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FGF-23, hsCRP, Cardiovascular Events, and the Benefit of Canagliflozin in the CANVAS Trial

Aranya Punithan1, Ehsan Ghamarian2, Daniela Grothe3

  • 1Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Cardiovascular Division, Women's College Hospital, Toronto, Ontario, Canada.

JACC. Advances
|October 28, 2025
PubMed

Insights

Fibroblast growth factor 23 (FGF-23) and high-sensitivity C-reactive protein (hsCRP) indicate higher cardiovascular risk in type 2 diabetes patients. However, these biomarkers did not predict preferential benefit from canagliflozin treatment.

Area of Science:

  • Cardiology
  • Endocrinology
  • Biomarker Research

Background:

  • The CANVAS trial investigated cardiorenal biomarkers, including fibroblast growth factor 23 (FGF-23) and high-sensitivity C-reactive protein (hsCRP), for risk prediction in type 2 diabetes.
  • Sodium-glucose co-transporter 2 (SGLT2) inhibitor therapy is a key treatment for type 2 diabetes, and understanding its impact on cardiovascular outcomes is crucial.
  • Assessing the utility of FGF-23 and hsCRP in predicting cardiovascular events and treatment response to SGLT2 inhibitors provides valuable clinical insights.

Purpose of the Study:

  • To evaluate the prognostic value of FGF-23 and hsCRP in predicting adverse cardiovascular (CV) outcomes.
  • To assess the role of these biomarkers in determining treatment response to SGLT2 inhibitor therapy.
  • To explore the association of FGF-23 and hsCRP levels with composite CV death or hospitalization for heart failure (HHF), HHF, CV death, and major adverse CV events.

Main Methods:

  • Longitudinal biomarker samples from 3,188 participants of the CANVAS trial were analyzed.
  • Multivariable Cox proportional hazard models were used to assess the association between FGF-23, hsCRP, and CV outcomes, adjusted for clinical factors and injury markers.
  • Participants were stratified into low-risk (quartiles 1-3) and high-risk (quartile 4) groups based on FGF-23 and hsCRP levels for multimarker risk assessment.

Main Results:

  • Elevated FGF-23 levels (quartile 4) were significantly associated with increased risk of CV death/HHF and HHF.
  • Higher hsCRP levels (quartile 4) were significantly associated with increased risk of CV death and major adverse CV events.
  • Canagliflozin demonstrated a consistent treatment effect across both high- and low-risk groups defined by FGF-23 and hsCRP levels, with no significant interaction.

Conclusions:

  • FGF-23 and hsCRP serve as valuable biomarkers associated with elevated cardiovascular risk in patients with type 2 diabetes.
  • These biomarkers did not identify a subgroup of patients who experienced a preferential benefit from canagliflozin treatment.
  • The findings underscore the importance of these biomarkers for risk stratification but highlight limitations in predicting personalized treatment response to SGLT2 inhibitors.
Abstract

Keywords:
FGF-23SGLT2 inhibitorcanagliflozincardiovascular outcomeshsCRP

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