THE ASSOCIATION BETWEEN N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE AND CARDIOVASCULAR DISEASE IS CONDITIONED BY PRESENCE OF INCREASED ARTERIAL STIFFNESS

Abstract

Abstract Objective: The aim of this study was to evaluate whether the cardiovascular risk associated with increased N-terminal pro-brain natriuretic peptide (NT-proBNP) is modified by arterial stiffness assessed as carotid to femoral pulse wave velocity (PWV) in apparently healthy individuals. Design and method: This was a population-based cohort study comprising of 1858 healthy subjects included in the 10-year follow-up of the MONItoring of trends and determinants in CArdiovascular disease (MONICA) study. The primary outcome was major adverse cardiovascular events (MACE) after 16 years of follow-up. MACE was defined as cardiovascular death, sudden death, heart failure, arrhythmia, myocardial infarction, chronic ischemic heart disease, cerebrovascular disease, peripheral or central arterial disease. The association between NT-proBNP and MACE was evaluated with Cox proportional-hazards regression stratified for presence of increased arterial stiffness (PWV > 12m/s) and adjusted for traditional risk factors for cardiovascular disease. NT-proBNP was evaluated both as a continuous variable (log transformed) and dichotomously using the 90th percentile as cut-off (110pg/ml) allowing for group-wise comparisons. Results: 314 events were recorded during a median follow-up of 16.0 years (interquartile range: 14.7–16.0). In multivariable regression with both log (NT-proBNP) and log (PWV) included in the model, we found that log (NT-proBNP) was associated with MACE: HR = 1.28 [1.13–1.45] (P < 0.001). There was a significant positive interaction between log (NT-proBNP) and log (PWW): HR = 1.53 [1.02–2.29] (P = 0.042). In subjects with PWV < 12m/s, log (NT-proBNP) was not associated with MACE: HR = 1.07 [0.91–1.26] (P = 0.429). In subjects with increased PWV, log (NT-proBNP) was associated with MACE, HR = 1.68 [1.39–2–04] (P < 0.001). In multivariable categorical analysis using subjects with PWV < 12m/s and NT-proBNP < 110pg/ml as reference group we found: 1) Increased NT-proBNP without increased PWV was not associated with MACE: HR 0.92 [0.52–1.64] (P = 0.790). 2) Increased PWV and normal NT-proBNP showed borderline significant association with MACE HR 1.35 [0.99–1.84] (P = 0.052). 3) Increased PWV and increased NT-proBNP was associated with MACE: HR 3.21 [2.14–4.80] (P < 0.001). Conclusions: The association between increased NT-proBNP and MACE was positively modified by increased arterial stiffness. NT-proBNP was only associated with MACE in subjects with simultaneously increased arterial stiffness.