Last but not least, although the conclusion that extremely low BNP level is one of the causes for the development of cardiovascular diseases is consistent with previous reports (e.g., obesity is associated with higher IHD risk; low BNP is associated with the incidence of IHD; elevated cTnI level is associated with cardiovascular risks in the general population), we do not have prospective and direct evidence, which need to be obtained in the future. The gene discussed is NPPB; the disease is obesity due to melanocortin 4 receptor deficiency.