Incremental prognostic value of biomarkers in PARADIGM-HF

Eur J Heart Fail. 2023 Aug;25(8):1406-1414. doi: 10.1002/ejhf.2887. Epub 2023 Jun 4.

Abstract

Aims: It is uncertain how much candidate biomarkers improve risk prediction when added to comprehensive models including routinely collected clinical and laboratory variables in heart failure.

Methods and results: Aldosterone, cystatin C, high-sensitivity troponin T (hs-TnT), galectin-3, growth differentiation factor-15 (GDF-15), kidney injury molecule-1, matrix metalloproteinase-2 and -9, soluble suppression of tumourigenicity-2, tissue inhibitor of metalloproteinase-1 (TIMP-1) and urinary albumin to creatinine ratio were measured in 1559 of PARADIGM-HF participants. We tested whether these biomarkers, individually or collectively, improved the performance of the PREDICT-HF prognostic model, which includes clinical, routine laboratory, and natriuretic peptide data, for the primary endpoint and cardiovascular and all-cause mortality. The mean age of participants was 67.3 ± 9.9 years, 1254 (80.4%) were men and 1103 (71%) were in New York Heart Association class II. During a mean follow-up of 30.7 months, 300 patients experienced the primary outcome and 197 died. Added individually, only four biomarkers were independently associated with all outcomes: hs-TnT, GDF-15, cystatin C and TIMP-1. When all biomarkers were added simultaneously to the PREDICT-HF models, only hs-TnT remained an independent predictor of all three endpoints. GDF-15 also remained predictive of the primary endpoint; TIMP-1 was the only other predictor of both cardiovascular and all-cause mortality. Individually or in combination, these biomarkers did not lead to significant improvements in discrimination or reclassification.

Conclusions: None of the biomarkers studied individually or collectively led to a meaningful improvement in the prediction of outcomes over what is provided by clinical, routine laboratory, and natriuretic peptide variables.

Keywords: Biomarkers; Heart failure; Prediction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers
  • Cystatin C
  • Female
  • Growth Differentiation Factor 15*
  • Heart Failure* / diagnosis
  • Humans
  • Male
  • Matrix Metalloproteinase 2
  • Middle Aged
  • Natriuretic Peptide, Brain
  • Peptide Fragments
  • Prognosis
  • Tissue Inhibitor of Metalloproteinase-1
  • Troponin T

Substances

  • Growth Differentiation Factor 15
  • Cystatin C
  • Matrix Metalloproteinase 2
  • Tissue Inhibitor of Metalloproteinase-1
  • Biomarkers
  • Natriuretic Peptide, Brain
  • Troponin T
  • Peptide Fragments