Fibroblast Growth Factor 23 is a strong independent marker of worse cardiovascular outcomes after an acute coronary syndrome

Background and aims: This study aimed to assess the role of plasmatic fibroblast growth factor 23 (FGF23) as a prognostic marker after an acute coronary syndrome (ACS). Methods: This prospective and multicentric study included 1,190 patients with ACS. FGF23 plasma levels and other components of mineral metabolism (calcidiol, parathormone [PTH], klotho, and phosphate), lipids, troponin, high-sensitivity C-reactive protein, N-terminal-pro-brain natriuretic peptide and estimated glomerular filtration rate (eGFR) were measured at discharge. The primary outcome was a combination of acute ischemic events, heart failure (HF) and death. Secondary outcomes were the separate components of the primary outcome. Results: Median follow-up was 5.44 (3.03-7.46) years. 294 patients developed the primary outcome. Patients with FGF23 levels below the median were predominantly males, younger, and with lower load of cardiovascular risk factors. Calcidiol and PTH levels were lower among them. Multivariable analysis showed that FGF23 (HR 1.18 [1.08-1.29], p<0.001), calcidiol (HR 0.86 [0.74-1.00], p=0.046), previous CAD or cerebrovascular accidents, and hypertension were independent predictors of the primary outcome. The predictive power of FGF23 was homogeneous across different subgroups of population. FGF23 resulted an independent predictor of HF (HR 1.38 [1.22-1.57], p<0.001), and death (HR 1.21 [1.07-1.37], p=0.002), but not of acute ischemic events. According to renal function, FGF-23 was an independent predictor for the primary outcome in patients with estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73m2. Conclusions: FGF23 is a strong, independent predictor of HF and death among patients with ACS. This effect is homogeneous across different subgroups of population and not limited to patients with chronic kidney disease (CKD). ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by grants from Instituto de Salud Carlos III (ISCIII) (PI17/01495; PI20/00923), Ministry of Science and innovation (RTC2019-006826-1), and Institute of heart de Salud Carlos III FEDER (FJD biobank: RD09/0076/00101). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Statement: The research protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the human research committees of the institutions participating in this study: Fundación Jiménez Díaz, Hospital Fundación Alcorcón, Hospital de Fuenlabrada, Hospital Universitario Puerta de Hierro Majadahonda, and Hospital Universitario de Móstoles. All patients signed informed consent documents. All patients signed informed consent documents. Date of approval by the Ethics Committee was 24th April 2007 (act number 05-07). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable Data are available