Ravassa Susana, López Begoña, Querejeta Ramón, Echegaray Kattalin, San José Gorka, Moreno María U, Beaumont Francisco J, González Arantxa, Díez Javier
aProgram of Cardiovascular Diseases, Centre for Applied Medical Research, University of NavarrabIdiSNA, Navarra Institute for Health Research, PamplonacDivision of Cardiology, Donostia University Hospital, University of the Basque Country, and Biodonostia Research Institute, San SebastiandDepartment of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain.
J Hypertens. 2017 Apr;35(4):853-861. doi: 10.1097/HJH.0000000000001258.
Myocardial fibrosis is associated with alterations in the cross-linking and deposition of collagen type I (CCL and CD, respectively). We aimed to evaluate whether the combination of circulating biomarkers of CCL [the carboxy-terminal telopeptide of collagen type I to matrix metalloproteinase-1 ratio (CITP : MMP-1)] and CD [the carboxy-terminal propeptide of procollagen type I (PICP)] identifies myocardial fibrosis phenotypes with distinct clinical outcome in hypertensive patients with heart failure.
Endomyocardial biopsies and blood samples from 38 patients (small cohort), and blood samples from 203 patients (large cohort) were analyzed. Myocardial CCL and CD were assessed by histological methods. Serum PICP, CITP, and MMP-1 were determined by ELISA.
Small cohort: CITP : MMP-1 cutoff 1.968 or less and PICP cutoff at least 110.8 ng/ml were used for predicting high CCL and severe CD, respectively. Large cohort: as defined by the above thresholds, patients were categorized into four subgroups based on the presence (+) or absence (-) of high CCL and severe CD. Compared with CCL-CD-, the adjusted hazard ratios for a composite end point of heart failure hospitalization or cardiovascular death over 5 years in CCL-CD+, CCL+CD-, and CCL+CD+ were 1.11 (P = 0.79), 1.99 (P = 0.07), and 2.18 (P = 0.04), respectively (P for trend = 0.005). In addition, the categorization based on CCL and CD yielded integrated discrimination (P = 0.03) and net reclassification (P = 0.01) improvements for the mentioned outcome.
The combination of low serum CITP : MMP-1 ratio and high serum PICP identifies hypertensive patients with heart failure presenting with a phenotype of myocardial fibrosis characterized by the concurrence of excessive CCL and CD and associated with poor outcome.
心肌纤维化与I型胶原的交联和沉积改变（分别为CCL和CD）相关。我们旨在评估循环生物标志物CCL [I型胶原羧基末端肽与基质金属蛋白酶-1的比值（CITP : MMP-1）] 和CD [I型前胶原羧基末端前肽（PICP）] 的组合是否能识别出心力衰竭高血压患者中具有不同临床结局的心肌纤维化表型。
分析了38例患者（小队列）的心内膜心肌活检和血样，以及203例患者（大队列）的血样。通过组织学方法评估心肌CCL和CD。采用酶联免疫吸附测定法测定血清PICP、CITP和MMP-1。
小队列：CITP : MMP-1临界值为1.968及以下和PICP临界值至少为110.8 ng/ml分别用于预测高CCL和严重CD。大队列：根据上述阈值定义，患者根据高CCL和严重CD的存在（+）或不存在（-）分为四个亚组。与CCL-CD-相比, CCL-CD+、CCL+CD-和CCL+CD+组在5年内心力衰竭住院或心血管死亡复合终点的校正风险比分别为1.11（P = 0.79）、1.99（P = 0.07）和2.18（P = 0.04）（趋势P值 = 0.005）。此外，基于CCL和CD的分类对上述结局产生了综合判别改善（P = 0.03）和净重新分类改善（P = 0.01）。
低血清CITP : MMP-1比值和高血清PICP的组合可识别出心力衰竭高血压患者，这些患者表现为心肌纤维化表型，其特征为CCL和CD同时过度，并与不良结局相关。
