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

Objective: The relationship between remnant-like particle cholesterol (RLP-C) levels and the progression of atrial fibrillation (AF) is not known. This research aimed to explore the association of RLP-C with long-term AF recurrence events post-radiofrequency catheter ablation (RFCA) of AF. Methods: In total 320 patients with AF who were subjected to the first RFCA were included in this research. Baseline information and laboratory data of patients were retrospectively collected, and a 1-year follow-up was completed. The follow-up endpoint was defined as an AF recurrence event occurring after 3 months. Afterward, a multivariate Cox regression model was constructed to analyze the risk factors that affect AF recurrence. Results: AF recurrence occurred in 103 patients (32.2%) within 3-12 months after RFCA. Based on the multivariate Cox regression analysis, Early recurrence (ER) [hazard ratio (HR) =1.57, 95% confidence interval (CI): 1.04-2.36, P = 0.032)], coronary artery disease (CAD) (HR = 2.03, 95% CI: 1.22-3.38, P = 0.006), left atrium anterior-posterior diameter (LAD) (HR = 1.07, 95% CI: 1.03-1.10, P < 0.001), triglyceride (TG) (HR = 1.51, 95% CI: 1.16-1.96, P = 0.002), low-density lipoprotein cholesterol (LDL-C) (HR = 0.74, 95% CI: 0.55-0.98, P = 0.036), and RLP-C (HR = 0.75 per 0.1 mmol/L increase, 95% CI: 0.68-0.83, P < 0.001) were linked to the risk of AF recurrence. Among them, the relationship between RLP-C and AF recurrence was found for the first time. The predictive value of RLP-C for AF recurrence was analyzed utilizing receiver operating characteristic (ROC) curves [area under the curve (AUC) = 0.81, 95% CI: 0.77-0.86, P < 0.001]. Subsequently, the optimal threshold value of RLP-C was determined to be 0.645 mmol/L with a sensitivity of 87.4% and a specificity of 63.6% based on the Youden index. Additionally, Kaplan-Meier analysis indicated a lower AF recurrence rate in the >0.645 mmol/L group than in the ≤0.645 mmol/L group (Log-rank P < 0.001). Conclusion: Low levels of RLP-C are associated with a higher risk of AF recurrence post-RFCA, suggesting that RLP-C may be a biomarker that helps to identify long-term AF recurrence.

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

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

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

AIMS: This 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. METHODS: 792 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. RESULTS: 222 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. CONCLUSIONS: The 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.

Triglyceride-rich lipoproteins, apolipoprotein C-III, angiopoietin-like protein 3, and cardiovascular events in older adults: Atherosclerosis Risk in Communities (ARIC) study.

AIMS: Despite statin and antihypertensive therapies, older Americans have high atherosclerotic cardiovascular disease (ASCVD) risk. Novel measures of triglyceride-rich lipoproteins, low-density lipoprotein triglycerides (LDL-TG), and remnant-like particle cholesterol (RLP-C), are associated with ASCVD in middle-aged adults. Polymorphisms in genes encoding angiopoietin-related protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III), two proteins involved in triglyceride catabolism, are associated with increased risk for hypertriglyceridaemia and ASCVD and are potential therapeutic targets. We examined associations of LDL-TG, RLP-C, apoC-III, and ANGPTL3 levels with ASCVD events in older adults in the Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS: In 6359 participants (mean age 75.8 ± 5.3 years) followed for ASCVD events [coronary heart disease (CHD) or ischaemic stroke] up to 6 years, associations between LDL-TG, RLP-C, apoC-III, and ANGPTL3 and ASCVD events were assessed using Cox regression. With adjustment for age, sex, and race, RLP-C, LDL-TG, apoC-III, and ANGPTL3 (as continuous variables) were significantly associated with CHD. However, after adjustment for traditional risk factors and lipid-lowering medications, only LDL-TG and ANGPTL3 were significantly associated with ASCVD events [hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.25-2.37 per log unit increase in LDL-TG; HR 1.63, 95% CI 1.17-2.28 per log unit increase in ANGPTL3]. CONCLUSIONS: In older adults, LDL-TG, RLP-C, apoC-III, and ANGPTL3 were associated with CHD events in minimally adjusted models; LDL-TG and ANGPTL3 remained independent predictors of ASCVD events with further adjustment. Future studies should assess potential benefit of lowering hepatic apoC-III or ANGPTL3 expression in patients with elevated triglyceride-rich lipoproteins.

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

BACKGROUND: Remnant-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. METHODS: This 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. RESULTS: The 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. CONCLUSION: We 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.

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

BACKGROUND@#Remnant-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.@*METHODS@#This 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.@*RESULTS@#The 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.@*CONCLUSION@#We 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.

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

BACKGROUND: It 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. METHODS: The 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. RESULTS: Estimated 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. CONCLUSIONS: High estimated RLP-C level is a significant predictor for recurrent adverse events in patients with diabetes and NSTE-ACS treated with PCI.

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 AIMS: It 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. METHODS: The 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. RESULTS: The 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). CONCLUSIONS: RLP-C was proved to be an independent risk factor for menopausal women with CAD and DM.

Effects of Dietary Blueberry (Vaccinium ashei Reade) Leaves on Mildly Postprandial Hypertriglyceridemia.

Prevention of postprandial hypertriglyceridemia is an important consideration for reducing the risk of developing cardiovascular disease. While blueberry fruits have been reported to ameliorate lipid metabolism in humans, there are only few research reports on the effects of blueberry leaves (BL). Here, we investigated the efficacy of BL on postprandial hyperlipidemia in subjects with high fasting triacylglycerol (TG) concentrations. Randomized, double-blind, cross-over design study was conducted. The subjects consumed a BL containing beverage or a placebo beverage before a fat-enriched test meal. Blood samples were collected prior to and 1, 2, 3, 4, and 5 hours after consuming the test beverage. The postprandial serum TG and remnant-like particle cholesterol (RLP-C) concentrations were significantly lower in the BL beverage compared with those in the placebo beverage. Additionally, BL was more effective in subjects with high fasting ghrelin with gastric emptying function. In current study, fasting ghrelin correlated with the increase in postprandial serum TG, suggesting that BL ameliorates hypertriglyceridemia through delayed gastric emptying. In conclusion, this pilot study suggests that BL may be useful as an early dietary therapy for treating postprandial hyperlipidemia.

Combined Effect of Small Dense Low-Density Lipoprotein Cholesterol (sdLDL-C) and Remnant-Like Particle Cholesterol (RLP-C) on Low-Grade Inflammation.

AIMS: Small dense low-density lipoprotein cholesterol (sdLDL-C) and remnant-like particle cholesterol (RLP-C) are the novel atherosclerotic risk factors and might be strongly associated with inflammation. The basic evidence supports that sdLDL and RLP have some different mechanisms inducing an inflammatory response. Many studies have focused on the mechanism of inflammation of sdLDL-C or RLP-C per se, with limited data on the association between sdLDL-C and RLP-C in the real-world, population-based setting. Thus, the aim of this study was to investigate the association between sdLDL-C and RLP-C with inflammation. METHODS: We examined the baseline cross-sectional data of participants from the Jichi Medical School-II Cohort Study. In total, 5,305 participants (2,439 men and 2,866 women) were included in this study. RESULTS: Of all quartiles of sdLDL-C, the fourth had the highest high-sensitivity C-reactive protein (hs-CRP) level. Once adjusted for age, sex, smoking status, homeostasis model assessment of insulin resistance, antidyslipidemic and antihyperglycemic medication use, and RLP-C, sdLDL-C was significantly and positively associated with hs-CRP (geometric mean, 95% confidence interval (CI), 0.36 mg/L (0.34-0.38 mg/L), 0.37 mg/L (0.35-0.39 mg/L), 0.40 mg/L (0.37-0.42 mg/L) versus 0.44 mg/L (0.42-0.47 mg/L), P＜0.001 for trend). After stratifying the participants into four sdLDL-C×four RLP-C categories, the group in the fourth sdLDL-C quartile and the forth RLP-C quartile had the highest hs-CRP level (geometric mean, 95% CI, 0.52 mg/L, 0.48-0.57 mg/L, interaction P=0.75). CONCLUSIONS: SdLDL-C and RLP-C had different associations with inflammation. Our results support sdLDL-C as the potential novel factor of cardiovascular disease, independently of RLP-C.

Association between plasma essential amino acids and atherogenic lipid profile in a Chinese population: A cross-sectional study.

BACKGROUND AND AIMS: The association between amino acids and small dense low-density lipoprotein cholesterol (sdLDL-C) and remnant-like particle cholesterol (RLP-C) remains poorly understood. This study aims to investigate the association between plasma essential amino acids (EAAs) and atherogenic lipid profiles. METHODS: Plasma amino acid levels of 475 individuals were measured using liquid chromatography-mass spectrometry. SdLDL-C, RLP-C, and other lipid components were evaluated. Associations between EAAs and lipid components or dyslipidemia were determined using correlation analysis and multivariate logistic regression. RESULTS: Concentrations of plasma branched-chain amino acid (BCAA) were positively correlated with sdLDL-C, RLP-C, and triglycerides (TG) levels, but inversely correlated with high-density lipoprotein cholesterol (HDL-C). In contrast, threonine concentration was inversely correlated with sdLDL-C, RLP-C, and TG. Compared with the lowest tertile, individuals in the highest tertile of plasma total BCAAs level had an odds ratio (OR) of 2.33 (95% confidence interval [CI]: 1.35, 4.03) for the risk of high sdLDL-C, 3.63 (95%CI: 1.69, 7.80) for the risk of high RLP-C, 3.10 (95%CI: 1.66, 5.80) for the risk of high TG, and 3.67 (95%CI: 2.00, 6.73) for atherogenic lipid triad (all p < 0.01). In contrast, compared with the lowest tertile, individuals in the highest plasma threonine tertile had a 43% lower OR for high sdLDL-C, 56% lower OR for high TG, and 55% lower OR for lipid triad risk (all p < 0.05). CONCLUSIONS: Among the EAAs evaluated, elevated plasma BCAAs were significantly associated with increased risk of atherogenic lipid profile. In contrast, elevated threonine was associated with reduced risk of atherogenic lipid profile.

Remnant lipoproteins play an important role of in-stent restenosis in type 2 diabetes undergoing percutaneous coronary intervention: a single-centre observational cohort study.

BACKGROUND: Increasing evidence has suggested that the presence of remnant lipoproteins is a significant risk factor for atherosclerosis. Remnant lipoproteins are lipoproteins that are rich in triglycerides (TGs), and the main components include very-low-density lipoprotein (VLDL) in the fasting state. Diabetic patients often have hypertriglyceridemia with elevated levels of VLDL cholesterol but normal levels of low-density lipoprotein cholesterol (LDL-C). The aim of the present study was to elucidate the potential role of remnant lipoproteins-induced atherosclerosis in the occurrence and development of in-stent restenosis (ISR) in diabetic patients with coronary artery disease. METHODS: The present study enrolled 2312 patients with type 2 diabetes mellitus who underwent percutaneous coronary intervention from January 2013 to December 2014 and who were followed up by angiography. Patients were divided into two groups based on the presence or absence of ISR, and multivariate Cox's proportional hazards regression modelling showed that remnant-like particle cholesterol (RLP-C) was an independent risk factor for ISR. According to the receiver operating characteristic curve, the optimal cutoff point of the RLP-C was identified, and the patients were further divided into 2 groups. Propensity score matching analysis was performed, and 762 pairs were successfully matched. Log-rank tests were used to compare Kaplan-Meier curves for overall follow-up to assess ISR. RESULTS: The multivariate Cox's proportional hazards regression analysis showed that RLP-C was independently associated with ISR, and the baseline RLP-C level at 0.505 mmol/L was identified as the optimal cutoff point to predict ISR. Patients were divided into 2 groups by RLP levels. After propensity score matching analysis, a total of 762 pairs matched patients were generated. Kaplan-Meier curves showed that the estimated cumulative rate of ISR was significantly higher in patients with RLP-C levels ≥ 0.505 mmol/L (log-rank P < 0.001; HR equal to 4.175, 95% CI = 3.045-5.723, P < 0.001) compared to patients with RLP-C levels < 0.505 mmol/L. CONCLUSIONS: The present study emphasized the importance of remnant-like particle cholesterol in cardiovascular pathology in diabetic patients. Physicians should take measures to control RLP-C below the level of 0.505 mmol/L to better prevent of in-stent restenosis in diabetic patients.

Postprandial Hyperchylomicronemia and Thin-Cap Fibroatheroma in Nonculprit Lesions.

Objective- Although postprandial hypertriglyceridemia can be a risk factor for coronary artery disease, the extent of its significance remains unknown. This study aimed to investigate the correlation between the postprandial lipid profiles rigorously estimated with the meal tolerance test and the presence of lipid-rich plaque, such as thin-cap fibroatheroma (TCFA), in the nonculprit lesion. Approach and Results- A total of 30 patients with stable coronary artery disease who underwent a multivessel examination using optical coherence tomography during catheter intervention for the culprit lesion were enrolled. Patients were divided into 2 groups: patients with TCFA (fibrous cap thickness ≤65 µm) in the nonculprit lesion and those without TCFA. Serum remnant-like particle-cholesterol and ApoB-48 (apolipoprotein B-48) levels were measured during the meal tolerance test. The value of remnant-like particle-cholesterol was significantly greater in the TCFA group than in the non-TCFA group ( P=0.045). Although the baseline ApoB-48 level was similar, the increase in the ApoB-48 level was significantly higher in the TCFA group than in the non-TCFA group ( P=0.028). In addition, the baseline apolipoprotein C-III levels was significantly greater in the TCFA group ( P=0.003). These indexes were independent predictors of the presence of TCFA (ΔApoB-48: odds ratio, 1.608; 95% confidence interval, 1.040-2.486; P=0.032; apolipoprotein C-III: odds ratio, 2.581; 95% confidence interval, 1.177-5.661; P=0.018). Conclusions- Postprandial hyperchylomicronemia correlates with the presence of TCFA in the nonculprit lesion and may be a residual risk factor for coronary artery disease.

Triglyceride-Rich Lipoprotein Cholesterol and Risk of Cardiovascular Events Among Patients Receiving Statin Therapy in the TNT Trial.

BACKGROUND: Mendelian randomization data suggest that the genetic determinants of lifetime higher triglyceride-rich lipoprotein-cholesterol (TRL-C) are causally related to cardiovascular disease and therefore a potential therapeutic target. The relevance of TRL-C among patients receiving statins is unknown. We assessed the relationship between TRL-C and cardiovascular risk, and whether this risk was modifiable among patients receiving statins in the TNT trial (Treating to New Targets). METHODS: Patients with coronary heart disease and low-density lipoprotein cholesterol (LDL-C) 130 to 250 mg/dL entered an 8-week run-in phase with atorvastatin 10 mg/d (ATV10). After this period, participants with LDL-C <130 mg/dL entered the randomized phase with ATV10 (n=5006) versus atorvastatin 80 mg/d (ATV80, n=4995). The primary end point was coronary heart disease death, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke (major adverse cardiovascular events [MACE]). TRL-C was calculated as total cholesterol minus high-density lipoprotein cholesterol minus LDL-C. The effect of atorvastatin on TRL-C was assessed during the run-in phase (ATV10) and randomized phase (ATV80 versus ATV10). The risk of MACE was assessed across quintiles (Q) of baseline TRL-C (and, for comparison, by baseline triglycerides and non-high-density lipoprotein cholesterol) during the randomized period. Last, the association between TRL-C changes with atorvastatin and cardiovascular risk was assessed by multivariate Cox regression. RESULTS: ATV10 reduced TRL-C 10.7% from an initial TRL-C of 33.9±16.6 mg/dL. ATV80 led to an additional 15.4% reduction. Cardiovascular risk factors positively correlated with TRL-C. Among patients receiving ATV10, higher TRL-C was associated with higher 5-year MACE rates (Q1=9.7%, Q5=13.8%; hazard ratio Q5-versus-Q1, 1.48; 95% confidence interval, 1.15-1.92; P-trend<0.0001). ATV80 (versus ATV10) did not significantly alter the risk of MACE in Q1-Q2, but significantly reduced risk in Q3-Q5 (relative risk reduction, 29%-41%; all P<0.0250), with evidence of effect modification ( P-homogeneity=0.0053); results were consistent for triglycerides ( P-homogeneity=0.0101) and directionally similar for non-high-density lipoprotein cholesterol ( P-homogeneity=0.1387). Last, in adjusted analyses, a 1 SD percentage reduction in TRL-C with atorvastatin resulted in a significant lower risk of MACE (hazard ratio, 0.93; 95% confidence interval, 0.86-1.00; P=0.0482) independent of the reduction in LDL-C and of similar magnitude to that per 1 SD lowering in LDL-C (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95; P=0.0008). CONCLUSIONS: The present post hoc analysis from TNT shows that increased TRL-C levels are associated with an increased cardiovascular risk and provides evidence for the cardiovascular benefit of lipid lowering with statins among patients who have coronary heart disease with high TRL-C. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00327691.

Icosapent ethyl (eicosapentaenoic acid ethyl ester): Effects on remnant-like particle cholesterol from the MARINE and ANCHOR studies.

BACKGROUND AND AIMS: Remnant-like particle cholesterol (RLP-C) is atherogenic and may increase atherosclerotic cardiovascular disease risk. Icosapent ethyl is a high-purity prescription eicosapentaenoic acid ethyl ester (approved as an adjunct to diet to reduce triglyceride [TG] levels in adult patients with TGs ≥500 mg/dL [≥5.65 mmol/L] at 4 g/day). In the MARINE and ANCHOR studies, icosapent ethyl reduced TG and other atherogenic lipid parameter levels without increasing low-density lipoprotein cholesterol (LDL-C) levels. This exploratory analysis evaluated the effects of icosapent ethyl on calculated and directly measured RLP-C. METHODS: MARINE (TGs ≥500 and ≤2000 mg/dL [≥5.65 mmol/L and ≤22.6 mmol/L]) and ANCHOR (TGs ≥200 and <500 mg/dL [≥2.26 and <5.65 mmol/L] despite statin-controlled LDL-C) were phase 3, 12-week, double-blind studies that randomized adult patients to icosapent ethyl 4 g/day, 2 g/day, or placebo. This analysis assessed median percent change from baseline to study end in directly measured (immunoseparation assay) RLP-C levels (MARINE, n = 218; ANCHOR, n = 252) and calculated RLP-C levels in the full populations. RESULTS: Icosapent ethyl 4 g/day significantly reduced directly measured RLP-C levels -29.8% (p = 0.004) in MARINE and -25.8% (p = 0.0001) in ANCHOR versus placebo, and also reduced directly measured RLP-C levels to a greater extent in subgroups with higher versus lower baseline TG levels, in patients receiving statins versus no statins (MARINE), and in patients receiving medium/higher-intensity versus lower-intensity statins (ANCHOR). Strong correlations were found between calculated and directly measured RLP-C for baseline, end-of-treatment, and percent change values in ANCHOR and MARINE (0.73-0.92; p < 0.0001 for all). CONCLUSIONS: Icosapent ethyl 4 g/day significantly reduced calculated and directly measured RLP-C levels versus placebo in patients with elevated TG levels from the MARINE and ANCHOR studies.

Serum remnant-like particle cholesterol concentration and its clinical significance in the patients with type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective To investigate the change of serum remnant like particle cholesterol (RLP C) and the association of RLP C with diabetic nephropathy (DN) in the patients with type 2 diabetes mellitus (DM). Methods Serum RLP C concentration was assayed by immunoseparation method. Plasma ? granule membrane glycoprotein 140 (GMP140) and nitric oxide (NO) levels were also measured. Urinary albumin excretion rate (UAER) was measured by radioimmunoassay, and the patients with type 2 DM were assigned to three groups according to UAER 〔35 without DN (D 1 group, UAER200 ?g/min)〕. Results Serum RLP C concentration in 96 patients with type 2 DM was significantly increased compared to that in 44 normal controls (NC) 〔(0.281?0.162)mmol/L vs (0.193?0.125)mmol/L, P