N-Terminal Pro-Brain Type Natriuretic Peptide Predicts Cardiovascular Events Independently of Arterial Stiffness, Assessed By Carotid-to-Femoral Pulse Wave Velocity, in Apparently Healthy Subjects.

AIM: This study aimed to evaluate whether N-terminal pro-brain natriuretic peptide (NT-proBNP) and carotid-to-femoral pulse wave velocity (PWV) carried independent prognostic value in predicting cardiovascular events in apparently healthy individuals beyond traditional risk factors. METHODS: A total of 1,872 participants aged 41, 51, 61, or 71 years from the MONItoring of trends and determinants in CArdiovascular disease (MONICA) study were included. Traditional risk factors were assessed, including: smoking status; mean systolic and diastolic blood pressure; body mass index; fasting plasma glucose; serum triglycerides; total, high-density, and low-density lipoprotein cholesterol; NT-proBNP; and PWV. The principal endpoint that was assessed during 16 years of follow-up was a composite of major adverse cardiovascular events (MACE). The secondary endpoints were cardiovascular mortality (CVM), hospitalisation for coronary artery disease (CAD), and a composite of hospitalisation for heart failure (HF) or atrial fibrillation (AF). RESULTS: At baseline, NT-proBNP was associated with PWV (ß=0.14; p<0.001), but not after adjustment for traditional risk factors (ß=-0.01; p=0.67). In models including traditional risk factors and PWV, NT-proBNP was associated with all four outcomes (HRMACE=1.33, 95% CI 1.16-1.52; HRCVM=2.02, 95% CI 1.65-2.48; HRCAD=1.29, 95% CI 1.07-1.55; and HRHF or AF=1.79, 95% CI 1.40-2.28). In the same model, PWV was only associated with CVM (HRCVM=1.20, 95% CI 1.01-1.41). No interactions between NT-proBNP and PWV were found. N-terminal pro-brain natriuretic peptide significantly improved net reclassification (NRI) for MACE (NRI=0.12; p=0.03), CVM (NRI=0.33; p<0.001), and HF or AF (NRI=0.33; p<0.001) beyond traditional risk factors, while PWV did not aid in net reclassification improvement for any endpoint. CONCLUSIONS: In apparently healthy individuals, NT-proBNP and PWV predicted cardiovascular events independently. N-terminal pro-brain natriuretic peptide improved reclassification for the prediction of MACE, CVM, and hospitalisation for HF or AF beyond traditional risk factors, while PWV did not.

Circulating biomarkers for long-term cardiovascular risk stratification in apparently healthy individuals from the MONICA 10 cohort.

AIMS: The aim of this study was to examine whether high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble urokinase plasminogen activator receptor (suPAR) carried incremental prognostic value in predicting cardiovascular morbidity and mortality beyond traditional risk factors in apparently healthy individuals. METHODS AND RESULTS: This was a prospective population-based cohort study comprising 1951 subjects included in the 10-year follow-up of the MONItoring of trends and determinants in CArdiovascular disease (MONICA) study, between 1993 and 1994. The principal endpoint was death from cardiovascular causes. Secondary endpoints were death from any cause, coronary artery disease, heart failure, and cerebrovascular disease. Predictive capabilities of each of the three biomarkers were tested using Cox proportional-hazards regression, Harrell's concordance index (C-index), and net reclassification improvement (NRI). Study participants were aged 41, 51, 61, or 71 years, and equally distributed between the two sexes. During a median follow-up of 18.5 years (interquartile range: 18.1-19.0), 177 (9.1%) subjects died from a cardiovascular cause. Hs-CRP (adjusted standardized hazard ratio (HR): 1.37, 95% confidence interval (CI): 1.17-1.60), NT-proBNP (HR: 1.90, 95% CI: 1.58-2.29), and suPAR (HR: 1.35, 95% CI: 1.17-1.57) were all significantly associated with cardiovascular deaths after adjustment for age, sex, smoking status, systolic blood pressure, and total cholesterol (p < 0.001 for all). Furthermore, all three biomarkers were significantly associated with significant NRI. However, only NT-proBNP significantly raised the C-index in predicting death from cardiovascular causes when added to the risk factors (C-index 0.860 versus 0.847; p = 0.02). CONCLUSIONS: Hs-CRP, suPAR, and particularly NT-proBNP predicted cardiovascular death and may enhance prognostication beyond traditional risk factors in apparently healthy individuals.