The promising role of Klotho and FGF23 proteins in the diagnosis of myocardial infarction in acute coronary syndrome

Background Klotho and fibroblast growth factor 23 (FGF23), the interrelated endocrine regulators of mineral metabolism, are increasingly recognised as important proteins in cardiovascular health. The balance between Klotho and FGF23 can influence the systemic response to cardiac stress and injury. Purpose This study aimed to evaluate Klotho and FGF23 as diagnostic biomarkers for myocardial infarction (MI) in acute coronary syndrome (ACS). Methods This retrospective study included 102 patients with MI, in which plasma concentration of Klotho and FGF23 was measured at admission, and at 6, 24, and 24–48 h post-admission. Changes in Klotho and FGF23 levels were analysed in relation to key clinical variables, including cardiac biomarkers, and patient characteristics (age, gender, comorbidities). Receiver operating characteristic (ROC) curves (MI patients compared with non-MI healthy individuals) and multivariate linear regression analysis were conducted to assess the association of Klotho and FGF23 with MI and other risk factors. Results There was a significant decline in Klotho concentration within 24–48 h post-admission as compared to the levels at admission (p=0.001), at 6 (p=0.007) and 24 h (p=0.04) post-admission. There was a significant increase in FGF23 concentration (p=0.027) and a decrease in Klotho/FGF23 concentration ratio (p=0.005) within 24–48 h post-admission as compared to the levels at admission. Klotho concentration at admission showed fair diagnostic accuracy with an AUC of 0.71 (p=0.003), while the best performance for FGF23 was observed at 24–48 h post-admission (AUC=0.86; p<0.0001). The Klotho/FGF23 ratio demonstrated the strongest diagnostic performance. At admission, the AUC for the Klotho/FGF23 ratio was 0.77 (p=0.001), while excellent performance was achieved after 24-48 h with an AUC of 0.90 (p<0.0001). Multivariate linear regression analysis showed that the presence of MI was significantly associated with higher Klotho concentration at admission (β=202.2; p=0.013) and with elevated FGF23 concentration after 24-48 h (β=950; p=0.002). MI was also inversely associated with the Klotho/FGF23 ratio at 24-48 h post-admission (β= –2.79; p<0.0001). Conclusions Klotho and FGF23 exhibited distinct temporal patterns following MI, which may not only reflect cardiac injury but also provide insight into the pathophysiological mechanisms and compensatory responses following MI. Monitoring their dynamics could support early diagnosis, and their ratio improves discrimination of MI within ACS beyond either marker alone. Thus, the potential role of Klotho and FGF23 as complementary tools to traditional markers of MI was shown.