Obesity Paradox: Conditioning on Disease Enhances Biases in Estimating the Mortality Risks of Obesity
In a wide variety of disease states, obese persons have been shown to experience lower mortality and better survival than that shown by the nonobese. These states include diabetes,1–3 coronary artery disease,4,5 heart failure,6 peripheral arterial disease,5 hypertension,7 chronic obstructive pulmonary disease,8 lung cancer,9 and esophageal adenocarcinoma.10 Superior survival among the obese patients has also been demonstrated after myocardial infarction,11 coronary revascularization,12 and angiography,13 and among hemodialysis patients.14 Better survival for obese patients in these disease states is considered paradoxical because obesity is associated with higher mortality in the vast majority of studies where it has been investigated.15 In this article, we argue that the obesity paradox is a product of statistical biases. Although these biases are present in most observational cohort studies of the mortality risks of obesity, they are exaggerated when attention is limited to populations that are conditioned on a disease state. We demonstrate these biases through formal reasoning and by application to a population with diabetes and prediabetes.