The Adipokine Hypothesis and Inflammation: Explaining Pathogenesis and Guiding Treatment

In this solo episode of The TellTale Heart: The Pharmacist Cardiovascular Digest, host Craig Beavers, PharmD, FACC, FAHA, FCCP, BCCP, BCPS (AQ-Cardiology), CACP, sets the stage for content ahead of the upcoming American Heart Association (AHA) Scientific Sessions meeting. He previews future podcast series exploring hypertrophic cardiomyopathy and cardiac amyloidosis, emphasizing the goal of providing pharmacists and clinicians with fresh perspectives on evolving cardiovascular topics. Beavers also shares plans for new multimedia initiatives—including video segments and potential live-streaming from the AHA meeting—aimed at engaging listeners and expanding the podcast’s educational reach.

The main focus of this episode is a discussion of the newly proposed "Adipokine Hypothesis" model of heart failure with preserved ejection fraction (HFpEF). This hypothesis, recently published in the Journal of the American College of Cardiology (JACC), suggests that bioactive mediators released from adipose tissue—known as adipokine—may serve as central drivers of HFpEF by promoting inflammation, fibrosis, and microvascular dysfunction. This framework could unify previously contrasting theories about HFpEF’s mechanisms, especially in patients with obesity and metabolic dysfunction. The hypothesis has the potential to advance drug development, biomarker discovery, and personalized medicine, while also addressing challenges such as phenotypic variability, measurement limitations, and establishing causality. For pharmacists, Beavers says that understanding adipokine biology could influence risk stratification, patient counseling, and therapeutic choices involving glucagon-like peptide-1 (GLP-1) receptor agonists or sodium-glucose cotransporter 2 (SGLT2) inhibitors.

In the latter half, Beavers turns to a JACC scientific statement on inflammation and cardiovascular disease, underscoring how inflammation is not merely a consequence but an active driver of atherosclerosis and heart failure. He reviews decades of evidence—from CRP and IL-6 studies to clinical trials—that demonstrate the benefits of targeting inflammation to reduce cardiovascular risk. Beavers encourages pharmacists to consider “residual inflammatory risk” even in patients with well-controlled low-density lipoprotein levels and to optimize therapies that offer anti-inflammatory benefits (eg, statins, SGLT2 inhibitors, GLP-1 agonists).

Pharmacists have an expanding role in precision medicine. They identify at-risk patients, interpret biomarkers, and integrate new anti-inflammatory and metabolic therapies into practice, positioning themselves as key contributors in the future of cardiovascular prevention and heart failure care.