Epidemiologic insights on the role of fibroblast growth factor 23 in cardiovascular disease

Abstract

Purpose of Review Fibroblast growth factor 23 (FGF23) regulates phosphate and vitamin D homeostasis and rises as kidney function declines. Animal studies have demonstrated direct and indirect effects of FGF23 that may promote heart disease. Herein we review the recent epidemiologic literature evaluating the relationship between FGF23 and cardiovascular disease. Recent Findings In observational prospective studies higher FGF23 associates with greater risk of incident cardiovascular disease including ischemic heart disease, stroke, heart failure, and atrial fibrillation. These studies establish a temporal sequence of events over long term-follow up that suggest a possible role of FGF23 in cardiovascular disease pathogenesis. In most studies risk is generally graded, however in the largest study to date, higher FGF23 within the low-normal range was not associated with higher risk. In several recent studies higher FGF23 associated more strongly with risk of congestive heart failure compared with atherosclerotic events, a finding consistent with surrogate endpoints and animal experiments. Currently the utility of FGF23 as a predictive biomarker of cardiovascular risk is not established, and interventions to reduce FGF23 need to be studied to confirm its possible pathophysiologic role. Summary Higher FGF23 is associated with the subsequent development of cardiovascular disease, and perhaps most notably heart failure, in a growing number of studies. These findings bolster ongoing efforts to lower FGF23 using strategies to reduce phosphate intake and absorption.

Fibroblast Growth Factor 23 Predicts All-Cause Mortality in a Dose-Response Fashion in Pre-Dialysis Patients with Chronic Kidney Disease

“…Mounting evidence revealed the close relationship between excess serum FGF23 and cardiac events and all-cause mortality in the CKD population [11][12][13][14] . While it is not merely a biomarker, research showed the biological relevance of elevated FGF23 and adverse outcomes: apart from dysregulated phosphorus metabolism, excess FGF23 could induce vascular calcification and myocardial hypertrophy in both klotho-dependent or -independent ways [15,16] . Based on the associations between the FGF23 and CVD in pathogenesis, the factor is expected to be a predictor with high specificity in CVD.…”

The Association of Fgf23 and Inflammation in Heart Failure with Normal Kidney Function

“…C-reactive protein serves as an excellent biomarker indicating low grade inflammation and together with several other cytokines (Tumor necrosis factor alpha, Interleukin 6) is associated with heart failure even in a doseresponse relationship [3,4]. Fibroblast growth factor-23, in combination with the modulating co-receptor α-Klotho, is a phosphationic hormone produced by osteocytes and regulates calcium and phosphate homeostasis which are cornerstones for bone integrity [5]. FGF23 was extensively studied in renal dysfunction and inflammation [6][7][8][9][10].…”

“…FGF23 was extensively studied in renal dysfunction and inflammation [6][7][8][9][10]. Recently, FGF23 was associated with atrial fibrillation, left ventricular hypertrophy, as well as morbidity and mortality in heart failure [5,11,12]. However, most studies of FGF23 and heart failure are confounded by chronic kidney disease which is accompanied by disturbed mineral-, blood and Iron-homeostasis as well as inflammationall of them interacting with FGF23making it difficult to explain a direct role of FGF23 on the heart [13][14][15].…”

Update on Chronic Kidney Disease Mineral and Bone Disorder in Cardiovascular Disease

“…14,24–33 Like phosphorus, increased cardiovascular risk associated with higher FGF23 was reported in a wide variety of groups including those with ESRD, CKD, and the general population with the strongest risks in patients with CKD and ESRD. 34 Although FGF23 has been associated with many non-cardiovascular outcomes as well, 29,33,35–38 some of the most commonly reported and robust associations are with heart failure. 34…”

“…34 Although FGF23 has been associated with many non-cardiovascular outcomes as well, 29,33,35–38 some of the most commonly reported and robust associations are with heart failure. 34…”