Fibrosis as measured by the biomarker, tissue inhibitor metalloproteinase-1, predicts mortality in Age Gene Environment Susceptibility-Reykjavik (AGES-Reykjavik) Study
Fibrosis as measured by the biomarker, tissue inhibitor metalloproteinase-1, predicts mortality in Age Gene Environment Susceptibility-Reykjavik (AGES-Reykjavik) Study
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DOI：
10.1093/eurheartj/ehx510
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发表时间：
2017-12-07
影响因子：
39.3
通讯作者：
Arai, Andrew E.
中科院分区：
文献类型：
--
作者：
LaRocca, Gina;Aspelund, Thor;Arai, Andrew E.
纤维化是许多慢性炎症性疾病的关键病理过程，我们假设纤维化的生物标志物组织金属蛋白酶抑制剂-1和基质金属蛋白酶-9（TIMP-1和MMP-9）可以预测全因死亡率，并在调整临床和其他生物标志物后评估这些生物标志物的增量价值。基线考克斯比例风险回归模型是基于Fragrance Risk Score变量;我们加入了TIMP-1、MMP-9、血清高敏C反应蛋白（hsCRP）和估计的肾小球滤过率（eGFR）。主要结局是10年全因死亡率。死亡原因分为心血管死亡（CVD）、癌症死亡和其他原因。参与者平均年龄为76岁，43%为男性。10年死亡率为41%（2263例死亡）。其中，915人（16.6%）死于心血管疾病（CVD），543人（9.9%）死于癌症，805人（14.6%）死于其他原因。对于10年死亡率，年龄是最强的预测因素（对数似然卡方（2）= 798.7，P < 0.0001），其次是TIMP-1（卡方（2）= 125.2，P < 0.0001），女性，目前吸烟者，糖尿病，总胆固醇，eGFR（卡方（2）16.7，P < 0.0001），体重指数，hsCRP（χ 2 = 11.3，P = 0.0008）。TIMP-1和hsCRP在5年生存率[净重新分类指数（NRI）分别为0.28和0.19，均P < 0.0001]和10年生存率（NRI分别为0.19和0.11，均具有统计学显著性）方面具有最高的连续净重新分类改善。TIMP-1是年龄后全因死亡率的最强预测因子。调节细胞外基质稳态和纤维化过程的代谢途径似乎与病理学相关，并且具有重要意义。
Fibrosis is a key pathological process in many chronic inflammatory disease states.We hypothesized that tissue inhibitor metalloproteinase-1 and matrix metalloproteinase-9 (TIMP-1 and MMP-9), biomarkers of fibrosis, would predict all-cause mortality and we assessed the incremental value of these biomarkers when adjusting for clinical and other biomarkers.The cohort included 5511 community-dwelling participants in the AGES-Reykjavik Study. The baseline Cox proportional hazards regression model was based on the Framingham Risk Score variables; we added TIMP-1, MMP-9, serum high-sensitivity C-reactive protein (hsCRP), and estimated glomerular filtration rate (eGFR). The primary outcome was all-cause 10-year mortality. Cause of death was categorized as cardiovascular death (CVD), cancer death, and other causes.Participants averaged 76 years and 43% were male. Ten-year mortality was 41% (2263 deaths). Of these, 915 (16.6%) died of cardiovascular disease (CVD), 543 (9.9%) with cancer, and 805 (14.6%) from other causes. For 10-year mortality, age was the strongest predictor (log likelihood chi(2) = 798.7, P < 0.0001), followed by TIMP-1 (chi(2) = 125.2, P < 0.0001), female gender, current smoker, diabetes mellitus, total cholesterol, eGFR (chi(2) 16.7, P < 0.0001), body mass index, and hsCRP (chi(2) 11.3, P = 0.0008) in that order. TIMP-1 and hsCRP had the highest continuous net reclassification improvement over the baseline model for 5-year survival [net reclassification index (NRI) 0.28 and 0.19, respectively, both P < 0.0001] and for 10-year survival (NRI 0.19 and 0.11, respectively, both statistically significant).TIMP-1 is the strongest predictor of all-cause mortality after age. The metabolic pathways regulating extracellular matrix homeostasis and fibrogenic processes appear pathologically relevant and are prognostically important.