Beyond Obesity: Metabolic status as key driver for cardiovascular outcomes in patients undergoing invasive coronary angiography.

Aim: Metabolic disorders are established risk factors for coronary artery disease (CAD) and major adverse cardiovascular events (MACE). Although obesity is closely associated with metabolic disease, data on its role as a separate cardiovascular risk modifier in metabolically healthy individuals are limited, particularly in patients with CAD. Thus, this study aims to investigate risk profiles of metabolic phenotypes on outcomes in patients undergoing invasive coronary angiography (ICA).

Methods: 12-,760 patients evaluated for chronic coronary syndrome (CCS) were distinguished into four metabolic phenotypes: metabolically healthy/unhealthy non-obese/obese (MHN, MHO, MUN, MUO). The association of metabolic phenotypes with outcome was assessed using Cox regression models, adjusted for age, sex, and renal dysfunction.

Results: Within the total study cohort (median age 68 years, 57.3% male), 56.5% presented metabolically healthy (43.3% MHN; 13.1% MHO) and 43.5% metabolically unhealthy (28.3% MUN; 15.2% MUO). Irrespective of CCS, metabolic phenotypes showed different risks for MACE, all-cause mortality, and revascularization. While metabolic disease emerged as a robust predictor of events, obesity alone did not (e.g., in patients with obstructive CCS: MHO vs. MHN: adj. HR 0.947 [95% CI 0.728 - 1.231], p = 0.683; MUO vs. MUN: adj. HR 0.974 [95% CI 0.809 - 1.172], p = 0.780). However, metabolically healthy individuals experienced lower event rates with increasing BMI.

Conclusions: This study indicates metabolic health, rather than obesity, is a key predictor of adverse events in CCS prevention, revealing an obesity paradox in metabolically healthy individuals. Thus, cardiovascular risk assessment should prioritize metabolic health over BMI. Integrating metabolic profiling into routine evaluations may help optimize prevention and personalized treatment strategies.