Adipokines and Cardiometabolic Heart Failure with Preserved Ejection Fraction: A State-of-the-Art Review

Abstract

Background: Cardiometabolic heart failure with preserved ejection fraction (HFpEF) is largely driven by obesity-related factors, including adipokines and bioactive peptides primarily secreted by the adipose tissue, such as leptin, adiponectin, and resistin. These molecules link metabolic dysregulation to cardiovascular dysfunction, influencing HFpEF progression and patient outcomes Methods: A comprehensive literature search was conducted in PubMed up to 20 November 2024, using keywords and MeSH terms, such as "HFpEF", "adipokines", "leptin", "adiponectin", and "resistin", yielding 723 results. Boolean operators refined the search, and reference lists of key studies were reviewed. After screening for duplicates and irrelevant studies, 103 articles were included, providing data on adipokines' roles in HFpEF pathophysiology, biomarkers, and therapeutic implications.

Results: Both preclinical and clinical studies have demonstrated that adipokines play a role in modulating cardiovascular function, thereby contributing to the development of cardiometabolic HFpEF. Leptin promotes myocardial hypertrophy, fibrosis, endothelial dysfunction, and inflammation, though contradictory evidence suggests potential cardioprotective roles in subgroups like obese African American women. Adiponectin generally offers protective effects but presents a paradox, where elevated levels may correlate with worse outcomes, which may reflect either a compensatory response to cardiac dysfunction or a maladaptive state characterized by adiponectin resistance. Resistin is associated with increased cardiovascular risk through pro-inflammatory and pro-fibrotic effects, though its role in HFpEF requires further clarification. Other adipokines, like retinol-binding protein 4 and omentin-1, have emerged as potential contributors. Despite growing insights, clinical translation remains limited, underscoring a significant gap between experimental evidence and therapeutic application.

Conclusions: Future research should focus on targeted interventions that modulate adipokine pathways to potentially improve HFpEF outcomes. Innovative treatment strategies addressing underlying metabolic disturbances and adipokine dysregulation are essential for advancing the management of this challenging condition.

Keywords: adipokines; adiponectin; cardiology; cardiometabolic medicine; endocrinology; heart failure with preserved ejection fraction; leptin; metabolism; obesity; resistin.

Figure 1

Key cardiovascular effects of the major adipokines implicated in HFpEF pathophysiology.