A Large-Scale, Multi-Center Urine Biomarkers Identification of Coronary Heart Disease in TCM Syndrome Differentiation

Abstract

Coronary heart disease (CHD) threatens human health. The discovery and assessment of potential biometabolic markers for different syndrome types of CHD may contribute to decipher pathophysiological mechanisms and identify new targets for diagnosis and treatment. On the basis of UPLC-Q-TOF/MS metabolomics technology, urine samples of 1072 participants from nine centers, including normal control, phlegm and blood stasis (PBS) syndrome and Qi and Yin deficiency (QYD) syndrome, and other syndromes of CHD, were conducted to find biomarkers. Among them, the discovery set (n = 125) and the test set (n = 337) were used to identify and validate biomarkers, and the validation set (n = 610) was used for the application and evaluation of the support vector machine (SVM) prediction model. We discovered 15 CHD-PBS syndrome biomarkers and 12 CHD-QYD syndrome biomarkers, and the receiver-operator characteristic (ROC) area-under-the-curve (AUC) values of them were 0.963 and 0.990. The established SVM model has a good diagnostic ability and can well distinguish the two syndromes of CHD with a high predicted accuracy >98.0%. The discovery of biomarkers and metabolic pathways in different syndrome types of CHD provides a basis for the diagnosis and evaluation of CHD, thereby improving the accurate diagnosis and precise treatment level of Chinese medicine.

Metabolic Profiling Analysis of Patients With Coronary Heart Disease Undergoing Xuefu Zhuyu Decoction Treatment

“…The key pathogenesis of CHD is based on the abnormal metabolism of myocardial substrates and the disturbance of energy metabolism induced by myocardial ischemia or hypoxia (Doenst et al, 2013). A recent study found that metabolites involved in the TCA cycle and amino acid metabolism (tryptophan, arginine, and proline metabolism) were significantly decreased in fasting morning urine of CHD patients with Qi and Yin deficiency syndrome, suggesting that the metabolites in amino acid metabolism and TCA cycle were partially the material foundation of Qi (Zhou et al, 2019). In TCM theory, Qi is the commander of blood.…”

“…Therefore, metabolic abnormality plays a key role in affecting the development and prognosis of CHD (Nicholson et al, 1999; Kordalewska and Markuszewski, 2015). Recently, it was found that metabolites involved in amino acid metabolism and tricarboxylic acid (TCA) cycle might partially constitute the material foundation of Qi, according to the Qi and blood theory of TCM (Zhou et al, 2019). Therefore, we studied differential metabolites in the serum of CHD patients to explore the effects of TCM on regulating Qi and promoting blood circulation.…”

Metabonomics Study on Serum Characteristic Metabolites of Psoriasis Vulgaris Patients With Blood-Stasis Syndrome

“…Applying metabonomics approaches to material basis study of TCM syndrome differentiation is a beneficial attempt. Metabonomics technology research based on liquid chromatography coupled with mass spectrometry (LC-MS) and gas chromatography coupled with mass spectrometry (GC-MS) has been applied in the TCM syndrome differentiation studies and biomarker identification in coronary heart disease (Zhou et al, 2019) and rheumatoid arthritis (Gu et al, 2012). However, few studies were undertaken to explore the objective material basis of the TCM syndrome differentiation in patients with psoriasis.…”

The RIGHT Extension Statement for Traditional Chinese Medicine: Development, Recommendations, and Explanation

“…For item 7 (S3 in the checklist of the RIGHT-TCM), it is recommended to describe whether to treat disease based on the syndrome differentiation of TCM. Syndrome differentiation is an important basic concept of TCM [ [23] , [24] , [25] ]. It is the process of applying “principle-method-recipe-medicines” to clinical practice.…”