Research progress on the correlation between TCM syndromes of coronary heart disease and blood biochemical indexes

Shan-Shan Ding ,Li-Li Yu ,Rong Li

1.Macau University of Science and Technology,Macau 999078 China

2.First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China

Keywords:Coronary heart disease (CHD)TCM syndromes Blood biochemical indexes

ABSTRACT The researches on the correlation between TCM syndromes of coronary heart disease and blood biochemical indexes from Jan.2011 to Jul.2020 were reviewed,in order to explore the association of different TCM syndromes of coronary heart disease with blood biochemical indexes,such as blood lipid metabolism,inflammatory factors,coagulation-fibrinolysis system,blood rheology and vascular endothelial function,which was hoped to provide a guidance on the clinical combined application of TCM syndrome differentiation and biochemical indexes of coronary heart disease,so as to promote the objectification and standardization of TCM syndrome differentiation.

Coronary atherosclerotic heart disease (CHD),referred to as coronary heart disease,belongs to the category of "f chest stuffiness and pains" in traditional Chinese medicine(TCM).The basic pathogenesis of CHD is essential empty and out solid,deficiency of Yin,Yang or Qi is reason,and cold,phlegm,dampness,qi stagnation or blood stasis blocks the heart vessel is outer phenomenon.The treatment of CHD based on syndrome differentiation has a long history.However,in the actual diagnosis and treatment process,the traditional "four diagnostic methods" have some problems,such as strong subjectivity,disunity of clinical syndromes and high dependence on clinical experience,which affect the accuracy of syndrome differentiation.It provides objective basis for TCM differentiation of symptoms and signs.

Centering on this idea,the author extracted "coronary heart disease","Syndrome type/syndrome of TCM","biochemical index","laboratory examination" and other key words of information.A total of 93 related journal papers were retrieved from "CNKI"and "Wanfang Database" from 2011 to July 2020.It contains 77 research literature,17 reviewed literature.It was found that the most commonly involved correlation indicators mainly included lipid metabolism,inflammatory factors,coagulation factors and hemorheology,vascular endothelial function and so on.The above commonly used correlation index research is briefly reviewed.The objective is to explore the correlation between different TCM syndromes of CHD and blood biochemical indicators,so as to provide more sufficient scientific basis for clinical application of biochemical indicators to guide CHD syndrome differentiation.

1.Blood iochemical indexes and TCM syndromes of CHD

1.1 Blood lipid metabolism

Atherosclerosis(AS) is an important pathological basis of CHD,and dyslipidemia is an important risk factor for AS.When blood lipid metabolism is disturbed,hemodynamic abnormalities occur.The function of vascular endothelial cells is impaired,macrophages are transformed from monocytes and secrete a large number of inflammatory factors,and lipid deposition accumulates in the coronary artery wall,resulting in stenosis and occlusion of the coronary artery lumen.These are closely related to the formation and development of CHD [1].From the perspective of TCM,hyperlipidemia patients usually like to eat greasy food,which will lead to Qi-ji disorder of spleen and stomach,phlegm-dampness accumulated in blood vessels.Eventually it leads to blockages in the heart,which can lead to the disease.

Meng [2] analyzed the lipid levels of 300 CHD patients and found that the levels of low-density lipoprotein (LDL-C),small and dense LOW-density lipoprotein cholesterol (sd LDL-C) and total cholesterol (TC) in patients with phlegm obstructing the heart vessels syndrome were higher than those in patients with other syndromes.Jiang [3] analyzed 335 patients with CHD,and found that the number of patients with phlegm obstructing the heart vessels was the largest,and the levels of TC and LDL-C in these patients were significantly higher than those in other syndromes.Wang [4] analyzed 120 CHD patients and found that the levels of TC,LDL-C and Apolipoprotein A1 (APO-A1) in patients with phlegm-turbid-stasis and phlegm turbidity and blood stasis syndrome were significantly higher than those in patients with other syndromes,and the elevated level of TG in patients with phlegm turbidity and blood stasis syndrome was significantly higher than those in patients with other syndromes.Li [5] analyzed the high-density lipoprotein cholesterol (HDL-C)level of 411 patients with unstable CHD angina.The results showed that the HDL-C level of patients with qi deficiency syndrome was higher than that of patients without qi deficiency syndrome.HDL-C level in patients with blood stasis syndrome was lower than that in patients without blood stasis syndrome.Zhang [6] analyzed 100 CHD patients and found that the levels of LDL-C,TC and Apolipoprotein B (ApoB) in patients with phlegm-obstructed cardiomyopathy were significantly higher than those of other syndromes,and the TC levels in patients with phlegm accumulation syndrome and heart blood stasis syndrome were significantly higher than those of other syndromes.

The above studies indicate that the lipid metabolism index has guiding significance for CHD TCM syndrome differentiation and classification.CHD patients with abnormally elevated LDL-C,TC,apolipoprotein and other indicators were mainly manifested as phlegm turbidness and blood stasis syndrome.These indexes have reference value for distinguishing phlegm-turbidity from nonphlegm-turbidity,blood stasis from non-blood stasis.Abnormal elevation of HDL-C level in CHD patients is often accompanied by qi deficiency syndrome.It has reference value for distinguishing qi deficiency syndrome from non-qi deficiency syndrome.

1.2 Inflammatory factors

Chronic immune injury is the key to the formation of AS [7].By influencing the course of AS,inflammatory factors are involved in the whole process of CHD formation,development and prognosis [8].

1.2.1 C-reactive protein/hyper sensitive C-reactive protein(CRP/ HS-CRP)

CRP is an important sensitive indicator of the level of inflammatory response.It partly reflects levels of inflammation and plaque stability.And it is an independent risk factor and predictor of cardiovascular adverse events.Compared with CRP,HS-CRP has higher sensitivity and accuracy,and is of higher value in the early diagnosis,disease condition and prognosis assessment of CHD [9].Sun [10] analyzed THE CRP level of 185 CHD patients,and found that the CRP level of patients with heart blood stasis syndrome,heart collaterals obstruction due to phlegm accumulation syndrome and heart-Yin deficiency syndrome were significantly higher than that of other syndrome types.Wen [11] compared the elevated HS-CRP level of 427 CHD patients,and found that the elevated Hs-CRP level of patients with phlegm-blood stasis syndrome was significantly higher than that of patients with other syndromes.

1.2.2 Homocysteine (Hcy)

As an independent risk factor for CHD,Hcy is significantly associated with arterial thrombotic cardiovascular and cerebrovascular diseases [12].It can participate in the process of AS by influencing the inflammatory reaction process,lipid metabolism and blood circulation.Liu [13] found that Hcy was related to CHD through single-factor analysis.It can be used as a basis for diagnosis,treatment and prevention of CHD.Meng [1] found that the Hcy level of CHD patients with phlegm-obstructed heart pulse syndrome was higher than that of other syndromes.Qiu [14] analyzed the Hcy level of 278 CHD patients.She found that patients with heart collaterals obstruction due tophlegm accumulation syndrome and qi stagnation and blood stasis syndrome had higher HCY levels than patients with qi deficiency and blood stasis syndrome,qi-yin deficiency syndrome or heart blood stasis syndrome.The HCY level of patients with the last three types of syndrome was higher than that of yin deficiency of heart and kidney.Patients with syndrome yang-qi deficiency syndrome had the lowest HCY level.Zhang [15] analyzed 299 patients with CHD,and found that the Hcy level of patients with qiyin deficiency syndrome,Phlegm,heat and blood stasis syndrome was higher than that of patients with other syndromes.

1.2.3 Interleukin (IL)

IL is a lymphatic factor that can influence and promote the formation of AS,leading to the rupture of AS plaques and even thrombosis [8].Yu [16] analyzed the IL level of 143 patients with acute coronary syndrome (ACS).He found that IL-35 levels were higher in patients with qi stagnation and blood stasis syndrome and yin blood deficiency syndrome.IL-17 levels were higher in patients with yangqi deficiency syndrome and phlegm turbidity obstruction syndrome.IL-17 and IL-35 were more significantly correlated with the yang-qi deficiency syndrome.Chen [17] analyzed the IL-6 level of 122 CHD stable angina pectoris (SAP) patients.He found that IL-6 levels were closely related to phlegm and blood stasis syndrome.The level of IL-6 in patients with mutual phlegm and blood stasis was higher than that in patients with other syndromes,and there was no statistical difference between the sputum and blood stasis groups.

1.2.4 Lipoplotein-associated phospholipase A2(LP-PLA2)

Lp-PLA2 is an independent risk factor for cardiovascular disease and has vascular specificity.Lp-pla2 level not only reflects the degree of coronary artery stenosis,but also has reference value in predicting the occurrence of cardiovascular events [18-20].Meng [1] found that the level of LP-PLA2 in CHD patients with phlegm-obstructed heart collaterals syndrome was higher than that of other syndromes.Kuang [21] analyzed LP-PLA2 levels of 90 CHD patients and found that the indicators of blood stasis and phlegm turbidity syndrome were significantly higher than those of other non-phlegm and nonstasis syndrome.

1.2.5 Uric acid(UA)

The relationship between UA and CHD and other cardiovascular diseases is close.

It can participate in the occurrence and development of CHD by promoting inflammatory response,accelerating thrombosis,and affecting the antioxidant mechanism [22].In addition,CHD patients were often complicated with hypertension and diabetes,and were often accompanied by varying degrees of impaired renal function,so that UA could not be normally metabolized out of the body.Li [4]studied the UA level of CHD patients and found that the abnormal rate of UA level in patients with phlegm syndrome was significantly higher than that in patients without phlegm syndrome.UA can not be discharged from the body in time as the toxin of sputum turbidiousness in blood.This will lead to the blockage of the arteries and veins of turbidite accumulation,followed by abnormal elevation of UA and aggravation of chest pain.

The above numerous studies have shown that patients with concurrent phlegm,blood stasis and yin deficiency syndrome have a more obvious inflammatory response.The vascular inflammatory reaction of CHD is correlated with phlegm turbidness,blood stasis and yin deficiency syndrome.The above levels of inflammatory factors can be used as a reference for the identification of phlegm and blood stasis and yin deficiency.

1.3 Coagulation-fibrinolysis system and blood rheology

Studies have suggested that [23],hemorheology,inflammatory response and dyslipidemia metabolism jointly participate in the process of vascular endothelial cell function damage.They interact and play an important role in the occurrence and development of CHD.The coagulation and fibrinolysis system maintains the normal blood flow of the body,and the two interact to maintain the dynamic balance [24].Patients with CHD have an imbalance of coagulation and fibrinolysis.Their clotting factor activity increased abnormally,leading to thrombosis in the coronary arteries and the blockage of the lumen.The blood flow in the coronary arteries is blocked,and myocardial ischemia and hypoxia lead to ischemic heart disease.It can be considered that the occurrence of CHD angina caused by hemodynamic disorder and imbalance of coagulation and fibrinolysis system is similar to the "stagnation leading to pain" in traditional Chinese medicine.The pathological process of thrombus formation and occlusion of blood vessels is similar to that of mutual knot of phlegm and blood stasis and blockage of heart arteries.The abnormal hemorheology,coagulation and fibrinolysis may be closely related to phlegm syndrome and stasis syndrome.

Dong [25] analyzed the biochemical indexes of 100 CHD patients and found that fibrinogen (Fib) had the highest diagnostic specificity for phlegm-obstructed blood stasis and qi-yin deficiency syndrome.The levels of P-selectin (Ps) and vascular pseudohemophilia factor(vWF) were the most significant in the increase of qi stagnation and blood stasis syndrome.Combined detection of D-dimer (D-D)and brain natriuretic peptide precursor (proBNP),combined detection of vWF,Ps and Hcy is more significant for the diagnosis of qi deficiency and blood stasis and qi stagnation and blood stasis syndrome.Zhang [26] tested the coagulation indexes of 120 CHD patients.She found that patients with phlegm-turbid stasis syndrome had higher activity of exogenous coagulation pathway,and prothrombin time activity (PT%) was significantly higher than those with qi deficiency and blood stasis syndrome and qi stagnation and blood stasis syndrome,suggesting a higher possibility of thrombotic events.Wen [10] found that different coagulation indexes could be used to differentiate and diagnose CHD TCM syndromes.Fib can be used for the differential diagnosis of phlegm blocking blood stasis and qi and Yin deficiency syndrome.D-d can be used for the differential diagnosis of qi stagnation and blood stasis and qi-yin deficiency syndrome.D-D combined with Hcy can be used for the differential diagnosis of qi deficiency and blood stasis;D-D combined with brain natriuretic peptide precursor (proBNP) can be used for the differential diagnosis of qi stagnation and blood stasis syndrome and qi-yin deficiency syndrome.

Wang [27] analyzed the hemorheological indicators of 136 CHD patients,including whole blood viscosity,plasma viscosity,hematocrit,reduction viscosity of whole blood,fibrinogen quantification,red blood cell aggregation index and red blood cell deformation index.The results showed that CHD TCM syndromes were correlated with hemorheology.Erythrocyte distribution width(RDW) is a related factor of hemorheology [28].Yang [29] analyzed and compared RDW and mean platelet volume (MPV) values of 326 CHD patients.The levels of RDW and MPV in patients with excess syndrome were lower than those in patients with deficiency syndrome.The levels of RDW and MPV in the excess syndrome is qi stagnation

1.4 Vascular endothelial function

Vascular endothelial cell injury and dysfunction are important factors in the development of AS.Vasosystolic and diastolic dysfunction runs through the whole CHD process [30-31].Ma [32]believed that "vascular endothelium" could be similar to "pulse"in TCM.A blockage in the pulse can cause blood to fail to flow.When the structural and functional dysfunction of the veins occurs,the corporeal evil blocks the heart collaterals.Therefore,qi and blood can't run smoothly,which leads to the occurrence of blood stasis syndrome.Endothelin (ET) and nitric oxide (NO) are released synthetically by endothelial cells.They are antagonistic active substances with vasoconstriction and relaxation function and are commonly used to assess vascular endothelial cell function [33-34].Wu[35] detected ET values of 60 CHD patients.The results showed that the ET level of excess syndrome patients was significantly higher than that of other syndromes,and heart blood stasis syndrome was higher than that of phlegm-obstructed heart collaterals syndrome.Ren [36] measured the plasma level of Big ET-1 in 405 CHD patients.The results showed that the level of Big ET-1 in patients with blood stasis syndrome was significantly higher than that in patients without blood stasis syndrome.It is suggesting that Big ET-1 may be related to blood stasis syndrome.Studys [37-38] detected and compared the serum NO level of 165 CHD patients.It found that the NO level of healthy control group was significantly higher than that of CHD patients.The NO level of patients with phlegm-obstructed heart collaterals and heart blood stasis syndrome,was significantly lower than that of patients with other syndromes,and patients with yangqi deficiency was significantly lower than that in patients with yincold stagnation syndrome,heart-kidney yin deficiency and qi-yin deficiency syndrome.Therefore,it can be concluded that ET level can guide the syndrome differentiation of blood stasis,while NO level can provide a reference for the syndrome differentiation of phlegm turbiditis.

2.Summary

To sum up,different biochemical indexes are correlated with different TCM syndromes of CHD,which can guide the differentiation of CHD syndrome and provide reference for it.Lipid metabolites accumulate in the blood vessel wall in the form of phlegm and turbidite,phlegm and blood stasis among guitar,closed resistance heart vein.Inflammatory factors have stronger guiding significance in the differentiation of sputum blockage,blood stasis and yin deficiency.Phlegm and blood stasis unite each other and consume Yin.The mutual accumulation of phlegm and blood leads to the consumption of yin.Coagulation and fibrinolysis system and hemorheology indexes have higher reference value for the differentiation of blood stasis,phlegm turbid,qi stagnation and qi deficiency,which are suitable for the tangibility of pathogenic factors blocking veins,qi blocking veins and qi deficiency pushing blood without force.Vascular endothelial dysfunction also has the strongest correlation with phlegm turbid and blood stasis,which is related to vascular injury,poor circulation of qi and blood,and obstruction of arteries and veins by pathogenic factors.

While progress has been made in the research on the correlation between modernization index and CHD TCM syndrome differentiation,there are also many problems.First of all,because there are many criteria for CHD syndrome differentiation,different studies choose different criteria for CHD syndrome differentiation,and the results are not the same.

Then,at present,most of the researches adopt the compound syndrome type of TRADITIONAL Chinese medicine to conduct the classification research,such as deficiency of qi and blood stasis,deficiency of qi and Yin,etc.,which cannot avoid the occurrence of repetition or inclusion problems.Finally,most of the current studies are confined to the correlation between a single indicator and syndrome type.However,the development of CHD course is a complex process,and single indicator detection lacks specificity.To some extent,combined multi-indicator detection can better explore the correlation between index-related pathology and syndrome type.To sum up,in the future scientific research work,attention should be paid to the standardization of syndrome differentiation classification standards,the selection of appropriate specific indicators and the working idea of multiple indicators combined detection,the development of the corresponding clinical verification,and the promotion of the standardization,standardization and objectification of TCM syndrome differentiation.