Study Debunks Obesity Paradox in HF, Encourages BMI Alternatives

Body mass index (BMI) is a poor measure of adiposity and its use may be responsible for a misguided belief in an obesity survival paradox in patients with heart failure and reduced ejection fraction (HFrEF), a new study suggests.

Using alternative measures that take into account factors other than height or weight, plus the addition of prognostic variables, eliminated any survival advantage in those with a BMI of 25 kg/m² or higher. Additionally, greater adiposity on waist-to-height ratio was associated with a higher rate of hospital admission for worsening HF and CV-related death.

The study essentially debunks the “obesity survival paradox,” a term used to describe the surprising finding that patients with higher BMI, including those who fall into the category of obese, have better survival than those with a low BMI, said senior author John McMurray, MD (University of Glasgow, Scotland).

“BMI 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,” McMurray said in an email. “In heart failure, fluid retention may increase body weight.”

He said the study findings suggest that adopting alternative indices to BMI such as waist-to-heigh ratio might better account for sex- and race-based differences in stature, as well as differences in the distribution of body fat that are obscured when only BMI is used.

In the United Kingdom, the National Institute for Health and Care Excellence (NICE) has suggested that waist-to-height ratio should replace BMI in the evaluation of adiposity. Similarly, in the United States, several organizations and expert panels, including those from the American Heart Association, the American College of Cardiology, the Obesity Society, and the Endocrine Society, have made clear that waist circumference is distinct from BMI and recommend that both be measured even in those with normal body weight.

In an editorial accompanying the new study in the European Heart Journal, Ryosuke Sato, MD, PhD (University of Göttingen Medical Center, Germany) and Stephan von Haehling, MD, PhD (German Center for Cardiovascular Research, Göttingen), point out that a major shortcoming of BMI is that it “lumps together pathologies that may not be related at all.”

They further note that the accumulation of visceral and intramuscular fat and reduced muscle mass have been shown to be negative predictors of survival in patients with HF.

“This knowledge underlines the importance of assessing body composition using anthropometric indices other than BMI in patients with cardiovascular illnesses, in particular in patients with HF,” Sato and von Haehling say.

Another important point, the editorialists add, is that few studies supporting the obesity survival paradox in HF ever adjusted for natriuretic peptide levels, “the most important prognostic biomarker in HF.”

Differences Apparent With Adjustment

McMurray and colleagues led by Jawad Butt, MD (Copenhagen University Hospital—Rigshospitalet, Denmark), conducted a post hoc analysis of 1,832 women and 6,567 men with HFrEF enrolled in the international PARADIGM-HF trial, which compared sacubitril/valsartan (Entresto; Novartis) and enalapril and had a primary outcome of HF hospitalization or CV death.

The median BMI was similar in men and women at 27.5 kg/m² and 27.6 kg/m², respectively. While patients with higher BMI had lower natriuretic peptide levels, they had higher urinary cGMP/BNP ratio, a marker of tissue responsiveness to natriuretic peptides.

In minimally adjusted analyses, being overweight or obese as defined by BMI categories (≥ 25) was associated with a lower risk of all-cause mortality and CV death, with rates of 6.7 per 100,000 among those with BMI of ≥ 35 versus 9.5 per 100,000 for those with BMI of 18.5-24.9. However, after adjustment for prognostic variables, including NT-proBNP, the association between higher BMI and lower mortality was eliminated, while the association between higher BMI (≥ 35) and HF hospitalization was accentuated (HR 1.43; 95% CI 1.15-1.78).

Median waist-to-height ratio also was similar in men and women at 0.58 and 0.59, respectively. In minimally adjusted analyses, the primary outcome was similar between patients in the normal-weight BMI range and BMI ≥ 35, although all-cause mortality was lower at 7.3 versus 9.1 per 100,000 in the highest versus normal range, respectively. However, HF hospitalization was higher in the BMI ≥ 35 group.

Adjustment for prognostic variables resulted in elimination of the association between higher waist-to-height ratio and lower risk of death, but not the higher risk of HF hospitalization for the highest BMI group.

Looking at other anthropometric measures, body roundness index and relative fat mass, together with adjustment for prognostic variables, also showed an association with greater risk of HF hospitalization.

Debating the Obesity Paradox

Carl Lavie, MD (John Ochsner Heart and Vascular Institute, New Orleans, LA), an early investigator of the obesity paradox who has written extensively on the topic, told TCTMD that there are a few studies that support the obesity paradox in HF patients with central obesity as defined by waist circumference as opposed to waist-to-height ratio.

“This paper is good, but there is no information on physical activity or cardiorespiratory fitness, which markedly alters the relationship between adiposity and clinical outcomes in CVD, including HF,” Lavie added. In a recent study, even very small gains in cardiorespiratory fitness were powerful predictors of future risk of all-cause mortality.

Sato and von Haehling say the findings suggest the need to study the impact of waist-to-height ratio on outcomes in those with heart failure with preserved ejection fraction (HFpEF) and in lean patients, and they note that efforts are needed “to validate the effect of weight loss in ‘truly’ obese HF patients with a high [waist-to-height ratio].”

They further add that combining waist-to-height ratio with skeletal muscle mass evaluation via bioelectrical impedance analysis or dual-energy X-ray absorptiometry (DEXA), may lead to even better risk stratification of HFrEF patients.

To TCTMD, McMurray said while the point about imaging is well taken, “the problem is, imaging everyone with DEXA, CT, or MRI scans isn’t easy [or] feasible.” However, McMurray and colleagues agree that there does seem to be a rationale for studying the effect of weight loss in obese HF patients since the study provides strong evidence that the obesity survival paradox is likely an artifact of unadjusted analyses of BMI.