After years of trying to discover how obesity could be an independent risk factor for the development of heart failure but somehow linked to improved survival among these patients, researchers have concluded that BMI obesity no longer appeared to hold counterintuitive protective effects after comprehensive adjustment for natriuretic peptides and other prognostic variables.
Their present findings result from a post-hoc analysis based on PARADIGM, a large multinational trial of more than 8 000 people with heart failure with reduced ejection fraction (HFrEF).
Eliminating this so-called “obesity paradox”, researchers found that study participants with the highest BMIs actually had excess combined heart failure hospitalisations and cardiovascular deaths, according to Dr John McMurray of British Heart Foundation Cardiovascular Research Centre, University of Glasgow, and colleagues.
Both increased BMI and waist-to-height ratio, another index of adiposity, were associated with a higher risk of heart failure hospitalisation specifically in this trial of people with HFrEF.
“Greater adiposity was associated with worse symptoms and health-related quality of life, irrespective of the anthropometric index used,” the study authors reported in the European Heart Journal.
“We knew that obesity must be bad rather than good, and reckoned that part of the problem was that BMI was a weak indicator of how much fatty tissue a patient has,” McMurray said.
BMI, a blanket index derived from a person’s weight and height, is known to ignore the location or amount of body fat relative to muscle, bone and retained fluid.
Alternative anthropometric indices proposed include waist circumference, waist-to-hip ratio, weight-adjusted-weight index, body shape index, body roundness index, and relative fat mass. The waist-to-height ratio in particular may be helpful for capturing, to some extent, sex- and race-based differences in stature and the distribution of body fat, said McMurray and colleagues.
In fact, the UK’s National Institute for Health and Care Excellence last year suggested that waist-to-height ratio should replace BMI in the evaluation of adiposity. The recommendation is that a person’s waist size should be less than half of height in the general population.
This should be extended to patients with heart failure as well, McMurray said.
Current guidelines do not provide any recommendation regarding weight management in HFrEF.
“Unfortunately, few randomised controlled trials using dietary and exercise intervention, bariatric surgery, or novel pharmacological therapies have been conducted in patients with HFrEF, although the latter are being investigated in individuals with HFpEF (heart failure with preserved ejection fraction),” McMurray and colleagues wrote.
The main findings of the PARADIGM study, reported in 2014, found that angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (Entresto) significantly reduced events compared with angiotensin-converting enzyme inhibitor enalapril.
Benefits of ARNI therapy did not vary by BMI or waist-to-height ratio in the latest report.
No index of adiposity significantly predicted all-cause mortality or cardiovascular death, either.
Study participants had a median BMI of 27.5 kg/m2 and 27.6 kg/m2 between men and women, and a median waist-to-height ratio of 0.58 and 0.59, respectively.
McMurray’s team acknowledged the possibility of unmeasured confounding remains in their analysis. The investigators lacked information on patients’ cardiorespiratory fitness, for example. The number of people with a low BMI or waist-to-height ratio was also very small.
“Of further interest, therefore, is whether similar results could be obtained in other populations with lower levels of BMI, like Asians,” said Dr Ryosuke Sato and Dr Stephan von Haehling, both of University of Göttingen Medical Center, Germany.
Even the waist-to-height ratio favoured by McMurray’s group has its limitations, the duo noted.
“(Waist-to-height ratio) is an anthropometric index that reflects central obesity well but is not an adequate measure of skeletal muscle mass. As such, this index cannot specify ‘sarcopenic obesity’, (sic) a serious pathological condition that involves both fat accumulation and reduced skeletal muscle mass,” they cautioned.
“Combining (waist-to-height ratio) with skeletal muscle mass evaluation, e.g. by bioelectrical impedance analysis (BIA) or dual-energy X-ray absorptiometry (DEXA), may lead to even better risk stratification of HFrEF patients.”
Study details
Anthropometric measures and adverse outcomes in heart failure with reduced ejection fraction: revisiting the obesity paradox
Jawad Butt, Mark Petrie, Pardeep Jhund, Naveed Sattar, Akshay Desai, Lars Køber, Jean Rouleau, Karl Swedberg, Michael Zile, Scott Solomon et al.
Published in European Heart Journal on 22 March 2023
Abstract
Aims
Although body mass index (BMI) is the most commonly used anthropometric measure, newer indices such as the waist-to-height ratio, better reflect the location and amount of ectopic fat, as well as the weight of the skeleton, and may be more useful.
Methods and results
The prognostic value of several newer anthropometric indices was compared with that of BMI in patients with heart failure (HF) and reduced ejection fraction (HFrEF) enrolled in prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure. The primary outcome was HF hospitalization or cardiovascular death. The association between anthropometric indices and outcomes were comprehensively adjusted for other prognostic variables, including natriuretic peptides. An ‘obesity-survival paradox’ related to lower mortality risk in those with BMI ≥25 kg/m2 (compared with normal weight) was identified but this was eliminated by adjustment for other prognostic variables. This paradox was less evident for waist-to-height ratio (as an exemplar of indices not incorporating weight) and eliminated by adjustment: the adjusted hazard ratio (aHR) for all-cause mortality, for quintile 5 vs. quintile 1, was 1.10 [95% confidence interval (CI) 0.87–1.39]. However, both BMI and waist-to-height ratio showed that greater adiposity was associated with a higher risk of the primary outcome and HF hospitalisation; this was more evident for waist-to-height ratio and persisted after adjustment e.g. the aHR for HF hospitalisation for quintile 5 vs. quintile 1 of waist-to-height ratio was 1.39 (95% CI 1.06–1.81).
Conclusion
In patients with HFrEF, alternative anthropometric measurements showed no evidence for an ‘obesity-survival paradox’. Newer indices that do not incorporate weight showed that greater adiposity was clearly associated with a higher risk of HF hospitalisation.
NEJM PARADIGM article – Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure
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