The obesity paradox in HFrEF revisited
Anthropometric measures and adverse outcomes in heart failure with reduced ejection fraction: revisiting the obesity paradox
Literature - Butt JH, Petrie MC, Jhund PS, et al. - Eur Heart J. 2023 Mar 22:ehad083. doi: 10.1093/eurheartj/ehad083.Introduction and methods
Background
In HFrEF, the term ‘obesity paradox’ is used for the observation that obesity is a predictor of better prognosis and longer survival [1,2]. While obesity must be avoided to prevent the disease, once a person has the disease, the presence of obesity is actually beneficial. In general, these associations are based on BMI, an anthropometric measurement that has its limitations as a measure of obesity. For example, BMI does not take into account the location of body fat and its amount relative to muscle mass nor skeletal weight, which can vary by gender, age and race [3-6]. In addition, the relationship between BMI (and possibly any other anthropometric measurement) and outcome in patients with HFrEF is confounded by the relationship between obesity and natriuretic peptide levels [7,8]. Recently, the National Institute for Health and Care Excellence in the UK has proposed the use of waist-to-height ratio instead of BMI in the evaluation of obesity [9,10].
Aim of the study
This study examined the relationship between anthropometric measurements – specifically BMI and waist-to-height ratio – and the risk of hospitalization for HF or cardiovascular death. It also examined the extent to which there is an obesity paradox with the waist-to-height ratio, that does not include weight as opposed to BMI.
Methods
The researchers performed an analysis of data from the PARADIGM-HF study [11]. In this prematurely terminated, multicenter, double-blind phase 3 study, 8399 patients ≥18 years of age with HF, an LVEF ≤40% and symptoms in NYHA class II-IV who additionally had elevated natriuretic peptide levels or had been hospitalized for HF in the past 12 months participated. Participants were randomized to sacubitril/valsartan or enalapril. They were divided into the following 5 WHO categories for BMI: ‘underweight’ (<18.5 kg/m2), ‘normal weight’ (18.5-24.9 kg/m2), ‘overweight’ (25-29.9 kg/m2); ‘obesity class I’ (30-34.9 kg/m2) and ‘obesity class II or III’ (≥35 kg/m²) and into quintiles for waist-to-height ratio. The median follow-up was 27 months.
Outcomes
The primary outcome was a composite of hospitalization for HF or cardiovascular death. In addition, individual components of the primary outcome, non-cardiovascular and all-cause death were examined. The analyses were adjusted for prognostic factors, including NT-proBNP levels.
Main results
BMI
- After adjustment for prognostic factors, including NT-proBNP levels, only patients with class II or III obesity had a higher risk of hospitalization for HF or cardiovascular death than normal-weight patients (HR: 1.24; 95%-CI: 1.05-1.48.
- After adjusting for prognostic factors, including NT-proBNP levels, patients with class II or III obesity also had a higher risk of hospitalization for HF than normal-weight patients (HR: 1.43; 95%-CI: 1.15-1.78).
- In contrast, the risk of cardiovascular and all-cause death was lower in overweight, obesity class I or obesity class II-III patients compared with normal-weight patients; after adjustment for prognostic factors, including NT-proBNP levels, the obesity paradox was no longer present.
Waist-to-height ratio
- After adjusting for prognostic factors, including NT-proBNP levels, patients in the middle quintile (HR: 1.24; 95%-CI: 1.06-1.46) and highest quintile (HR: 1.27; 95%-CI: 1.03-1.55) had a higher risk of hospitalization for HF or cardiovascular death than patients in the lowest quintile.
- After adjustment for prognostic factors, including NT-proBNP levels, patients in the middle quintile (HR: 1.31; 95%-CI: 1.05-1.62) and highest quintile HR: 1.39; 95%-CI: 1.06-1.81) also had a higher risk of hospitalization for HF than patients in the lowest quintile.
- In contrast, the risk of all-cause death was lower in patients in the highest quintile (HR: 0.82; 95%-CI: 0.69-0.97), compared with patients in the lowest quintile; after adjustment for prognostic factors, including NT-proBNP levels, this obesity paradox disappeared.
Conclusion
This analysis of data from the PARADIGM-HF study shows no evidence for a BMI-related obesity paradox in patients with HFrEF after adjusting for prognostic factors, including NT-proBNP levels. Even less evidence for such a paradox was found for the waist-to-height ratio, that does not include weight.
References
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7. Horwich TB, Hamilton MA, Fonarow GC. B-type natriuretic peptide levels in obese patients with advanced heart failure. J Am Coll Cardiol. 2006;47:85-90.
8. Mehra MR, Uber PA, Park MH, et al. Obesity and suppressed B-type natriuretic peptide levels in heart failure. J Am Coll Cardiol. 2004;43:1590-5. https://doi.org/10.1016/j.jacc.2003.10.066
9. Ashwell M, Gibson S. Waist-to-height ratio as an indicator of early health risk: simpler and more predictive than using a matrix based on BMI and waist circumference. BMJ Open. 2016;6:e010159.
10. National Institute for Health and Care Excellence. Obesity: identification, assessment and management. https://www.nice.org.uk/guidance/cg189/resources/obesity-identification-assessmentand-management-pdf-35109821097925. Geraadpleegd op 27 maart 2023.
11. McMurray JJ, Packer M, Desai AS, et al; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004.
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