Biomarker of Collagen Turnover (C-Terminal Telopeptide) and Prognosis in Patients With Non- ST -Elevation Acute Coronary Syndromes

J Am Heart Assoc. 2019 May 7;8(9):e011444. doi: 10.1161/JAHA.118.011444.

Abstract

Background Small studies have suggested an association between markers of collagen turnover and adverse outcomes in heart failure ( HF ). We examined C-terminal telopeptide (beta- CT x) and the risk of cardiovascular death or new or worsening HF in non- ST -elevation acute coronary syndrome. Methods and Results We measured baseline serum beta- CT x, NT -pro BNP (N-terminal pro-B-type natriuretic peptide), hsTnT (high-sensitivity cardiac troponin T) and hs CRP (high-sensitivity C-reactive protein) (Roche Diagnostics) in a nested biomarker analysis (n=4094) from a study of patients with non- ST -elevation acute coronary syndrome. The relationship between quartiles of beta- CT x and cardiovascular death or HF over a median follow-up time of 12 months was analyzed using adjusted Cox models. Higher beta- CT x levels identified a significantly higher risk of cardiovascular death/ HF (Q4 10.9% versus Q1 3.8%, Logrank P<0.001). After multivariable adjustment, beta- CT x in the top quartile (Q4) was associated with cardiovascular death/ HF (Q4 versus Q1: adjusted hazard ratio 2.22 [1.50-3.27]) and its components (Q4 versus Q1: cardiovascular death: adjusted hazard ratio 2.48 [1.46-4.21]; HF : adjusted hazard ratio 2.04 [1.26-3.30]). In an adjusted multimarker model including NT -pro BNP , hsTnT, and hs CRP , beta- CT x remained independently associated with cardiovascular death/ HF (Q4 versus Q1: adjusted hazard ratio 1.98 [1.34-2.93]) and its components. Beta- CT x correlated weakly with NT -pro BNP ( r=0.17, P<0.001) and left ventricular ejection fraction ( r=-0.05, P=0.008) and did not correlate with hsTnT ( r=0.02, P=0.20), or hs CRP ( r=-0.03, P=0.09). Conclusions Levels of beta- CT x, a biomarker of collagen turnover, were associated with cardiovascular death and HF in patients with non- ST -elevation acute coronary syndrome. This biomarker, which correlated only weakly or not significantly with traditional biomarkers of cardiovascular death and HF , may provide complementary pathobiological insight and risk stratification in these patients.

Keywords: C‐terminal telopeptide; beta‐CTx; cardiovascular death; collagen turnover; heart failure.

Publication types

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

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / mortality
  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Collagen Type I / blood*
  • Disease Progression
  • Female
  • Heart Failure / mortality
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Non-ST Elevated Myocardial Infarction / blood*
  • Non-ST Elevated Myocardial Infarction / diagnosis
  • Non-ST Elevated Myocardial Infarction / mortality
  • Peptide Fragments / blood
  • Peptides / blood*
  • Predictive Value of Tests
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Troponin T / blood

Substances

  • Biomarkers
  • Collagen Type I
  • Peptide Fragments
  • Peptides
  • Troponin T
  • collagen type I trimeric cross-linked peptide
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • C-Reactive Protein