Background Fibroblast growth factor-23 (FGF-23) has been hypothesized to play a role in the increased risk of cardiovascular disease in patients with CKD.

Methods We identified prospective studies reporting associations between FGF-23 concentration and risk of cardiovascular events. Maximally adjusted risk ratios (RRs) were extracted for each outcome and scaled to a comparison of the top versus bottom third of the baseline FGF-23 concentration, and the results aggregated.

Results Depending on the assay used, median FGF-23 concentrations were 43–74 RU/ml and 38–47 pg/ml in 17 general population cohorts; 102–392 RU/ml in nine cohorts of patients with CKD not requiring dialysis; and 79–4212 RU/ml and 2526–5555 pg/ml in eight cohorts of patients on dialysis. Overall, comparing participants in the top and bottom FGF-23 concentration thirds, the summary RRs (95% confidence intervals [95% CIs]) were 1.33 (1.12 to 1.58) for myocardial infarction, 1.26 (1.13 to 1.41) for stroke, 1.48 (1.29 to 1.69) for heart failure, 1.42 (1.27 to 1.60) for cardiovascular mortality, and 1.70 (1.52 to 1.91) for all-cause mortality. The summary RR for noncardiovascular mortality, calculated indirectly, was 1.52 (95% CI, 1.28 to 1.79). When studies were ordered by average differences in FGF-23 concentration between the top and bottom thirds, there was no trend in RRs across the studies.

Conclusions The similarly-sized associations between increased FGF-23 concentration and cardiovascular (atherosclerotic and nonatherosclerotic) and noncardiovascular outcomes, together with the absence of any exposure–response relationship, suggest that the relationship between FGF-23 and cardiovascular disease risk may be noncausal.

背景成纤维细胞生长因子 23 (FGF-23) 被假设在 CKD 患者心血管疾病风险增加中发挥作用。

方法我们确定了报告 FGF-23 浓度与心血管事件风险之间关联的前瞻性研究。提取每个结果的最大调整风险比 (RR)，并按比例比较基线 FGF-23 浓度的顶部三分之一和底部三分之一，然后汇总结果。

结果根据所使用的检测方法，17 个一般人群队列中 FGF-23 浓度中位数分别为 43-74 RU/ml 和 38-47 pg/ml；九组不需要透析的 CKD 患者为 102–392 RU/ml；8 组透析患者的血浆浓度分别为 79-4212 RU/ml 和 2526-5555 pg/ml。总体而言，比较 FGF-23 浓度顶部和底部三分之一的参与者，心肌梗塞的总结 RR（95% 置信区间 [95% CI]）为 1.33（1.12 至 1.58），中风为 1.26（1.13 至 1.41），1.48心力衰竭死亡率为 1.29 至 1.69，心血管死亡率为 1.42（1.27 至 1.60），全因死亡率为 1.70（1.52 至 1.91）。间接计算的非心血管死亡率的汇总 RR 为 1.52（95% CI，1.28 至 1.79）。当研究按照顶部和底部三分之一之间 FGF-23 浓度的平均差异进行排序时，所有研究中的 RR 没有趋势。

结论FGF-23 浓度增加与心血管（动脉粥样硬化和非动脉粥样硬化）和非心血管结局之间的相关性相似，并且不存在任何暴露-反应关系，表明 FGF-23 与心血管疾病风险之间的关系可能是非因果关系。