NPPB and arteriolosclerosis: 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.