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

Abstract

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 (β=0.14; p<0.001), but not after adjustment for traditional risk factors (β=-0.01; p=0.67). In models including traditional risk factors and PWV, NT-proBNP was associated with all four outcomes (HR_MACE=1.33, 95% CI 1.16-1.52; HR_CVM=2.02, 95% CI 1.65-2.48; HR_CAD=1.29, 95% CI 1.07-1.55; and HR_{HF or AF}=1.79, 95% CI 1.40-2.28). In the same model, PWV was only associated with CVM (HR_CVM=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.

Keywords: Arterial stiffness; Cardiovascular disease; Carotid-to-femoral pulse wave velocity; N-terminal pro-brain type natriuretic peptide; Prognosis; Risk.