Debunking the myth: There is no ‘obesity paradox’, new data suggest

Using alternative anthropometric measurements, a post hoc analysis that used data from the PARADIGM-HF* trial debunked the BMI-related ‘obesity paradox’ in a large cohort of patients with chronic heart failure with reduced ejection fraction (HFrEF).

“It has been suggested that living with obesity is a good thing for patients with HFrEF … We knew this could not be correct, and that obesity must be bad rather than good. We reckoned that part of the problem was that BMI was a weak indicator of how much fatty tissue a patient has,” said Professor John McMurray from the University of Glasgow, UK, in a press release.

“[Indeed, our findings showed that] obesity is not good and is bad in patients with HFrEF,” McMurray stressed.

 

A look into the obesity paradox

It has been over 2 decades since this paradox was initially reported in patients on maintenance haemodialysis, with other large HF trials corroborating its existence. [Kidney Int 1999;55:1560-1567; Circulation 2007;116:627-636; Exp Gerontol 2017;87:1-7] The paradox states that HF patients who were overweight or obese were less likely to be hospitalized or to die compared with individuals of normal weight.

However, this was mostly based on BMI which, according to McMurray, “does not take into account the location [or distribution of body fat] or its amount relative to muscle or the weight of the skeleton, which may differ according to sex, age, and race. In HF specifically, retained fluid also contributes to body weight.”

 

Tipping the scales: waist-to-height ratio

McMurray and his team revisited the obesity paradox using a newer index: Waist-to-height ratio (WHtR). In the UK, the NICE** now recommends WHtR instead of BMI for evaluating adiposity. [www.nice.org.uk/guidance/cg189/resources/obesity-identification-assessment- and-management-pdf-35109821097925, accessed June 19, 2023; BMJ Open 2016;6:e010159]

They used data from 6,567 men and 1,832 women enrolled in PARADIGM-HF. Of these, about 99 percent had data on WHtR. Data on body roundness index, body shape index, relative fat mass, waist circumference, and weight-adjusted-waist index were also available, but the trial’s focus was on WHtR. [Eur Heart J 2023;44:1136-1153]

After adjusting for all*** prognostic variables, in both BMI and WHtR analyses, greater adiposity was associated with a higher risk of the primary outcome of hospitalization for HF (hHF) or cardiovascular (CV) death (adjusted hazard ratios [aHRs], 1.24 and 1.27). For WHtR, comparisons were made between quintile (Q)5 and Q1, whereas for BMI, it was between obese class II/III (BMI ≥35) and normal-weight (BMI 18.5–24.9) individuals.

The higher risk of the composite primary outcome in individuals with greater adiposity was more apparent using WHtR than BMI, the researchers noted. “[The] newer indices incorporate waist circumference and height, with the former better reflecting intra-abdominal fat (‘central obesity’) and the latter accounting for sex- and race-based differences in stature and skeletal weight.”

When evaluating outcomes separately, the obesity paradox using WHtR disappeared for all-cause mortality (aHR, 1.10) but not for hHF (aHR, 1.39). “[This suggests that] the top 20 percent of people with the most fat had a 39-percent increased risk of being hospitalized for HF compared with people in the bottom 20 percent who had the least fat,” explained first author Dr Jawad Butt from the Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark, in a press release.

More fat = worse, NOT better, outcomes

In sum, the study showed that when body fat was measured using a different index, there was no ‘obesity survival paradox’. “It is indices that do not include weight such as WHtR that have clarified the true relationship between body fat and patient outcomes in our study, showing that greater adiposity is actually associated with worse not better outcomes, including high rates of hospitalization and worse health-related quality of life,” McMurray explained in detail.

“These observations raise the question as to whether weight loss might improve outcomes, and we need trials to test this,” he added. As there are no specific recommendations in the ESC or ACC/AHA^# guidelines on weight management in HFrEF patients, effective and safe weight loss strategies for this patient subgroup are warranted. [Eur Heart J 2021;42:3599-3726; Circulation;2022:e895-e1032]

“[The findings are] important because the underdiagnosis of HF in people living with obesity is a major issue in primary care. Symptoms of breathlessness are often dismissed as due solely to obesity. Obesity is a risk factor and driver of HF. In the past, weight loss may have been a concern for patients with HFrEF. Today, it is obesity,” McMurray said.

 

Sounding the alarm

“The present findings raise the alarm over the term ‘obesity paradox’, which has been claimed to be based on BMI … BMI lumps together pathologies that may not be related at all,” wrote Professor Stephan von Haehling and Dr Ryosuke Sato, both from the University of Göttingen Medical Center in Germany, in an accompanying editorial. [Eur Heart J 2023;44:1154-1156]

“Can we tell obese HF patients just to stay as they are? To adequately address this question, not only should the obesity paradox be revisited even in patients with HFpEF and in lean HF patients by WHtR … [F]urther tests are warranted to validate the effect of weight loss in ‘truly’ obese HF patients with a high WHtR,” they said.