Marthi A, et al. - Researchers tested the premise that fibroblast growth factor-23 (FGF-23) plays a role in the increased risk of cardiovascular disease in patients with CKD. A possibly noncausal link between FGF-23 and cardiovascular disease risk was suggested by the observed similarly-sized links between increased FGF-23 concentration and cardiovascular (atherosclerotic and nonatherosclerotic) and noncardiovascular outcomes and by the reported absence of any exposure-response relationship.

Methods

• Prospective studies reporting links between FGF-23 concentration and risk of cardiovascular events were identified.
• For each outcome, extraction of maximally adjusted risk ratios (RRs) was done and scaled to a comparison of the top vs bottom third of the baseline FGF-23 concentration, then the results were aggregated.

Results

• The measured median FGF-23 concentrations, depending on the assay used, 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.
• The summary RRs (95% confidence intervals [95% CIs]) revealed in comparisons of participants in the top and bottom FGF-23 concentration thirds were as follows: 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.
• Data showed the summary RR for noncardiovascular mortality, calculated indirectly, was 1.52 (95% CI, 1.28 to 1.79).
• No trend in RRs was seen across the studies when studies were ordered by average differences in FGF-23 concentration between the top and bottom thirds.