From risk enrichment to clinical utility: next steps for peri-aortic cardiovascular age

This commentary refers to ‘Peri-aortic fat to assess cardiovascular aging using an AI-driven radiomic biomarker’, by M. Lebowitz et al. , https://doi.org/10.1093/eurheartj/ehag498 and the discussion piece ‘Peri-aortic radiomic cardiovascular age: net benefit and intervenability’, by Y. Xiao, https://doi.org/10.1093/eurheartj/ehag687. We thank Xiao for the thoughtful discussion of the translational path for peri-aortic adipose tissue (PAAT)-derived cardiovascular age (CV-Age). 1 We agree that clinical net benefit and modifiability are central next questions. We wish to clarify, however, that our study positioned PAAT ΔAge as an opportunistic risk-enrichment biomarker, not as a treatment-selection tool or surrogate endpoint. 1 Across four heterogeneous CT cohorts, ΔAge stratified major adverse cardiovascular event risk and modestly improved PREVENT reclassification; these findings support prognostic enrichment, not clinical readiness. Xiao appropriately notes that the positive categorical net reclassification improvement reflected improved classification among participants who experienced events. This gain was accompanied by reduced specificity among those who remained event-free, particularly at lower baseline risk. 1 Because decision-curve analysis was not performed, our study did not establish whether these reclassification gains translate into clinical net benefit across clinically relevant thresholds. 2 Whether these gains produce net benefit depends on the setting in which the biomarker is used: the population evaluated, the threshold for action, the evaluation or treatment triggered, and the relative consequences of missed events and unnecessary intervention. These elements should be prespecified and evaluated in prospective implementation studies. Until then, PAAT CV-Age should complement, rather than replace, established risk assessment.