Nighttime home blood pressure as a mediator of N-terminal pro-brain natriuretic peptide in cardiovascular events

We tested our hypothesis that the association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiovascular disease (CVD) events is mediated in part by a pathway of increased nighttime blood pressure (BP) that involves volume overload. We used the data from the Japan Morning Surge-Home Blood Pressure (J-HOP) Nocturnal BP Study, which targeted 2476 Japanese participants who had a history of or risk for CVD (mean age 63.8 +/- 10.2 years), along with their measured nighttime BP values assessed by a home BP device (measured at 2:00, 3:00 and 4:00 a.m.) and NT-proBNP levels. At baseline, elevated daytime (average of morning and evening) and nighttime home systolic BP (SBP) were independently associated with log-transformed NT-proBNP levels after adjustment for cardiovascular risk factors. During a median follow-up of 7.2 years, 150 participants experienced a CVD event (62 stroke events and 88 coronary artery disease events). After adjustment for cardiovascular risk factors and nighttime SBP, increased log-transformed NT-proBNP levels were independently associated with CVD events (hazard ratio [HR] per 1 unit, 1.67; 95% confidence interval [CI]: 1.16-2.40). Elevated nighttime home SBP was also independently associated with CVD events after adjustment for cardiovascular risk and log-transformed NT-proBNP (HR per standard deviation, 1.22; 95% CI: 1.001-1.50). The percentage of the association between NT-proBNP and CVD events mediated by nighttime home SBP was 15%. Our findings indicate a physiological pathway in which increased nighttime SBP contributes to the impact of elevated NT-proBNP levels on the incidence of CVD.