Fibroblast growth factor 23 is associated with risk of intracerebral hemorrhage

Background and purpose Fibroblast growth factor 23 (FGF23) is an osteogenic hormone associated with chronic kidney disease and is an emerging risk factor for several cardiovascular diseases. The association of FGF23 with stroke is unclear. The aim of this study was to investigate the association of FGF23 with incident intracerebral hemorrhage (ICH). Methods This was a nested case-control study of 220 ICH cases and 244 age- and sex-matched controls from the population-based Malmo Diet and Cancer Study (n = 28,449). Incident ICH cases were ascertained using national registers and classified by bleeding location. Logistic regression was used to study the association of plasma levels of FGF23 with incident ICH, adjusting for potential ICH risk factors. Subgroup analyses were performed for lobar and non-lobar ICH, fatal ICH, ICH with large volume and ICH with poor functional outcome, respectively. Results Higher FGF23 levels at baseline were significantly associated with incident ICH. After multivariable adjustment, the odds ratio for the association with all ICH was 1.84 (95% confidence interval [CI] 1.25-2.71, p = 0.002) per doubling of FGF23 concentration. For lobar and non-lobar ICH, odds ratios were 1.73 (95% CI 1.04-2.87, p = 0.035) and 2.13 (95% CI 1.32-3.45, p = 0.002), respectively. FGF23 was also significantly associated with fatal ICH, ICH with large volume and ICH with poor functional outcome. Conclusions Higher FGF23 was associated with incident ICH in this nested case-control study. Further studies are required to explore whether the association is causal.

Automated summary

Higher baseline FGF23 levels were significantly associated with incident intracerebral hemorrhage (ICH), particularly in lobar and non-lobar ICH. FGF23 was also significantly associated with fatal ICH, ICH with large volume, and ICH with poor functional outcome. Further studies are needed to determine if this association is causal.