Obesity paradox in cardiovascular disease: where do we stand?

Salvatore Carbone, Justin M Canada, Hayley E Billingsley, Mohammad S Siddiqui, Andrew Elagizi, Carl J Lavie, Salvatore Carbone, Justin M Canada, Hayley E Billingsley, Mohammad S Siddiqui, Andrew Elagizi, Carl J Lavie

Abstract

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: body composition; cardiorespiratory fitness; cardiovascular disease; obesity; obesity paradox.

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Obesity phenotypes, cardiac function and cardiorespiratory fitness. The figure highlights the proposed major role of lean mass in the development of cardiac dysfunction and cardiorespiratory fitness, suggesting that individuals with similar body mass index (BMI) can present a different body composition, resulting in different cardiac function and cardiorespiratory fitness. Reprinted from Mayo Clin Proc., 92(2), Carbone S, Lavie CJ, Arena R. Obesity and heart failure: focus on the obesity paradox, 266–279, Copyright (2017), with permission from Elsevier.
Figure 2
Figure 2
Obesity and risk for heart failure. Obesity increases the risk of heart failure (HF), particularly of HF with preserved ejection fraction (HFpEF) (top panel) compared to HF with reduced ejection fraction (HFrEF) (bottom panel). Reprinted from J Am Coll Cardiol, 69(9), Pandey A, LaMonte M, Klein L, et al, Relationship between physical activity, body mass index, and risk of heart failure, :1129–1142, Copyright (2017), with permission from Elsevier.
Figure 3
Figure 3
Body composition and heart failure. Proposed mechanisms driving obesity to heart failure (HF) and to the obesity paradox once HF is diagnosed. The dark blue arrows indicate the potential detrimental effects of body composition components (fat mass and lean mass) on cardiac function and eventually HF development. The light blue arrows indicate the potential mechanisms by which body composition improves cardiorespiratory fitness (CRF). Reprinted from Mayo Clin Proc., 92(2), Carbone S, Lavie CJ, Arena R. Obesity and heart failure: focus on the obesity paradox, 266–279, Copyright (2017), with permission from Elsevier. Abbreviations: IL, interleukin; LV, left ventricular; LVH, LV hypertrophy; SVR, systemic vascular resistance; TNF-α, tumor necrosis factor α.
Figure 4
Figure 4
Body fat and systemic inflammation in coronary heart disease. Survival estimates (Kaplan–Meier) by body fat (BF) and high-sensitivity C-reactive protein (hsCRP) strata: low hsCRP = CRPInt J Obes (Lond). 2016;40(11):1730–1735.
Figure 5
Figure 5
Relationship between body composition phenotypes, cardiorespiratory fitness (CRF) and muscle strength in heart failure. Body composition compartments changes can directly affect CRF and muscle strength in patients with heart failure. Reproduced with permission from Ventura HO, Carbone S, Lavie CJ. Muscling up to improve heart failure prognosis. Eur J Heart Fail. 2018;20(11):1588–1590. © 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.

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Source: PubMed

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