Tài liệu The relationship between coronary artery lesions with some risk factors, inflammatory markers in patients with chronic coronary artery disease

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MINISTRY OF EDUCATION MINISTRY OF DEFENCE AND TRAINING MILITARY MEDICAL UNIVERSITY NGUYEN THANH XUAN THE RELATIONSHIP BETWEEN CORONARY ARTERY LESIONS WITH SOME RISK FACTORS, INFLAMMATORY MARKERS IN PATIENTS WITH CHRONIC CORONARY ARTERY DISEASE Speciality: Cardiology Code: 62 72 01 41 SUMMARY OF MEDICAL DOCTORAL THESIS Ha Noi – 2014 The work was completed at the Military Medical University Full name of supervisor: 1. Associate Professor. Nguyen Oanh Oanh, MD.PhD 2. Associate Professor. Le Van Dong, MD. PhD. The Objection 1: The Objection 2: The Objection 3: Can be found the thesis in: 1. National Library 2. The Library of the Military Medicine University LIST OF WORKS OF RESEARCH HAS PUBLISHED AUTHOR RELATED TO THE THESIS 1. Nguyễn Thanh Xuân, Nguyễn Oanh Oanh, Lê Văn Đông, “Nghiên cứu mối liên quan giữa mức độ tổn thương động mạch vành với một số yếu tố nguy cơ tim mạch”. Tạp chí Y Dược học Quân sự, Vol 39, N01, tháng 01/2014, tr: 88-93. 2. Nguyễn Thanh Xuân, Nguyễn Oanh Oanh, Đỗ Khắc Đại, Lê Văn Đông, “Nghiên cứu nồng độ và mối liên quan của interleukin 6, interleukin 10 với mức độ tổn thương động mạch vành ở bệnh nhân bệnh động mạch vành mạn tính”. Tạp chí Y Dược học Quân sự, Vol 39, N02, tháng 02/2014, tr: 222-226. 1 BACKGROUND Coronary artery disease (CAD) is a common disease in developed countries, it has trend increasing in developing countries, including Vietnam. These risk factors include old age, male gender, smoking, dyslipidemia, hypertension and diabetes. These factors increase in the blood, they impact on vascular endothelium and causing endothelial dysfunction, they activation of inflammatory cells releasing inflammatory markers. The inflammatory marker activate other inflammatory cells releasing series of inflammatory markers and cause to reaction local inflammatory to form atherosclerotic of arterial wall. In Vietnam there are a number of studies have mentioned the role of inflammatory markers with rick factors of CAD. However, no study has specifically mentioned to overall picture of proinflammatory markers, anti-inflammatory lesions with coronary atherosclerosis. Therefore, the question is whether there is relationship between inflammatory markers with different degree of damage of the coronary arteries, there is a relationship between risk factors and inflammatory markers in coronary artery disease? In order to solve this question, study should be conducted multiple inflammatory markers (proinflammatory and anti-inflammatory), assessed the relationship between inflammatory markers and traditional risk factors in atherosclerotic lesions of coronary arteries. From which the project "The relationship between coronary artery lesions with some risk factors, inflammatory markers in patients with chronic coronary artery disease”. " be done with two objectives: 2 1) Survey rate and characteristics of some cardiovascular risk factors, inflammatory markers levels plasma in patients with chronic coronary artery disease in 103 Military Hospital. 2) Assessment of the relationship between characteristics of coronary lesions on angiography images with some cardiovascular risk factors and inflammatory markers. * The meaning and practice of science topics Determination characteristics and relationship of these risk factors, inflammatory markers (IL-2, IL6, IL-8) and antiinflammatory (IL-10). The results of this study are a new contribution to cardiology practices in cardiology in Vietnam. It helps clinicians understand more the pathophysiological mechanisms of atherosclerosis, improve diagnosis, treatment and prevention of heart disease in general, and coronary artery disease particularly. * Structure of the thesis The thesis has 119 pages, backgroud has 2 pages, conclusion has 2 pages, recommendation has 1 page. The thesis has 4 chapters: Chapter 1: Overview has 31 pages, chapters 2: object and methodology study have 20 pages, chapters 3: Results of study has 30 pages, chapter 4: discussion has 33 pages. Thesis has 45 tables, 10 pictures, 9 charts and 131 references (23 Vietnamese, 108 English). ABBREVIATIONS AHA: American Heart Association BMI: Body mass index CRP: C- Reactive Protein IL:interleukin HDL-c: High density lipoprotein cholesterol LDL-c: Low density lipoprotein cholesterol TNF: Tumor Necrosis Factor Th: helper T cell 3 CHAPTER 1: OVERVIEW 1.1.1. The concept of chronic coronary artery disease Chronic coronary artery disease also known as ischemia heart muscle disease, coronary insufficiency, coronary atherosclerotic disease. Divided into two groups: (1) stable angina is the most common form. (2) Missing local myocardial quietly. 1.1.2.2. The risk factors of coronary artery disease Along with the increase of coronary artery disease, the risk factors of coronary artery disease is detected and a list of the risk factors are increasing longer. These risk factors cannot be interference: age, sex, genetic factors These risk factors can be changed: hypertension, dyslipidemia, smoking, obesity, diabetes and insulin resistance 1.2.2. The role of inflammation in atherosclerosis formation * The role of macrophages in the development of plaque In patients with high blood cholesterol, LDL-c invasive and accumulate in arterial endothelium, the metabolic products, other factors impact to damage destruction vascular endothelial cell. Macrophages and monocytes migrate to phagocyt debris, drops cholesterol and transformed into foam cells, trigger inflammatory reaction and damaging tissue (Goran K Hansson, 2005). * The role of lymphocytes T and inflammation In components of atherosclerotic lesion has immune cells. including T cells, cells rewind, monocytes, macrophages, mast cells and other leukocyte cells. In this type Th1 cells secrete proinflammatory cytokines, to activation macrophages and causing inflammation (Elisabetta Profumo, 2012). 4 * The anti-inflammatory factors Th2 cells secrete anti-inflammatory cytokines, inhibition of inflammatory reactions can promote immune to prevent atherosclerosis. The balance of inflammatory and antiinflammatory cytokines can decide the development of sclerosis plaques (Frostegard J 1999; Shimizu K, Shichiri M, 2004; Uyemura K, Demer LL, 1996). Representing the antiinflammatory marker IL (interleukin)-10, growth factors stimulate β (TGF-β). Larisa (2009), rate IL-6/IL-10 higher in the group with coronary artery disease have complications of myocardial infarction than chronic coronary artery disease. * The relationship between inflammation and the risk factors The intrusion of LDL-c, adipose tissue cytokines including leptin, adiponectin, and resistin. They may damage to the endothelial cells and activating increased production of proinflammatory markers and inflammation under the endothelial layer and formation of atherosclerosis (Antonino Tuttolomondo, 2010). Several studies showed that the relationship between traditional risk factors (obesity, smoking, hypertension, dyslipidemia, increased blood glucose) with inflammatory markers. They are related, the correlation clinical significance in atherosclerotic coronary (Raul Altman, 2003). Mahinda Y (2009), Peter Libby (2002), Ying Yin (2013). The adjustment of these risk factors can reduce in inflammatory markers plasma, and reducing complications of coronary artery disease (Esposito K, 2003; Weihong Tang, 2007). * Group inflammatory markers: IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-17, IL-18, TNF-α, GM-CSF, IFN-γ (Enrique Z Fisman, 2003). 5 * Group anti-inflammatory marker: IL-4, IL-10, IL-11, IL12, Il-13. 1.3. THE STUDIES ABOUT INFLAMATORY MARKER IN CORONARY ARTERY DISEASE Tchernof A (2002). Study 61 female patients with obesity (BMI: 35,6 ± 5 kg/m2), if body weight had reduced 15,6%, CRP plasma level would have reduced 32,3% (from 3,06 ± 0,69 mg/ml to 1,63 ±0,75 mg/ml), p< 0,0001. Alan D. Simon, M.D (2001). Results showed that coronary artery disease group have higher IL-2 plasma level than the group subjects, p <0.05. Mehdi Hassanzadeh et al (2006). Results showed that chronic coronary artery disease group have higher IL-6, TNFα plasma level than the group subjects, p <0.05. Larisa (2009), Results showed that myocardial infarction group has lower IL-10 plasma level than group stable angina. There is a negative correlation between IL-6 and IL-10 plasma level. Mustafa Aydin (2009), in Turkish, patients with coronary artery disease have higher TNFα plasma level than group coronary artery disease, p <0.05. Thomas B. Martins (2006). Study complexity of 8 cytokines, results showed that there are differences between coronary artery disease group and the control group, level in plasma of IL-2 (p <0.05), IL-6 (p <0.001), IL-8 (p> 0, 05), IL10 (p> 0.05), and TNF-α (p> 0.05), IFN-γ (p> 0.05) and CRP (p> 0.05). Nguyen Kim Luu (2012), results showed that the control group has higher IL-10 plasma level and lower TNF-α plasma level than diabetic patients with obese group (p <0.05) . 6 Le Thi Bich Thuan (2005), there is a positive correlation between CRP with traditional risk factors such as: cholesterol, diabetes mellitus, hypertension. Le Thi Thu Trang, in 2011, results showed that CRP plasma level (mg/l) and IL-6 plasma level (pg/ml) are higher in hypertension group than not hypertensive group, p < 0.0001. Chapter 2: SUBJECTS AND RESEARCH METHODOLOGY 2.1. Study subjects: 109 patients, results of coronary angiography divided into 02 groups. 2.1.1. Group I: 31 patients had stenosis <50% diameter of coronary artery lumen (control group). 2.1.2.Nhom II: 78 patients had stenosis ≥ 50% diameter of coronary artery lumen (chronic coronary artery disease group). 1.3. The standard of selecting patients Patients was hospitalized with chest pain. Patient has a risk factors: hypertension, dyslipidemia, smoking, overweight, diabetes, advanced age. Electrocardiography, echocardiography had images of myocardial ischemia or suspected myocardial ischemia. Results of coronary angiography had significant stenosis or stenosis not significant. 2.1.4. Elimination standards Myocardial infarction during the acute phase, severe cardiac arrhythmias. Congenital anomalies of coronary arteries, muscle bridge. Patients have embolismto in CA (blood clots, air, wale array ...). The system disease have causing inflammation of coronary arteries (Kawasaki disease, Takayasu, lupus erythematosus system ...). Coronary artery damage caused by radiation therapy. Injury or cerebral vascular accident less than 3 months. Infections, arthritis, patients had to surgical. 7 2.2. Research Methodology 2.2.1. Study design: cross-sectional descriptive and have comparison with the control group. 2.2.2. The steps taken to select research subjects Step 1: Clinical examination, making patients records, Who had been primary diagnosis was chronic coronary artery disease (stable angina). Step 2: Biochemical tests, ECG, echocardiography. Step 3: Selection of study patients. Step 4: patients are eligible for blood collection, separation and preservation of plasma samples at 70ºC negative until test. Step 5: Selective coronary arteriography under the designation. 2.2.4. Subclinical examination methods * Method perform some biochemical tests + Quantification of lipid components: Quantification of triglyceride, LDL-c plasma level by the method of enzymatic. Quantification of HDL-c plasma level by the method of immunofluorescence. + The blood glucose levels: by the method of optical enzymatic (GOD- PAP) + Quantification of cytokines levels: conducting tests to detect 8 cytokines by the method of sandwich immunofluorescence (interferon [INF-γ], IL-2, IL-4, IL-6, IL-8, IL -10, TNF-α, GMCSF). Unit: pg/ml. + Quantification of CRP levels: at the Department of Biochemistry 103 military hospital. Unit: mg/l 2.3. Some standards used in this study 2.3.1. Diagnosis of angina pectoris: Meets three of the following 8 Characteristics: (1) Substernal chest discomfort of characteristic quality and duration; (2) Provoked by exertion or emotional stress; (3) Relieved by rest and/or use nitrat. 2.3.2. Diagnosis of hypertension: According to JNC VII (Joint National Committee - 2003). Patients had hypertension when systolic blood pressure ≥ 140 mmHg and diastolic blood pressure ≥ 90 mmHg. 2.3.3. Diagnosis of overweight: According to BMI applies to Asians, overweight are calculated BMI ≥ 23 kg/m2. 2.3.4. Diagnosis of diabetes: according to World Health Organization in 2006: (1) fasting glucose levels (at least 8 hours after eating) > 7 mmol/L, at least 2 consecutively tests. (2) test is a blood glucose levels any of the day > 11.1 mmol/L. (3) blood plasma glucose levels test after drinking 75 grams of glucose 2 hours ≥ 11.1mmol/L (glucose tolerance test). 2.3.5. Diagnosis of dyslipidemia: according to the Vietnam Heart Association. 2.3.6. Standard risk stratification of CRP plasma levels for cardiovascular disease: follow the guidelines of the American Heart Association 2003: CRP plasma levels <1 mg/l at low risk, 1-3 mg/l at moderate risk, > 3 mg/l at higher risk for cardiovascular disease. 2.3.7. Electrocardiography: ST segment elevation down to was ischemic under endothelium, sideways or angling down to ≥ 1 mm and prolonged 0,06-0,08s. 2.3.8. Some other standards * Diagnosis of arrhythmias: unevenly pulse, electrical cardiac had arrhythmias with degrees. * Diagnosis of Heart Failure: according to NYHA 9 * The diagnosis of acute myocardial infarction: chest pain, electrocardiogram, cardiac enzymes, results of coronary angiography. * Diagnostic history of myocardial infarction: ECG had waveform Q wide and deep. Results of coronary angiography had images of chronic arterial occlusion and collateral circulation. 2.3.9. Resutls of coronary angiography * Patients group with 50-74% diameter stenosis and patients group with ≥ 75% diameter stenosis. * Patients with ≥ 50% diameter stenosis in a branch or many main coronary branches. * Characteristics of coronary lesion according to the ACC / AHA 1988: (1) Type A; (2) Type B; (3) Type C. 2.4. Data processing The data collected were coded and managed by Microsoft Office Excel software 2003, and data processing according to medical statistics algorithms, using SPSS 15.0 (Statistical Package for Science software). 10 CHAPTER 3: STUDY RESULTS 3.1. CHARACTERISTICS OF STUDY SUBJECTS 3.1.1. General Characteristics Table 3.1. Gender and age characteristics of the study subjects Gender, age Group I Group II (year) (n=31) (n=78) Men 20 64,5% 67 85,9% p <0,05 Chronic coronary artery disease group had higher rate of men than the control group (p <0.05). 3.2. CHARACTERISTICS OF SOME RISK FACTORS, LEVELS OF INFLAMMATORY MARKER PLASMA IN STUDY GROUP OBJECTS Table 3.10. Table 3.11. Ratio of risk factors between chronic coronary artery disease groups and control groups Risk factors Men Group I Group II (n=31) (n= 78) p 20 64,5% 67 85,9% <0,05 BMI (kg/m ) ≥ 23 6 19,4% 45 57,7% <0,05 Smoking 9 29,0% 43 55,1% <0,05 Hypertension 14 45,2% 55 70,5% <0,05 Dyslipidemia 17 54,8% 60 76,9% <0,05 Diabetes 6 19,4% 33 42,3% <0,05 ≥ 4 risk factors 12 38,7% 62 79,5% <0,05 2 Chronic coronary artery disease group had higher rate of men, smoking, hypertension, dyslipidemia, diabetes and combination of risk factors than the control group (p<0,05). 11 Table 3:14. Inflammatory markers plasma levels between chronic coronary artery disease groups and control groups Group I (n=31) Group II (n= 78) p IL-6 pg/ml 3,6 ± 3,3 9,3 ± 13,9 <0,05 IL-10 pg/ml 14,7 ± 42,4 4,3 ± 1,8 <0,05 0,7 ± 0,3 2,5 ± 3,8 <0,01 Marker IL6/IL10 Chronic coronary artery disease group had higher IL-6 plasma levels, rate of IL-6/IL-10 and lower IL-10 plasma levels than control groups p<0,05. Table 3:15. Point cut Rate of IL-6/IL-10 plasma levels is suggested to differentiate between chronic coronary artery disease groups and control groups AUC Indicators (95% CI) IL-6/IL-10 0,897 Cut Se Sp point % % 0,870 82,05 93,55 p <0,0001 Table 3:16. Table 3:17. Rate of risk factors between degree of stenosis moderate and severe stenosis Risk factors 50 -74% ≥ 75% (n = 16) (n = 62) p Men 11 68,8% 56 90,3% < 0,05 Diabetes 3 18,8% 30 48,4% < 0,05 ≥ 4 risk factors 9 56,3% 53 85,5% < 0,05 Coronary stenosis ≥ 75% diameter group had higher rate of men, diabetes and combining multiple risk factors than coronary stenosis 50-74% diameter, p <0.05. 12 Table 3:18. Table 3:19. Rate of risk factors between the groups narrow one or multiple main coronary branches YTNC One branch Multiple branch (n=30) (n=48) p age ≥ 60 14 46,7% 35 72,9% < 0,05 Diabetes 7 23,3% 26 54,2% < 0,05 ≥ 4 risk factors 18 60,0% 44 91,7% < 0,05 Multiple main coronary branches narrow group had higher rate age ≥ 60 year, diabetes, combined risk factors than one main branches narrow group, p<0,05. Table 3:20. Rate of some risk factors with characteristics coronary lesions Type A Type B Type C (n=22) (1) (n=35) (2) (n=21) (3) n % n % n % Smoking 10 45,5 19 54,3 14 66,7 p1-3< 0,05 Diabetes 6 27,3 17 48,6 10 47,6 p1-2,3< 0,05 Risk factors p Type C group had higher rate of smoking, diabetes than type A group, p<0,05. Table 3:21. Comparison of inflammatory markers plasma levels with degree of coronary stenosis 50 -74% ≥ 75% CRP (mg/l) 2,3 ± 1,7 4,9 ± 5,0 < 0,05 IL-8 (pg/ml) 4,6 ± 2,8 24,6 ± 60,1 < 0,05 Marker p Coronary stenosis ≥ 75% diameter group had higher CRP, IL-6 plasma levels than coronary stenosis 50-74% diameter group, p<0,05. 13 Table 3:22. Ratio increases of inflammatory markers plasma levels on the severity of coronary stenosis Value comparison ≥ 75% 50 -74% p CRP > 3** (mg/l) 3 18,8% 33 53,2% <0,05 IL-2 ≥ 1,3* (pg/ml) 0 0,0% 16 25,8% <0,05 IL-6 ≥ 3,6 * (pg/ml) 3 18,8% 53 85,5% <0,01 * Value compared with the average value of inflammatory markers plasma levels of coronary stenosis group < 50% diameter. ** The value of CRP plasma levels at high risk for cardiovascular disease. Coronary stenosis severity group had higher rates increases of CRP, IL-2, IL-6 plasma levels moderate narrow group, p <0.05. Table 3:25. Ratio increases of inflammatory markers plasma levels according to number branch lesions Value comparison IL-2 ≥ 1,3*(pg/ml) One Multiple (n=30) (n=48) 2 6,7% 14 29,2% p p<0,05 Multiple main coronary branches narrow group had higher IL-2 plasma levels than one coronary branches narrow, p<0,05. Table 3:26. Table 3:27. Comparison of inflammatory markers plasma levels of according to coronary lesions types(pg / ml) Markers IL-6 IL-6 ≥ 3,6 * Type A Type B Type C (n=22) (n=35) (n=21) 4,4±2,8 10,6±18,2 12,1±11,7 p1-3<0,05 100 p1-2<0,05 % p1,2-3<0,05 9 40,9 % 26 74,3 % 21 p * Value compared with the average value of inflammatory markers plasma levels of coronary stenosis group < 50% diameter. 14 Type C coronary lesions group had higher IL-6 plasma levels and rates increasing of IL-6 plasma levels than type A (p <0.05). 3.3.3. The relationship between risk factors with inflammatory markers plasma levels in the chronic coronary artery disease group Table 3:30. Relationship between inflammatory markers plasma levels with smoking group Markers IL- 8 (pg/ml) No smoke Smoking (n= 35) (n= 43) X ± SD X ± SD 7,3 ± 11,0 31,2 ± 70,8 p <0,05 Smoking group had higher IL-8 plasma levels than no smoke group, p <0.05. Table 3:32. Ratio increases of inflammatory markers levels with overweight group (kg/m2 ) Markers IL-6 ≥ 3,6* pg/ml BMI < 23 BMI ≥ 23 (n=33) (n=45) 16 48,5% 33 73,3% p <0,05 * Value compared with the average value of inflammatory markers plasma levels of coronary stenosis group < 50% diameter Patients with overweight had higher rate increases of IL-6 plasma levels than patients with BMI < 23 kg/m2, p < 0.05. 15 Bảng 3.34. Ratio increases of inflamatory markers plasma levels with hypertension group Markers No hypertension Hypertension (n=23) (n=55) p IL-2 ≥ 1,3 pg/ml 1 4,3% 15 27,3% <0,05 IL-6 ≥ 3,6 pg/ml 13 56,5% 43 78,2% <0,05 Hypertention group had higher rates increases of IL-2, IL-6 plasma level than no hypertention group, p< 0,05. Bảng 3.36. Ratio increase of inflamatory marker plasma levels with diabetes mellitus group Markers TNF-α ≥ 1,8pg/ml No diabetes Diabetes (n=45) (n=33) 16 p 35,6% 21 63,6% <0,05 Diabetes mellitus group had hihger rates increase of TNF-α plasma levels than no diabetes, p< 0,05. Table 3:37. Table 3:38. Relationship between inflammatory markersplasma levels with dyslipidemia group No Marker viêm dyslipidemia Dyslipidemia (n=60) (n=18) IL- 8 pg/ml * IL-6 ≥ 3,6 pg/ml 6,4 ± 6,4 8 44,4% p 24,7 ± 61,1 <0,05 43 <0,05 71,7% * Value compared with the average value of inflammatory markers plasma levels of coronary stenosis group < 50% diameter Dyslipidemia group had higher IL-8 plasma levels and rate increases IL-6 plasma levels than no dyslipidemia group, p<0,05. 16 DISCUSSION 4.1.1. Gender and age characteristics of the study subjects Study had 109 patients, including 87 patients with coronary artery disease, 31 patients with the control group (coronary artery stenosis is not significantly through selective coronary angiography). Patients with chronic coronary artery disease had higher rate of male than the control group (85.90%; 64.52%, p <0.05), no significant differences were found between CAD and the control group with age (Table 3.1). This result are similar with the results of other authors. Do Thi Thu Ha (2010), the CAD had rate of men accounted for 75.3%. Pham Vu Thu Ha (2012), males 75.3%, females 24.7%. Radoslaw Krecki (2010), patients with CAD had higher rate of men than the control group (74%, 53%, p <0.05). 4.2.1. Characteristics of some risk factors in the study group The study results showed that the chronic CAD group had higher rate of risk factors than the control group: males (85.9%, 64.5%), hypertension (70.5%, 45.2%), smoking (55.13%, 29.03%), dyslipidemia (76.9%, 54.8%), overweight (57.69%, 19.4%), diabetes (42.3%, 19.4%) (p < 0.05) (Table 3.10), combined least 4 risk factors (79.5% versus 38.7%) (p <0.0001) (Table 3.11). This results are similar to other studies, Jennifer K. Pai (2004), K Tanaka (2001), Michael Miller (2011), Paul M. Ridker (2000), Thomas B. Martins (2006), Vladimira Muzakova (2010). 4.2.2. Characteristics of inflammatory markers in the study group 17 In the study, patients with chronic CAD had higher inflammatory markers plasma levels than the control group: IL-6 (13.9 ± 9.3 pg/ml; 3.6 ± 3.3 pg/ml), ratio of IL-6/IL-10 plasma levels (2.5 ± 3.8; 0.7 ± 0.3). However patients with chronic CAD had lower IL-10 plasma levels than the control group (4.3 ± 1.8 pg/ml; 14.7 ± 42.4 pg/ml), p <0.05 (table 3.14). Le Thi Bich Thuan (2005), Barbara J.M.H. Jefferis (2011). Hem C. Jha (2010), Santanu Biswas (2010), Thomas B. Martins (2006). 4.3.1. Relationship between the degree of coronary artery lesions with some cardiovascular risk factors * Hypertension: Ratio of hypertension patients in severity of coronary artery stenosis (74.2%), multiple coronary artery stenosis (77.1%) and type B lesions (80.0%) were higher than in moderate of coronary artery stenosis (56.3%), one coronary artery stenosis (60.0%), type A lesions (59.1%). However, no significant difference were found (p > 0.05; table 3.16, 3.18 table; table 3.20). Similar to the results of the author James S.Zebrack (2002), K Nakajima (2004). * Dyslipidemia: Ratio of dyslipidemia patients in severity of coronary artery stenosis (79.0%) and multiple coronary artery stenosis (81.3%) were higher than moderate of coronary artery stenosis (68.8%), one coronary artery stenosis (70.0%) (p> 0.05; table 3.16, 3.18 table). The results of other studies, gotto AM (1977), Basil N. Saeed (2011), Gösta (1986), Radoslaw Krecki (2010), Yasar Kucukardali (2008). * Diabetes: Ratio of diabetes in severity of coronary artery stenosis (48.4%), multiple coronary artery stenosis (54.2%),
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