Soluble klotho and mortality: The Ludwigshafen Risk and Cardiovascular Health Study

•We evaluate the role of soluble klotho as mortality risk factor in patients with coronary angiography.•Soluble klotho levels do predict mortality risk over 9.9 years of follow-up.•Soluble klotho adds little to future risk prediction, which clarifies an important aspect within the klotho-FGF23-axis.

BackgroundExperimental evidence suggests that soluble klotho (s-klotho), a co-receptor for fibroblast growth factor 23 (FGF23), may modulate cardiovascular risk through multiple mechanisms. However, the predictive value of s-klotho in patients remains unclear. Therefore, the present study examined in a large cohort of patients referred for coronary angiography whether s-klotho is associated with cardiovascular and total mortality.MethodsThe longitudinal associations between baseline s-klotho and FGF23 concentrations and mortality were evaluated in 2948 participants of the Ludwigshafen Risk and Cardiovascular Health Study (LURIC), referred for coronary angiography.ResultsMean age of participants was: 63 ± 10 years. Patients with diabetes mellitus (n = 1136) had elevated s-klotho: [440 (430-449) versus 414 (406-421) pg/mL, p < 0.001]. S-klotho decreased in parallel to glomerular filtration rate (GFR) and increased in parallel to FGF23. During a median follow-up of 9.9 years, 874 deaths (30%) occurred, 539 (18%) of which were cardiovascular. After adjustment for cardiovascular risk factors, the hazard ratios in the fourth quartile compared to the first quartile of s-klotho were 1.14 (95%CI, 0.94-1.38; p = 0.187) for all-cause mortality and 1.03 (95%CI, 0.80-1.31; p = 0.845) for cardiovascular mortality. Excess mortality prediction by high levels of baseline FGF23 was not modified by adjustment for baseline s-klotho levels.ConclusionsKlotho does not add predictive power to cardiovascular and mortality risk assessment in patients with normal renal function.