Adverse outcomes according to metabolic status in obese and overweight patients with atrial fibrillation: a report from the GLORIA-AF Phase II and III Registry

Abstract Background The "obesity paradox" has been repeatedly described in atrial fibrillation (AF). Metabolic status has been proposed as a potential determinant of cardiovascular risk, particularly in overweight and obese patients, whereby ‘metabolically healthy’ and ‘metabolically unhealthy’ overweight/obesity subgroups can be defined. Purpose We aimed to explore the association between metabolic status, body mass index (BMI) and natural history of patients with recently diagnosed AF. Methods Eligible patients for GLORIA-AF registry Phases II and III were adults (age ≥18) with a recent diagnosis of AF (<3 months before enrolment, or <4.5 months in Latin America) and a CHA2DS2VASc score ≥1. For this analysis, we included patients with BMIs between 18.5 and 60 kg/m2 and with complete data on determinants of metabolic status (hypertension, diabetes mellitus (DM) and hyperlipidemia). We categorised patients according to BMI (normal weight [18.5-24.9 kg/m2], overweight [25.0-29.9 kg/m2], obesity [30.0-60.0 kg/m2]) and metabolic status (unhealthy status defined as the presence of at least one factors among hypertension, DM and hyperlipidemia; healthy status defined as having none of these three factors). We analysed the odds of receiving oral anticoagulant (OAC) and other treatments, as well as the risk of major adverse outcomes, using multivariable Cox regression analyses with a primary outcome of a composite of all-cause death and major adverse cardiovascular events (MACE). Results 24,828 (mean age 70.1±10.3, females 44.6%) patients were included. The most represented group was the overweight unhealthy (8,161, 32.9%), followed by obese unhealthy (7,485, 30.1%), normal weight unhealthy (5,115, 20.6%), normal weight healthy (1,778, 7.2%), overweight healthy (1,508, 6.1%), and obese healthy (781, 3.1%). Among the obese patients, females were mostly metabolically healthy (51.0% vs. 44.9%). Higher BMI was associated with metabolic unhealthy status, and higher odds of receiving OAC (Figure 1; OR (95%CI) for OAC prescription in obese vs. normal weight patients: 2.22 [2.00-2.45]) and other treatments. Compared to normal weight healthy patients, normal weight unhealthy patients showed a higher risk of the primary composite outcome (adjusted Hazard Ratio (aHR): 1.20, 95%CI: 1.01-1.42, p=0.039) and thromboembolism, while no significant difference for the risk of the primary outcome or thromboembolism was observed for the other groups (Figure 2). Metabolically healthy obese group was associated with a reduced risk of cardiovascular death (aHR: 0.35, 95%CI:0.14-0.88, p=0.026) and MACE (aHR:0.56, 95%CI:0.33-0.93, p=0.024). In all weight groups, unhealthy metabolic status was associated with an increased risk of major bleeding. Conclusions Increasing BMI was associated with poor metabolic status, and with more intensive therapeutic management. The risk of outcomes was heterogenous among BMI groups, with metabolically unhealthy subjects having a poorer prognosis.Odds of receiving OAC according to BMIAdjusted Cox regression analysis