Association of NT-ProBNP, Blood Pressure, and Cardiovascular Events: The ARIC Study

J Am Coll Cardiol. 2021 Feb 9;77(5):559-571. doi: 10.1016/j.jacc.2020.11.063.


Background: Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.

Objectives: This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.

Methods: Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors.

Results: There were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to <300 or 300 pg/ml, compared with NT-proBNP <100 pg/ml) was associated with a graded increased risk for CVD events and mortality. Participants with SBP 130 to 139 mm Hg but NT-proBNP ≥300 pg/ml had a hazards ratio of 3.4 for CVD (95% confidence interval: 2.44 to 4.77) compared with a NT-proBNP of <100 pg/ml and SBP of 140 to 149 mm Hg.

Conclusions: Elevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.

Keywords: NT-proBNP; blood pressure; cardiac biomarkers; cardiovascular disease; cardiovascular risk assessment.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomarkers / blood
  • Blood Pressure / physiology*
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / physiopathology
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Population Surveillance / methods*
  • Prospective Studies
  • Protein Precursors
  • Risk Assessment / methods*
  • Risk Factors
  • United States / epidemiology


  • Biomarkers
  • Peptide Fragments
  • Protein Precursors
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain