You Zhou ¹ Yingli Xie ² Jingjing Dong ² Kunlun He ^1*

• ¹ Nankai University, Tianjin, China
• ² The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan Province, China

Background: Metabolic disorders and overweight or obesity are highly prevalent and intricately linked in patients with chronic heart failure (CHF). However, it remains unclear whether there is an interactive effect between these conditions and the prognosis of heart failure, and whether such an interaction is influenced by stratification based on age and sex. Methods: A total of 4,955 patients with CHF were enrolled in this study. Metabolic status was assessed according to the presence or absence of metabolic syndrome (MetS). BMI categories included normal weight and overweight or obesity (BMI < 24, ≥ 24 kg/m2). Patients were divided into four phenotypes according to their metabolic status and BMI: metabolically healthy with normal weight (MHNW), metabolically unhealthy with normal weight (MUNW), metabolically healthy with overweight or obesity (MHO), and metabolically unhealthy with overweight or obesity (MUO). The incidence of primary outcomes, including all-cause and cardiovascular (CV) death, was recorded. Results: During a mean follow-up of 3.14 years, a total of 1,388 (28.0%) all-cause deaths and 815 (16.4%) CV deaths were documented. Compared to patients with the MHNW phenotype, those with the MUNW (adjusted hazard ratio [aHR], 1.66; 95% confidence interval [CI], 1.38–2.00) or MUO (aHR, 1.42 [95% CI, 1.24–1.63]) phenotypes had a greater risk of all-cause death, and those with the MHO phenotype (aHR, 0.61 [95% CI, 0.51–0.72]) had a lower risk of all-cause death. Moreover, the above phenomenon existed mainly among males and elderly females (aged ≥ 60 years). In nonelderly females (aged < 60 years), the detrimental effects of MetS were lower (aHR, 1.05 [95% CI, 0.63–1.75] among MUNW group and aHR, 0.52 [95% CI, 0.34–0.80] among MUO group), whereas the protective effects of having overweight or obesity persisted irrespective of metabolic status (aHR, 0.43 [95% CI, 0.26–0.69] among MHO group and aHR, 0.52 [95% CI, 0.34–0.80] among MUO group). Conclusions: In male and elderly female patients with CHF, the detrimental effects of MetS outweighed the protective benefits of having overweight or obesity. Conversely, in nonelderly females, the protective effects of having overweight or obesity were significantly greater than the adverse impacts of MetS.