Cachectic biomarkers as confounders behind the obesity paradox in patients with acute decompensated heart failure

Obesity is a risk factor for heart failure (HF) development but is associated with a lower incidence of mortality in HF patients. This obesity paradox may be confounded by unrecognized comorbidities, including cachexia.

A retrospective assessment was conducted using data from a prospectively recruiting multicenter registry, which included consecutive acute heart failure patients. A low, normal, and high body mass index (BMI) was defined as <20 kg/m², 20-25 kg/m², and ≥25 kg/m², respectively. Cachexia was defined as a combination of BMI < 20 kg/m² and any biochemical abnormalities including albumin, hemoglobin, or C-reactive protein. Patients with either of the three biochemical abnormalities were categorized as those with cachectic biomarkers. Two-year all-cause, cardiac, and noncardiac mortality were evaluated.

This study evaluated 3314 patients (mean BMI, 22 ± 4 kg/m² [low BMI with cachexia, 828 (25%); low BMI without cachexia, 273 (8%); normal BMI, 1584 (48%); high BMI, 629 (19%)]). Overall, an increase of 1 point in BMI was associated with a decreased incidence of all-cause mortality (adjusted hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.90-0.94; p < 0.001). Regardless of the mode of death, the low BMI with cachexia indicated the worst prognosis, while the low BMI without cachexia showed a similar prognosis to the normal BMI. Cachectic biomarkers, which were observed more frequently in the low BMI, predicted a higher incidence of 2-year all-cause mortality across the BMI categories (adjusted HR for the low BMI, 1.90; 95% CI, 1.30-2.77; p = 0.001; adjusted HR for the normal BMI, 1.94; 95% CI, 1.34-2.79; p < 0.001; adjusted HR for the high BMI, 3.60; 95% CI, 1.61-8.08; p = 0.002).

BMI could be only a surrogate marker. The cachectic biomarkers may reflect the underlying conditions and contribute to elucidating the obesity paradox.