Abstract: TH-OR29
Association of the Ratio of Intact-to-C-terminal Fibroblast Growth Factor 23 with Heart Failure with Preserved Ejection Fraction
Session Information
- CKD-MBD and Kidney Stones: Novel Insights
October 24, 2024 | Location: Room 6D, Convention Center
Abstract Time: 04:40 PM - 04:50 PM
Category: Bone and Mineral Metabolism
- 502 Bone and Mineral Metabolism: Clinical
Authors
- Akwo, Elvis Abang, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Robinson-Cohen, Cassianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Perwad, Farzana, University of California San Francisco, San Francisco, California, United States
- Ix, Joachim H., University of California San Diego, La Jolla, California, United States
- David, Valentin, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background
Previous studies report an association between high levels of circulating fibroblast growth factor 23 (FGF23) and the risk of heart failure with preserved ejection fraction (HFpEF) particularly in chronic kideney disease (CKD). One such mechanism for FGF23 elevation is decreased proteolytic cleavage marked by increased circulating intact-to-C-terminal FGF23 ratio (iFGF23:cFGF23). The aim of this study was to investigate the association between the iFGF23:cFGF23 ratio and the risk of HFpEF using a two-sample Mendelian Randomization (MR) approach.
Methods
Genetic instruments were independent significant single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) of iFGF23:cFGF23 ratio in 745 participants in the Cardiovascular Health Study. Summary-level data for HFpEF were from a GWAS conducted among 17,030 participants in Vanderbilt’s DNA Biobank (BioVU). The main analysis was conducted using the random-effects inverse variance weighted (IVW) estimator. Sensitivity analyses used the weighted median and MR-Egger methods. Analyses were performed separately in individuals of European and African ancestry and then meta-analyzed.
Results
In the transethnic meta-analysis, genetically predicted higher values of the iFGF23:cFGF23 ratio were associated with greater odds of HFpEF (OR=1.07, 95%CI: 1.02-1.12, p=0.007). The MR estimate was consistent in models adjusted for eGFR (OR=1.06, 95%CI: 1.02-1.12, p=0.02) and across statistical approaches (weighted median and MR-Egger). The p-value for the MR-Egger intercept test was consistently greater than 0.05 across analytic subgroups suggesting no evidence of directional pleiotropy.
Conclusion
This MR suggests that higher values of iFGF23:cFGF23 – a marker of decreased FGF23 cleavage – is associated with greater risk of HFpEF. Additional work into the mechanisms of FGF23 elevation in CKD and its relationship with heart failure is needed.
Funding
- NIDDK Support