Obesity paradox in cardiovascular disease: where do we stand?

Salvatore Carbone,1 Justin M Canada,1 Hayley E Billingsley,1,2 Mohammad S Siddiqui,3 Andrew Elagizi,4 Carl J Lavie41VCU Pauley Heart Center, Department of Internal Medicine, Richmond, VA, USA; 2Kinesiology and Health Sciences, College of Humanities & Science, Richmond, VA, USA; 3Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, USA; 4John Ochsner Heart and Vascular Institute, Ochsner Clinical School-the University of Queensland School of Medicine, New Orleans, LA, USAAbstract: Obesity is associated with an increased risk of developing cardiovascular disease (CVD), particularly heart failure (HF) and coronary heart disease (CHD). The mechanisms through which obesity increases CVD risk involve changes in body composition that can affect hemodynamics and alters heart structure. Pro-inflammatory cytokines produced by the adipose tissue itself which can induce cardiac dysfunction and can promote the formation of atherosclerotic plaques. When obesity and HF or CHD coexist, individuals with class I obesity present a more favorable prognosis compared to individuals who are normal or underweight. This phenomenon has been termed the “obesity paradox.” Obesity is defined as an excess fat mass (FM), but individuals with obesity typically also present with an increased amount of lean mass (LM). The increase in LM may explain part of the obesity paradox as it is associated with improved cardiorespiratory fitness (CRF), a major determinant of clinical outcomes in the general population, but particularly in those with CVD, including HF. While increased LM is a stronger prognosticator in HF compared to FM, in patients with CHD excess FM can exert protective effects particularly when not associated with increased systemic inflammation. In the present review, we discuss the mechanisms through which obesity may increase the risk for CVD, and how it may exert protective effects in the setting of established CVD, with a focus on body composition. We also highlight the importance of measuring or estimating CRF, including body composition-adjusted measures of CRF (ie, lean peak oxygen consumption) for an improved risk status stratification in patients with CVD and finally, we discuss the potential non-pharmacologic therapeutics, such as exercise training and dietary interventions, aimed at improving CRF and perhaps clinical outcomes.Keywords: obesity, cardiovascular disease, obesity paradox, body composition, cardiorespiratory fitnes