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Abstract: TH-PO185

FGF23 as a Risk Factor for Cardiovascular Events and Mortality in Patients in the EVOLVE Trial

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Danese, Mark D., Outcomes Insights, Inc., Westlake Village, CA, California, United States
  • Chertow, Glenn Matthew, Stanford University School of Medicine, Palo Alto, California, United States
  • Cooper, Kerry, Amgen Inc., Thousand Oaks, California, United States
  • Halperin, Marc, Outcomes Insights, Inc, Westlake Village, California, United States
  • Stark, William W., Amgen INC, Newbury Park, California, United States
  • Wheeler, David C., University College London, London, LoNDON, United Kingdom
  • Block, Geoffrey A., Colorado Kidney Care, Denver, Colorado, United States
Background

Risk factors for all-cause mortality and cardiovascular events in dialysis patients with CKD-MBD have not been fully elucidated. Historically, analyses using mineral metabolism biomarkers to predict clinical outcomes have used neither FGF23 nor clinically-adjudicated events.

Methods

We evaluated FGF23 and other risk factors using data from EVOLVE, a randomized, double-blind placebo-controlled, event-driven trial (N=3883 with CKD-MBD) in which subjects were followed for up to 64 months. EVOLVE compared cinacalcet to placebo with a composite endpoint of death, myocardial infarction, hospitalization for unstable angina, heart failure (HF), or peripheral vascular event. Inclusion criteria included PTH ≥300 pg/mL, calcium ≥8.4 mg/dL, and phosphorus ≥5.3 mg/dL. Our study quantified FGF23-associated risk following dose titration (week 20). We used Cox proportional hazards models to estimate the relative risk of the composite endpoint and its components, adjusting for age, albumin, race, sex, smoking status, Hb, P, Ca, PTH, and alkaline phosphatase as well as history of diabetes, coronary artery disease, HF, and stroke. Laboratory values and age were modeled using penalized splines to allow for a flexible relationship between the measure and risk (e.g., S or U-shaped).

Results

We included 2,411 patients who were event-free at week 20, and had an FGF23 measure. There were 1100 events (526 deaths and 574 non-fatal events). In adjusted models, higher log FGF23 was associated with a higher risk of the composite endpoint and its components. See Figure.

Conclusion

FGF23 appears to be an important, independent risk factor for mortality and CV events in addition to those traditionally associated with CKD-MBD.

Association of Log(FGF23) with the Composite Endpoint and its Components

Funding

  • Commercial Support