First, BNP can augment cerebral blood flow reduction and ischemia damage by reducing local blood volume and blood pressure.[28] We showed that elevated plasma BNP level is associated with ischemic CSVD in an adjusted model, suggesting that ischemic damage in the brain could be a potential source of circulating BNP independent of heart disease.[29] Second, higher level of BNP and CSVD might share vascular risk factors, such as aging, diabetes, dyslipidemia, and hypertension, which can cause arteriolosclerosis and lead to clinical or subclinical cerebral injury. This evidence concerns the gene NPPB and hypertensive disorder.