Okamoto Emi E, Sherbuk Jacqueline E, Clark Eva H, Marks Morgan A, Gandarilla Omar, Galdos-Cardenas Gerson, Vasquez-Villar Angel, Choi Jeong, Crawford Thomas C, Do Rose Q, Fernandez Antonio B, Colanzi Rony, Flores-Franco Jorge Luis, Gilman Robert H, Bern Caryn
New York University School of Medicine, New York, New York, United States of America.
Baylor College of Medicine, Houston, Texas, United States of America.
PLoS Negl Trop Dis. 2014 Oct 2;8(10):e3227. doi: 10.1371/journal.pntd.0003227. eCollection 2014 Oct.
Twenty to thirty percent of persons with Trypanosoma cruzi infection eventually develop cardiomyopathy. If an early indicator were to be identified and validated in longitudinal studies, this could enable treatment to be prioritized for those at highest risk. We evaluated cardiac and extracellular matrix remodeling markers across cardiac stages in T. cruzi infected (Tc+) and uninfected (Tc-) individuals.
Participants were recruited in a public hospital in Santa Cruz, Bolivia and assigned cardiac severity stages by electrocardiogram and echocardiogram. BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2 were measured in specimens from 265 individuals using multiplex bead systems. Biomarker levels were compared between Tc+ and Tc- groups, and across cardiac stages. Receivers operating characteristic (ROC) curves were created; for markers with area under curve>0.60, logistic regression was performed.
Analyses stratified by cardiac stage showed no significant differences in biomarker levels by Tc infection status. Among Tc+ individuals, those with cardiac insufficiency had higher levels of BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 than those with normal ejection fraction and left ventricular diameter. No individual marker distinguished between the two earliest Tc+ stages, but in ROC-based analyses, MMP-2/MMP-9 ratio was significantly higher in those with than those without ECG abnormalities.
BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 levels rose with increasing severity stage but did not distinguish between Chagas cardiomyopathy and other cardiomyopathies. Among Tc+ individuals without cardiac insufficiency, only the MMP-2/MMP-9 ratio differed between those with and without ECG changes.
20%至30%的克氏锥虫感染患者最终会发展为心肌病。如果能在纵向研究中识别并验证一个早期指标,这将有助于为风险最高的患者优先安排治疗。我们评估了克氏锥虫感染(Tc+)和未感染(Tc-)个体在心脏各阶段的心脏和细胞外基质重塑标志物。
在玻利维亚圣克鲁斯的一家公立医院招募参与者,并通过心电图和超声心动图确定心脏严重程度阶段。使用多重微珠系统检测了265名个体标本中的脑钠肽(BNP)、N末端脑钠肽原(NTproBNP)、肌酸激酶同工酶(CKMB)、肌钙蛋白I、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制因子-1(TIMP-1)、金属蛋白酶组织抑制因子-2(TIMP-2)、转化生长因子β1(TGFb1)和转化生长因子β2(TGFb2)。比较了Tc+组和Tc-组之间以及不同心脏阶段的生物标志物水平。绘制了受试者工作特征(ROC)曲线;对于曲线下面积>0.60的标志物,进行了逻辑回归分析。
按心脏阶段分层的分析显示,生物标志物水平在Tc感染状态方面无显著差异。在Tc+个体中,心脏功能不全者的BNP、NTproBNP、肌钙蛋白I、MMP-2、TIMP-1和TIMP-2水平高于射血分数和左心室直径正常者。没有单个标志物能区分Tc+的两个最早阶段,但在基于ROC的分析中,有心电图异常者的MMP-2/MMP-9比值显著高于无异常者。
BNP、NTproBNP、肌钙蛋白I、MMP-2、TIMP-1和TIMP-2水平随严重程度阶段的增加而升高,但不能区分恰加斯心肌病和其他心肌病。在无心脏功能不全的Tc+个体中,有心电图改变者与无心电图改变者之间仅MMP-2/MMP-9比值存在差异。