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Association of small dense low-density lipoprotein with cardiovascular outcome in patients with coronary artery disease and diabetes: a prospective, observational cohort study.

ABSTRACT: BACKGROUND:Elevation in small dense low-density lipoprotein (sdLDL) is common in patients with diabetes mellitus (DM), which has already been reported to be associated with incidence of coronary artery disease (CAD). The aim of the present study was to investigate the prognostic value of plasma sdLDL level in patients with stable CAD and DM. METHODS:A total of 4148 consecutive patients with stable CAD were prospectively enrolled into the study and followed up for major cardiovascular events (MACEs) up to 8.5 years. Plasma sdLDL level was measured in each patient by a direct method using automated chemistry analyzer. The patients were subsequently divided into four groups by the quartiles of sdLDL and the association of sdLDL level with MACEs in different status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] was evaluated. RESULTS:A total of 464 MACEs were documented. Both Kaplan-Meier analysis and Cox regression analysis indicated that the patients in quartile 4 but not quartile 2 or 3 of sdLDL level had significantly higher rate of MACEs than that in lowest quartile. When the prognostic value of high sdLDL was assessed in different glucose metabolism status, the results showed that the high sdLDL plus DM was associated with worse outcome after adjustment of confounding risk factors (hazard ratio: 1.83, 95% confident interval: 1.24-2.70, p?

SUBMITTER: Jin JL

PROVIDER: S-EPMC7118853 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Association of small dense low-density lipoprotein with cardiovascular outcome in patients with coronary artery disease and diabetes: a prospective, observational cohort study.

Jin Jing-Lu JL Zhang Hui-Wen HW Cao Ye-Xuan YX Liu Hui-Hui HH Hua Qi Q Li Yan-Fang YF Zhang Yan Y Wu Na-Qiong NQ Zhu Cheng-Gang CG Xu Rui-Xia RX Gao Ying Y Li Xiao-Lin XL Cui Chuan-Jue CJ Liu Geng G Sun Jing J Dong Qian Q Guo Yuan-Lin YL Li Jian-Jun JJ

Cardiovascular diabetology 20200403 1

<h4>Background</h4>Elevation in small dense low-density lipoprotein (sdLDL) is common in patients with diabetes mellitus (DM), which has already been reported to be associated with incidence of coronary artery disease (CAD). The aim of the present study was to investigate the prognostic value of plasma sdLDL level in patients with stable CAD and DM.<h4>Methods</h4>A total of 4148 consecutive patients with stable CAD were prospectively enrolled into the study and followed up for major cardiovascu ...[more]

PMID: 32245386

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Project description:BackgroundResidual risk remained significant despite effective low density lipoprotein cholesterol (LDL-C) lowering treatment. Small dense low density lipoprotein cholesterol (sdLDL-C) as part of LDL-C has been found to be predictor of coronary heart disease (CHD) and cardiovascular (CV) events in patients with stable CHD independently of LDL-C. However, to date, few studies have explored the role of sdLDL-C in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). Accordingly, this study aimed to evaluate the association of sdLDL-C with CV events in patients with ACS undergoing PCI.MethodsPatients hospitalized with ACS undergoing PCI were enrolled and followed up for 18 months. The risk of sdLDL-C for CV events was compared according to sdLDL-C quartiles. The primary outcome was major cardiovascular and cerebrovascular adverse events (MACCE), which was the composite of all cause of death, nonfatal myocardial infarction (MI), nonfatal stroke or unplanned repeat revascularization. A Cox proportional hazards regression model was performed to estimate the risk of CV events. Subgroup analysis according to diabetes status and LDL-C were performed separately for MACCE.ResultsA total of 6092 patients were included in the analysis (age: 60.2 ± 10.13 years, male: 75.3%, BMI: 25.9 ± 3.33 kg/m2, dyslipidemia: 74.1% and diabetes: 44.5%). During 18 months of follow-up, 320 (5.2%) incident CV events occurred. Compared to the lowest sdLDL-C quartile group, patients in the highest quartile had a greater risk of CV events after multivariable adjustment (HR 1.92; 95% CI 1.37-2.70). In addition, it was mainly due to the increase of unplanned repeat revascularization. In the subgroup analyses, significant association was observed regardless of level of LDL-C and diabetes status.ConclusionsPatients with elevated sdLDL-C have a higher risk of CV events in Chinese patients with ACS undergoing PCI, providing additional value for better risk assessment.

Project description:BackgroundIncreasing evidence showed that carbamylated lipoprotein accelerated atherosclerosis. However, whether such modification of high-density lipoprotein (HDL) particles alters in type 2 diabetes mellitus (T2DM) patients and facilitates vascular complications remains unclear. We aimed to investigate the alteration of the carbamylation in HDL among T2DM patients and clarify its potential role in atherogenesis.MethodsA total of 148 consecutive T2DM patients undergoning angiography and 40 age- and gender-matched control subjects were included. HDL was isolated from plasma samples, and the concentration of HDL carbamyl-lysine (HDL-CBL) was measured. Furthermore, the HDL from subjects and in-vitro carbamylated HDL (C-HDL) was incubated with endothelial cells and monocyte to endothelial cell adhesion. Adhesion molecule expression and signaling pathway were detected.ResultsCompared with the control group, the HDL-CBL level was remarkably increased in T2DM patients (6.13 ± 1.94 vs 12.00 ± 4.06 (ng/mg), P < 0.001). Of note, HDL-CBL demonstrated a more significant increase in T2DM patients with coronary artery disease (CAD) (n = 102) than those without CAD (n = 46) (12.75 ± 3.82 vs. 10.35 ± 4.11(ng/mg), P = 0.001). Multivariate logistic regression analysis demonstrated that higher HDL-CBL level was independently associated with a higher prevalence of CAD in diabetic patients after adjusting for established cofounders (adjusted odds ratio 1.174, 95% confidence Interval 1.045-1.319, p = 0.017). HDL from diabetic patients with CAD enhanced greater monocyte adhesion than that from the non-CAD or the control group (P < 0.001). Such pro-atherogenic capacity of diabetic HDL positively correlated with HDL-CBL level. Furthermore, in-vitro incubation of carbamylated HDL (C-HDL) with endothelial promoted monocyte to endothelial cell adhesion, induced upregulation of cell adhesion molecules expression, and activated NF-κB/p65 signaling in endothelial cells. Inhibiting carbamylation of HDL or NF-κB activation attenuated the monocyte to endothelial cell adhesion and cell surface adhesion molecules expression.ConclusionsOur study identified elevated carbamylation modification of HDL from T2DM patients, especially in those with concomitant CAD. We also evidenced that C-HDL enhanced monocyte to endothelial cell adhesion, indicating a potential pro-atherogenic role of C-HDL in atherosclerosis among T2DM patients. Trial registration https://register.clinicaltrials.gov , NCT04390711 Registered on 14 May 2020; Retrospectively registered.

Project description:Background/objectivesEndoscopic coronary artery bypass grafting (Endo-CABG) is a minimally invasive CABG procedure with retrograde arterial perfusion. The main objective of this study is to assess neurocognitive outcome after Endo-CABG.Methods/designIn this prospective observational cohort study, patients were categorised into: Endo-CABG (n = 60), a comparative Percutaneous Coronary Intervention (PCI) group (n = 60) and a healthy volunteer group (n = 60). A clinical neurological examination was performed both pre- and postoperatively, delirium was assessed postoperatively. A battery of 6 neurocognitive tests, Quality of life (QoL) and the level of depressive feelings were measured at baseline and after 3 months. Patient Satisfaction after Endo-CABG was assessed at 3-month follow-up. Primary endpoints were incidence of postoperative cognitive dysfunction (POCD), stroke and delirium after Endo-CABG. Secondary endpoints were QOL, patient satisfaction and the incidence of depressive feelings after Endo-CABG.ResultsIn total, 1 patient after Endo-CABG (1.72%) and 1 patient after PCI (1.67%) suffered from stroke during the 3-month follow-up. POCD in a patient is defined as a Reliable Change Index ?-1.645 or Z-score ?-1.645 in at least two tests, and was found in respectively 5 and 6 patients 3 months after Endo-CABG and PCI. Total incidence of POCD/stroke was not different (PCI: n= 7 [15.9%]; Endo-CABG: n= 6 [13.0%], p = 0.732). ICU delirium after Endo-CABG was found in 5 (8.6%) patients. QoL increased significantly three months after Endo-CABG and was comparable with QoL level after PCI and in the control group. Patient satisfaction after Endo-CABG and PCI was comparable. At follow-up, the level of depressive feelings was decreased in all groups.ConclusionsThe incidence of poor neurocognitive outcome, including stroke, POCD and postoperative ICU delirium until three months after Endo-CABG is low and comparable with PCI.Trial registrationRegistered on ClinicalTrials.gov (NCT02979782).

Project description:BACKGROUND:Apolipoprotein CIII (apoCIII) is associated with triglyceride-rich lipoprotein metabolism and has emerged as independent marker for risk of cardiovascular disease. The objective was to test whether apoCIII is regulated postprandially and whether apoCIII concentrations in native and chylomicron-free serum predict future cardiovascular events in patients with stable coronary artery disease (CAD). METHODS:ApoCIII concentrations were measured in native and chylomicron-free serum in the fasting state and after a standardized oral fat load test in 195 patients with stable CAD. Clinical follow-up was 48?months. Chylomicron-free serum was prepared by ultracentrifugation (18,000?rpm, 3?h). The log-rank test and Cox regression analyses were used to investigate the association of apoCIII with recurrent cardiovascular events. RESULTS:Of the 195 patients included, 92 had a cardiovascular event, and 103 did not. 97% were treated with a statin. No significant changes in apoCIII concentration were observed after the oral fat load test. The apoCIII concentration was associated with event-free survival independent of conventional risk factors. This association reached statistical significance only for apoCIII concentration measured in chylomicron-free serum (hazard ratio [95% confidence interval] for apoCIII above the mean: postprandial: 1.67 (1.06-2.29), P?=?0.028, fasting: 2.09 (1.32-3.32), P?=?0.002), but not for apoCIII concentration measured in native serum (postprandial: 1.47 [0.89-2.43], P?=?0.133, fasting: 1.56 [0.95-2.58], P?=?0.081). The effects were independent of other risk factors. CONCLUSIONS:ApoCIII concentrations in chylomicron-free serum are independently associated with event-free survival in patients with CAD both in fasting and postprandial state. This findings support considering apoCIII for risk assessment and attempting to test the hypothesis that lowering apoCIII reduces residual cardiovascular risk. TAKE HOME MESSAGE:Apolipoprotein CIII concentration measured in chylomicron-free serum predicts recurrent cardiovascular events in patients with stable coronary artery disease. TRIAL REGISTRATION:The trial which included the participants of this study was registered at https://clinicaltrials.gov (NCT00628524) on March 5, 2008.

Project description:INTRODUCTION:Adverse neurocognitive outcomes are still an important cause of morbidity and mortality after cardiac surgery. The most common neurocognitive disorders after conventional cardiac surgery are postoperative cognitive dysfunction (POCD), stroke and delirium. Minimal invasive cardiac procedures have recently been introduced into practice. Endoscopic coronary artery bypass grafting (Endo-CABG) is a minimal invasive cardiac procedure based on the conventional CABG procedure. Neurocognitive outcome after minimal invasive cardiac surgery, including Endo-CABG, has never been studied. Therefore, the main objective of this study is to examine neurocognitive outcome after Endo-CABG. METHODS AND ANALYSIS:We will perform a prospective observational cohort study including 150 patients. Patients are categorised into three groups: (1) patients undergoing Endo-CABG, (2) patients undergoing a percutaneous coronary intervention and (3) a healthy volunteer group. All patients in the Endo-CABG group will be treated following a uniform, standardised protocol. To assess neurocognitive outcome after surgery, a battery of six neurocognitive tests will be administered at baseline and at 3-month follow-up. In the Endo-CABG group, a neurological examination will be performed at baseline and postoperatively and delirium will be scored at the intensive care unit. Quality of life (QOL), anxiety and depression will be assessed at baseline and at 3-month follow-up. Satisfaction with Endo-CABG will be assessed at 3-month follow-up. Primary endpoints are the incidence of POCD, stroke and delirium after Endo-CABG. Secondary endpoints are QOL after Endo-CABG, patient satisfaction with Endo-CABG and the incidence of anxiety and depression after Endo-CABG. ETHICS AND DISSEMINATION:The neurological outcome after minimal invasive coronary artery surgery study has received approval of the Jessa Hospital ethics board. It is estimated that the trial will be executed from December 2016 to January 2018, including enrolment and follow-up. Analysis of data, followed by publication of the results, is expected in 2018. TRIAL REGISTRATION NUMBER:NCT02979782.

Project description:Background Elevated plasma levels of direct low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), low-density lipoprotein (LDL) triglycerides, triglycerides, triglyceride-rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and lipoprotein(a) have all been associated with incident atherosclerotic cardiovascular disease (ASCVD). Our goal was to assess which parameters were most strongly associated with ASCVD risk. Methods and Results Plasma total cholesterol, triglycerides, high-density lipoprotein cholesterol, direct LDL-C, sdLDL-C, LDL triglycerides, remnant lipoprotein particle cholesterol, triglyceride-rich lipoprotein cholesterol, and lipoprotein(a) were measured using standardized automated analysis (coefficients of variation, <5.0%) in samples from 3094 fasting subjects free of ASCVD. Of these subjects, 20.2% developed ASCVD over 16 years. On univariate analysis, all ASCVD risk factors were significantly associated with incident ASCVD, as well as the following specialized lipoprotein parameters: sdLDL-C, LDL triglycerides, triglycerides, triglyceride-rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and direct LDL-C. Only sdLDL-C, direct LDL-C, and lipoprotein(a) were significant on multivariate analysis and net reclassification after adjustment for standard risk factors (age, sex, hypertension, diabetes mellitus, smoking, total cholesterol, and high-density lipoprotein cholesterol). Using the pooled cohort equation, many specialized lipoprotein parameters individually added significant information, but no parameter added significant information once sdLDL-C (hazard ratio, 1.42; P<0.0001) was in the model. These results for sdLDL-C were confirmed by adjusted discordance analysis versus calculated non-high-density lipoprotein cholesterol, in contrast to LDL triglycerides. Conclusions sdLDL-C, direct LDL-C, and lipoprotein(a) all contributed significantly to ASCVD risk on multivariate analysis, but no parameter added significant risk information to the pooled cohort equation once sdLDL-C was in the model. Our data indicate that small dense LDL is the most atherogenic lipoprotein parameter.

Dataset Information

Association of small dense low-density lipoprotein with cardiovascular outcome in patients with coronary artery disease and diabetes: a prospective, observational cohort study.

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Association of small dense low-density lipoprotein with cardiovascular outcome in patients with coronary artery disease and diabetes: a prospective, observational cohort study.

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