ETD

• acute coronary syndrome
• atherosclerosis
• cardiometabolic phenotyping
• cardiovascular risk
• epicardial adipose tissue
• inflammation
• myocardial infarction
• oral glucose tolerance test
• prognostic stratification

Background: Dysglycemia is highly prevalent among patients with acute coronary syndrome (ACS) and is associated with adverse cardiovascular outcomes. However, conventional diabetes screening based on fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) frequently fails to identify a substantial proportion of patients with impaired glucose regulation. Oral glucose tolerance testing (OGTT) represents the most sensitive method for detecting abnormalities in post-challenge glucose metabolism, but its incremental value for cardiometabolic phenotyping and prognostic stratification after myocardial infarction remains incompletely defined.
Objectives: This study aimed to evaluate the additional diagnostic and prognostic value of systematic OGTT beyond standard diabetes screening in patients hospitalized for ACS. Furthermore, we sought to characterize the cardiometabolic profile associated with OGTT-defined metabolic phenotypes through a comprehensive multiparametric assessment including epicardial adipose tissue (EAT), inflammatory biomarkers, markers of myocardial stress, and indices of systemic atherosclerotic burden.
Methods: In this prospective single-center study, 306 consecutive patients admitted for ACS underwent metabolic screening including FPG, HbA1c, and a 75-g OGTT before hospital discharge. Patients were classified as normoglycaemic, prediabetic, or diabetic according to comprehensive metabolic phenotyping. Clinical characteristics, laboratory biomarkers, ankle–brachial index (ABI), coronary angiographic findings, and echocardiographic assessment of EAT were collected. Patients were prospectively followed for the occurrence of all-cause death, heart failure hospitalization, recurrent ACS, and elective coronary revascularization.
Results: The median age of the study population was 67 years (IQR 58–75 years), and 19.0% were female. Using conventional screening based on FPG and HbA1c, 18.6% of patients were classified as normoglycemic, 42.5% as prediabetic, and 38.9% as diabetic. Following OGTT implementation, diabetes prevalence increased markedly to 54.2%, while normoglycemia decreased to 10.8%. Overall, OGTT led to metabolic reclassification in 19.6% of the cohort and identified 47 additional patients (15.4% of the overall population) with previously unrecognized diabetes mellitus. Worsening metabolic phenotype was associated with progressively older age, a higher prevalence of hypertension, chronic kidney disease, and previous coronary artery disease. Dysglycemic patients exhibited a more adverse biological profile characterized by higher NT-proBNP and C-reactive protein levels, lower hemoglobin concentrations, and reduced estimated glomerular filtration rate. Epicardial fat thickness progressively increased across metabolic categories, ranging from 5.4 mm in normoglycemic individuals to 7.5 mm in diabetic patients (p=0.001), whereas minimum ABI progressively decreased from 1.22 to 1.13 (p=0.003). Similarly, multivessel coronary artery disease became increasingly prevalent across worsening metabolic phenotypes (36.4%, 46.7%, and 58.2%, respectively; p=0.031). During a median follow-up of 386 days (IQR 321–736 days), the incidence of the primary composite endpoint progressively increased from normoglycemia to prediabetes and diabetes (6.1%, 15.9%, and 19.3%, respectively; log-rank p=0.0108). No deaths or heart failure hospitalizations occurred among normoglycemic patients. All-cause mortality increased from 0% in normoglycemia to 5.0% in prediabetes and 8.1% in diabetes (log-rank p=0.042), while heart failure hospitalization occurred exclusively among dysglycemic individuals (0%, 5.0%, and 10.3%, respectively; log-rank p=0.022). In adjusted Cox regression analyses, diabetes was associated with an almost fourfold higher risk of adverse outcomes (HR 3.90, 95% CI 0.89–17.09). Among patients without previously known diabetes, HbA1c showed only moderate diagnostic accuracy for detecting OGTT-defined diabetes (AUC 0.71, 95% CI 0.62–0.80). The conventional diagnostic threshold of 6.5% demonstrated excellent specificity (98.1%) but very poor sensitivity (12.8%).
Conclusions: Systematic implementation of OGTT after ACS substantially improves the detection of previously unrecognized dysglycemia and results in clinically meaningful metabolic reclassification. Beyond its diagnostic role, OGTT identifies a progressive cardiometabolic risk continuum characterized by increased inflammatory burden, greater epicardial adiposity, more extensive coronary and peripheral atherosclerotic disease, and worse long-term clinical outcomes. These findings support the use of OGTT not only as a diagnostic tool but also as an instrument for comprehensive cardiometabolic phenotyping and prognostic stratification following myocardial infarction.