Similar threshold- or plateau-dependent dynamics are observed in other medical contexts: for example, glycated hemoglobin (HbA1c) rises steeply in micro- and macrovascular risk up to ~7–8 % (23), serum creatinine increases sharply with early declines in glomerular filtration rate (GFR) but shows smaller, non-linear changes with further reductions (24), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) rises with worsening heart failure before plateauing at severe disease stages (25). This evidence concerns the gene NPPB and heart failure.