Defending the Con Side: Obesity Paradox Does Not Exist

The elegant review of Hainer and Aldhoon-Hainerov a, “Obesity Paradox Does Exist” (1), rightly points out that the so-called reverse epidemiology of a better outcome associated with obesity occurs only in patients with established cardiovascular (CV) disease (CVD) including heart failure (refs. 1–35 in the review by Hainer and Aldhoon-Hainerov a (1). At the primary prevention level, however, studying large cohorts, e.g., the population of 359,387 participants recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study with a follow-up of 9.7 years (2), increased waist circumference as a surrogate of obesity clearly was a strong predictor of increased mortality, and there are numerous similar studies confirming the primary importance of obesity in the context of a higher total mortality or CV morbidity and mortality, as discussed further in this article. This notion has not been challenged in the article of Hainer and AldhoonHainerov a (1). Furthermore, it has to be kept in mind that epidemiology never proves causality, even it is reverse and contrary to the expectation. Indeed, there may be many reasons why this reverse epidemiologymay be seen in patients with CVD, including selection bias, treatment bias, distinct phenotypes of CVD patients including weight differences and differences in prognosis, a multitude of comorbidities and confounders, and last but not least, anabolic deficiency or the malnutrition-inflammation syndrome. This article attempts to address all of these important issues and, in the last part, also evaluates the beneficial effects of weight loss in prospective long-term studies on overall mortality, CV morbidity and mortality, and type 2diabetes. Randomized controlled trials (RCTs) are thought to provide the top class of scientific evidence as well as the strongest recommendations for therapy. Most RCTs on weight loss and CV benefit, however, are still ongoing, and only a few have reported outcomes to date.