Clinical efficacy of angina pectoris after pci in patients with coronary heart disease complicated with type 2 diabetes by Yiqi Yangyin and Huatan Tongluo recipe

Zi-Ting Ni, Zheng-Bin Shao

1. Anhui University of Chinese Medicine, Hefei 230038

2. The First Affiliated Hospital of Anhui University of Chinese Medicine;Institute of cardiovascular disease, Anhui College of traditional Chinese Medicine, Hefei 230031

Keywords:

ABSTRACT

1. Introduction

In recent years, with the decrease of people's activity and the change of diet structure, the incidence rate of diabetes has gradually increased.Some studies have shown that the degree of coronary artery damage in patients with coronary heart disease and diabetes is higher than that in patients with single coronary heart disease[1].Coronary heart disease and diabetes have many same pathogenesis.And coronary heart disease with diabetes is a common clinical complication, easy to aggravate each other's disease development. At present, percutaneous coronary intervention (PCI) is the most common minimally invasive surgery in the treatment of coronary heart disease. Although it can restore the blood flow of the main coronary artery, some patients still have chest tightness and chest pain after operation, which is because in addition to the main coronary artery lesions in patients with type 2 diabetes mellitus, the microvascular lesions are also common [2]. With more and more attention paid to coronary microvascular dysfunction, the concept of microvascular angina (MVA) has also been clarified [3].Many scholars have pointed out that MVA is closely related to inflammatory response [4,5,6]. The injury of microvasculature affects myocardial perfusion and has a direct relationship with cardiac function. For this kind of disease, there is no targeted drug in clinical. In clinical, this part of patients still feel fear and depression due to the standardized medication and the symptoms of angina after PCI, which aあects their normal life, and the longterm emotional accumulation is prone to depression. In this study, 62 inpatients with coronary heart disease and type 2 diabetes mellitus who were admitted to our department from September 2017 to September 2019 were selected as the research objects to observe the changes of each index before and after treatment.

2. Materials and methods

2.1 Clinical data

From September 2017 to September 2019, 62 patients with coronary heart disease and type 2 diabetes mellitus were selected for PCI. Randomly divided into control group (n = 31, male 17, female 14) and treatment group (n = 31, male 19, female 12). The treatment group was 69.00 ± 5.79 years old. The control group was 69.00 ± 6.03 years old. There was no significant diあerence in gender, age, course of disease and other related clinical factors between the two groups.

2.2 Diagnosis and syndrome differentiation criteria

The diagnosis standards of coronary heart disease and type 2 diabetes refer to the diagnosis standards of coronary atherosclerotic heart disease[7] and the prevention and treatment guidelines of type 2 diabetes[8] issued by the Ministry of health of the people's Republic of China in 2010. The patients with deficiency of both qi and Yin, phlegm and blood stasis should refer to the standard in guiding principles for clinical research of new Chinese medicine[9]. Reference[10] of angina grading was made.

2.3 Inclusion and exclusion criteria

2.3.1 Inclusion criteria

It not only meets the diagnostic criteria of coronary heart disease and type 2 diabetes, but also shows obvious stenosis(＞50%) in patients with angina after PCI. At the same time, it can satisfy the classification of deficiency of both qi and yin or the combination of phlegm and blood stasis.

2.3.2 Exclusion criteria

Other diseases that may cause chest pain, such as myocardial infarction, neurosis, pulmonary embolism, digestive tract diseases, etc., are excluded； patients with hypertension whose blood pressure is not controlled and up to standard, serious diabetic complications, severe damage of liver and kidney function, malignant tumor and psychosis, and those who are allergic to traditional Chinese medicine are excluded.

2.4 Treatment

The control group was given basic treatment. In the treatment group, Yiqi Yangyin and Huatan Tongluo granules were added to the basic treatment. Drug composition: Dangshen 30g, Huangjing 20g, Huangqi 20g, Danshen 20g, Gualou 20g, Chuanxiong 15g. Take one dose in the morning and evening, one month is one course of treatment.

2.5Observation index

Before and after a course of interventional therapy, observe (1) the curative eあect of traditional Chinese medicine； (2) the curative effect of angina pectoris； (3) the index of cardiac function: the change of left ventricular ejection fraction(LVEF), B-type natriuretic peptide(BNP), metabolic equivalent(METs)； (4) adjust the TIMI frame count (cTFC) of coronary artery after 3 months； (5) the serum inflammatory factors: hs-CRP, IL-6(IL-6), TNF-α.

2.6 Efficacy criteria

2.6.1 Traditional Chinese Medicine(TCM) syndrome Reference document[9]

Significant effect: chest pain,lip and tongue purple darkness improved significantly, after one course of treatment, the score decreased≥70%. Eあective: chest pain, lip and tongue purple darknessimproved, after one course of treatment, the score decreased≥30%. Invalid: chest pain, lip and tongue purple darkness did not improve, after one course of treatment, the score decreased＜30%.

Table 1 Comparison of BNP、LVEF、METs between two groups(±s)

Table 1 Comparison of BNP、LVEF、METs between two groups(±s)

Note：①＊P＜0.05：Comparison with before treatment；②＃P＜0.05：Comparison with the contrast group after treatment.

GroupnLVEF/%Intra group comparisonBNP/(pg/ml)Intra group comparison Before treatment comparisonMETsIntra group treatmenttpBefore treatment After treatmenttpBefore treatment After After treatmentzp Contrast31 57.19±4.76 67.77±2.43 14.266 0.000＊ 5.58±1.37 6.09±0.71 2.275 0.03＊ 124.24±74.29 36.78±13.29 4.86 0.00＊Treatment 31 55.03±4.29 69.13±2.74 15.669 0.000＊ 5.27±1.28 7.65±0.73 8.958 0.000＊ 123.83±72.44 28.06±9.72 4.86 0.00＊Comparison among groups t1.8782.0580.9438.548Z-0.70-2.964 p0.0650.044＊＃0.349 0.000＊＃P 0.9440.03＊＃

Table 2 Comparison of CTFC in coronary arteries between two groups(±s)

Table 2 Comparison of CTFC in coronary arteries between two groups(±s)

Note：①＊P＜0.05：Comparison with before treatment；②＃P＜0.05：Comparison with the contrast group after treatment.

GroupnLADIntra group comparisonLCXIntra group comparisonRCAIntra group comparison Before treatment treatmenttpBefore treatment After treatmenttpBefore treatment After After treatmenttp Contrast31 45.44±12.36 34.51±8.49 3.712 0.001＊ 42.79±6.1233.38±6.99＊＃5.511 0.000＊ 45.77±10.9534.90±6.58＊＃5.283 0.000＊Treatment 31 45.25±11.52 29.75±4.78 9.282 0.000＊ 42.68±7.22 29.66±4.84 8.148 0.000＊ 45.78±10.70 29.65±6.58 12.822 0.000＊Comparison among groups t0.632.7190.652.4380.0043.141 p0.9500.009＊＃0.9490.018＊＃0.9970.003＊＃

Table 3 Comparison of inflammatory factors between two groups(±s)

Table 3 Comparison of inflammatory factors between two groups(±s)

Note：①＊P＜0.05：Comparison with before treatment；②＃P＜0.05：Comparison with the contrast group after treatment.

Groupnhs-CRP/(mg/ml）Intra group comparisonTNF-α(ng/ml)Intra group comparison Before treatment comparisonIL-6(pg/ml)Intra group treatmenttpBefore treatment After treatmenttpBefore treatment After After treatmentzp Contrast31 5.24±1.36 1.61±0.74 25.019 0.00＊ 44.74±14.97 34.98±8.40 7.843 0.00＊ 238.60±19.26 190.97±9.09 25.513 0.000＊Treatment 31 5.22±1.41 1.19±0.44 20.22 0.00＊ 46.41±13.31 28.95±5.78 12.233 0.00＊ 243.31±16.70 125.84±13.75 33.294 0.000＊Comparison among groups t0.0452.7780.4653.2901.02722.002 p0.9640.007＊＃0.6430.02＊＃0.3080.000＊＃

2.6.2 Effect of angina pectoris Reference document[11]

Significant effect: angina disappeared or improved to level2； effective: angina significantly reduced or improved to level≥1； ineあective: symptoms are basically the same as before treatment.

2.6 Statistical treatment

Spss21.0 software was selected to analyze the data.χ2 test was used to compare the curative eあect of TCM syndrome and angina pectoris. The measurement data is indicated by mean±standard deviation(±s).T test and Wilcoxon rank sum test were used for data comparison between two groups. In the same group, paired t-test was used. When p＜0.05 or 0.01, there was statistical significance.

3. Result

3.1 Comparison of therapeutic effects of TCM Syndromes

According to the results, there were 18 cases in the treatment group is Significant eあect, 11 cases in the treatment group is eあective and 2 cases in the treatment group is invalid. The control group was 10 cases, 12 cases and 9 cases respectively. The total eあective rate of the two groups (93.55%＞70.97%) was statistically significant (χ2 = 5.415, P=0.02＜0.05). It shows that the eあect of the control group is obviously worse than that of the treatment group.

3.2 Comparison of the effects of angina pectoris between the two groups

According to the results, there were 22 cases in the treatment group is Significant eあect, 8 cases in the treatment group is eあective and 1 cases in the treatment group is invalid. The control group was 10 cases, 13 cases and 8 cases respectively. The total eあective rate of the two groups (96.77%＞74.19%) was statistically significant (χ2 =6.369,P=0.012＜0.05).It shows that the eあect of angina in the treatment group is better than that in the control group.

3.3 Comparison of BNP, LVEF and METs between the two groups

There was no significant difference in BNP, LVEF and METs between the two groups before treatment (P＞0.05). After one course of treatment, each index was significantly diあerent from that before treatment (P＜0.01)； after treatment, BNP and LVEF% in the treatment group were statistically significant compared with that in the control group (P＜0.05), Mets was statistically significant (P＜ 0.01)； it showed that this prescription could significantly improve the heart function of patients. Table 1 for details.

3.4 Comparison of TIMI frame count (CTFC) corrected by coronary artery (LAD, LCX, RCA) between the two groups:

There was no significant difference in CTFC values of lad, LCX and RCA between the two groups before treatment (P＞0.05). After treatment, there was significant diあerence in LAD and RCA CTFC count between the treatment group and the control group（P＜0.01），LCX CTFC count was statistically significant compared with the control group(P＜0.05)。It is suggested that this prescription is of great significance to improve the microcirculation of patients with coronary heart disease and type 2 diabetes mellitus after PCI.Table 2 for details.

3.5 Comparison of inflammatory factors (hs-CRP, IL-6, TNF-α) between the two groups:

There was no significant difference in hs-CRP, IL-6 and TNF-α between the two groups before treatment (P＞0.05). After treatment, there were significant statistical diあerences between the indexes before and after treatment (P＜0.01).After treatment, there were significant diあerences in hs-CRP and TNF-αbetween the treatment group and the control group (P＜0.01), and in IL-6 between the treatment group and the control group (P＜0.05).Table 3 for details.

4.Disscussion

According to the national large-scale investigation on the causes of death of diabetes patients [12], among the causes of death of type 2 diabetes patients in 15 top-ranking hospitals in the capital from 1991 to 2005, the proportion of cardiovascular diseases reached 19.9%, ranking first. At the same time, patients with these two diseases have worse vascular conditions than patients with coronary heart disease. Some studies have shown that [13], most of these patients with coronary artery disease are multi vessel lesions, and the degree of stenosis and morphological lesions are more serious. Percutaneous coronary intervention is the main method to restore the blood flow of the diseased vessels in patients with severe stenosis. However, it can be found in clinical practice that some patients with coronary heart disease still have symptoms of chest pain and chest distress after PCI, even though the angiogram shows that the narrow coronary artery has been opened, but there is still no perfusion or poor perfusion of myocardial tissue, insuきcient perfusion of coronary microcirculation, etc. Traditional Chinese medicine has its unique advantages in improving microcirculation, myocardial perfusion and angina after PCI in patients with coronary heart disease and type 2 diabetes.

Liang Guoqing et al[13] found that the TCM syndrome type of coronary heart disease patients with diabetes was based on deficiency of both Qi and Yin, with stasis blocking phlegm and coagulation as the standard. Coronary heart disease belongs to the category of "chest obstruction" in traditional Chinese medicine, and type 2 diabetes belongs to the category of "thirst". Xiaoke is based on Yin deficiency and hot and dry. The course of the disease is delayed. It consumes Qi and injures Yin, resulting in deficiency of both qi and Yin. And the blood stasis caused by the injury of collaterals for a long time or the internal heat due to yin deficiency and fluid consumption. Deficiency of yin and dryness of heat result in phlegm, and stagnation of phlegm and blood stasis.

The prescription of Nourishing Qi, nourishing yin and removing phlegm and dredging collaterals takes dangshen, which is the essential medicine for invigorating lung and spleen, as the monarch drug. Some studies have shown that dangshen has many functions, such as protecting myocardial cells, inhibiting myocardial cell oxidation, improving myocardial energy metabolism, improving cardiac function, improving exercise tolerance, improving microcirculation and so on. Astragalus membranaceus is sweet and warm. It is good at Invigorating Qi, nourishing body and strengthening the body surface. It must be used together with dangshen to play the Qi and blood eあect of heart stirring. Some studies have shown that Astragalus membranaceus has the eあect of protecting ischemic myocardium. Huangjing has the eあect of Invigorating Qi and nourishing Yin, and its eあective components have the effect of anti-inflammatory and hypoglycemic[16]. Both of them are oきcial drugs, and they are combined with dangshen to strengthen the eあect of benefiting qi and nourishing yin. Salvia miltiorrhiza and Trichosanthes are all adjuvants. They are cold in nature and taste. It can prevent the tonic medicine from too warm in Xinwen, so as to avoid blood consumption. Trichosanthes and Salvia miltiorrhiza are commonly used drugs to treat angina pectoris of coronary heart disease. They have the eあects of antiinflammatory and anti thrombus, increasing myocardial blood supply and improving heart function. Ligusticum chuanxiong is good at promoting blood circulation and Qi to relieve pain, and ligustrazine can significantly improve the cardiac function and ejection fraction of adriamycin induced cardiomyocyte apoptosis in SD rats[17]. The whole prescription is simplified, and only six drugs can be used together to benefit Qi and Yin, dissipate phlegm and dredge collaterals.

CTFC is one of the objective indexes to evaluate coronary microvascular perfusion, which is more scientific than TIMI classification. According to Xuanbing[18], CTFC can be used as a predictor to evaluate the prognosis of patients after PCI. Some studies have shown that[19], metabolic equivalent is related to coronary artery disease and can be used to evaluate cardiopulmonary function. This study shows that Yiqi Yangyin, Huatan Tongluo recipe can significantly improve cTFC and metabolic equivalent in patients with coronary heart disease and type 2 diabetes mellitus after PCI, suggesting that this recipe has a significant effect on improving myocardial microcirculation disorder, and can eあectively improve the cardiac function and long-term prognosis of patients after PCI.

In recent years, hs-CRP, IL-6 and TNF-α are important markers of inflammatory response, which have special significance in assessing cardiovascular and cerebrovascular events[20]. Hs-CRP is a representative index reflecting microcirculation disturbance after PCI[21]. The level of IL-6 has predictive value for microvascular disorders in patients with coronary heart disease[22], which is related to the level of myocardial injury.It is suggested that the long-term prognosis of patients in the elevated group is significantly worse than that in the decreased group. TNF-α is a well-known index to evaluate the degree of inflammation. When the level of TNF-α in patients with coronary heart disease increases, the number of coronary vascular lesions will change significantly, which can be used to evaluate the prognosis of coronary heart disease[24]. TNF-α participates in the pathological process of myocardial ischemia injury, reflects the degree of myocardial ischemia and necrosis, and can evaluate the severity and clinical eあect of coronary heart disease[25]. Through clinical application, this prescription has achieved satisfactory results in reducing angina attack, improving cardiac function, inhibiting inflammatory reaction and improving microcirculation.