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'Obesity Paradox' in Heart Failure Debunked

The 'obesity paradox' does not exist, according to researchers who suggested that in patients with heart failure, waist-to-height ratio was a better indicator of outcomes than BMI.

Obesity has repeatedly been shown to be an independent risk factor for the development of heart failure (HF), however, its prognostic importance in established HF, especially HF with reduced ejection fraction (HFrEF), is less clear, with an 'obesity-survival paradox' described in patients with HFrEF, the authors of a new study pointed out.

In the study, published in the European Heart Journal, the authors described the 'obesity paradox' as related to "counter-intuitive" findings implying that, although overweight or obese people were at greater risk of developing heart problems, once a person had developed a heart condition, those with higher body mass index (BMI) appeared to do better and were less likely to die than those of normal weight.

Professor John McMurray, professor of medical cardiology, University of Glasgow, who led the new research, said: "It has been suggested that living with obesity is a good thing for patients with heart failure and reduced ejection fraction."

The authors highlighted that various explanations had been suggested for this paradox, including the fact that once someone had developed heart problems, some extra fat is somehow protective against further health problems and death, especially as "people who developed a severe and chronic illness often lose weight".

However, now researchers claim to have debunked the idea of an 'obesity paradox'.

Professor McMurray stressed that he and the other researchers knew that "obesity must be bad rather than good", and commented: "We reckoned that part of the problem was that body mass index was a weak indicator of how much fatty tissue a patient has."

BMI Has Many Limitations

Although BMI was the most commonly used anthropometric measure, newer indices such as the waist-to-height ratio better reflected the location and amount of ectopic fat, as well as the weight of the skeleton, and may be more useful, suggested the authors. They explained that the associations between obesity and outcomes in HFrEF had generally been based on BMI, which had many limitations as a measure of adiposity. "It does not take into account the location 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 heart failure specifically, there is also the contribution of retained fluid to body weight," they underlined. 

In an accompanying editorial, Professor Stephan von Haehling, consultant cardiologist, and Dr Ryosuke Sato, a research fellow, both at the University of Göttingen Medical Center in Germany, stressed that BMI "fails to take account of the body's composition of fat, muscle and bone, or where the fat is distributed". They challenged whether it would be "feasible to assume that an American professional wrestler (more muscle) and a Japanese sumo wrestler (more fat) with the same BMI would have a similar risk of cardiovascular disease?" 

'Obesity Paradox' Disappeared After Prognostic Variables Adjustment

To investigate their hypothesis, the researchers used data from 1832 women and 6567 men with heart failure and reduced ejection fraction who were enrolled in the PARADIGM-HF international study - a randomised, double-blind, placebo-controlled trial in patients with chronic HFrEF, evaluating the efficacy and safety of the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan compared with enalapril, added to standard care. 

The prognostic value of several newer anthropometric indices were compared with that of BMI in patients with HFrEF to determine the impact on global mortality and morbidity in heart failure. The primary outcome was heart failure hospitalisation or cardiovascular death. The association between anthropometric indices and outcomes were comprehensively adjusted for other prognostic variables, including natriuretic peptides. 

"Natriuretic peptides are the single most important prognostic variable in patients with heart failure. Normally, levels of natriuretic peptides rise in people with heart failure, but patients living with obesity have lower levels than those who are normal weight," explained Professor McMurray.

The researchers confirmed an 'obesity-survival paradox' related to lower mortality risk in those with BMI ≥25 kg/m2 compared with normal weight but pointed out that this was "eliminated by adjustment for other prognostic variables". 

"If doctors measure the ratio of waist to height of their patients, rather than looking at their BMI, the supposed survival advantage for people with a BMI of 25 kg/m2 or more disappears," the authors revealed.

Dr Jawad Butt, research fellow from Copenhagen University Hospital, Rigshospitalet, and first author of the study, said: "The paradox was far less evident when we looked at waist-to-height ratios, and it disappeared after adjustment for prognostic variables. After adjustment, both BMI and waist-to-height ratio showed that more body fat was associated with a greater risk of death or hospitalisation for heart failure, but this was more evident for waist-to-height ratio."

He highlighted that when looking at waist-to-height ratio, the researchers found that the top quintile with the most fat had a 39% increased risk of being hospitalised for heart failure compared with people in the bottom quintile with the least fat.

Obesity is a Risk Factor and Driver of Heart Failure

"Our study shows there is no 'obesity survival paradox' when we use better ways of measuring body fat," exclaimed Professor McMurray. "It is indices that do not include weight, such as waist-to-height ratio, 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 hospitalisation and worse health-related quality of life," he enlightened.

The authors acknowledged a number of limitations of the study, including that it can be more difficult to measure body shapes accurately when measurements are carried out by different people, and that the analysis was carried out on measurements and other data taken at the time participants joined the study and did not take account of any changes in weight or waist circumference during the follow-up period.

Asked to comment by Medscape News UK , Dr Sonya Babu-Narayan, associate medical director at the British Heart Foundation, said: "This study shows that the claim that people with heart failure who are also living with obesity may sometimes be better off than those who are lean is wrong. It shows the need to look beyond body mass index, which has many limitations."

Professor McMurray illuminated: "In the past weight loss may have been a concern for patients with heart failure and reduced ejection fraction, today it is obesity, which is not good, and is bad in patients with heart failure and reduced ejection fraction."

He postulated that weight loss might improve outcomes in patients with heart failure, and added that trials were needed to test this. 

"In the UK, the National Institute for Health and Care Excellence, NICE, now recommends that waist-to-height ratio instead of BMI is used for the general population, and we should support this for patients with heart failure too," he beseeched.

The PARADIGM-HF trial was funded by Novartis. Professors McMurray and Jhund are supported by British Heart Foundation Centre of Research Excellence Grant.