Residual risk in coronary artery disease: identification of cardio-reno-metabolic and psychosocial phenotypes in a Latin American Cohort of the INTERASPIRE registry.

BACKGROUND: Residual cardiovascular risk remains substantial in patients with established coronary artery disease despite contemporary secondary prevention strategies. Conventional approaches focused on isolated risk factors may fail to capture the multidimensional heterogeneity of this population. PURPOSE: To identify distinct clinical phenotypes using an unsupervised analytical approach and to explore their association with recurrent cardiovascular events. METHODS: We conducted a multicenter observational study based on the INTERASPIRE registry, including 592 Latin American patients with prior acute coronary syndrome or coronary revascularization. Variables from a standardized interview were grouped into demographic, clinical, metabolic, and psychosocial domains. After variable selection, clustering was performed using Partitioning Around Medoids with Gower distance. Associations with 12-month cardiovascular events were assessed using Kaplan-Meier analysis and Cox regression models. RESULTS: Three phenotypes were identified. Cluster 1 (42%) included younger patients with lower comorbidity burden and lower psychosocial vulnerability. Cluster 2 (27%) showed greater psychosocial burden and an adverse lipid profile, defining a higher-risk phenotype. Cluster 3 (31%) included older patients with multiple comorbidities and greater renal dysfunction. During 12-month follow-up, 7% experienced cardiovascular events. Event rates differed across clusters (3%, 10%, and 9%; log-rank p = 0.02). Compared with cluster 1, only cluster 2 showed increased risk (HR 2.66; 95% CI 1.11-6.39; p = 0.029). CONCLUSIONS: Unsupervised phenotyping identified three clinical profiles with distinct prognostic implications. Residual cardiovascular risk appears to reflect the interaction of lipid, renal, and psychosocial domains beyond traditional risk factors.