The triglyceride-glucose index shows a stronger association with complex coronary artery disease than the ACEF score among young and middle-aged adults with aortic valve calcification

Background: Aortic valve calcification (AVC) is an active pathophysiological process that shares metabolic risk factors with coronary artery disease (CAD). However, whether AVC modifies the associations between metabolic or physiological risk indices and coronary anatomical complexity remains uncertain, particularly in younger populations. This study aimed to determine if AVC alters the relationships of the triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, and the ACEF score, an indicator of physiological reserve, with anatomically complex CAD, and to compare their predictive performance in young and middle-aged adults. Methods: This cross-sectional study enrolled 326 consecutive patients aged 18-65 years who underwent coronary angiography. For the primary analysis of coronary lesion complexity, 66 patients with prior revascularization history were excluded, yielding a final analytic cohort of 260 patients. Anatomically complex CAD was defined as a SYNTAX score ≥23. AVC status, determined by echocardiography, was evaluated as a potential modifier. Multivariable logistic regression models were used to assess the associations of the TyG index and ACEF score with complex CAD, followed by formal testing for interaction between each index and AVC status. When significant interactions were identified, stratified analyses were performed. The discriminatory performance was evaluated using receiver operating characteristic (ROC) curve analysis in the analytic cohort and within AVC-stratified subgroups, with formal comparison of area under the curve (AUC) values between subgroups. Results: for interaction = 0.002). In patients with AVC, the TyG index emerged as an independent predictor of complex CAD (adjusted OR 3.82, 95% CI 1.69-8.63; AUC = 0.714), whereas the ACEF score was no longer significantly associated with lesion complexity. Conversely, in patients without AVC, the ACEF score remained a strong predictor of complex CAD, while the TyG index showed no significant predictive value. Notably, despite exhibiting more anatomically severe CAD, patients with AVC had a lower incidence of acute myocardial infarction compared with those without AVC (31.9% vs. 46.5%). Conclusion: Among young and middle-aged adults, AVC identifies a distinct phenotype of metabolically driven, anatomically complex CAD. In this context, the TyG index provides superior and phenotype-specific predictive value, supporting its integration into pathophysiology-informed risk stratification strategies for younger patients with CAD.