Protective role of protein Klotho biomarker in acute heart failure

Abstract

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by a grant from the Institute of Medical Sciences, Univeristy of Opole, Poland Background Klotho is an antiaging protein with pleiotropic actions that exerts organ protection. There is evidence that Klotho protein acts as a human aging-suppression molecule and correlates with life span, coronary artery disease, atherosclerosis, and osteoporosis. In laboratory models of damage, an increased expression of Klotho protein in human cardiac myocytes and release of Klotho protein into the extracellular space suggests a potential compensatory and cardioprotective effect. The aim of the present study was to assess changes of Klotho protein levels during an episode of acute heart failure (AHF) as well as its long-term prognostic utility in population of AHF patients compared to other biomarkers. Methods We analysed 112 consecutive patients admitted to ICCU between June 2019 and January 2021 due to hight-risk AHF. Blood samples were collected on admission, at discharge as well as at the 30-day. Patients were then followed-up for all-cause mortality and rehospitalizations due to heart failure. Results Patients (N=112; median age 68 years, 75% men, median left ventricular ejection fraction 30% [IQR 20-38%]) had median admission levels of Klotho protein = 670 pg/ml [501-851], FGF-23 = 1278 pg/ml [283-4429], NT-proBNP = 5361 ng/l [3019-13182], and GDF-15 = 4582 pg/ml [3028-9081]. Klotho protein decreased by 19% from admission to discharge and then increased by 13% from discharge to 30-day (P<0.001). During median 478 days follow-up 40 patients (36%) died or were hospitalised due to heart failure - they were older, more often with new onset AHF, of ischaemic aetiology and diabetics. Patients with lower levels of Klotho protein (in the 1st as well as in the 2nd quartile) had higher mortality (Figure). ROC analyses showed Klotho had comparable predictive value of unfavourable prognosis as other biomarkers (GDF-15, NT-proBNP). Conclusion The levels of Klotho protein in patients with AHF are higher compared to healthy population and they show dynamics dependent on the clinical state what indicates the utility of Klotho as a typical biomarker. Lower values of Klotho protein in AHF patients are associated with higher mortality which may suggests protective effect of higher Klotho levels.