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

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‐CTx) 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‐CTx, NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), hsTnT (high‐sensitivity cardiac troponin T) and hsCRP (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‐CTx and cardiovascular death or HF over a median follow‐up time of 12 months was analyzed using adjusted Cox models. Higher beta‐CTx 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‐CTx 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‐proBNP, hsTnT, and hsCRP, beta‐CTx remained independently associated with cardiovascular death/HF (Q4 versus Q1: adjusted hazard ratio 1.98 [1.34–2.93]) and its components. Beta‐CTx correlated weakly with NT‐proBNP (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 hsCRP (r=−0.03, P=0.09). CONCLUSIONS: Levels of beta‐CTx, 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.