Divisions of Neurology Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States of America; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States of America.
Divisions of Neurology Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States of America.
J Neurol Sci. 2024 Jun 15;461:123053. doi: 10.1016/j.jns.2024.123053. Epub 2024 May 14.
Friedreich ataxia is a progressive autosomal recessive neurodegenerative disorder characterized by ataxia, dyscoordination, and cardiomyopathy. A subset of patients with Friedreich ataxia have elevated levels of serum cardiac troponin I, but associations with disease outcomes and features of cardiomyopathy remain unclear. In this study, we characterized clinically obtained serum cardiac biomarker levels including troponin I, troponin T, and B-type natriuretic peptide in subjects with Friedreich ataxia and evaluated their association with markers of disease. While unprovoked troponin I levels were elevated in 36% of the cohort, cTnI levels associated with a cardiac event (provoked) were higher than unprovoked levels. In multivariate linear regression models, younger age predicted increased troponin I values, and in logistic regression models younger age, female sex, and marginally longer GAA repeat length predicted abnormal troponin I levels. In subjects with multiple assessments, mean unprovoked troponin I levels decreased slightly over time. The presence of abnormal troponin I values and their levels were predicted by echocardiographic measures of hypertrophy. In addition, troponin I levels predicted long-term markers of clinical cardiac dysfunction over time to a modest degree. Consequently, troponin I values provide a marker of hypertrophy but only a minimally predictive biomarker for later cardiac manifestations of disease such as systolic dysfunction or arrhythmia.
弗里德里希共济失调是一种进行性常染色体隐性神经退行性疾病,其特征为共济失调、运动不协调和心肌病。一部分弗里德里希共济失调患者的血清心肌肌钙蛋白 I 水平升高,但与疾病结局和心肌病特征的相关性尚不清楚。在这项研究中,我们对弗里德里希共济失调患者的临床获得的血清心脏生物标志物水平(包括肌钙蛋白 I、肌钙蛋白 T 和 B 型利钠肽)进行了描述,并评估了它们与疾病标志物的相关性。虽然在 36%的队列中未诱发的肌钙蛋白 I 水平升高,但诱发的 cTnI 水平高于未诱发的水平。在多元线性回归模型中,年龄较小预测肌钙蛋白 I 值增加,而在逻辑回归模型中,年龄较小、女性和 GAA 重复长度略长预测肌钙蛋白 I 水平异常。在多次评估的受试者中,未诱发的肌钙蛋白 I 水平随时间略有下降。肌钙蛋白 I 值的异常存在及其水平可由超声心动图测量的肥厚来预测。此外,肌钙蛋白 I 水平在一定程度上预测了长期的临床心脏功能障碍标志物。因此,肌钙蛋白 I 值提供了一种肥厚的标志物,但对疾病后期心脏表现(如收缩功能障碍或心律失常)的预测作用很小。