Prevalence of triglyceride deposit cardiomyovasculopathy among patients with acute coronary syndrome
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PROVIDER: S-EPMC10927025 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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| S-EPMC10067465 | biostudies-literature
Project description:Triglyceride deposit cardiomyovasculopathy (TGCV) is a newly identified disease that was discovered in individuals who required cardiac transplantation in Japan in 2008. Defective intracellular lipolysis causes triglyceride (TG) accumulation in the myocardium and coronary artery vascular smooth muscle cells, which results in severe heart failure and coronary artery disease with poor prognosis. A known cause of TGCV is a genetic deficiency of adipose triglyceride lipase (ATGL), a rate-limiting enzyme in the intracellular hydrolysis of TG. TGCV is classified into primary TGCV with ATGL mutations and idiopathic TGCV without ATGL mutations. Since its discovery, the Japan TGCV Study Group has attempted to elucidate its pathophysiology, develop diagnostic procedures, and specific treatment. Myocardial scintigraphy with iodine-123-β-methyl iodophenyl-pentadecanoic acid (123I-BMIPP) is a unique imaging modality for evaluating myocardial lipolysis in vivo. The washout rate of 123I-BMIPP is an essential indicator for the diagnosis of TGCV. Along with our efforts to provide awareness of and insights into this disease concept, we found that the cumulative number of clinically diagnosed patients has reached >200 and the cases are distributed throughout Japan. In addition, we successfully completed three investigator-initiated clinical trials of a potential therapeutic agent (CNT-01) for TGCV, which was assigned by the Ministry of Health, Labour, and Welfare, Japan, under the SAKIGAKE Designation System in June 2020. Here, we provide the Diagnostic Criteria 2020 for TGCV in order to further promote this "rare and intractable disease" project.
| S-EPMC10133930 | biostudies-literature
Project description: Not available
| S-EPMC7414388 | biostudies-literature
Project description:BackgroundTriglyceride deposit cardiomyovasculopathy (TGCV) is a rare disease, characterized by the massive accumulation of triglyceride (TG) in multiple tissues, especially skeletal muscle, heart muscle and the coronary artery. TGCV is caused by mutation of adipose triglyceride lipase, which is an essential molecule for the hydrolysis of TG. TGCV is at high risk for skeletal myopathy and heart dysfunction, and therefore premature death. Development of therapeutic methods for TGCV is highly desirable. This study aims to discover specific molecules responsible for TGCV pathogenesis.MethodsTo identify differentially expressed proteins in TGCV patient cells, the stable isotope labeling with amino acids in cell culture (SILAC) method coupled with LC-MS/MS was performed using skin fibroblast cells derived from two TGCV patients and three healthy volunteers. Altered protein expression in TGCV cells was confirmed using the selected reaction monitoring (SRM) method. Microarray-based transcriptome analysis was simultaneously performed to identify changes in gene expression in TGCV cells.ResultsUsing SILAC proteomics, 4033 proteins were quantified, 53 of which showed significantly altered expression in both TGCV patient cells. Twenty altered proteins were chosen and confirmed using SRM. SRM analysis successfully quantified 14 proteins, 13 of which showed the same trend as SILAC proteomics. The altered protein expression data set was used in Ingenuity Pathway Analysis (IPA), and significant networks were identified. Several of these proteins have been previously implicated in lipid metabolism, while others represent new therapeutic targets or markers for TGCV. Microarray analysis quantified 20743 transcripts, and 252 genes showed significantly altered expression in both TGCV patient cells. Ten altered genes were chosen, 9 of which were successfully confirmed using quantitative RT-PCR. Biological networks of altered genes were analyzed using an IPA search.ConclusionsWe performed the SILAC- and SRM-based identification-through-confirmation study using skin fibroblast cells derived from TGCV patients, and first identified altered proteins specific for TGCV. Microarray analysis also identified changes in gene expression. The functional networks of the altered proteins and genes are discussed. Our findings will be exploited to elucidate the pathogenesis of TGCV and discover clinically relevant molecules for TGCV in the near future.
| S-EPMC3891998 | biostudies-literature
Project description:Primary triglyceride deposit cardiomyovasculopathy (P-TGCV), caused by a rare genetic mutation in PNPLA2 encoding adipose triglyceride lipase (ATGL), exhibits severe cardiomyocyte steatosis and heart failure. Here, we report the case of a 51-year-old man with P-TGCV homozygous for a novel PNPLA2 mutation (c.446C > G, P149R) in the catalytic domain of ATGL. Analyses of endomyocardial biopsy specimens and in vitro expression experiments showed mutant protein expression with conserved lipid binding, but reduced lipolytic activity, indicating mutation pathogenicity.
| S-EPMC9945797 | biostudies-literature
Project description:AimThe triglyceride-glucose (TyG) index has been shown to be an independent predictor for the progression and prognosis of coronary artery disease (CAD). Whether the TyG index predicts the severity of CAD in patients presenting with acute coronary syndrome (ACS) remains unknown.MethodsA total of 1,007 individuals presenting with ACS undergoing coronary angiography were stratified according to the tertiles of the TyG index and The Synergy Between Percutaneous Coronary Intervention (SYNTAX) score (SYNTAX score ≤ 22 versus SYNTAX score > 22). CAD complexity was determined by the SYNTAX score.ResultsAfter adjusting for multiple confounding factors, the TyG index was still an independent risk factor for mid/high SYNTAX scores (SYNTAX score > 22, OR 2.6452, 95% CI 1.9020-3.6786, P < 0.0001). Compared with the lowest tertile of the TyG (T1) group, the risk for a mid/high SYNTAX score in the T2 and T3 groups was 2.574-fold higher (OR, 2.574; 95% CI 1.610-4.112; P < 0.001) and 3.732-fold higher (OR, 3.732; 95% CI 2.330-5.975; P < 0.001), respectively. Furthermore, there was a dose‒response relationship between the TyG index and the risk of complicated CAD (SYNTAX score > 22; nonlinear P = 0.200). The risk for a mid/high SYNTAX score in the T2 and T3 groups was significantly higher in normoglycemia, prediabetes mellitus, and diabetes mellitus subgroups.ConclusionsA higher TyG index was associated with the presence of a higher coronary anatomical complexity (SYNTAX score > 22) in ACS patients, irrespective of diabetes mellitus status. The TyG index might serve as a noninvasive predictor of CAD complexity in ACS patients and could potentially influence the management and therapeutic approach.
| S-EPMC10010005 | biostudies-literature
Project description:This study investigated whether the triglyceride (TG) glucose (TyG) index at diagnosis could predict acute coronary syndrome (ACS) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The medical records of 152 AAV were reviewed. Clinical and laboratory data were collected. The TyG index was calculated by TyG index = Ln (fasting TG (mg/dL) × fasting glucose (mg/dL)/2). The cut-offs of Birmingham vasculitis activity score (BVAS) and the TyG were obtained by the receiver operator characteristic (ROC) curve and the highest tertile (9.011). The mean age was 57.2 years and 32.9% were male. AAV patients with a TyG index ≥ 9.011 exhibited a lower cumulative ACS-free survival rate than those with a TyG index < 9.011. However, a TyG index ≥ 9.011 was not independently associated with ACS in the multivariable Cox analysis. Meanwhile, there might be a close relationship for predicting ACS among the TyG index, metabolic syndrome (MetS), and BVAS. AAV patients with a TyG index ≥ 9.011 exhibited a higher risk for MetS than those with a TyG index < 9.011 (relative risk 2.833). AAV patients with BVAS ≥ 11.5 also exhibited a higher risk for ACS than those with BVAS < 11.5 (relative risk 10.225). Both AAV patients with MetS and those with BVAS ≥11.5 exhibited lower cumulative ACS-free survival rates than those without. The TyG index at AAV diagnosis could estimate the concurrent presence of MetS and predict the occurrence of ACS during follow-up along with high BVAS at diagnosis in patients with AAV.
| S-EPMC9221824 | biostudies-literature
Project description:BackgroundThe triglyceride-glucose (TyG) index, which is a reliable substitute indicator for insulin resistance, has been considered an independent risk factor for long-term outcomes in patients with cardiovascular disease. However, it remains unknown whether the TyG index is associated with poor prognosis in acute coronary syndrome (ACS) patients with prior coronary artery bypass grafting (CABG) undergoing percutaneous coronary intervention (PCI).MethodsA total of 1158 ACS patients with prior CABG undergoing PCI were retrospectively studied. The TyG index was calculated by ln[fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unplanned repeat revascularization.ResultsDuring a median of 42-month follow-up, 350 patients (30.2%) experienced at least one endpoint event. Based on the optimal cut-off value of the TyG index, patients were divided into the high TyG index group and the low TyG index group. Patients in the high TyG index group had higher risks of MACCE (35.3% vs. 25.3%, p < 0.001), major adverse cardiovascular events (MACE) (31.1% vs. 23.4%, p = 0.003), nonfatal stroke (4.2% vs. 1.9%, p = 0.022) and unplanned repeat revascularization (19.4% vs. 11.3%, p < 0.001) than those in the low TyG index group. Cox regression analysis demonstrated that there was an independent association between the TyG index and MACCE regardless of whether the TyG index was a continuous or categorical variable (HR 1.42, 95% CI 1.09-1.86, p = 0.009; HR 1.53, 95% CI 1.16-2.01, p = 0.003, respectively). Restricted cubic spline curve exhibited that the relationship between the TyG index and MACCE was linear (p for non-linear = 0.595, p for overall = 0.005). By incorporating the TyG index groups into baseline risk model, the accuracy of predicting MACCE was improved [AUC: baseline risk model, 0.618 vs. baseline risk model + TyG index groups, 0.636, p for comparison = 0.042].ConclusionsThe TyG index is independently associated with MACCE, suggesting that the TyG index may serve as a valid indicator for predicting poor prognosis in ACS patients with prior CABG undergoing PCI.
| S-EPMC10612342 | biostudies-literature
Project description:BackgroundThe prognostic value of triglyceride-glucose (TyG) has been well described in patients with coronary artery disease (CAD). Hyperhomocysteinemia (HHcy) promotes insulin resistance and has also been regarded as a potential risk factor for cardiovascular disease. However, the prognostic value of TyG in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and the interaction between TyG and HHcy remain unclear.MethodsA total of 1,734 ACS patients undergoing PCI were continuously enrolled between June 2016 and November 2017 at Beijing Anzhen Hospital. Patients were categorized into four groups based on HHcy status and the optimal cut-off value of TyG. The primary endpoint was major adverse cardiovascular events (MACE), a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unplanned repeat revascularization.ResultsOver a median follow-up of 927 days, 358 patients (20.6%) experienced MACE. The Kaplan-Meier curves showed significant differences in the cumulative incidence of MACE among prespecified groups (p < 0.001). Multivariable Cox regression analysis revealed that higher TyG was significantly associated with an increased risk of MACE in patients without HHcy (HR: 2.36, 95% CI: 1.53-3.64, p < 0.001), but not in patients with HHcy (HR: 1.31, 95% CI: 0.60-2.87, p = 0.503). Restricted cubic splines only demonstrated the prognostic value of TyG in patients without HHcy. A significant interaction was observed for MACE between TyG and HHcy (p for interaction = 0.01).ConclusionsThe prognostic value of TyG was modified by HHcy in ACS patients undergoing PCI. Higher TyG was only associated with an increased risk of MACE in ACS patients without HHcy, but not in ACS patients with HHcy.
| S-EPMC11757877 | biostudies-literature
Project description:The incidence and impact of malnutrition on acute coronary syndrome (ACS) remain unclear. This study aimed to evaluate the prevalence, clinical relevance, and prognostic outcomes of malnutrition in patients with ACS treated with percutaneous coronary intervention. This retrospective study included 1930 consecutive patients with ACS undergoing percutaneous coronary intervention and assessed their nutritional status using 3 scoring systems: Controlling Nutritional Status score, nutritional risk index (NRI), and prognostic nutritional index (PNI). The primary endpoint was all-cause mortality. The Controlling Nutritional Status, NRI, and PNI scores showed that 5.2%, 17.5%, and 3.9% of patients were moderately or severely malnourished, respectively. During a median follow-up of 67.2 months (interquartile range: 46.8-88.5 months), 74 (3.8%) patients died. Malnutrition was associated with a significantly increased risk for all-cause mortality compared with good nutrition (adjusted hazard ratios for moderate and severe malnutrition, respectively: 5.65 [95% confidence interval: 3.27-9.78] and 15.26 [7.50-31.05] for the NRI score, 5.53 [2.10-14.49] and 11.08 [5.69-21.59] for the PNI; P < .001). The current findings demonstrated that malnutrition is prevalent among patients with ACS and is closely associated with increased mortality. Further study is needed to evaluate the effects of nutritional interventions on the outcomes of patients with ACS.
| S-EPMC9410591 | biostudies-literature