High percent body fat mass predicts lower risk of cardiac events in patients with heart failure: an explanation of the obesity paradox

Abstract

Background Although high body mass index (BMI) is a risk factor of heart failure (HF), HF patients with a higher BMI had a lower mortality rate than that in HF patients with normal or lower BMI, a phenomenon that has been termed the “obesity paradox”. However, the relationship between body composition, i.e., fat or muscle mass, and clinical outcome in HF remains unclear. Methods We retrospectively analyzed data for 198 consecutive HF patients (76 years of age; males, 49%). Patients who were admitted to our institute for diagnosis and management of HF and received a dual-energy X-ray absorptiometry scan were included regardless of left ventricular ejection fraction (LVEF) categories. Muscle wasting was defined as appendicular skeletal muscle mass index < 7.0 kg/m2 in males and < 5.4 kg/m2 in females. Increased percent body fat mass (increased FM) was defined as percent body fat > 25% in males and > 30% in females. Results The median age of the patients was 76 years (interquartile range [IQR], 67–82 years) and 49% of them were male. The median LVEF was 47% (IQR, 33–63%) and 33% of the patients had heart failure with reduced ejection fraction. Increased FM and muscle wasting were observed in 58 and 67% of the enrolled patients, respectively. During a 180-day follow-up period, 32 patients (16%) had cardiac events defined as cardiac death or readmission by worsening HF or arrhythmia. Kaplan-Meier survival curves showed that patients with increased FM had a lower cardiac event rate than did patients without increased FM (11.4% vs. 22.6%, p = 0.03). Kaplan-Meier curves of cardiac event rates did not differ between patients with and those without muscle wasting (16.5% vs. 15.4%, p = 0.93). In multivariate Cox regression analyses, increased FM was independently associated with lower cardiac event rates (hazard ratio: 0.45, 95% confidence interval: 0.22–0.93) after adjustment for age, sex, diabetes, muscle wasting, and renal function. Conclusions High percent body fat mass is associated with lower risk of short-term cardiac events in HF patients.

Natriuretic Peptide Clearance Receptor (NPR-C) Pathway as a Novel Therapeutic Target in Obesity-Related Heart Failure With Preserved Ejection Fraction (HFpEF)

“…In a cohort of 150 patients hospitalized with HFpEF, higher BMI values were associated with lower mortality (Stavrakis et al, 2013). Consistently, a U-shaped relationship between BMI and mortality has been reported for HFpEF (Kapoor and Heidenreich, 2010;Padwal et al, 2014;Ohori et al, 2021).…”

“…The authors found that a lowered BMI may be a significant predictive factor for the frequency of hospitalizations and increased mortality (Nishikido et al, 2019). Similarly, other studies have shown that increased body fat mass, but not appendicular skeletal muscle mass, corresponds to a lower risk of short-term cardiac events in HF patients (Thomas et al, 2019;Ohori et al, 2021). Every 5-unit increase in BMI corresponds to a 10% reduction in mortality (Fonarow et al, 2007).…”

“…Although the potential underlying mechanisms of the obesity paradox have been extensively studied (Hamzeh et al, 2017;Thomas et al, 2019;Ohori et al, 2021), little attention has been given to the possible pathophysiological role of NPR-C. Crandall et al (1989) studied the effects of weight reduction on NPR-C gene expression in an experimental obesity-associated HFpEF model. A cohort of patients who were subjected to a 15-week period of caloric restriction had, on average, a 40% reduction in body weight.…”

“…Some evidence suggests that the prognostic impact of increased body fat mass may also be lost systematically as the disease progresses, and HF severity may overcome percent body fat in the prediction of short-term cardiovascular events (Ohori et al, 2021). Indeed, while fat mass may be associated with better survival in patients with advanced HF, cardiac cachexia (nonintentional weight loss) may be a stronger independent predictor for mortality (Janovska et al, 2020).…”

Comparison on two algorithms of skeletal muscle mass index: an observational study in 141,451 Chinese adults

“…However, changes in SMH with different BMI groups is completely different from the ones in the existing researches [37,38]. Numerous studies have shown that the incidence of chronic diseases is different with different BMI [39]. Therefore, using different methods to calculate skeletal muscle mass parameters has different clinical guidance signi cance.…”