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676 Obesity, Central Adiposity, and Fitness: Understanding the Obesity Paradox in the Context of Other Cardiometabolic Parameters A higher body mass index (BMI) and lower levels of physical activity (PA) or cardiorespiratory fitness (CRF) are associated with increased risk of heart failure (HF), with recent studies demonstrating a dosedependent association between BMI, PA levels, and the risk of HF. However, in patients with established HF, several studies have demonstrated the phenomenon of the obesity paradox, such that higher BMI levels are associated with better outcomes, particularly a lower risk of mortality. The obesity paradox has also been observed in patients with other cardiovascular (CV) conditions, including coronary heart disease (CHD) and atrial fibrillation (AF). Several investigators have attributed this paradox to systematic biases in the analytical approaches such as residual confounding, survivorship bias among obese patients, and collider-stratification bias. Others have proposed a biological explanation, suggesting that overweight and obese patients with established cardiovascular disease (CVD) have greater metabolic reserve, favorable immune modulation and neurohormonal alterations, and greater tolerability of evidence-based therapies, which may mediate the observed lower mortality risk. Furthermore, BMI is a poor estimate of overall adiposity because it fails to distinguish between lean and fat mass and between the types of adipose tissue depots such as visceral and subcutaneous stores. This is particularly relevant because several studies have demonstrated that higher amounts of visceral adipose tissue and lower lean mass are associated with a greater risk of adverse CV events, independent of BMI. Taken together, more work is needed to better understand the biology underlying the phenomenon of the obesity paradox. In this issue of the Proceedings, studies by He et al and McAuley et al have attempted to bridge this knowledge gap by studying the role of