Key result
SGLT2 inhibitors and GLP-1 receptor agonists mitigate endothelial dysfunction and residual inflammation driving HFpEF progression.
Why the study?
HFpEF remains a major cardiology challenge characterized by multifactorial pathophysiology and limited therapeutic response, prompting an analysis of endothelial dysfunction, residual inflammation, and emerging therapeutic perspectives targeting these mechanisms.
Does targeting endothelial dysfunction and residual inflammation with emerging therapies (such as SGLT2 inhibitors, GLP-1 receptor agonists, statins, NO-cGMP-PKG modulators, and interleukin blockers) improve vascular function and clinical outcomes in adult patients with heart failure with preserved ejection fraction (HFpEF)?
Does targeting endothelial dysfunction and residual inflammation with emerging therapies (such as SGLT2 inhibitors, GLP-1 receptor agonists, statins, NO-cGMP-PKG modulators, and interleukin blockers) improve vascular function and clinical outcomes in adult patients with heart failure with preserved ejection fraction (HFpEF)?
This narrative review highlights that endothelial dysfunction and chronic low-grade inflammation are central pathophysiological drivers in HFpEF, supporting an integrated therapeutic model combining metabolic, vascular, and anti-inflammatory modulation.
Answers are grounded in this paper and cite their sources.
Supports targeting endothelial dysfunction and IL-6/TNF-α inflammation in HFpEF; leaves open adoption of SGLT2 inhibitors or GLP-1 agonists pending RCTs.
Heart failure with preserved ejection fraction (HFpEF) remains one of the greatest challenges in modern cardiology, characterized by multifactorial pathophysiology and limited therapeutic response. This study aimed to critically analyze the scientific evidence on endothelial dysfunction and residual inflammation in HFpEF, as well as to identify emerging therapeutic perspectives targeting these mechanisms. A Narrative Review of the Literature was conducted using PubMed, Scopus, ScienceDirect, and SciELO databases, including studies published between 2013 and 2025. The results show that HFpEF is a multisystemic condition in which endothelial dysfunction acts as a key pathophysiological axis, mediating vascular stiffness and impaired diastolic function. Residual inflammation, driven by cytokines such as IL-6 and TNF-α, perpetuates oxidative stress and endothelial senescence, promoting microvascular remodeling and clinical deterioration. Therapeutically, SGLT2 inhibitors, GLP-1 receptor agonists, statins, and NO-cGMP-PKG pathway modulators demonstrate vascular and anti-inflammatory benefits, while interleukin-targeted therapies emerge as complementary strategies. It is concluded that restoring endothelial function and controlling low-grade chronic inflammation are central goals for future interventions, representing an integrated therapeutic model that combines vascular, metabolic, and immunological modulation in HFpEF management.
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Medeiros et al. (2025) conducted a review in Heart failure with preserved ejection fraction (HFpEF). SGLT2 inhibitors, GLP-1 receptor agonists, statins, NO-cGMP-PKG pathway modulators, and interleukin blockers was evaluated on Endothelial function restoration, arterial stiffness reduction, and modulation of residual inflammation. Endothelial dysfunction and residual inflammation mediated by IL-6 and TNF-α drive HFpEF progression, which can be mitigated by SGLT2 inhibitors, GLP-1 receptor agonists, and anti-IL therapies.
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