This systematic review evaluates the combined role of epicardial fat thickness (EFT) and B-type natriuretic peptide (BNP)/N-terminal pro B-type natriuretic peptide (NT-proBNP) in HF risk stratification, examining their pathophysiological interplay and clinical utility across diverse populations, including a wide age range, various comorbidities (e.g., obesity, diabetes, and systemic sclerosis), and geographic regions. The gene discussed is NPPB; the disease is obesity disorder.