Serum Matrix Metalloproteinases as Quantitative Biomarkers for Myocardial Fibrosis and Sudden Cardiac Death Risk Stratification in Patients With Hypertrophic Cardiomyopathy
Serum Matrix Metalloproteinases as Quantitative Biomarkers for Myocardial Fibrosis and Sudden Cardiac Death Risk Stratification in Patients With Hypertrophic Cardiomyopathy
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DOI：
10.1016/j.cardfail.2016.03.010
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发表时间：
2016-10-01
影响因子：
6
通讯作者：
Patten, Monica
中科院分区：
文献类型：
--
作者：
Muench, Julia;Avanesov, Maxim;Patten, Monica
背景：肥厚型心肌病（HCM）与室性心动过速（VT）引起的心源性猝死风险增加相关，心肌纤维化是一个重要的危险因素。几种基质金属蛋白酶 (MMP) 和原胶原 N 末端前肽 (PNP) 参与胶原蛋白更新，并作为纤维化生物标志物进行讨论。我们的目的是在 HCM 患者的晚期钆增强心脏磁共振成像 (LGE-CMR) 和/或心脏事件（晕厥、VT）中鉴定与心肌纤维化相关的生物标志物。 方法和结果：在 54 名 HCM 患者（年龄 55.9 +/- 14.3 岁，50% 女性）中，通过 LGE-CMR 量化纤维化。通过酶联免疫吸附测定法分析 MMP-1、-2、-3、-9 和 MMP 组织抑制剂 (TIMP) 1 的血清浓度，通过放射免疫测定法分析 PINP、PIIINP 和 I 型胶原 C 末端端肽 (ICTP) 浓度。 MMP-9 与 LGE-CMR 中的纤维化相关（平均增加 0.66 g/单位 MMP9 [95% 置信区间 [CI] 0.50-0.82]；P < .001），并且与女性心脏事件相关（比值比 [OR] 1.07 [1.01-1.12]，P = .01），但与男性无关。女性 MMP-2 水平升高与纤维化程度降低相关（0.05 [-0.09 至 -0.01]；P = .015）。 MMP-3 水平与心脏事件呈正相关（OR 1.13 [1.05-1.22]；P = .001），与纤维化和性别无关。未检测到 MMP-1、TIMP-1、PNP 和 ICTP 之间的关联。结论：这些数据表明，MMP-9 是女性 HCM 患者纤维化和心脏事件的有用生物标志物，而 MMP-3 与独立于纤维化和性别的较高事件发生率相关。
Background: Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of sudden cardiac death due to ventricular tachycardia (VT), and myocardial fibrosis reflects an important risk factor. Several matrix metalloproteinases (MMPs) and procollagen N-terminal propeptides (PNPs) are involved in collagen turnover and discussed as fibrosis biomarkers. We aimed to identify biomarkers that correlate with myocardial fibrosis in late-gadolinium-enhancement cardiac magnetic resonance imaging (LGE-CMR) and/or cardiac events (syncope, VT) in HCM patients.Methods and Results: In 54 HCM patients (age 55.9 +/- 14.3 y, 50% female) fibrosis was quantified by LGE-CMR. Serum concentrations of MMP-1,-2,-3,-9, and tissue inhibitor of MMP (TIMP) 1 were analyzed by means of enzyme-linked immunosorbent assay and PINP, PIIINP, and type I collagen C-terminal telopeptide (ICTP) concentrations by radioimmunoassay. MMP-9 was associated with fibrosis in LGE-CMR (mean increase 0.66 g/unit MMP9 [95% confidence interval [CI] 0.50-0.82]; P < .001) and with cardiac events in women (odds ratio [OR] 1.07 [1.01-1.12], P = .01) but not in men. Increased MMP-2 levels in women were associated with lower fibrosis (0.05 [-0.09 to -0.01]; P = .015). MMP-3 levels were positively associated with cardiac events (OR 1.13 [1.05-1.22]; P = .001) independently from fibrosis and sex. No association was detected for MMP-1, TIMP-1, PNPs, and ICTP.Conclusions: These data suggest that MMP-9 is a useful biomarker for fibrosis and cardiac events in female HCM patients, whereas MMP-3 is associated with a higher event rate independent from fibrosis and sex.