glycemic response and lipid parameters in overweight adults with and without impaired fasting glucose (IFG) in India. An ad-hoc analysis assessed the supplement’s effects on glycemic and lipid parameters in overweight adults with and without IFG. Methods: This was a randomized, double-blind, single-center study including 96 subjects. Among them, 26 subjects had IFG (100-125 mg/dL). After an overnight fast and a high-fat standardized breakfast, subjects were stratified according to IFG status and randomized to a fiber-rich drink or an energy-matched non-fiber control drink. Blood was drawn at 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210- and 240-min following treatment administration to assess postprandial blood glucose, triglycerides, remnant-like particle-cholesterol (RLP-C) and insulin peaks. There was a 3-day washout period between treatments. Results: Subjects with IFG displayed significantly lowered Cmax for postprandial glucose with the fiber-rich supplement versus control (difference -4.64 mg/dL; p=0.0487). A lower postprandial triglyceride peak was also reported with the fiber-rich supplement; however, this difference was not statistically significant (difference -6.79 mg/dL; p=0.6116). In an ad-hoc analysis, in subjects without IFG, the fiber-rich drink had a larger effect than the control drink on the Cmax for postprandial glucose (difference-4.75 mg/dL [95% CI -7.37, -2.14]), RLP-C (-0.18 mmol/L [-0.35, -0.02] and insulin (-23.33 μIU/mL [-36.54, -10.13]). A single AE, that is mild diarrhea was reported but was not related to the experimental treatment. Conclusion: The fiber-rich nutritional supplement reduced maximum concentrations of postprandial blood glucose levels in overweight subjects with IFG without much influence on postprandial triglycerides.