Prognostic utility of triglyceride-rich lipoprotein-related markers in patients with coronary artery disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Cao YX
PROVIDER: S-EPMC7469882 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundRecent guidelines highlighted the association between atherosclerosis and triglyceride-enriched lipoproteins in patients with impaired glucose metabolism. However, evidence from prospective studies for long-term prognostic utility of low-density lipoprotein triglyceride (LDL-TG) in real-world patients with prediabetes (Pre-DM) or diabetes mellitus (DM) and coronary artery disease (CAD) is currently not available. The aim of the present study was to evaluate the impact of LDL-TG on major adverse cardiovascular events (MACEs) in patients with stable CAD under different glucose metabolism status.MethodsA total of 4381 patients with CAD were consecutively enrolled and plasma LDL-TG level was measured by an automated homogeneous assay. They were categorized according to both status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] and tertiles of LDL-TG. All subjects were followed up for the occurrence of MACEs.ResultsDuring a median of 5.1 (interquartile range 3.9 to 5.9) years' follow-up, 507 (11.6%) MACEs occurred. Cubic spline models showed a significant association between LDL-TG and MACEs in DM and Pre-DM but not in NGR. When the combined effect of elevated LDL-TG and glucose disorders was considered for risk stratification, the medium tertile of LDL-TG plus DM, and the highest tertile of LDL-TG plus Pre-DM or plus DM subgroups were associated with significantly higher risk of MACEs after adjustment of confounders including triglyceride [hazard ratios (95% confidence intervals): 1.843 (1.149-2.955), 1.828 (1.165-2.867), 2.212 (1.396-3.507), all p < 0.05]. Moreover, adding LDL-TG into the original model increased the C-statistic from 0.687 to 0.704 (∆C-statistic = 0.016, p = 0.028) and from 0.734 to 0.749 (∆C-statistic = 0.014, p = 0.002) in Pre-DM and DM, respectively.ConclusionsIn this longitudinal cohort study on real-world practice, higher LDL-TG was associated with worse outcomes among Pre-DM and DM patients with stable CAD.
| S-EPMC7520976 | biostudies-literature
Project description:Background Elevated lipoprotein(a) [Lp(a)] and fibrinogen (Fib) are both associated with coronary artery disease (CAD). The atherogenicity of Lp(a) can be partly due to the potentially antifibrinolytic categories. We hypothesize that patients with higher Lp(a) and Fib may have worse outcomes. Methods In this prospective study, we consecutively enrolled 8,417 Chinese patients with stable CAD from March 2011 to March 2017. All subjects were divided into 9 groups according to Lp(a) (Lp(a)-Low, Lp(a)-Medium, Lp(a)-High) and Fib levels (Fib-Low, Fib-Medium, Fib-High) and followed up for CVEs, including nonfatal acute myocardial infarction, stroke, and cardiovascular mortality. Kaplan–Meier, Cox regression and C-statistic analyses were performed. Results During a median of 37.1 months’ follow-up, 395 (4.7%) CVEs occurred. The occurrence of CVEs increased by Lp(a) (3.5 vs. 5.3 vs. 5.6%, p?=?0.001) and Fib (4.0 vs. 4.4 vs. 6.1%, p?<?0.001) categories. When further classified into 9 groups by Lp(a) and Fib levels, the CVEs were highest in the 9th (Lp(a)-High and Fib-High) compared with the 1st (Lp(a)-Low and Fib-Low) group (7.2 vs. 3.3%, p?<?0.001). The highest risk of subsequent CVEs was found in the 9th group (HRadjusted 2.656, 95% CI 1.628–4.333, p?<?0.001), which was more significant than Lp(a)-High (HRadjusted 1.786, 95% CI 1.315–2.426, p?<?0.001) or Fib-High (HRadjusted 1.558, 95% CI 1.162–2.089, p?=?0.003) group. Moreover, adding the combined Lp(a) and Fib increased the C-statistic by 0.013. Conclusion Combining Fib and Lp(a) enhance the prognostic value for incident CVEs beyond Lp(a) or Fib alone.
| S-EPMC7528376 | biostudies-literature
Project description:BackgroundElevated lipoprotein (a) is recognized as a risk factor for incident cardiovascular events in the general population and established cardiovascular disease patients. However, there are conflicting findings on the prognostic utility of elevated lipoprotein (a) level in patients with coronary artery disease (CAD).Thus, we performed a meta-analysis to evaluate the prognostic value of elevated lipoprotein (a) level in CAD patients.Methods and resultsA systematic literature search of PubMed and Embase databases was conducted until April 16, 2019. Observational studies reporting the prognostic value of elevated lipoprotein (a) level for cardiac events (cardiac death and acute coronary syndrome), cardiovascular events (death, stroke, acute coronary syndrome or coronary revascularisation), cardiovascular death, and all-cause mortality in CAD patients were included. Pooled multivariable adjusted risk ratio (RR) and 95% confidence interval (CI) for the highest vs. the lowest lipoprotein (a) level were utilized to calculate the prognostic value. Seventeen studies enrolling 283,328 patients were identified. Meta-analysis indicated that elevated lipoprotein (a) level was independently associated with an increased risk of cardiac events (RR 1.78; 95% CI 1.31-2.42) and cardiovascular events (RR 1.29; 95% CI 1.17-1.42) in CAD patients. However, elevated lipoprotein (a) level was not significantly associated with an increased risk of cardiovascular mortality (RR 1.43; 95% CI 0.94-2.18) and all-cause mortality (RR 1.35; 95% CI 0.93-1.95).ConclusionsElevated lipoprotein (a) level is an independent predictor of cardiac and cardiovascular events in CAD patients. Measurement of lipoprotein (a) level has potential to improve the risk stratification among patients with CAD.
| S-EPMC6615167 | biostudies-literature
Project description:Coronary artery disease (CAD) and myocardial infarction (MI) are recognized as leading causes of mortality in developed countries. Although typically associated with behavioral risk factors, such as smoking, sedentary lifestyle, and poor dietary habits, such vascular phenotypes have also long been recognized as being related to genetic background. We review the currently available data concerning genetic markers for CAD in English and non-English articles with English abstracts published between 2003 and 2018. As genetic testing is increasingly available, it may be possible to identify adequate genetic markers representing the risk profile and to use them in a clinical setting.
| S-EPMC6122104 | biostudies-literature
Project description:BACKGROUND:The role of triglyceride (TG) in secondary prevention of patients with coronary artery disease (CAD) was debated. In the present study, we assessed the association between admission TG levels and long-term mortality risk in CAD patients. METHODS:A retrospective analysis was conducted from a single registered database. 3061 consecutive patients with CAD confirmed by coronary angiography were enrolled and were grouped into 3 categories by the tertiles of admission serum TG levels. The primary end point in this study was all-cause mortality and the secondary end point was cardiovascular mortality. RESULTS:The mean follow-up time was 26.9?±?13.6?months and death events occurred in 258 cases and cardiovascular death events occurred in 146 cases. Cumulative survival curves indicated that the risk of all-cause death decreased with increasing TG level (Tertile 1 vs. Tertile 2 vs. Tertile 3?=?10.3% vs. 8.6% vs. 6.3%, log rank test for overall p?=?0.001). Cox regression analysis showed an independent correlation between TG level and risk of all-cause mortality [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.86] and cardiovascular mortality (HR 0.67, 95% CI 0.51-0.89) in total patients with CAD. Subgroup analysis found the similar results in patients with acute coronary syndrome and acute myocardial infarction. CONCLUSIONS:This study found an inverse association between TG levels and mortality risk in CAD patients, which suggests that the "TG paradox" may exist in CAD patients. TRIAL REGISTRATION:ChiCTR, ChiCTR-OOC-17010433 . Registered 17 February 2017 - Retrospectively registered.
| S-EPMC6343235 | biostudies-other
Project description:BackgroundElevated triglyceride-rich lipoprotein (TRL) and small-dense low-density lipoprotein (sdLDL) particles are hallmarks of atherogenic dyslipidemia, and their cholesterol content is hypothesized to drive atherosclerotic risk. Prospective epidemiological data pertaining to cholesterol content of TRLs and sdLDL in primary prevention populations are mostly limited to coronary heart disease.ObjectivesThe purpose of this study was to prospectively evaluate whether triglyceride-rich lipoprotein cholesterol (TRL-C) and small-dense low-density lipoprotein cholesterol (sdLDL-C) concentrations associate with composite and individual incident cardiovascular disease (CVD) outcomes including myocardial infarction (MI), ischemic stroke (IS), and peripheral artery disease (PAD).MethodsIn a prospective case-cohort study within the Women's Health Study, TRL-C and sdLDL-C (mg/dl) were directly measured in baseline blood specimens of case subjects (n = 480) and the reference subcohort (n = 496). Risk associations were evaluated for total CVD (MI, IS, PAD, and CVD death), coronary and cerebrovascular disease (MI, IS, CVD death), and individual outcomes (MI, IS, and PAD). Models were adjusted for traditional risk factors, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein.ResultsThe risk of both composite outcomes significantly increased across quartiles of TRL-C and sdLDL-C. TRL-C was significantly associated with MI and PAD (MI hazard ratio [HR]Q4: 3.05 [95% confidence interval (CI): 1.46 to 6.39]; ptrend = 0.002; PAD HRQ4: 2.58 [95% CI: 1.18 to 5.63]; ptrend = 0.019), whereas sdLDL-C was significantly associated with MI alone (HRQ4: 3.71 [95% CI: 1.59 to 8.63]; ptrend < 0.001). Both markers weakly associated with IS. Association patterns were similar for continuous exposures and, for TRL-C, among subjects with low atherogenic particle concentrations (apolipoprotein B <100 mg/dl).ConclusionsTRL-C strongly associates with future MI and PAD events, whereas sdLDL-C strongly associates with MI alone. These findings signal that the cholesterol content of TRLs and sdLDL influence atherogenesis independently of low-density lipoprotein cholesterol, and high sensitivity C-reactive protein, with potentially different potency across vascular beds. (Women's Health Study; NCT00000479).
| S-EPMC8064770 | biostudies-literature
Project description:Background and Aims: Inflammasome-mediated caspase-1 activity regulates the maturation and release of the pro-inflammatory cytokines interleukin (IL)-1M-CM-^_ and IL-18. Recently, we showed that caspase-1 deficiency strongly reduces high fat diet-induced adiposity although the mechanism is still unclear. We now aimed to elucidate the mechanism by which caspase-1 deficiency reduces modulates resistance to high fat diet-feeding fat accumulation in adipose tissue by focusing on the role of caspase-1 in the regulation of triglyceride (TG)-rich lipoprotein metabolism. Methods: Caspase-1 deficient and wild-type mice (both C57Bl/6 background) were used to determine postprandial TG kinetics, intestinal TG absorption, VLDL-TG production as well as TG clearance, all of which strongly contribute to the supply of TG for storage in adipose tissue. Micro-array and qPCR analysis were used to unravel intestinal and hepatic metabolic pathways involved. Results: Caspase-1 deficiency reduced the postprandial response to an oral lipid load, while tissue specific clearance of TG-rich lipoproteins was not changed. Indeed, an oral olive oil gavage containing [3H]TG revealed that caspase-1 deficiency significantly decreased intestinal chylomicron-TG production and reduced the uptake of [3H]TG-derived FA by liver, muscle, and adipose tissue. Similarly, caspase-1 deficiency reduced the hepatic VLDL-TG production without reducing VLDL-apoB production, despite an elevated hepatic TG content. Pathway analysis revealed that caspase-1 deficiency reduces intestinal and hepatic expression of genes involved in lipogenesis. Conclusions: Absence of caspase-1 reduces assembly and secretion of TG-rich lipoproteins, thereby reducing the availability of TG-derived FA for uptake by peripheral organs including adipose tissue. We anticipate that caspase-1 represents a novel link between innate immunity and lipid metabolism. Keywords: Expression profiling by array Wild-type (WT) and Casp1-null mice were maintained at lab chow. Animals, aged between 14 and 16 weeks (n=3 per genotype), were killed and liver and intestinal segments were removed. Livers were isolated from mice that were fasted over night, whereas intesines were removed from mice 2 hrs after they received an oral lipid load.Total RNA was isolated and subjected to gene expression profiling.
2013-09-15 | E-GEOD-32515 | biostudies-arrayexpress
Project description:Background and Aims: Inflammasome-mediated caspase-1 activity regulates the maturation and release of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-18. Recently, we showed that caspase-1 deficiency strongly reduces high fat diet-induced adiposity although the mechanism is still unclear. We now aimed to elucidate the mechanism by which caspase-1 deficiency reduces modulates resistance to high fat diet-feeding fat accumulation in adipose tissue by focusing on the role of caspase-1 in the regulation of triglyceride (TG)-rich lipoprotein metabolism. Methods: Caspase-1 deficient and wild-type mice (both C57Bl/6 background) were used to determine postprandial TG kinetics, intestinal TG absorption, VLDL-TG production as well as TG clearance, all of which strongly contribute to the supply of TG for storage in adipose tissue. Micro-array and qPCR analysis were used to unravel intestinal and hepatic metabolic pathways involved. Results: Caspase-1 deficiency reduced the postprandial response to an oral lipid load, while tissue specific clearance of TG-rich lipoproteins was not changed. Indeed, an oral olive oil gavage containing [3H]TG revealed that caspase-1 deficiency significantly decreased intestinal chylomicron-TG production and reduced the uptake of [3H]TG-derived FA by liver, muscle, and adipose tissue. Similarly, caspase-1 deficiency reduced the hepatic VLDL-TG production without reducing VLDL-apoB production, despite an elevated hepatic TG content. Pathway analysis revealed that caspase-1 deficiency reduces intestinal and hepatic expression of genes involved in lipogenesis. Conclusions: Absence of caspase-1 reduces assembly and secretion of TG-rich lipoproteins, thereby reducing the availability of TG-derived FA for uptake by peripheral organs including adipose tissue. We anticipate that caspase-1 represents a novel link between innate immunity and lipid metabolism. Keywords: Expression profiling by array
2013-09-15 | GSE32515 | GEO
Project description:Coronary artery disease (CAD) and the frequently coexisting aortic valve stenosis (AS) are the heart diseases accounting for the highest proportion of cardiac surgeries. Routine biomarkers for an earl detection of either of these atherosclerotic-rooted conditions would be important to anticipate the diagnosis and to evaluate their severity with imaging techniques before they become advanced to the point where intervention or surgery have limited therapeutic benefit. Urine is an attractive biofluid for biomarker assessment, provided the noninvasive nature of its collection. Therefore, we conducted a shotgun proteomics analysis of urine collected from 12 CAD and/or AS patients and 11 cardiovascular disease-free controls, aiming at identification of putative molecular candidates that could differentiate these diseases from healthy subjects
2022-12-18 | PXD036800 | Pride
Project description:ObjectiveIncreasing evidence emphasizes the implications of dysregulated apoptosis and autophagy cellular processes in coronary artery disease (CAD). Herein, we aimed to explore apoptosis- and autophagy-related long noncoding RNAs (lncRNAs) in peripheral blood of CAD patients.MethodsThe mRNA and lncRNA expression profiles were retrieved from the Gene Expression Omnibus (GEO) database. With ∣fold change | >1.5 and adjusted p value < 0.05, differentially expressed apoptosis- and autophagy-related mRNAs were screened between CAD and healthy blood samples. Also, differentially expressed lncRNAs were identified for CAD. Using the psych package, apoptosis- and autophagy-related lncRNAs were defined with Spearson's correlation analysis. Receiver operating characteristic (ROC) curves were conducted for the assessment of the diagnosed efficacy of these apoptosis- and autophagy-related lncRNAs.ResultsOur results showed that 24 apoptosis- and autophagy-related mRNAs were abnormally expressed in CAD than normal controls. 12 circulating upregulated and 1 downregulated apoptosis- and autophagy-related lncRNAs were identified for CAD. The ROCs confirmed that AC004485.3 (AUC = 0.899), AC004920.3 (AUC = 0.93), AJ006998.2 (AUC = 0.776), H19 (AUC = 0.943), RP5-902P8.10 (AUC = 0.956), RP5-1114G22.2 (AUC = 0.883), RP11-247A12.1 (AUC = 0.885), RP11-288L9.4 (AUC = 0.928), RP11-344B5.2 (AUC = 0.858), RP11-452C8.1 (AUC = 0.929), RP11-565A3.1 (AUC = 0.893), and XXbac-B33L19.4 (AUC = 0.932) exhibited good performance in differentiating CAD from healthy controls.ConclusionCollectively, our findings proposed that circulating apoptosis- and autophagy-related lncRNAs could become underlying diagnostic markers for CAD in clinical practice.
| S-EPMC8426068 | biostudies-literature