1 TIMI Study Group Division of Cardiovascular Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA.
2 Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA.
J Am Heart Assoc. 2019 May 7;8(9):e011444. doi: 10.1161/JAHA.118.011444.
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.
一些小型研究提示，在心力衰竭（HF）患者中，胶原转化标志物与不良结局之间存在相关性。我们研究了 C 端肽（β-CTX）与非 ST 段抬高型急性冠状动脉综合征患者心血管死亡或新发或恶化 HF 的风险。
我们对非 ST 段抬高型急性冠状动脉综合征患者的一项研究（n=4094）进行了嵌套生物标志物分析，检测了基线血清β-CTX、NT-proBNP（N 末端 pro-B 型利钠肽）、hsTnT（高敏心肌肌钙蛋白 T）和 hsCRP（高敏 C 反应蛋白）（罗氏诊断）。采用调整后的 Cox 模型分析了β-CTX 四分位数与中位随访时间 12 个月期间心血管死亡或 HF 的关系。更高的β-CTX 水平表明心血管死亡/HF 的风险显著增加（Q4：10.9% vs Q1：3.8%，Logrank P<0.001）。经多变量调整后，β-CTX 处于最高四分位数（Q4）与心血管死亡/HF 相关（Q4 与 Q1：调整后的危险比 2.22 [1.50-3.27]）及其组成部分（Q4 与 Q1：心血管死亡：调整后的危险比 2.48 [1.46-4.21]；HF：调整后的危险比 2.04 [1.26-3.30]）。在包括 NT-proBNP、hsTnT 和 hsCRP 的调整后多标志物模型中，β-CTX 与心血管死亡/HF 仍独立相关（Q4 与 Q1：调整后的危险比 1.98 [1.34-2.93]）及其组成部分。β-CTX 与 NT-proBNP 弱相关（r=0.17，P<0.001）和左心室射血分数（r=-0.05，P=0.008），与 hsTnT 不相关（r=0.02，P=0.20），与 hsCRP 不相关（r=-0.03，P=0.09）。
在非 ST 段抬高型急性冠状动脉综合征患者中，胶原转化标志物β-CTX 水平与心血管死亡和 HF 相关。这种与心血管死亡和 HF 的传统生物标志物相关性弱或无统计学意义的生物标志物，可能为这些患者提供补充的病理生物学见解和风险分层。
