The selection of the five molecules (RBP4, LCN2/NGAL, ApoM, Klotho and Matrix Gla protein) was not arbitrary but guided by the CKM pathophysiology proposed in the 2023 AHA Scientific Statement [1], which highlights oxidative stress, inflammation, endothelial dysfunction and insulin resistance as core mechanisms. Here, LCN2 is linked to endothelial dysfunction.