Usefulness of Multiple Biomarkers for Predicting Incident Major Adverse Cardiac Events in Patients Who Underwent Diagnostic Coronary Angiography (from the Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA] Study).


Journal Article

We sought to develop a multiple biomarker approach for prediction of incident major adverse cardiac events (MACE; composite of cardiovascular death, myocardial infarction, and stroke) in patients referred for coronary angiography. In a 649-participant training cohort, predictors of MACE within 1 year were identified using least-angle regression; over 50 clinical variables and 109 biomarkers were analyzed. Predictive models were generated using least absolute shrinkage and selection operator with logistic regression. A score derived from the final model was developed and evaluated with a 278-patient validation set during a median of 3.6 years follow-up. The scoring system consisted of N-terminal pro B-type natriuretic peptide (NT-proBNP), kidney injury molecule-1, osteopontin, and tissue inhibitor of metalloproteinase-1; no clinical variables were retained in the predictive model. In the validation cohort, each biomarker improved model discrimination or calibration for MACE; the final model had an area under the curve (AUC) of 0.79 (p <0.001), higher than AUC for clinical variables alone (0.75). In net reclassification improvement analyses, addition of other markers to NT-proBNP resulted in significant improvement (net reclassification improvement 0.45; p = 0.008). At the optimal score cutoff, we found 64% sensitivity, 76% specificity, 28% positive predictive value, and 93% negative predictive value for 1-year MACE. Time-to-first MACE was shorter in those with an elevated score (p <0.001); such risk extended to at least to 4 years. In conclusion, in a cohort of patients who underwent coronary angiography, we describe a novel multiple biomarker score for incident MACE within 1 year (NCT00842868).

Full Text

Duke Authors

Cited Authors

  • McCarthy, CP; van Kimmenade, RRJ; Gaggin, HK; Simon, ML; Ibrahim, NE; Gandhi, P; Kelly, N; Motiwala, SR; Belcher, AM; Harisiades, J; Magaret, CA; Rhyne, RF; Januzzi, JL

Published Date

  • July 2017

Published In

Volume / Issue

  • 120 / 1

Start / End Page

  • 25 - 32

PubMed ID

  • 28487034

Pubmed Central ID

  • 28487034

Electronic International Standard Serial Number (EISSN)

  • 1879-1913

International Standard Serial Number (ISSN)

  • 0002-9149

Digital Object Identifier (DOI)

  • 10.1016/j.amjcard.2017.03.265


  • eng