Temporal Biomarker Profiling Reveals Longitudinal Changes in Risk of Death or Myocardial Infarction in Non-ST-Segment Elevation Acute Coronary Syndrome

Clin Chem. 2017 Jul;63(7):1214-1226. doi: 10.1373/clinchem.2016.265272. Epub 2017 May 17.

Abstract

Background: There are conflicting data on whether changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) concentrations between time points (delta NT-proBNP and hs-CRP) are associated with a change in prognosis.

Methods: We measured NT-proBNP and hs-CRP at 3 time points in 1665 patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). Cox proportional hazards was applied to the delta between temporal measurements to determine the continuous association with cardiovascular events. Effect estimates for delta NT-proBNP and hs-CRP are presented per 40% increase as the basic unit of temporal change.

Results: Median NT-proBNP was 370.0 (25th, 75th percentiles, 130.0, 996.0), 340.0 (135.0, 875.0), and 267.0 (111.0, 684.0) ng/L; and median hs-CRP was 4.6 (1.7, 13.1), 1.9 (0.8, 4.5), and 1.8 (0.8, 4.4) mg/L at baseline, 30 days, and 6 months, respectively. The deltas between baseline and 6 months were the most prognostically informative. Every +40% increase of delta NT-proBNP (baseline to 6 months) was associated with a 14% greater risk of cardiovascular death (adjusted hazard ratio (HR) 1.14, 95% CI, 1.03-1.27) and with a 14% greater risk of all-cause death (adjusted HR 1.14, 95% CI, 1.04-1.26), while every +40% increase of delta hs-CRP (baseline to 6 months) was associated with a 9% greater risk of the composite end point (adjusted HR 1.09, 95% CI, 1.02-1.17) and a 10% greater risk of myocardial infarction (adjusted HR 1.10, 95%, CI 1.00-1.20).

Conclusions: Temporal changes in NT-proBNP and hs-CRP are quantitatively associated with future cardiovascular events, supporting their role in dynamic risk stratification of NSTEACS.

Clinical trial registration: ClinicalTrials.gov identifier NCT00699998.

MeSH terms

  • Acute Coronary Syndrome / complications*
  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / genetics
  • Acute Coronary Syndrome / mortality*
  • Aged
  • Biomarkers / analysis*
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / etiology*
  • Myocardial Infarction / mortality
  • Natriuretic Peptide, Brain / blood
  • Proteogenomics*
  • Risk Factors
  • Time Factors

Substances

  • Biomarkers
  • Natriuretic Peptide, Brain
  • C-Reactive Protein

Associated data

  • ClinicalTrials.gov/NCT00699998