MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES NGUYEN CAM THACH STUDY ON PLASMA APOLIPOPROTEIN CONCENTRATION IN PATIENTS WITH ATHE[.]
MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES NGUYEN CAM THACH STUDY ON PLASMA APOLIPOPROTEIN CONCENTRATION IN PATIENTS WITH ATHEROSCLEROTIC ISCHEMIC STROKE Speciality: Neurology Code: 62720147 ABSTRACT OF MEDICAL PHD THESIS HaNoi - 2021 THE THESIS WAS DONE IN: 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Supervisor: PhD Nguyen Van Tuyen Assoc Prof PhD Nguyen Hoang Ngoc Reviewer: This thesis will be presented at Institute Council at: 108 Institute of Clinical Medical and Pharmaceutical Sciences Day Month Year The thesis can be found at: National Library of Vietnam Library of 108 Institute of Clinical Medical and Pharmaceutical Sciences INTRODUCTION Stroke is a global health problem, the third leading cause of death after cardiovascular disease and cancer, but the leading cause of disability in humans, ischemic stroke (IS) accounts for 80% to 85% of all strokes Patients with ischemic stroke have a high rate of recurrence or death The main cause of IS is atherosclerosis Therefore, the prevention of atherosclerosis will reduce the rate of new cases as well as the mortality and disability rates for patients with IS One of the important measures in the prevention and treatment of atherosclerotic disease is the control of lipoproteins (cholesterol, HDL, LDL ) However, sometimes these indicators not fully reflect disease risk due to changes in cholesterol between close tests Recent studies have shown the role of apolipoproteins such as apolipoprotein A-I (apoA-I), apolipoprotein B (apoB) and the apoB/apoA-I ratio that can be used as predictors and assessment of the risk of IS with other lipid indices; These indicators reflect the balance between atherogenic lipoproteins and antiatherogenic lipoproteins; Reflecting Intracranial atherosclerosis (ICAS), even plasma apoA1 UP concentration is considered as a biomarker in early prediction of IS Besides, testing for apolipoproitein has some advantages over lipoproteins such as accuracy, convenience and efficiency Studies have also shown that atherosclerosis can occur in the intracranial and extracranial arteries and that intracranial atherosclerosis is more likely in blacks and Asians than in whites Therefore, it is very important to study and apply apolipoproteins to predict cerebral atherosclerosis and intracranial atherosclerosis in Vietnamese people However, until now, the research and application of the apolipoprotein test to monitor, predict and prevent ischemic stroke have received little attention and only focused on cardiovascular diseases From the above reasons, we study the thesis “Study on plasma apolipoprotein concentration in patients with atherosclerotic ischemic stroke” has been conducted with two following purposes: Describe clinical characteristics, imaging characteristics and changes in plasma apolipoprotein concentration in patients with atherosclerotic ischemic stroke Evaluation of the relationship between the concentration of some apolipoproteins in plasma and the state of cerebral atherosclerosis Thesis layout: The thesis is presented on 133 pages, including: introduction 02 pages, overview 38 pages, subjects and methods 26 pages, research results 30 pages, discussion 34 pages, conclusion 02 pages, recommendations 01 page The thesis has 36 tables, 15 charts, 22 figures, 133 references (23 Vietnamese documents and 110 English documents) Chapter OVERVIEW 1.1 The concept of stroke The World Health Organization definition of stroke in 1989 1.2 Classification of ischemic stroke Classification of ischemic stroke according to TOAST 1.3 Anatomy of cerebral arteries 1.3.1 Carotid arteries 1.3.2 Vertebral artery, basilar artery 1.4 Clinical and imaging of ischemic stroke 1.4.1 Clinical of ischemic stroke 1.4.2 Imaging of ischemic stroke 1.5 Cerebral atherosclerosis 1.5.1 Mechanism of atherosclerosis Atherosclerosis is the result of hyperlipidemia and lipid oxidation The atherosclerosis process follows stages: Fatty streaks formation, atheroma formation, atherosclerotic plaques formation 1.5.2 Epidemiology of cerebral atherosclerosis 1.5.3 Some characteristics of cerebral atherosclerosis - Some characteristics of atherosclerosis according to cerebral artery location: Overall, intracranial atherosclerosis develops ≈20 years later in life compared with atherosclerosis in extracranial arterial beds Intracranial atherosclerotic stenoses were described as dynamic lesions showing progression and regression - Difference between ICAS and ECAS: Two major characteristics that distinguish intracranial and extracranial atherosclerosis are the later onset and the more stable plaque phenotype in intracranial arteries, which may be explained by the distinct characteristics of the intracranial Arteries It can be explained because the wall structure of the intracranial arteries has its own characteristics compared with the extracranial arteries Intracranial arteries are less sensitive to hypercholesterolemia In intracranial arteries, LDL, Ox-LDL, macrophages are less infiltrated and antioxidant enzymes are more active than in extracranial arteries 1.5.4 Differences in the location of cerebral atherosclerosis between races Studies have shown that ICAS is more common in Asians, blacks than whites However, due to the recent availability of non-invasive vascular imaging techniques that can assess intracranial cerebral arteries, there are a growing number of studies on risk factors for ICAS to explain this difference 1.6 The role of apolipoproteins in atherosclerosis 1.6.1 General knowledge of apolipoproteins 1.6.2 The role of apolipoprotein A-I in atherosclerosis ApoA-I has anti-atherosclerotic effects In peripheral tissues (including atheroma), HDL picks up excess cholesterol and transports it back to the liver The reverse transport mechanism of HDL is the only way for cells to remove excess cholesterol and helps protect arteries, eliminating the accumulation and deposition of lipoproteins that cause atherosclerosis ApoA-I activates enzymes that transport cholesterol from tissues into HDL and allows HDL to recognize and bind to receptors in the liver at the end of transport 1.6.3 The role of apolipoprotein B in atherosclerosis ApoB has a central role in the development of atherosclerosis In apoB, there are binding sites for proteoglycan, so atherogenic lipoproteins will penetrate and stay in the arterial wall This is an important factor in the formation of atheroma 1.6.4 The role of the apoB/apoA-I ratio in the assessment of atherosclerosis The apoB/apoA-I ratio represents a balance between the apoBrich cholesterol particles and the anti-atherogenic apoA-I-rich cholesterol particles When this balance is disrupted, it will lead to an increase or decrease in the risk of atherosclerosis, for example, an increase in the apoB/apoA-I ratio will increase the risk of atherosclerosis 1.7 Studies on apolipoprotein in atherosclerotic ischemic stroke 1.7.1 Overseas studies A study by Koren-Morag et al: the hazard ratios (HR) for incident ischemic cerebrovascular events associated with the top versus bottom quartile of Apo B was 1.68, of Apo A-I 0.71, and of Apo A-I/Apo B ratio 0.51 These indicators have a role in predicting atherosclerotic ischemic stroke In 2009 Michael S Kostapanos, et al studied 163 patients with ischemic stroke The concentration of apoA-I in the group of patients was lower than that of the control group The apoB concentration and apoB/apoA-I ratio of the disease group were higher than that of the control group The ratio apoB/apoA-I is a predictor of ischemic stroke in the elderly A study in Korea by Jong-Ho Park et al in 2011 showed that the apoB/apoA-I ratio is a biomarker for intracranial atherosclerosis in Asian patients with ischemic stroke According to a study by Shilpasree A.S et al (2013): a group of patients with ischemic stroke had decreased apoA-I concentrations, increased apoB concentrations, and increased apoB/apoA-I ratios compared with the control group The apoB concentration, apoA-I concentration and apoB/apoA-I ratio are significant in predicting the risk of ischemic stroke Hongli Dong analyzed studies of apolipoproteins from 1991 to 2015, and found that decreased apoA-I concentration, increased apoB concentration, and increased apoB/apoA-I ratios were risk factors for ischemic stroke A retrospective study by Yu-Ching Chou showed that apoB and apoB/apoA-I ratio were both better predictors of ischemic stroke than total cholesterol, LDL, and cholesterol/HDL ratio In 2020, Yang et al studied on 658 patients with ischemic stroke and TIA, the results: the ratio apoB/apoA-I was associated with ICAS more than other lipid indices (TC/HDL, LDL/ HDL, nonHDL/HDL) 1.7.2 In-country studies So far, in-country studies have only focused on lipoproteins Research by author Do Thi Khanh Hy (2008): people with apoAI concentration 90 mg/dl is 6.9 times, when the ratio apoA-I/apoB < 1.2 is 9.8 times if compared with normal people Truong Thanh Son et al (2017): Triglyceride is the only plasma lipid index associated with the risk of ischemic stroke TC/HDL index is an important atherogenic index for patients with ischemic heart disease According to Nguyen Cong Hoan (2018): there is a relationship between a decrease in HDL alone and degrees of carotid stenosis due to atherosclerosis (p < 0.05) Chapter SUBJECTS AND METHODS 2.1 Studying subjects 2.1.1 Patient group Including 248 ischemic stroke patients who were hospitalized treated at the Stroke Center - 108 Military Central Hospital from October 2017 to December 2019 and these patients were divided into groups: - The ischemic stroke group due to large artery atherosclerosis (LAA) has 146 patients and is divided into subgroups: + Intracranial atherosclerotic ischemic stroke subgroup, n = 88 patients + Subgroup of extracranial atherosclerotic ischemic stroke, n = 31 patients + Subgroup of intracranial and extracranial atherosclerotic ischemic stroke, n = 27 patients - The ischemic stroke group due to small artery occlusion (SAO): 102 patients * Selection criteria for study patients - Clinical criteria: according to the definition of stroke by the World Health Organization (1989) - Paraclinical criteria: all patients were scanned with one or more methods: CT, CTA, MRI, MRA to determine the location, number, and size of infarcts and cerebral artery stenosis and occlusion * Criteria to divide the ischemic stroke group due to large artery atherosclerosis and the small artery occlusion group according to TOAST - Ischemic stroke group due to LAA: patients with impaired cortical function or brain stem dysfunction or cerebellar dysfunction CT and MRI: cortical or cerebellar and brainstem lesions or bilateral cerebral infarction > 1.5cm There is stenosis of more than 50% of the affected artery Exclude cardiovascular causes - Ischemic stroke group due to small artery occlusion: have typical lacunar infarct syndrome The image of the MRI film shows an infarction of the brain stem or cerebral hemisphere less than 1.5cm in diameter There was no evidence of embolism from the heart and atherosclerosis of the great vessels * Exclusive criterial - Patients with ischemic stroke have heart valve disease, arrhythmia, complete arrhythmic atrial fibrillation on electrocardiogram, arterial disease or a history of the above diseases Patients with ischemic stroke who have a pacemaker or have factors that cannot be computed tomography, magnetic resonance imaging - Patients with ischemic stroke due to rare causes: hypercoagulable disorder, sickle cell disease, systemic lupus erythematosus, arteritis, AIDS - Patients with diseases: heart failure, kidney failure, cirrhosis of the liver, thyroid cancer - Patients are taking drugs that affect the test such as carbamazepine, estrogen, ethanol, lovastatin, simvastatin 2.1.2 Control group Including 40 people selected at random during the health examination at 108 Central Military Hospital, they all had MRI and MRA scans Selected at the same time as the patient group, adjusted for age, gender, underlying medical condition, race, genetics, and epidemiology compared with the patient group * Selection criteria for the control group - No stroke, no history of stroke or transient ischemic attack at the time of the study - No diseases such as heart failure, cirrhosis of the liver, kidney failure, cancer - No symptoms of stroke (clinical and CT, MRI) - Voluntary participation in the research program * Exclusive criterial People who are taking drugs that affect the test such as carbamazepine, estrogen, ethanol, lovastatin, simvastatin 2.2 Research methodology 2.2.1 Study design Prospective study and cross sectional study with comparison group 2.2.2 Sample size Formula for calculating sample size for case-control studies: n is the minimum sample size for each group; Z is the value from the normal distribution; Ϭ is the common standard deviation of the two groups; d is the acceptable error level Substitute the data into the formula to calculate sample size = 40 2.2.3 Study devices Automated biochemical analyzer AU5800 of Beckman Coulter; 32 slice CT computed tomography scan - Siemens; Philips EPIQ Dupplex ultrasound; 3Tesla Achieva, Philips, The Netherlands The testing and diagnostic imaging equipment belonged to the Center Lab, the Diagnostic Imaging Center - 108 Central Military Hospital 2.3 Research content 2.3.1 Data collection - Collect personal information, history, risk factors, medical history - Clinical examination, test orders + Hematological and Biochemical tests: blood count, routine biochemical tests and apo indexes (apolipoprotein A-I, apolipoprotein B and apoB/apoA-I) + Echocardiography, electrocardiogram + Duplex extracranial carotid ultrasound: evaluate atherosclerotic stenosis of the common carotid artery and the extracranial internal carotid artery + All patients were taken CT, CTA to determine the location, number and size of infarcts and narrowed or blocked cerebral blood vessels For patients who not have a CTA (drug allergy ) or CTA does not detect lesions or the results are inconsistent with clinical symptoms, the patient will be taken for an MRA + 100% of the control group received MRI, MRA to exclude IS 2.3.2 Variables Clinical research - Risk factors: smoking, alcohol abuse, overweight and obesity (body mass index), high blood pressure (JNC VII 2014), type diabetes (American Diabetes Association - ADA 2019), lipid metabolism disorders (ATP III 2001), metabolic syndrome (World Diabetes Association) - Disorders of consciousness (Glasgow scale), muscle strength (British Medical Research Council), clinical status (National Institutes of Health's stroke scale - NIHSS) Subclinical research - Imaging studies: CT, CTA, MRI, MRA Method to determine % of arterial stenosis according to WASID and NASCET - Test some hematological and biochemical indicators - Quantification of apolipoprotein A-I, apolipoprotein B in plasma: immunoassay for turbidity 2.4 Data analysis The data is processed by a medical statistic method with SPSS 16.0 software for Window 2.5 Ethical consideration: This study was a descriptive study and was approved by the ethics committee of the 108 Clinical Institute of Medical Sciences Chapter RESEARCH RESULTS 3.1 Patient’s general characteristics 3.1.1 Gender and age characteristics Table 3.1 Gender characteristics of the groups IS group due to IS group due Control group LAA SAO (n = 40) Gender (n = 146) (n = 102 ) n % n % n % Male 118 80.82 78 76.47 27 67,50 Female 28 19.18 24 23.53 13 32,50 M/F 4.2/1 3.3/1 2.08/1 p > 0,05 > 0,05 Comment: The percentage of males was the highest in all groups Table 3.2 Age characteristics of the groups Age < 50 50 - 70 > 70 Mean±SD IS group due to LAA (n = 146) n % 14 9.59 96 65.75 36 24.66 63.75 12.64 IS group due to SAO (n = 102 ) n % 6,86 64 62,75 31 30,39 63.75 12.65 Control group (n = 40) n % 15 20 50 14 35 61.85 12.54 p > 0,05 > 0,05 Comment: the mean age and proportion of patients in each age group between the groups were not different with p > 0.05 3.1.2 BMI characteristics There was no difference in mean BMI, as well as in the proportion of thin, normal, overweight and obese patients between the groups (control, IS due to LAA, IS due to SAO) 3.1.3 Characteristics of some diseases and blood biochemical indexes Results: the proportion of patients according to diseases (hypertension, type diabetes, lipid metabolism disorders, metabolic syndrome, overweight-obesity) did not differ between the groups (p> 0.05) The control group had lower concentrations of glucose, triglycerides, and higher HDL concentrations than IS due to LAA and IS due to SAO (p < 0.01) 11 Table 3.9 Prevalence by the position of artery stenosis and occlusion of the ischemic stroke group due to LAA Extracranial arteries Intracranial arteries Carotid artery Vertebral artery, basilar artery CCA ICA VA ICA MCA ACA PCA BA VA Arteries M1 M2 M3 A1 A2 P1 P2 n 52 15 64 14 3 28 13 % 0.9 24.3 3.7 29.9 6.6 1.4 1.4 0.5 3.7 1.4 13.1 6.1 Comment: Atherosclerosis in the M1 segment of the middle cerebral artery had the highest rate (29.9%), the lowest was in the anterior cerebral artery A2 (0.5%) Table 3.10 Prevalence by the degree of artery stenosis and occlusion of the ischemic stroke group due to LAA Degree Moderate Severe Occlusion Total Ischemic stroke subtypes due to LAA ICAS ECAS ICAS + ECAS n = 88 n = 31 n = 27 n % n % n % 9.1 9.7 0 17 19.3 6.5 18.5 63 26 22 71.6 83.9 81.5 88 100.0 31 100.0 27 100.0 Total (n,%) 11 (7.53) 24 (16.44) 111 (76.03) 146 (100.0) Comment: The percentage of patients with arterial occlusion was the highest in each subgroup Table 3.11 Prevalence by number of artery stenosis and occlusion of the ischemic stroke group due to LAA Number of Total Ischemic stroke subtypes due to LAA positions (n,%) ICAS ECAS ICAS + ECAS n = 88 n = 31 n = 27 n % n % n % position 67 22 0.0 89 (60.96) 76.1 71.0 > position 21 23.9 29.0 27 100.0 57 (39.04) Total 88 100.0 31 100.0 27 100.0 146 (100.0) Comment: the rate of patients with stenosis, occlusion at one site in the ICAS subgroup was 76.1%; ECAS subgroup is 71.0%; for the whole group is 60.96% 12 3.3 Changes in the concentration of some apolipoproteins in the plasma of patients with atherosclerotic ischemic stroke 3.3.1 Apo index of the ischemic stroke group due to LAA, ischemic stroke group due to SAO and the control group Table 3.12 Comparison of apo index between the ischemic stroke group due to LAA with the control group Apo index IS group due to LAA (n = 146) ApoA-I (g/l, Mean ± SD) 1.28 0.23 ApoB (g/l, Mean ± SD) 1.31 0.29 apoB/apoA-I (Mean ± SD) 1.06 0.34 Control group (n = 40) 1.58 0.26 0.92 0.27 0.59 0.20 p < 0.01 < 0.01 < 0.01 Comment: The IS group due to LAA had lower apoA-I concentration, and higher apoB concentration and apoB/apoA-I ratio than the control group (p < 0.01) Table 3.13 Comparison of apo index of ischemic stroke group due to SAO with control group Apo index ApoA-I (g/l, Mean ± SD) IS group due to SAO (n = 102) 1.51 0.28 Control group (n = 40) 1.58 0.26 p > 0.05 ApoB (g/l, Mean ± SD) apoB/apoA-I (Mean ± SD) 1.03 0.27 0.70 0.23 0.92 0.27 0.59 0.20 < 0.05 < 0.05 Comment: apoB concentration, apoB/apoA-I ratio of IS group due to SAO were higher than the control group (p < 0.05) Table 3.14 Comparison of apo index of ischemic stroke group due to LAA with ischemic stroke group due to SAO Apo index ApoA-I (g/l, Mean ± SD) IS group due to LAA (n = 146) 1.28 0.23 IS group due to LAA (n = 102) 1.51 0.28 p < 0.01 ApoB (g/l, Mean ± SD) apoB/apoA-I (Mean ± SD) 1.31 0.29 1.06 0.34 1.03 0.27 0.7 0.23 < 0.01 < 0.01 Comment: the IS group due to LAA had lower apoA-I concentration; apoB concentration, apoB/apoA-I ratio were higher than those of IS group due to SAO (p < 0.01) 13 3.4 The relationship between plasma apolipoprotein concentration and cerebral atherosclerosis 3.4.1 Relationship between apo index and ischemic stroke due to LAA and ischemic stroke due to SAO We analyzed univariate logistic regression of factors related to ischemic stroke due to LAA and ischemic stroke due to SAO including male, over 65 years old, hypertension, diabetes type diabetes, lipid metabolism disorders, high cholesterol, high LDL, increased triglycerides, low HDL, metabolic syndrome, overweight - obesity, smoking, alcoholism, apoA-I, apoB, apoB/apoA -I result: high cholesterol; smoking addiction; apoA-I; apoB; apoB/apoA-I was associated with IS due to LAA (p < 0.05) Table 3.15 Factors associated with ischemic stroke due to LAA in multivariate regression analysis Variables OR CI 95% p Smoking addiction 0.504 0.249 - 1.019 0.056 High cholesterol 1.085 0.543 - 2.166 0.818 apoA-I 1.143 0.054 - 24.150 0.932 apoB 0.592 0.016 - 22.385 0.777 apoB/apoA-I ratio 1.244 1.130 - 1.369 0.032 Comment: In multivariable logistic regression analyses, only the ratio apoB/apoA-I was associated with ischemic stroke due to LAA (OR = 1.244; p = 0.032) Plot and calculate the area under the curve ROC = 75% with p = 0.001 so a high or low apoB/apoA-I ratio is valuable to distinguish between ischemic stroke due to LAA and ischemic stroke due to SAO Using Youden J index to determine the cut-off value of the ratio apoB/apoA-I = 0.995 in the prognosis of IS due to LAA Then, using this cut-off value, the sensitivity is 64% and the specificity is 83% 3.4.2 Relationship between apo index and position of artery stenosis and occlusion Table 3.16 Comparison of the apo index of IS group due to ICAS with IS group due to ECAS ICAS group ECAS group Apo index p n = 88 n = 31 apoA-I (Mean±SD, g/l) 1.28 ± 0.22 1.33 ± 0.24 > 0.05 apoB (Mean±SD, g/l) 1.34 ± 0.3 1.22 ± 0.27 < 0.05 apoB/apoA-I ratio (Mean±SD) 1.19 ± 0.33 0.97 ± 0.35 < 0.05 Comment: apoB concentration, apoB/apoA-I ratio of the ICAS group was higher than that of the ECAS group (p < 0.05) 14 We analyzed univariate logistic regression of factors related to IS due to ICAS including male, age over 65 years, hypertension, type diabetes, conversion disorder lipid metabolism, high cholesterol, high LDL, high triglycerides, low HDL, metabolic syndrome, overweight obesity, smoking, alcoholism, apoA-I, apoB, apoB/apoA-I ratio results: increased cholesterol; metabolic syndrome; apoB; the ratio apoB/apoA-I was associated with IS due to ICAS (p position (n=57) p Apo index of IS group due to LAA (Mean SD) apoA-I (g/l) apoB (g/l) apoB/apoA-I ratio 1.32 0.23 1.26 0.29 0.99 0.32 1.22 0.22 1.37 0.30 1.17 0.34 < 0.01 < 0.05 < 0.01 Comment: The group with position had a higher apoA-I concentration; apoB concentration, apoB/apoA-I ratio were lower than those in the many positions group (p 0.05 < 0.01 Comment: The area under the ROC curve of apoB/apoA-I ratio is larger than the area under the ROC curve of LDL/HDL and TC/HDL 16 3.4.6 Comparing the prognostic value of ICAS in ischemic stroke patients of apoB/apoA-I ratio with atherogenic indices Table 3.22 Prognostic value of ICAS in ischemic stroke patients of atherosclerotic indices and apoB/apoA-I ratio Index Area under the ROC curve CI 95% p LDL/HDL 0.47 0.36 - 0.58 > 0.05 TC/HDL 0.48 0.37 - 0.59 > 0.05 apoB/apoA-I 0.66 0.54 - 0.78 < 0.01 Comment: The area under the ROC curve of the apoB/apoA-I ratio is larger than that of the LDL/HDL and TC/HDL indexes 3.4.7 Correlation between apoB/apoA-I ratio and lipid indexes Table 3.23 Correlation between apoB/apoA-I and lipid indices IS due to LAA Cholesterol Triglycerid HDL LDL (n = 146) (mmol/l) (mmol/l) (mmol/l) (mmol/l) r = 0.419 r = 0.417 r = -0.329 r = 0.455 apoB/apoA-I ratio p < 0.01 p < 0.01 p < 0.01 p < 0.01 Comment: Average positive correlation between apoB/apoA-I ratio with cholesterol concentration, triglyceride concentration, LDL concentration and average negative correlation with HDL concentration Chapter DISCUSSION 4.1 General characteristics 4.1.1 Gender characteristics of the groups There is a difference in the proportion of men (or women) between the groups with p > 0.05 In all three groups, the proportion of men is the majority compared to women (table 3.1) The results are consistent with the studies of Nguyen Van Chuong; Nguyen Van Thong; Kalani (2020); Shilpasree (2013) 4.1.2 Age characteristics of the groups The mean age of the group of ischemic stroke due to large vessel atherosclerosis was 63.75±12.64, the group of ischemic stroke due to small artery occlusion: 63.75±12.65 The proportion of patients aged 50 - 70 was highest in both groups (table 3.2) The results are similar to those of Nguyen Hoang Ngoc (2012), Phan Viet Nga (2012), Shilpasree (2018), Kalani (2020) 4.1.3 BMI characteristics There was no difference in mean BMI, as well as in the proportion of patients who were underweight, normal, overweight and obese 17 between the groups (control, IS due to LAA, IS due to SAO) The results are different from those of authors Nguyen Minh Hien (2010), Suemoto (2018), Qian Y (2013) due to differences in research subjects, sample size and classification method 4.1.4 Characteristics of some diseases and blood biochemical indexes The proportion of patients based on each disease among the groups was not different with p>0.05 The control group had lower levels of glucose, triglycerides, and higher HDL levels than the IS group due to LAA and the IS group due to SAO (p