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脑源性神经营养因子作为生物标志物与左心室超声心动图指标联合用于潜在诊断冠心病的临床价值。

Clinical utility of brain-derived neurotrophic factor as a biomarker with left ventricular echocardiographic indices for potential diagnosis of coronary artery disease.

机构信息

Department of Cardiology, Chettinad Hospital and Research Institute, Chettinad Health City, Kelambakkam, Tamil Nadu, 603103, India.

School of Medicine, Department of Neurology, University of New Mexico Health Sciences Center, University of New Mexico, Albuquerque, USA.

出版信息

Sci Rep. 2020 Oct 1;10(1):16359. doi: 10.1038/s41598-020-73296-6.

Abstract

Brain-derived neurotrophic factor (BDNF) plays a central pivotal role in the development of the cardiovascular system. Recent evidence suggests that BDNF has adverse subclinical cardiac remodeling in participants with cardiovascular disease risk factors. Relating serum BDNF levels with two-dimensional echocardiographic indices will provide insights into the BDNF mediated pathophysiology in coronary artery disease (CAD) that may shed light upon potential diagnostic biomarkers. For the study, 221 participants were recruited and classified based on coronary angiogram examination as control (n = 105) and CAD (n = 116). All participants underwent routine blood investigation, two-dimensional echocardiography, and serum BDNF estimation. As a result, total cholesterol, triglyceride, low-density lipid, high-density lipid, HbA1c (glycosylated hemoglobin), serum creatinine, eosinophils, lymphocyte, monocytes, neutrophils, and platelets were significantly elevated in CAD individuals compared to controls. Notably, the serum BDNF was significantly lower in individuals with CAD (30.69 ± 5.45 ng/ml) than controls (46.58 ± 7.95 ng/ml). Multivariate regression analysis showed neutrophils, total cholesterol, left ventricular mass index, mitral inflow E/A ratio, and pulmonary vein AR duration were associated with low BDNF in CAD. Four independent support vector machine (SVM) models performed to ensure the BDNF level in the classification of CAD from healthy controls. Particularly, the model with serum BDNF concentration and blood parameters of CAD achieved significant improvement from 90.95 to 98.19% in detecting CAD from healthy controls. Overall, our analysis provides a significant molecular linkage between the serum BDNF level and cardiovascular function. Our results contribute to the emerging evidence of BDNF as a potential diagnostic value in CAD that might lead to clinical application.

摘要

脑源性神经营养因子(BDNF)在心血管系统的发育中起着核心关键作用。最近的证据表明,BDNF 对有心血管疾病危险因素的参与者存在不良的亚临床心脏重构作用。将血清 BDNF 水平与二维超声心动图指标相关联,将为冠心病(CAD)中 BDNF 介导的病理生理学提供深入了解,这可能为潜在的诊断生物标志物提供线索。在这项研究中,共招募了 221 名参与者,并根据冠状动脉造影检查将其分为对照组(n=105)和 CAD 组(n=116)。所有参与者都接受了常规血液检查、二维超声心动图和血清 BDNF 测定。结果显示,与对照组相比,CAD 患者的总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白、糖化血红蛋白(HbA1c)、血清肌酐、嗜酸性粒细胞、淋巴细胞、单核细胞、中性粒细胞和血小板显著升高。值得注意的是,CAD 患者的血清 BDNF 水平明显低于对照组(30.69±5.45ng/ml 比 46.58±7.95ng/ml)。多变量回归分析显示,中性粒细胞、总胆固醇、左心室质量指数、二尖瓣血流 E/A 比值和肺静脉 AR 持续时间与 CAD 中的低 BDNF 相关。四个独立的支持向量机(SVM)模型用于确保 BDNF 水平在 CAD 与健康对照组的分类中具有良好的分类效果。特别是,使用血清 BDNF 浓度和 CAD 血液参数的模型在从健康对照组中检测 CAD 方面取得了显著的改善,从 90.95%提高到了 98.19%。总之,我们的分析提供了血清 BDNF 水平与心血管功能之间的重要分子联系。我们的结果为 BDNF 作为 CAD 潜在诊断价值提供了新的证据,可能导致其在临床上的应用。

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