Obesity and Heart Failure: Can Nutritional Status Explain the Paradoxical Relationship?

Overweight and obesity are usually defined as a body mass index (BMI) ≥ 25 kg/m 2 and ≥ 30 kg/m 2 , respectively [1]. The World Health Organization (WHO) more broadlydefines these categories as abnormal or excessive amounts of fat mass (FM) [1]. Regardless of definition, obesity is recognized as a significant risk factor for developingtype 2 diabetes mellitus, hypertension, dyslipidemia and cardio-vascular disease [1-6]. Heart failure (HF), defined as " a complex clinical syndrome that results from any structural or functional impairment of ventricular filling and/or ejection of blood " , affects 38 million people worldwide, including 5.7 million in the United States [7]. HF is the most common cause of hospital admissions for Americans age 65 years and older [7,8]. A strong relationship exists between HF and obesity [5,6]. For every 1 kg/m 2 increase in BMI, the risk of developing HF increases by 5-7% [4], and almost half of all patients diagnosed with HF are obese [6]. While an abnormally high BMI is a risk factor for HF, overweight and obesity exert protective effects after the onset of HF. This phenomenon is commonly termed the " obesity paradox " [4,9-15]. In this editorial we describe the mechanisms through which obesity adversely affects cardiac function and discuss the contribution of body composition to the obesity paradox. In obese individuals, increases in central blood volume (CBV), stroke volume (SV), and, as a result, cardiac output (CO), are accompanied by a reduction in systemic vascular resistance (SVR) without a significant increase in heart rate [4,9-15]. This persistent increase in CO results in an increased cardiac workload that evolves into left ventricular (LV) dilatation, followed by a compensatory hypertrophic response [4,16-18]. These hemodynamic changes seem to be mostly related to an increased amount of lean mass (LM) (a surrogate for skeletal muscle mass) [10-14]. Higher levels of LM, and not FM, have been associated with increased blood flow [19] and possibly CBV, SV and CO. It is necessary to note that BMI does not distinguish between LM and FM and that an increased BMI may indicate an increased amount of LM, FM or a combination of both [20-27]. This distinction is important since low levels of LM are indicative of a poor prognosis in individuals with normal or reduced levels of FM and low levels of LM (i.e., sarcopenia) [28,30] or increased levels of FM and reduced amount of LM (i.e., sarcopenic obesity) [29,30]. Obesity appears to affect diastolic function to a greater extent than systolic function [31-33]. Obesity can potentially impair diastolic function as a result of endocrine-like secretion of pro-inflammatory adipokines or cytokines from adipose tissue [34]. Increased levels of interleukins (IL)-1 and-18 as well as tumor necrosis factor-α have been observed in obese patients [34-37]. In obese patients with HF with preserved ejection fraction and diastolic dysfunction, blockade of the IL-1 receptor with anakinra, a recombinant IL-1 receptor