Review explores adipose tissue's role, natriuretic peptide paradox, and diagnostic challenges in obesity-related HFpEF

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome, often exacerbated by obesity and metabolic dysfunction. Adipose tissue (AT) is increasingly recognized as an active endocrine and immunological organ, secreting adipokines that can drive chronic low-grade inflammation, vascular endothelial dysfunction, and microcirculation damage, contributing to the metabolic HFpEF phenotype. A significant diagnostic challenge is the "obesity-natriuretic paradox," where obese individuals frequently exhibit lower natriuretic peptide (NP) concentrations despite an elevated risk of developing heart failure, complicating accurate assessment and prognosis.

This narrative review synthesized existing literature by conducting a search across major scientific databases, including Pubmed and Google. The search utilized specific keywords: HFpEF, obesity, adipose tissue, and natriuretic peptides. The authors aimed to discuss the intricate relationships between adipose tissue pathophysiology, HFpEF development, and observable natriuretic peptide concentrations, while also considering the clinical significance and diagnostic hurdles posed by these interactions. Additionally, the review highlighted current treatment strategies for the metabolic subtype of HFpEF and future therapeutic prospects.

The review highlights that dysfunctional adipose tissue, particularly visceral fat, acts as an active endocrine and immunological organ, secreting adipokines that contribute to chronic low-grade inflammation. This inflammation is implicated in vascular endothelial dysfunction and microcirculation damage, driving the common metabolic HFpEF phenotype. A central theme is the "obesity-natriuretic paradox," where individuals with increasing body mass index (BMI) often present with lower concentrations of natriuretic peptides (NPs), despite facing a greater hemodynamic burden and higher risk of developing heart failure. This paradox significantly impacts the diagnostic and prognostic assessment of HFpEF patients, as the "optimal" natriuretic peptide cutoff values for detecting heart failure remain a subject of ongoing debate. The authors discuss how these complex interactions necessitate a re-evaluation of diagnostic criteria and treatment approaches for obesity-related HFpEF.

The "adipokine hypothesis" posits that adipokines from dysfunctional adipose tissue induce chronic low-grade inflammation, leading to vascular damage and the metabolic HFpEF phenotype.