Obesity paradox in heart failure: A matter of debate

Nowadays obesity is becoming a global epidemic and public health problem in both children and adults.1–3 It is associated with numerous comorbidities such as cardiovascular diseases (CVDs), including atherosclerotic disease, chronic heart failure (CHF), arterial hypertension, type 2 diabetes, certain cancers and sleep apnoea/sleep-disordered breathing. Moreover, obesity is an independent risk factor for CVD development.1,2 Obesity defined by body mass index (BMI) is characterized by better prognosis and lower plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) in CHF patients.3 Obesity produces an increment in total blood volume and cardiac output that is caused in part by the increased metabolic demand induced by excess body weight.4,5 For centuries, the development of cachexia has been viewed as a sign of poor prognosis,6 and the research interest in CHF is still growing.7,8 While it is widely accepted that obesity increases the risk of developing heart disease, numerous publications proved that there is a statistically significant survival benefit in obese patients once they have been diagnosed with CVD.2,9–12 Adamopoulos et al. believed that the obesity paradox is only present in non-diabetic patients with CHF and not in patients with manifest type 2 diabetes.13 Overall, 29% of the 7788 participants in their analysis were diabetic, which is consistent with several other databases from large-scale CHF trials.13 In fact, the prevalence of diabetes is usually between 20% and 30% in such cohorts.14–16 According to Lavie et al., there are several possible explanations for the obesity paradox in heart failure: non-purposeful weight loss, greater metabolic reserves, less cachexia, protective cytokines or adipokines, earlier presentation due to symptomatology, attenuated response to the renin–angiotensin–aldosterone system, higher blood pressure leading to more optimized cardioprotective medications, different aetiology of heart failure, increased muscle mass and muscular strength in those with high BMI, implications related to cardiorespiratory fitness.17 In addition, von Haeling et al. believed that the analysis of body composition and its changes over time, as well as patterns of exercise capacity at baseline, were relied on in the published data from large-scale trials.18 Drawing conclusions from this data, it seems that weight reduction is not good advice for the heart failure patient. Moreover, there are a lot of discussions about the essentials of obesity paradox in specific subgroups, such as gender differences. Due to systolic CHF being more common in men, the majority of research has been conducted in predominantly male populations. This selection bias extends into studies of the obesity paradox in CHF despite accepted variations in fat distribution by sex: women may make up as little as 13% of a study population or the sex of participants may not be reported.19,20 However, only BMI was significant for the subgroup of women. And I believe that there is a need for further investigation of CHF outcomes in women. In addition, the levels of peak oxygen uptake (VO2) or minute ventilation (VE)/carbon dioxide production (VCO2) has been identified as an important predictor of survival in CHF.21,22 Chase et al. studied a cohort of 744 heart failure patients and found that while patients with obese BMI had significantly lower VE/VCO2 slopes than patients in normal and overweight BMI groups, ultimately VE/VCO2 was a strong independent predictor of improved survival irrespective of BMI.21 Lavie et al. demonstrated that physical capacity level may actually modify the obesity paradox: in 2066 patients with systolic heart failure, BMI was a significant predictor of age- and sex-adjusted survival in the group with low peak VO2 (<14 mL/O2 per kg) (p = 0.03) but not in the physically active patients. These findings indicated that favourable scores in core components of cardiorespiratory exercise testing might mitigate or even negate the impact of the obesity paradox in CHF, and that exercise training to improve cardiorespiratory fitness is reasonable even for the less obese.17 Moreover, there is a lack of information on obesity with or without low haemoglobin impact on VO2peak and the ability to optimize interpretation of cardiorespiratory exercise testing and exercise limitations in CHF. But van Iterson et al. claimed that the presence of the combination of CHF, obesity and low haemoglobin content triggers the strongest impairment in VO2peak.23 On the other hand, Jhund et al. observed elevation in high-sensitivity troponin T (hs-TnT) in a population with well-characterized heart failure with preserved ejection fraction (HFpEF), which was associated with larger left ventricular and atrial size, as well as higher NT-pro-BNP, and suggested that the ongoing myocardial chronic troponin release, because of either myocyte stretch or injury, may contribute to the pathophysiology of HFpEF.24 But there is still a gap regarding whether reduction in hs-TnT can be achieved and whether this would lead to improved outcomes in HFpEF. With regard to NT-pro-BNP, hs-TnT and tumorigenesis (sST2),25,26 the influence of BMI or per cent body fat (PBF) was much more prominent for NT-pro-BNP than for soluble suppression of sST2 and hs-TnT, as demonstrated through correlation and multivariate linear regression analyses. What is new, Aimo et al. found that these three biomarkers were independent predictors of outcome in all BMI categories and PBF tertiles, except for obese patients (BMI 30 kg/m2) or the highest PBF tertile, where only hs-TnT and sST2 remained independent predictors of all-cause and cardiovascular mortality, arguably establishing these biomarkers as the tests of choice for refined prognostication in obese patients with heart failure.3 In addition, results of a recent study showed that in parallel with increasing BMI or PBF there is an improvement in patient prognosis and a decrease in NT-pro-BNP, but not hs-TnT or sST2. At the same time, hs-TnT or sST2 are stronger predictors of outcome than NT-pro-BNP among obese patients.3 However, once a patient develops CHF, overweight and mild-to-moderate obesity are associated with better survival compared with patients with normal weight.27,28 The association of obesity and improved survival in heart failure patients is well established across multiple measures of adiposity. Furthermore, while intentional weight loss is known to improve haemodynamic function and cardiac structure in non-heart failure patients, further research is needed to generate evidence-based guidelines for weight management in established CHF.29 However, more complete understanding of obesity paradox and its difference in specific subgroups is needed and thus calls for further investigation, including the role of cardiorespiratory exercise. And it is clear that the new data about hs-TnT and sST2 must be implemented in daily practice and it will be advantageous to take into account all three discussed biomarkers (NT-pro-BNP, hs-TnT, sST2) and control them in CHF populations. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The author(s) received no financial support for the research, authorship, and/or publication of this article.