Prognostic value of human serum alpha-klotho concentrations in patients with heart failure with reduced ejection fraction

Abstract

Objective

Heart Failure (HF) is a major health problem with high prevalence and mortality. Identifying new biomarkers involved in controlling heart failure progression has become particularly important. This study evaluated the association between serum α-klotho concentrations and long-term all-cause mortality in patients with stable HF.

Design and methods

We analyzed serum α-klotho levels in 230 adults (135 patients with HF with reduced ejection fraction and 95 age and sex-matched healthy controls). A classification and regression tree analysis was used to stratify patients by α-klotho concentration, using all-cause mortality within a 5-year follow-up as the primary endpoint. Differences in log-NT-proBNP levels across α-klotho groups were assessed using the Kruskal-Wallis test with Dunn’s post-hoc comparisons. Kaplan-Meier survival analysis evaluated the association between α-klotho stratified groups and 5-year all-cause mortality.

Results

Patients with higher serum α-klotho levels had significantly lower mortality and lower log NT-proBNP across α-klotho groups (χ²(2) = 8.05, p = 0.018) when compared to lower α-klotho concentration levels. Kaplan-Meier curves show the significant difference in survival across α-klotho stratification (log-rank p < 0.01).

Conclusion

Patients with higher serum α-klotho concentrations were associated with lower log-NT-proBNP levels and better 5-year survival in all patients as well as in patients with heart failure, compared to those with lower. These findings support the role of α-klotho as a promising cardioprotective biomarker for risk stratification in patients with HF.