Elevated plasma lipoprotein(a) levels, diabetes mellitus, and obesity have been identified as risk factors, and disordered signaling, including NOTCH, myocardin, and WNT-beta-catenin pathways, seem to be strongly involved in the progression of fibrosis and calcification (for review, refer to [27]). The gene discussed is MYOCD; the disease is obesity due to melanocortin 4 receptor deficiency.