Abdominal Fat in Preserved-EF Heart Failure: No Obesity Paradox

Marlene Busko  

December 08, 2017

TOKYO, JAPAN — In an observational study of patients with heart failure with preserved ejection fraction (HFpEF), those with abdominal obesity, measured by waist circumference, showed increased risk of dying during a 3.4-year follow-up[1]. In contrast, HFpEF patients with a higher body-mass index (BMI) were less likely to die, consistent with an "obesity paradox."

The secondary analysis of >3000 patients in TOPCAT was published in the December 5, 2017 issue of the Journal of the American College of Cardiology by Drs Tetsuro Tsujimoto and Hiroshi Kajio (National Center for Global Health and Medicine, Tokyo, Japan).

The study showed that "not BMI, but abdominal obesity may be an important risk factor for mortality in HFpEF patients," Dr Tsujimoto told theheart.org | Medscape Cardiology in an email.

Reducing "abdominal obesity through diet, exercise, or both may represent the most basic and important treatment in patients with HFpEF."

This study shows that "although higher BMI is associated with better survival in HFpEF, it appears that abdominal obesity is not protective and actually detrimental," Dr Carl J Lavie (Ochsner Heart and Vascular Institute, New Orleans, LA), told theheart.org | Medscape Cardiology in an email. Lavie coauthored an accompanying editorial[2].

Ideally, patients with heart failure should try to lose abdominal fat without losing muscle. "It is hard to just lose weight in the waist," he conceded, "but if weight loss were done with exercise that included some resistance training or weight training/weight lifting, some muscle mass would be maintained."

Further research is needed to explain the seemingly-conflicting findings for waist circumference and BMI. "I would really like to know," Lavie said, "if all of the bad effects of abdominal obesity occurred with low BMI (this would represent sarcopenic obesity or 'skinny fat'), and was abdominal obesity also bad in those with a high BMI (maybe not)?"

Poorly Understood Pathophysiology

About half of patients with heart failure have HFpEF and this propotion is growing, but the pathophysiology is poorly understood, Tsujimoto and Kajio write.

"Recent reports have suggested that the development of HFpEF is associated with a systemic proinflammatory state related to commonly coexisting conditions, such as obesity, metabolic syndrome, diabetes, hypertension, lung disease, anemia, and smoking," they note.

To see if abdominal obesity in HFpEF is associated with an increased risk of mortality, the researchers identified 3310 patients in TOPCAT who had HFpEF and had been randomized to spironolactone or placebo.

Of these, 2413 patients had abdominal obesity, which was defined as a waist circumference of >88 cm in women and >102 cm in men.

Compared with the other patients, those with abdominal obesity were more likely to be women (58% vs 34% for men), black (9% vs 4% for other race groups), and never-smokers (55% vs 50%), and have NYHA class 3/4 (35% vs 25% for lower NYHA class) and BMI >30 kg/m2 (71% vs 12% for lower BMI).

They were also more likely to have diabetes, hypertension, dyslipidemia, MI, angina, atrial fibrillation, and chronic obstructive pulmonary disease; use ACE inhibitors or angiotensin receptor blockers, calcium-channel blockers, diuretics, or statins; and have lower eGFR, higher systolic blood pressure, and a faster heart rate.

During follow-up, 500 patients died. There were 46 deaths per 1000 person-years among patients with abdominal obesity and 41 deaths per 1000 person-years in the other patients

The unadjusted risk of all-cause, cardiovascular, and noncardiovascular mortality was similar in patients with and without abdominal obesity.

However, after adjustment for multiple variables, including BMI, having abdominal obesity was associated with a 52%, 50%, and 58% significantly increased risk of all-cause, cardiovascular, and noncardiovascular death, respectively.

Compared with patients with a normal BMI, all-cause mortality was lower in patients who were overweight or obese, even after adjustment for multiple variables, including abdominal obesity.

The clinical implications of this study are not clear, according to the editorialists, because it cannot establish causality, and it did not examine whether patients with HFpEF who reduce their waist size have a better prognosis.

"Further studies are needed," they conclude, "to better define ideal body composition, including BMI, waist circumference, and other depots of fat (visceral, subcutaneous, hepatic, pericardial, and so forth), for the primary and secondary prevention of HF, both HFrEF and HFpEF, as well as various interventions, including nutritional, specific weight-loss programs, including ones targeting abdominal obesity, physical activity/exercise, and increasing cardiorespiratory fitness on prognosis in patients with HF."

In a podcast that accompanied the article, JACC editor in chief Dr Valentin Fuster (Mount Sinai Medical Center, New York) said this paper is a reminder that "just as a rule of thumb, a high waist circumference tends to be related more to fat deposition than to . . . lean muscle; on the other hand, an increase in BMI can be related to both."

The study was supported by a grant from the Japan Society for the Promotion of Science. Lavie is the author of The Obesity Paradox. The study authors and editorialists report they have no other relevant disclosures.

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