Obesity and metabolic abnormalities: differential associations with subclinical atherosclerosis

Background & Aims: Obesity is associated with an increased risk of atherosclerosis, though recent evidence shows conflicting results. This study aimed to evaluate whether obesity or its associated metabolic abnormalities play a more significant role in atherosclerosis development in a primary care population. Methods: A cross-sectional study using data from the Cardiometabolic Risk Factor Registry (CARFARE) at Hospital Universitario Austral included adults undergoing their first healthcare visit for primary cardiovascular prevention. Participants were classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO), according to the BioShare-EU criteria and body mass index. Metabolic abnormalities (MAs) were defined by the same criteria. Atherosclerosis prevalence was analyzed using univariate analysis and multivariable logistic regression models. Results: Among 6,735 participants, 23.3% were MHNO, 3.13% MHO, 45.6% MUNO, and 25.9% MUO. MHO subjects were 10.1% of the obese population. In univariate analysis, atherosclerosis prevalence was higher in obese than non-obese individuals (57.1% vs. 52.0%, p=0.001), but lower in MHNO and MHO compared to MUNO and MUO groups (33.1% and 34.4% vs. 60.4% and 59.5%, p<0.0001). In multivariate regressions, these latter groups presented an increased adjusted odds ratio (aOR) of atherosclerosis compared to MHNO, while atherosclerosis prevalence was no different between the MHO and MHNO groups [aOR: 0.79 (95% CI 0.55-1.11)]. Moreover, in a second logistic regression model, MAs were independently associated with atherosclerosis [aOR: 1.84 (95% CI: 1.60-2.11)], while obesity was not [aOR: 0.91 (95% CI: 0.79-1.04)]. Conclusion: In this primary care population, the MHO phenotype was not associated with increased atherosclerosis. MAs, rather than obesity alone, were independently associated with atherosclerosis. These findings highlight the need for further longitudinal studies to clarify the interactions between obesity and metabolic health in atherosclerosis development.