Background Triglyceride glucose (TyG) index is considered a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular (CV) outcomes. However, the prognostic value of TyG index in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI) remains unclear. Methods A total of 1932 consecutive patients with T2DM and AMI were enrolled in this study. Patients were divided into tertiles according to their TyG index levels. The incidence of major adverse cardiac and cerebral events (MACCEs) was recorded. The TyG index was calculated as the ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. Results Competing risk regression revealed that the TyG index was positively associated with CV death [2.71(1.92 to 3.83), p < 0.001], non-fatal MI [2.02(1.32 to 3.11), p = 0.001], cardiac rehospitalization [2.42(1.81 to 3.24), p < 0.001], revascularization [2.41(1.63 to 3.55), p < 0.001] and composite MACCEs [2.32(1.92 to 2.80), p < 0.001]. The area under ROC curve of the TyG index for predicting the occurrence of MACCEs was 0.604 [(0.578 to 0.630), p < 0.001], with the cut-off value of 9.30. The addition of TyG index to a baseline risk model had an incremental effect on the predictive value for MACCEs [net reclassification improvement (NRI): 0.190 (0.094 to 0.337); integrated discrimination improvement (IDI): 0.027 (0.013 to 0.041); C-index: 0.685 (0.663 to 0.707), all p < 0.001]. Conclusions The TyG index was significantly associated with MACCEs, suggesting that the TyG index may be a valid marker for risk stratification and prognosis in patients with T2DM and AMI. Trial registration Retrospectively registered.

Background Triglyceride glucose (TyG) index is considered a new marker for metabolic disorders. Although recent studies have found an association between TyG index level and vascular disease development, the prognostic value of TyG index in patients with acute myocardial infarction (AMI) remains unclear. Methods A total of 3181 patients with AMI, who underwent coronary angiography, were identified from the Cardiovascular Center of Beijing Friendship Hospital Database Bank and included in the analysis. Patients were stratified into 2 groups according to their baseline TyG index levels: the TyG index <8.88 group and the TyG index ≥8.88 group. Clinical characteristics,biochemical parameters, and the incidence of major adverse cardiovascular events (MACEs) during a median of 33.3-month follow-up were recorded. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL) ×fasting plasma glucose (mg/dL)/2]. Results Compared with the TyG index<8.88 group, the TyG index≥8.88 group had significantly higher incidences of non-fatal MI, revascularization, cardiac rehospitalization and composite MACEs. Multivariable Cox regression models revealed that the TyG index was positively associated with all

To evaluate the prognostic value of triglyceride-glucose (TyG) index in nondiabetic patients with acute coronary syndrome (ACS) with low-density lipoprotein cholesterol (LDL-C) below 1.8 mmol/L. Methods: A total of 1655 nondiabetic patients with ACS with LDL-C below 1.8 mmol/L were included in the analysis. Patients were stratified into two groups. The incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, and major adverse cardiac and cerebral event during a median of 35.6-month follow-up were determined and compared between the two groups. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL) fasting plasma glucose (mg/dL)/2]. Results: Compared with the TyG index 8.33 group, the TyG index ≥ 8.33 group had a significantly higher incidence of AMI (21.2% vs. 15.2%, p 0.014) and larger infarct size in patients with AMI [the peak value of troponin I: 10.4 vs. 4.8 ng/ml, p 0.003; the peak value of Creatine kinase MB: 52.8 vs. 22.0 ng/ml, p 0.006; the peak value of myoglobin: 73.7 vs. 46.0 ng/ml, p 0.038]. Although there was no significant difference in mortality between the two groups, the incidence of revascularization of the TyG index ≥ 8.33 group was significantly higher than that of the TyG index 8.33 group (8.9% vs. 5.0%, p 0.035). A multivariable Cox regression revealed that the TyG index was positively associated with revascularization [hazard ratio, 1.67; 95% confidence interval, 1.02-2.75; p 0.043]. Conclusions:In nondiabetic patients with ACS with LDL-C below 1.8 mmol/L, a high TyG index level was associated with higher incidence of AMI, larger infarct size, and higher incidence of revascularization. A high TyG index level might be a valid predictor of subsequent revascularization.

Pregnancy-associated plasma protein A (PAPP-A) was previously reported to be an inflammatory biomarker and a prognostic marker of acute coronary syndrome (ACS) and involved in the process of atherosclerosis and plaque rupture. However, the role of PAPP-A in inflammation is poorly understood. In this study, we aimed to investigate the role of PAPP-A in macrophage activation and inflammatory cytokine production. RAW264.7 macrophages were treated with or without PAPP-A. Reverse-transcriptase quantitative real-time PCR (RT-qPCR) and Western blot were performed to detect gene and protein expressions. The concentration of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in culture supernatants was determined by ELISA. Results showed that PAPP-A significantly stimulated the expression of MCP-1, TNF-α, and IL-6 at both transcriptional and translational levels in a dose-dependent and time-dependent manner. The secretion of these inflammatory cytokines by macrophages was also increased after PAPP-A treatment. Moreover, PAPP-A activated the IGF-I/PI3K/Akt signaling pathway in macrophages. The PAPP-A-mediated upregulation of MCP-1, TNF-α, and IL-6 mRNA and protein levels were strongly inhibited by PI3K inhibitors or IGF-IR siRNA, indicating that the upregulation of MCP-1, TNF-α, and IL-6 could involve the IGF-I/PI3K/Akt pathway. Together, this study demonstrates that PAPP-A activates the macrophage signaling pathway (IGF-I/PI3K/Akt), which drives the expression and production of inflammatory cytokines known to contribute to the initiation and progression of ACS. These findings indicate that PAPP-A may play a proinflammatory role in the pathophysiology of ACS and serve as a potential therapeutic target.

The role of advanced glycation end products (AGEs) and its C-terminal truncated receptor (soluble receptor for advanced glycation end products, sRAGE) in ST-segment elevation myocardial infarction (STEMI) patients with or without diabetes is unknown. We compared their levels in patients with and without STEMI, as well as with and without diabetes. A prospective observational study was performed between December 2014 and December 2015. Study group included STEMI patients with coronary artery disease; control group included patients without coronary artery disease. Levels of AGEs and sRAGE were tested on Days 0, 2, and 5 after STEMI. Levels of creatine kinase-MB (CK-MB), cardiac troponin I, and N-terminal pro-brain natriuretic peptide (NT-proBNP) were tested on Days 0, 1, 2, and 3. Patient's diabetic status was determined by medical history or oral glucose tolerance test. Compared to patients in the control group, STEMI patients showed elevated levels of AGEs and sRAGE. In the STEMI group, diabetic patients had higher levels of AGEs and sRAGE compared to nondiabetic patients. The level of AGEs correlated with peak level of CK-MB in the overall population of patients with STEMI and with peak level of NT-proBNP in diabetic patients with STEMI. Levels of AGEs and sRAGE were elevated after STEMI, especially among patients with diabetes. These markers could serve to indicate the severity of myocardial injury and cardiac insufficiency, and play a potential role in predicting the prognosis of patients with STEMI.

Background: Current guidelines recommend angiotensin-converting-enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) as a first-line therapy in diabetic hypertensive patients and for secondary prevention in patients with obstructive coronary artery disease (OCAD). However, the effects of using ACEI/ARB before the initial diagnosis of OCAD on major adverse cardiac and cerebral event (MACCE) in diabetic hypertensive patients remain unclear. This study investigated whether using ACEI/ARB before the initial diagnosis of OCAD could be associated with improved clinical outcomes in diabetic hypertensive patients. Methods: A total of 2501 patients with hypertension and diabetes, who were first diagnosed with OCAD by coronary angiography, were included in the analysis. Of the 2501 patients, 1300 did not used ACEI/ARB before the initial diagnosis of OCAD [the ACEI/ARB(-) group]; 1201 did [the ACEI/ARB(+) group]. Propensity score matching at 1:1 was performed to select 1050 patients from each group. Incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, heart function, and subsequent MACCE during a median of 25.4-month follow-up were determined and compared between the 2 groups. Results: Compared with the ACEI/ARB(-) group, the ACEI/ARB(+) group had significantly lower incidence of AMI (22.5% vs. 28.4%, p < 0.05), smaller infarct size in patients with AMI (pTNI: 5.7 vs. 6.8 ng/ml, p < 0.05; pCKMB: 21.7 vs. 28.7 ng/ml, p < 0.05), better heart function (LVEF: 60.0 vs. 58.5%, p < 0.05), and lower incidences of non-fatal stroke (2.4% vs. 4.6%, p < 0.05) and composite MACCE (23.1% vs. 29.7%, p < 0.05). No prior ACEI/ARB therapy was significantly and independently associated with non-fatal stroke and composite MACCE. Conclusions: In diabetic hypertensive patients, treatment with ACEI/ARB before the initial diagnosis with OCAD was associated with decreased incidence of AMI, smaller infarct size, improved heart function, and lower incidences of non-fatal stroke and composite MACCE.

Background Triglyceride glucose (TyG) index is considered a new marker for metabolic disorders. Although recent studies have found an association between TyG index level and vascular disease development, the prognostic value of TyG index in patients with acute myocardial infarction (AMI) remains unclear. Methods A total of 3181 patients with AMI, who underwent coronary angiography, were identified from the Cardiovascular Center of Beijing Friendship Hospital Database Bank and included in the analysis. Patients were stratified into 2 groups according to their baseline TyG index levels: the TyG index <8.88 group and the TyG index ≥8.88 group. Clinical characteristics,biochemical parameters, and the incidence of major adverse cardiovascular events (MACEs) during a median of 33.3-month follow-up were recorded. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL) ×fasting plasma glucose (mg/dL)/2]. Results Compared with the TyG index<8.88 group, the TyG index≥8.88 group had significantly higher incidences of non-fatal MI, revascularization, cardiac rehospitalization and composite MACEs. Multivariable Cox regression models revealed that the TyG index was positively associated with all-cause death [HR (95% CI): 1.51 (1.10,2.06), P=0.010], cardiac death [HR (95%CI): 1.68 (1.19,2.38), P=0.004], revascularization [HR (95%CI): 1.50 (1.16,1.94), P=0.002], cardiac rehospitalization [HR (95%CI): 1.25 (1.05,1.49), P=0.012], and composite MACEs [HR (95%CI): 1.19 (1.01,1.41), P=0.046] in patients with AMI. The independent predictive effect of TyG index on all-cause death and cardiac death was mainly reflected in the subgroups of male gender, body mass index ≥25kg/m 2 , smoker, diabetes mellitus, estimated glomerular filtration rate (eGFR) ≥60ml/min/1.73m 2 , high-density lipoprotein cholesterol ≥1.01mmol/L and left ventricular ejection fraction (LVEF) ≥0.50. The results also revealed that diabetes mellitus, previous AMI, eGFR, LVEF, and multi-vessel/left main coronary artery lesions were independent predictors of MACEs in patients with AMI (all P<0.05). Conclusions High TyG index levels appeared to be associated with an increased risk of MACEs in patients with AMI. The TyG index might be a valid predictor of cardiovascular outcomes of patients with AMI.

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