Oxidized Lipoproteins as Independent Predictors of Major Adverse Cardiovascular Events in Type 2 Diabetes Mellitus with Coronary Heart Disease: A Multicenter Prospective Cohort Study.

BackgroundHigh-sensitivity troponin I (hs-Tnl) and B-type natriuretic peptide (BNP) are promising prognostic markers for coronary artery disease (CAD). This prospective cohort study investigated whether a combination of these cardiac biomarkers with conventional risk factors would add incremental value for the prediction of secondary major adverse cardiovascular events (MACEs) in patients with CAD, with and without type 2 diabetes mellitus (T2DM).MethodsBaseline plasma level of hs-Tnl and BNP was measured in 2275 Chinese patients with stable CAD. Patients were monitored for new-onset of MACE over a median of 51 months. Cox proportional hazard model and area under the receiver operating characteristic curve (AUC) were used to assess the association of cardiac biomarkers with MACE and their predictive values in relationship with or without T2DM.ResultsDuring the follow up period 402 (18%) patients experienced a new-onset MACE with hs-Tnl and BNP level significantly higher than in those without MACE. In multivariable analyses, patients with elevated hs-Tnl (hazard ratio, 1.75 [95% CI 1.41–2.17]; P < 0.001) and BNP (hazard ratio, 1.42 [95% CI 1.15–1.75]; P = 0.001) were significantly associated with an increased risk of MACE after adjustment for variables of a risk factor model of age, sex, T2DM and hypertension. The risk factor model had an AUC of 0.64 for MACE prediction. The AUC significantly increased to 0.68 by the addition of hs-Tnl to the risk factor model. Subgroup analyses showed that hs-Tnl and BNP remained significant predictors of MACE in both patients with and without T2DM in multivariable models with higher risk of MACE evident in those without T2DM. Among patients without T2DM, addition of each biomarker yielded greater predictive accuracy than in T2DM patients, with AUC further increased to 0.75 when a combination of hs-Tnl and BNP was added to the risk factor model (age, sex and hypertension).ConclusionsElevated hs-Tnl and BNP level are independent predictors of new-onset MACE in CAD patients, irrespective of diabetes status. Among CAD patients without T2DM, a combination of cardiac biomarkers hs-Tnl and BNP yield the greatest predictive value beyond conventional risk factors.

BackgroundThe purpose of this study was to explore the incremental predictive value of liver fat fraction (LFF) in forecasting major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM).MethodsWe prospectively enrolled 265 patients with T2DM who presented to our hospital with symptoms of chest distress and pain suggestive of coronary artery disease (CAD) between August 2021 and August 2022. All participants underwent both coronary computed tomography angiography (CCTA) and upper abdominal dual-layer spectral detector computed tomography (SDCT) examinations within a 7-day interval. Detailed clinical data, CCTA imaging features, and LFF determined by SDCT multi-material decomposition algorithm were meticulously recorded. MACE was defined as the occurrence of cardiac death, acute coronary syndrome (ACS), late-phase coronary revascularization procedures, and hospital admissions due to heart failure.ResultsAmong 265 patients (41% male), 51 cases of MACE were documented during a median follow-up of 30 months. The LFF in T2DM patients who experienced MACE was notably higher compared to those without MACE (p < 0.001). The LFF was divided into tertiles using the cutoffs of 4.10 and 8.30. Kaplan-Meier analysis indicated that patients with higher LFF were more likely to develop MACE, regardless of different subgroups in framingham risk score (FRS) or coronary artery calcium score (CACS). The multivariate Cox regression results indicated that, compared with patients in the lowest tertile, those in the second tertile (hazard ratio [HR] = 3.161, 95% confidence interval [CI] 1.163–8.593, P = 0.024) and third tertile (HR = 4.372, 95% CI 1.591–12.014, P = 0.004) had a significantly higher risk of MACE in patients with T2DM. Even after adjusting for early revascularization, both LFF tertile and CACS remained independently associated with MACE. Moreover, compared with the traditional FRS model, the model that included LFF, CACS, and FRS showed stable clinical net benefit and demonstrated better predictive performance, with a C-index of 0.725, a net reclassification improvement (NRI) of 0.397 (95% CI 0.187–0.528, P < 0.01), and an integrated discrimination improvement (IDI) of 0.100 (95% CI 0.043–0.190, P < 0.01).ConclusionsThe elevated LFF emerged as an independent prognostic factor for MACE in patients with T2DM. Incorporating LFF with FRS and CACS provided incremental predictive power for MACE in patients with T2DM.Graphical abstractResearch insightsWhat is currently known about this topic?T2DM is associated with increased MACE rates, underscoring the need for improved risk prediction. CACS is a well-established tool for MACE risk assessment but may not capture all risk factors. Hepatic steatosis is a common comorbidity in metabolic syndrome and T2DM.What is the key research question?Does the incorporation of LFF derived from SDCT into existing risk prediction models enhance the accuracy of MACE forecasting in patients with T2DM?What is new?SDCT-LFF measurement introduces a more accurate method for assessing hepatic steatosis. LFF as an independent predictor of MACE in T2DM patients is a novel finding. The study presents LFF as an additional tool for risk stratification, complementing FRS and CACS.How might this study influence clinical practice?Study findings may guide personalized prevention for T2DM patients at higher MACE risk.

Cardiovascular diseases are a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Acute kidney injury (AKI) has been increasingly recognized as a potential exacerbating factor for cardiovascular events in these patients. The CKD-REIN study aims to explore the relationship between AKI and the risk of major adverse cardiovascular events (MACE) in a cohort of CKD patients. We hypothesize that AKI is a significant and independent predictor of MACE in patients with CKD, and that the severity of AKI correlates with the risk of subsequent cardiovascular events. This prospective cohort study included 3033 adult CKD patients from 40 outpatient nephrology clinics in France. Patients were followed for a median of 5.2 years. AKI episodes were identified and staged based on the KDIGO-AKI criteria. Cardiovascular events, including myocardial infarction, stroke, heart failure hospitalization, and cardiovascular death, were systematically recorded. The association between AKI and MACE was analyzed using a multivariable Cox model, adjusting for confounders such as demographic characteristics, medical history, and baseline kidney function. During the follow-up, 530 patients experienced at least one episode of AKI. The cumulative incidence of MACE at 1 year post-AKI was 8.1%. Patients with AKI had a significantly increased risk of MACE, with an adjusted hazard ratio (HR) of 5.78 (P<.001). The risk was consistent across different MACE components and was independent of age, sex, CKD stage, or comorbidities. The risk of MACE was higher for more severe AKI stages and for AKI events requiring hospitalization or associated with incomplete renal recovery. The findings of this study confirm that AKI is a significant independent predictor of MACE in CKD patients, demonstrating a strong severity-response relationship. These results underscore the importance of vigilant cardiovascular monitoring and preventive strategies in CKD patients following AKI episodes. Understanding the mechanisms linking AKI to cardiovascular outcomes is crucial for developing targeted interventions to mitigate these risks.

Bile acids play important roles in lipid metabolism and glucose homeostasis. Limited research exist on the association between serum total bile acid (TBA) levels and major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS), particularly those with comorbid type 2 diabetes mellitus (T2DM). This study was conducted to examine the relationship between baseline serum TBA level and T2DM status in patients with ACS after percutaneous coronary intervention (PCI) and to identify the predictive value of TBA levels for a 2-year risk of MACEs. 425 ACS patients underwent PCI were recruited and divided into three groups based on baseline serum TBA concentration. An analysis of the association between the T2DM status and baseline serum TBA levels was conducted using univariate linear regression and multivariate linear regression. The predictive relevance of serum TBA levels was evaluated using the receiver operating characteristic (ROC) curve and Cox regression. Kaplan–Meier curves were employed to analyze the differences among groups in predicting MACEs over a 2-year follow-up period. Baseline serum TBA levels were higher in ACS patients who were diagnosed with T2DM (the median 3.6 µmol/L) than those without T2DM (the median 3.0 µmol/L). T2DM status in ACS patients was positively correlated with baseline serum TBA concentrations (β: 1.7, 95% confidence interval [CI] 0.3–3.0), particularly in the male (β: 2.0, 95% CI 0.3–3.6) and 50–69-year-old (β: 2.5, 95% CI 0.6–4.4) populations. The areas under the ROC curve of baseline serum TBA levels predicted MACEs in ACS and ACS-T2DM patients following PCI were 0.649 (95% CI 0.595–0.703) and 0.783 (95% CI 0.685–0.881), respectively. Furthermore, Cox regression analysis showed that baseline serum TBA level was associated with the occurrence of MACEs in patients with ACS after PCI over a 2-year follow-up period, especially in those diagnosed with T2DM, whose baseline TBA concentration was lower than 10.0 µmol/L. ACS Patients with T2DM had higher serum TBA levels. TBA level at baseline was an independent predictor of MACEs in ACS patients who underwent PCI, especially with comorbid T2DM.

Association of free fatty acids with long-term adverse outcomes in patients with premature myocardial infarction: a prospective cohort study

Triglyceride-glucose (TyG) is a vital marker for assessing cardiovascular risk and insulin resistance (IR) in individuals with Type 2 diabetes mellitus (T2DM) or metabolic dysfunction-associated steatotic liver disease (MASLD). Nevertheless, the prognostic significance of TyG, especially in patients manifesting both conditions, is insufficiently characterized. In this study, the association between TyG and the occurrence of major adverse cardiovascular events (MACEs) in patients concurrently diagnosed with T2DM and MASLD was examined. In this retrospective cohort study, 1021 patients diagnosed with both T2DM and MASLD at Wenzhou Hospital from 2019 to 2022 were encompassed. To explore the non-linear association between TyG and outcomes, such as all-cause mortality (ACM) or MACEs, a cox proportional hazards model was employed. Additionally, subgroups were analyzed to assess the consistency across different demographic and clinical subgroups. Furthermore, mediation analyses were conducted to investigate the potential mediating effects of body roundness index (BRI) and estimated glomerular filtration rate (eGFR). Parallel supportive analysis was performed on a cohort of 1343 individuals from NHANES 1999-2018. Over a median follow-up of 53.4 months, 62 instances of ACM and 101 MACEs were documented. Cox proportional hazards regression analysis revealed that an elevated TyG was significantly associated with an increased risk of mortality (HR = 1.85, 95% CI: 1.25, 2.73) and MACEs (HR = 1.71, 95% CI: 1.26, 2.33). Subgroup analysis revealed that the association between TyG and the risk of MACE is more prominent among individuals below 60. Mediation analysis revealed that eGFR mediated 8.8% of the total effect of TyG on ACM and 10.6% of the effect on MACEs. BRI accounted for 6.2% of the total effect of TyG on ACM. Incorporating TyG into conventional risk models significantly enhanced the predictive accuracy. This study established a strong association between TyG and both ACM and MACEs in patients with T2DM and MASLD in the Wenzhou cohort, with TyG-ACM association independently validated in the NHANES cohort.

Impact of gene polymorphisms, platelet reactivity, and the SYNTAX score on 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention: the GEPRESS study.

BackgroundAlthough studies have shown that glycemic variability is positively associated with an increased risk of cardiovascular disease, few studies have compared hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) variability with adverse cardiovascular events in patients with type 2 diabetes mellitus (T2DM).MethodsThis was a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Cox proportional hazards models were used to explore the relationship between HbA1c or FPG variability and the incidence of major adverse cardiovascular events (MACEs).ResultsIn total, 9,547 patients with T2DM were enrolled in this study. During the median 4.6 ± 1.5 years follow-up period, 907 patients developed MACEs. The risk of MACEs increased in the HbA1c variability group in each higher quartile of HbA1c variability (P < 0.01). Compared with those in the first quartile of HbA1c variability, patients in the fourth quartile had a hazard ratio of 1.37 (Model 2, 95% confidence interval: 1.13–1.67) for MACEs. Higher FPG variability was not associated with a higher risk of MACEs in patients with T2DM (P for trend=0.28). A U-shaped relationship was observed between HbA1c and FPG variability, and MACEs. Glucose control therapy modified the relationship between HbA1c and MACEs; participants with higher HbA1c variability receiving intensive glucose control were more likely to develop MACEs (P for interaction <0.01).ConclusionIn adults with T2DM, the relationship between glycemic variability evaluated using HbA1c and FPG was U-shaped, and an increase in HbA1c variability rather than FPG variability was significantly associated with MACEs. The relationship between HbA1c variability and MACEs was affected by the glucose control strategy, and a higher HbA1c variability was more strongly associated with MACEs in patients receiving an intensive glucose control strategy.

PurposeTo prove that cystatin C is a predictor of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI), either with ST-segment Elevation (AMI-EST) or without ST-segment elevation (AMI-NEST), without cardiogenic shock or renal impairment.Patient and MethodsThis was an observational cohort study. Samples were obtained from AMI patients who underwent PCI between February 2022 and March 2022 at the Intensive Cardiovascular Care Unit. Cystatin C levels were measured before PCI. MACE were observed within 6 months. Comparisons between normally distributed continuous data were performed using the t-test; Mann–Whitney test was used for non-normally distributed data. Categorical data were compared using the chi-squared test. The cut-off point of cystatin C levels to predict MACE was analyzed using Receiver Operating Characteristics (ROC).ResultsThe participants were 40 AMI patients, consisting of 32 patients (80%) with AMI-EST and eight patients (20%) diagnosed with AMI-NEST, who were evaluated for the occurrence of MACE within 6 months after PCI. Ten patients (25%) developed MACE during follow-up [(MACE (+)], and the rest were in the MACE (-) group. Cystatin C levels were significantly higher in the MACE (+) group (p=0.021). ROC analysis revealed a cystatin C level of 1.21 mg/dL; cystatin C > 1.21 is associated with MACE risk, showing a significant relationship with the odds ratio value reaching 26.00, with 95% CI (3.99–169.24).ConclusionCystatin C level is an independent predictor of MACE in patients with AMI without cardiogenic shock or renal impairment after PCI.

Prognostic value of CMR-derived extracellular volume in myocardial infarction with non-obstructive coronary arteries.

Background:Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to reduce major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk. However, the efficacy of GLP-1 RAs on the outcomes of MACEs across different racial and sex groups among patients with and without T2DM remains underexplored. Thus, this study aimed to evaluate the association between GLP-1 RAs and MACEs in patients with and without T2DM based on race and sex.Methods:We conducted a systematic literature search on the PubMed and Scopus databases, as well as ClinicalTrials.gov, for relevant randomized controlled trials (RCTs) from inception to July 5, 2025. Trials were eligible for inclusion if the included adults (≥18 years) had been randomized to a GLP-1 RA versus placebo group, and MACEs were reported as an outcome. Trials combining GLP-1 RAs with other investigational glucose-lowering agents were excluded. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effect model, and a p-value of <0.05 was considered statistically significant.Results:Nine RCTs involving 81,266 patients were included in the analysis. The mean age of patients was 65 years. Compared with the placebo, GLP-1 RAs significantly reduced the risk of MACEs in males (RR, 0.82; 95% CI: 0.77–0.86; p < 0.001) and females (RR, 0.81; 95% CI: 0.75–0.88; p < 0.001). Meanwhile, across racial groups, GLP-1 RAs significantly reduced the risk of MACEs in Caucasian patients (RR, 0.87; 95% CI: 0.79–0.96; p < 0.001) compared with placebo. However, no significant difference was observed for the risk of MACEs in Black patients (RR, 1.05; 95% CI: 0.72–1.53; p = 0.80) when comparing GLP-1 RAs with placebo.Conclusion:This meta-analysis demonstrates that GLP-1 RAs significantly reduce the risk of MACEs in both males and females, as well as across various racial groups in patients with or without T2DM. However, the lack of significant benefit in Black patients suggests potential racial disparities in the enrollment and efficacy of GLP-1 RAs for cardiovascular outcomes.

Objectives: The objective of this study investigated the relation between QT-dispersion (QTd) and both number of coronary artery disease and major adverse cardiovascular events (MACEs) among patients with type 2 diabetes after elective percutaneous coronary intervention (PCI). Methods: One hundred ischemic heart disease patients undergoing elective coronary angioplasty were included; 49 patients with diabetes (group I) and 51 patients without diabetes mellitus (group II). Based on the QTd parameter after PCI, both groups were subdivided into tertiles. Angiographic, electrocardiographic parameters, and MACE were compared. Results: Both QTd after PCI and delta QTd were correlated to the number of diseased coronary arteries and MACE in patients with diabetes compared to patients without diabetes. QTd was longer in patients with diabetes developing MACE than those without MACE (r = −0.31, P = 0.04). Conclusion: QTd after PCI and delta QTd are the independent predictors of MACE in patients with type 2 diabetes.

Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot that plays an important role in coronary atherosclerosis. In this study, our aim was to investigate the relationship between long-term major adverse cardiovascular events (MACEs) and EAT volume detected by coronary computed tomography angiography (CCTA) in patients with Type 2 diabetes mellitus (T2-DM) without previous coronary events.A total of 127 patients with diabetes who underwent CCTA between 2012 and 2014 were enrolled retrospectively. The study population was divided into 2 groups according to whether they experienced or did not experience MACE, which was defined as cardiac death, non-fatal myocardial infarction or unstable angina requiring hospitalization, coronary revascularizations (percutaneous coronary intervention or coronary artery bypass grafting surgery), heart failure, peripheral arterial disease, or ischemic stroke. In both groups, EAT volumes were measured by CCTA.During 60±7 months follow-up period, 22 participants experienced MACEs. Data were evaluated with univariate and multivariate analyses and receiver operating characteristic (ROC) analysis. Age, male sex, coronary artery disease, hemoglobin A1c, glucose, creatinine, C- reactive protein, and cholesterol levels were found to be associated with MACE. EAT volume (odds ratio [OR]: 1.027; 95% confidence interval [CI]: 1.010‒1.044, p=0.002) and low-density lipoprotein (OR: 1.015; 95% CI: 1.000‒1.030, p=0.050) were found to be independent predictors for MACE. ROC analysis indicated that EAT volumes >123.2 mL had a 72.7% sensitivity and a 77.1% specificity for predicting long-term MACE in patients with T2-DM (area under the curve: 0.820; 95% CI: 0.733-0.908).EAT volume is an independent predictor of long-term MACE in patients with T2-DM without previous coronary events. EAT volume may be used additionally in risk stratification for MACE besides the well-known vascular risk factors in patients with T2-DM.

BackgroundHigh blood pressure is a major risk factor for cardiovascular disease. Visit-to-visit blood pressure variability (BPV) has recently been shown to predict cardiovascular outcomes. We investigated the predictive value of BPV for major adverse cardiovascular events (MACE) among patients with coronary artery disease (CAD), with and without type 2 diabetes mellitus (T2DM).MethodsPatients with stable CAD were enrolled and monitored for new MACE. Visit-to-visit BPV was defined as the coefficient of variation (CV) of systolic and diastolic BP across clinic visits. Multivariable logistic regression analysis was performed to evaluate the association of BPV with MACE. Area under the receiver operating characteristic curve (AUC) was used to assess its predictive ability.ResultsAmong 1140 Chinese patients with stable CAD, 192 (17%) experienced a new MACE. In multivariable analyses, the risk of MACE was significantly associated with CV of systolic BP (odds ratio [OR] for highest versus lowest quartile, 3.30; 95% CI 1.97–5.54), and diastolic BP (OR for highest versus lowest quartile, 2.39; 95% CI 1.39–4.11), after adjustment for variables of the risk factor model (age, gender, T2DM, hypertension, antihypertensive agents, number of BP measurements) and mean BP. The risk factor model had an AUC of 0.70 for prediction of MACE. Adding systolic/diastolic CV into the risk factor model with mean BP significantly increased the AUC to 0.73/0.72 (P = 0.002/0.007). In subgroup analyses, higher CV of systolic BP remained significantly associated with an increased risk for MACE in patients with and without T2DM, whereas the association of CV of diastolic BP with MACE was observed only in those without T2DM.ConclusionsVisit-to-visit variability of systolic BP and of diastolic BP was an independent predictor of new MACE and provided incremental prognostic value beyond mean BP and conventional risk factors in patients with stable CAD. The association of BPV in CAD patients without T2DM with subsequent risk for MACE was stronger than in those with T2DM.

BackgroundThe triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and is associated with major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). However, the long-term effect of the TyG index on the incidence of MACEs remains unclear. We aimed to investigate the association between the cumulative TyG index and the risk of MACEs in patients with T2DM.MethodsThis post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial assessed patients’ (T2DM > 3 months) cumulative TyG index and MACE data from the study database. Five fasting blood glucose and triglyceride measurements, at baseline and the first four visits, were taken from 5695 participants who had not experienced MACEs. Cumulative exposure to the TyG index was calculated as the weighted sum of the mean TyG index value for each time interval (value × time). Multivariable-adjusted Cox proportional hazard models and restricted cubic spline analysis were used to determine the association between the cumulative TyG index and MACEs. The incremental predictive value of the cumulative TyG index was further assessed.ResultsOver a median follow-up of 5.09 years, 673 (11.82%) MACEs occurred, including 256 (4.50%) cardiovascular disease (CVD) deaths, 288 (5.06%) non-fatal myocardial infarctions (MIs), and 197 (3.46%) strokes. The risk of developing MACEs increased with the cumulative TyG index quartile. After adjusting for multiple potential confounders, the hazard ratios for the very high cumulative TyG index group versus the low group were 1.59 (95% confidence interval [CI], 1.17–2.16), 1.97 (95% CI 1.19–3.26), and 1.66 (95% CI 1.02–2.70) for overall MACEs, CVD death, and non-fatal MI, respectively. Restricted cubic spline analysis also showed a cumulative increase in the risk of MACEs with an increase in the magnitude of the cumulative TyG index. The addition of the cumulative TyG index to a conventional risk model for MACEs improved the C-statistics, net reclassification improvement value, and integrated discrimination improvement value.ConclusionsIn patients with T2DM, the cumulative TyG index independently predicts the incidence of MACEs, and monitoring the long-term TyG index may assist with optimized-for-risk stratification and outcome prediction for MACEs.Trial registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000620.