Revisiting the obesity paradox: lean body mass, fat mass, and mortality in patients with atrial fibrillation
Authors: Li J , Xu X Q , Yu Y F , Yu B W , Sun Y , Tan X , Wang B , Lu Y L , Wang N J 
Published: October 2024

Abstract

Background
Obesity has been associated with risk of atrial fibrillation (AF), but once AF is established, it seems to be favorable, which is termed the obesity paradox. However, body mass index (BMI), the commonly used anthropometric marker of obesity does not distinguish between fat and lean body mass, and could lead to the potential misclassification of risk categories. Understanding the role of fat and lean mass might provide new insights into the obesity paradox and promote targeted interventions in AF.

Purpose
To investigate the associations of BMI, lean body mass, and fat mass with all-cause mortality in patients with AF.

Methods
A total of 8,325 patients (mean age 62.1±6.07 years) with AF at baseline were included in the prospective cohort study using UK biobank data. Body composition data (fat mass and lean body mass) were estimated using an eight-contact electrode Tanita BC418MA segmental body composition analyser. Cox proportional hazards regression models were used to estimate the above associations.

Results
During a mean of 13.7 years of follow-up, 2,058 deaths were identified. A U-shaped association was observed between BMI and all-cause mortality. Multivariable adjusted Cox models including fat mass and lean body mass revealed U-shaped associations of fat and lean body mass with all-cause mortality. According to the restricted cubic spline models, the risk of all-cause mortality decreased until around 27 kg/m2 of BMI and increased afterward in both sexes. In women, the average fat mass and lean body mass with 27 kg/m2 of BMI were 27 and 42 kg, respectively. For fat mass, the risk of all-cause mortality decreased up to approximately 27 kg with a hazard ratio (HR) of 0.396 (95% confidence interval 0.383-0.410) per standard deviation (SD), and then increased with a HR of 1.323 (1.320-1.326) per SD. A larger reduction in risk was observed within the lower range until 42 kg of lean body mass with a HR per SD of 0.293 (0.275-0.312), which increased gradually thereafter with HR per SD of 1.174 (1.157-1.192). For men, the average fat mass and lean body mass with 27 kg/m2 of BMI were 22 and 60 kg, respectively. The risk of all-cause mortality decreased up to approximately 22 kg of fat mass with a HR of 0.427 (0.412-0.441) per SD, and then increased with a HR of 1.353 (1.348-1.359) per SD. A similar trend of risk reduction was observed until 60 kg of lean body mass [HR (0.443, 0.433-0.454) per SD], which increased gradually thereafter with HR per SD of 1.165 (1.162-1.167).

Conclusion
Our findings suggest that the associations between between fat and lean body mass, and mortality determined the shape of the association between BMI and mortality. The "obesity paradox" may be largely explained by both fat and lean body mass in AF. Maintaining healthy body composition is of critical importance to improve prognosis in AF. For patients with BMI ≥ 27 kg/m2, more emphasis should be placed on reducing fat mass than lean mass.Associations of BMI, WC, WHtR with deathAssociations of fat/lean mass with death