Research On Biological Diagnostic Patterns And Metabol Ites In Patients With Chronic Heart Failure Of Different TCM Syndromes

Object ivesThe purpose of the study of patients with chronic heart failure was to investigate the complicated TCM syndromes, in which the biological indexes used to build the diagnostic pattern for each syndrome based on data mining methods were adopted. We further analyzed the metabolites closely related to chronic heart failure and different syndromes by1H-NMR techniques, so as to provide new ideas in syndrome diagnosis, prevention and treatment of heart failure with TCM formulas.Methods1.Clinical cross-sectional study:630patients were enrolled and we discriminated syndromes under the criteria based on the demographic data, illness history as well as TCM four diagnostic information collected. Complicated TCM syndromes and related factors were described.2.Biological diagnostic pattern study:100patients with CHF were included and their physical and chemical indexes were analyzed by T-test, ROC curve and logistic regression to build the diagnosis pattern by means of artificial networks.3.The metabolic biomarker study:Plasma samples of46patients with chronic heart failure caused by coronary heart diseases and15healthy people were experimented by1H-NMR to find the metabolites related to chronic heart failure and different syndromes, PCA and OPLSDA methods were used and the results were compared.Results1.The male patients accounted for58.25%in630patients with CHF. Patients above70years occupied49.84%.Coronary heart diseases is the leading cause of chronic heart failure. Patients with NYHA cardiac function of grade III took up51.11%.The most common complications are hypertension, arrhythmia, diabetes diseases, cerebral vascular accident, hyperlipemia etc. There were8kinds of syndromes, qi deficiency was the most, followed by blood stasis and water retention, phlegm turbid, yin deficiency, yang deficiency, qi stagnation, heat. There were single syndrome to six syndrome combinations. Qi deficiency was the most common syndrome in single type, accounting for45.16%. Qi deficiency combined with blood stasis was the top two syndrome combination, accounting for53.98%. Qi deficiency and blood stasis combined with water retention was the top three syndrome combination, accounting for35.22%. Qi deficiency and blood stasis and water retention combined with Yang Deficiency syndrome was the top four syndrome combination, accounting for29.31%. Qi deficiency and blood stasis and water retention combined with yang deficiency as well as phlegm turbid was top five syndrome combination, accounting for58.70%. Three syndromes combination was the most common type. Sex, age, cause of illness, heart function and complications were related to the development of CHF.2. Characteristic indexes of qi deficiency includes:BASO,RBC,HGB etc; Characteristic indexes of blood stasis includes:LYMPH,LYMPHL,MONO etc; Characteristic indexes of phlegm turbid includes:WBC,NEUT,LYMPH etc; Characteristic indexes of water retention includes:WBC,BASO,NEUT1etc; Characteristic indexes of yin deficiency includes:WBC, MONO,EO etc; Characteristic indexes of yang deficiency includes:RBC,HGB,MCH etc. The accuracy of diagnosis pattern used by MLP was higher than80%on average for each syndrome in both training samples and validation samples.3.PC A and OPLSDA methods were used to analyze the distinguished metabolites between the patients and healthy people, including Lac, Cr, Tyr etc, and the OPLSDA methods had better classification. The characteristic metabolites of the blood stasis syndrome were as follows: Lac, Ala His etc increased while Gly,Val, Glu etc reduced; The characteristic metabolites of the phlegm turbid syndrome were as follows:Lac increased while Ala, Glu, Cho, Pro, Gly, HLDL, VLDL\LDL, UFA reduced; The characteristic metabolites of the water retention syndrome were as follows:Lac, Ala, N-Ac, O-Ac increased while Glu, Cho, TMAO, Pro, VLDL\LDL, UFA reduced; The characteristic metabolites of the yin deficiency syndrome were as follows:Lac, N-Ac, O-Ac, VLDL\LDL increased while Glu, Val, Pro, Ala, Carnitine reduced; The characteristic metabolites of the yang deficiency syndrome were as follows:Lac, Ala, N-Ac, Glutamate increased while Glu, HLDL, VLDL\LDL reduced.Conelusion1.More attention should be paid to the old in prevention and treatment of CHF. Getting rid of the risk factors, controlling the complications and avoiding bad habits play an important role in reducing the mortality and re-hospitalization rate of chronic heart failure patients. Qi deficiency, water retention, blood stasis, phlegm turbid, yin deficiency and yang deficiency are the basic syndromes in this disease. Qi deficiency and blood stasis combined with water retention is the key pathogenesis, which can help clinical doctors get a better understanding of the syndrome differentiation in the treatment of CHF.2.Qi deficiency syndrome related to anemia and decreased renal function; Blood stasis syndrome related to blood cell volume changes, inflammatory response etc; Phlegm turbid syndrome related to lipids disorder, inflammatory response, high UA level etc; Water retention syndrome related to inflammatory response, high UA level, immune activation etc. Yin deficiency syndrome related to inflammatory response, anemia, lipids disorder etc. Yang deficiency syndrome related to anemia, reduced liver function, immune activation etc. As far as the diagnosis model for each syndrome being concerned. We should make full use of all kinds of data mining methods to do the TCM syndrome research.3.The OPLSDA methods have great potential to distinguish the metabolic biomarkers, better than PCA in this study, which should be widely applied in clinical studies. We figured out the metabolic patterns of patients with CHF, related to the glucose, protein, lipid metabolism as well as energy supplication, which reflect the patho-physiological mechanisms of the diseases, such as nerve-endocrine disorders, immune dysfunction, microcirculation disorder and so on. Different metabolites were found in each TCM syndrome of CHF, which could be obviously seen from the small molecular metabolites, provided new ideas of syndrome diagnosis as well as the prevention and treatment of chronic heart failure by Traditional Chinese Medicine.