Patients with chronic kidney disease (CKD) also have a high risk of developing cardiovascular diseases. Fibroblast growth factor 23 (FGF-23) promotes phosphate secretion and vitamin D metabolism in the kidney, and the level of FGF-23 is elevated in CKD. Moreover, FGF-23 is itself associated with an increased risk of cardiovascular diseases, including atrial fibrillation (AF). So is FGF-23 the link between AF and CKD? A new report published in Circulation suggests that it might be.
“We wanted to determine if the altered mineral metabolism often seen in patients with CKD could explain the associated risk of AF,” explains lead author Jehu Mathew. The investigators measured FGF-23 levels in serum samples collected during two community-based cohort studies designed to assess cardiovascular risk factors—the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS). In total, the team analysed data from 6,398 participants from the MESA and 1,350 individuals from the CHS, all of whom were free from cardiovascular disease at initial assessment.
After adjusting for patient demographics and confounding factors, the investigators found that a two-fold rise in FGF-23 concentration was associated with a 41% increased risk of AF in the MESA cohort (HR 1.41, 95% CI 1.13–1.76, P = 0.003) and a 29% increased risk of AF in the CHS participants (HR 1.29, 95% CI 1.05–1.60, P = 0.018).
In the MESA, impaired renal function (an estimated glomerular filtration rate [eGFR] of <60 ml/min/1.73m2) was also associated with an increased risk of AF (HR 1.62, 95% CI 1.19–2.20). However, after adjustment for FGF-23, the hazard ratio dropped to 1.43 (95% CI 1.05–1.95). “In MESA, an association of low eGFR with incident AF was partially attenuated by adjusting for FGF-23 levels,” adds Mathew. “These results suggest that FGF-23 might, in part, mediate the known association of CKD with AF.”
Unfortunately, FGF-23 levels did not improve AF risk prediction, but as Mathew concludes, “[FGF-23] was examined in isolation, and a comprehensive evaluation of the renal–mineral–metabolism axis might yield different results”.
References
Mathew, J. S. et al. Fibroblast growth factor-23 and incident atrial fibrillation: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS). Circulation 10.1161/CIRCULATIONAHA.113.005499
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Geach, T. FGF-23 associated with incident AF—a link with CKD?. Nat Rev Cardiol 11, 436 (2014). https://doi.org/10.1038/nrcardio.2014.95
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DOI: https://doi.org/10.1038/nrcardio.2014.95
