such as elevated lipid levels, arterial hypertension,

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1 1 Impact of Gender and Other Risk Factors on Development of Coronary Artery Disease AIM, 11; 19(2): 1-14 Impact of Gender and Other Risk Factors on Development of Coronary Artery Disease (Comparison of Dobutamine Stress Echocardiography and Coronary Angiography) Nabil Naser 1, Marko Buksa 2, Sekib Sokolovic 2, Enisa Hodzic 2 Polyclinic Eurofarm center, Sarajevo, Bosnia and Herzegovina 1 Clinic for heart diseases, Clinical center of University of Sarajevo, Bosnia and Herzegovina 2 Original paper SUMMARY Objectives: The aim of this Study is to examine the development of ischaemic heart disease and occurrence of segmental wall motion abnormalities in men and women during Dobutamine stresss echocardiography in order to establish the impact of gender and other risk factors in development of coronary artery disease and the role of Dobutamine stress echocardiography in detecting and assessing the degree of myocardial ischemia and coronary stenosis in patients with suspected coronary artery disease in order to justify its wider application as a non-invasive diagnostic method. Research aim and purpose: Ischemic heart disease (IHD) causes more deaths, disability and economic loss in developed and developing countries than any other disease. Cardiovascular disease is the leading cause of ddath for women in western socitew. The epidemiology of the ischemic heart disease depends on fixed risk factors, such as sex, age and genetic predisposition, and on multiple risk factors that can be addressed, such as elevated lipid levels, arterial hypertension, diabetes mellitus, obesity, lifestyle (physical inactivity and stress), smoking, and alcohol consumption. Cardiovascular diseases are the leading cause of morbidity and mortality in B&H and, considering the exposure profile of the B&H population to risk factors (unhealthy diet, ubiquitous smoking and alcohol drinking habits, inadequate physical activity, inadequate culture of health), further growing trend of cardiovascular diseases can be expected. Patients and methods: The research study covered 86 adult subjects of both sexes with cardiac risk factors, referred to dobutamine stress echocardiography test as part of their cardiological evaluation. The patients for whom invasive cardiac diagnostics was indicated following the dobutamine stress echocardiography were subjected to left heart catheterization: ventriculography and coronary angiography. The parameters obtained and results of each method applied were statistically processed. Results: The study results obtained indicate a high degree of sensitivity, specificity and accuracy of the dobutamine stress echocardiography as a non-invasive diagnostic method compared to invasive diagnostics i.e. coronary angiography, which is the gold standard for the detection and evaluation of coronary artery diseases. Dobutamine stress test, may play a key role in the optimal identification of high risk groups of patients with hypertension, diabetes mellitus, obesity, lifestyle (physical inactivity and stress), smoking, and alcohol consumption. Conslusion: Echocardiographic measures of inducible wall motion abnormalities and global and regional left ventricular function are highly accurate in detecting CAD in women and men alike. The safety and cost-effectiveness of the dobutamine stress echocardiography as a diagnostic procedure has been proved. In modern cardiology, the DSE occupies a significant place in the evaluation of patients with known or suspected coronary artery disease, which has contributed to its accessibility and availability in a great number of centers. Key words: Dobutamine stress echocardiography, coronary angiography,. 1. INTRODUCTION Continuous development of economic opportunities, urbanization, radical changes in the nature of work-related activities and dramatic changes in lifestyle lead to a larger number of risk factors (stress, obesity, physical inactivity, elevated blood sugar and blood lipids, smoking and alcohol consumption) that directly affect the morbidity and mortality from cardiovascular diseases (1, 2, 3, 4, 5, 6, 7, 8, 9, 1). A serious problem in the whole world is ischemic heart disease (IHD), which causes high mortality, morbidity and disability for people at most productive age. The fight against this disease is one of the foremost health priorities (11, 12, 13). Early diagnosis of ischemic myocardial disease is an essential step towards reducing morbidity and mortality related to ischemic heart disease. The timely detection that diagnosing heart disease before its severe manifestations such as sudden death, myocardial infarction and heart failure, a major goal of modern diagnostic cardiology (14, 15, 16). 2. OBJECTIVES The purpose of this study is to assess development of ischaemic heart disease and occurrence of segmental wall motion abnormalities in men and women during dobutamine stresss echocardiography in order to establish the impact of gen- vol 19 no 2 JUNE 11 Original paper AIM, 11; 19(2): 1-14

2 (Comparison of Dobutamine Stress Echocardiography and Coronary Angiography) 11 der and other risk factors in development of coronary artery disease and the role of Dobutamine stress echocardiography in detecting myocardial ischemia and coronary stenosis in patients with suspected coronary artery disease in order to justify its wider application as a non-invasive diagnostic method. Also does noninvasive testing of coronary flow reserve during dobutamine stress echocardiography is an important diagnostic and prognostic indicator in the detection and treatment of coronary artery disease? 3. PATIENTS AND METHODOLOGY The retro-prospective study covered 86 adult subjects of both sexes, referred to dobutamine stress echocardiography test as part of their cardiological evaluation. The patients were examined using ATL HDI-5 ultrasound machine, equipped with broadbaande transducer (2-7MHz) for adult cardiac Echocardiographic examination and for assessing coronary flow reserve, the machine also equipped with MPT7-4 TEE multiplane transesophageal probe. The state of arte protocol was performed during dobutamine stress test. The drug was infused through an antecubital vein starting from dose 5 µg/kg/min. to maximal dose 4 µg/kg/min (mean peak dose 36.9 ± 4.3 µg/kg/ min.). To achieve 85% age predicted heart rate atropine in mean dose of 1.2 ±.8 was added in 54% of stuides at the top of maximal dobutamine dose. Ecochardiographic evaluation of LV wall motion was performed before and each step of dobutamine infusion, with the pateins in the supine letf lateral position. LV wall motion was evaluated in 17 segments. Positive stress echocardiography result 6 4 was defined as the new or extended left ventricular wall motion abnormality. At the same time during test the measurement of coronary flow reserve with high frequency imaging of left anterior descending coronary artery (LAD) was performed. The patients for whom invasive cardiac diagnostics was indicated following the Dobutamine stress echocardiography were subjected to heart catheterization- angiography. Coronary angiography was performed in all patients and coronary artery disease was defined as significant when diameter stenosis was more than 5%. Indices of diagnostic methods were calculated as ratio of the following values: sensitivity, specificity, positive predictive value, negative predictive value and accuracy. The parameters obtained and results of each method applied were statistically processed. (n=86) BMI < 25 kg/ /m2 BMI > 25 5 kg/m2 BM MI 27 kg/m2 Figure 1. Body mass index (BMI) in all patients (n=86) Figure 2. Presence of riskk factors (FR)) in all patients witho Bez out FR 1 FR 2 FR 3 FR 4 FR 5 FR Figure 2. Presence of risk factors (FR) in all patients (n=86) No. Demographics All patients 86 (1%) Age, yrs (SD) 57,1 ± 13 BMI 25kg/m 2 62 (72%) Men Women 56 (65%) 3 (35%) Age, yrs (SD) 57,5 ± 15 57,2 ± 18 Cardiovascular history and cardiac risk factors Hypertension 45 (8%) 24 (8%) Smoking 37 (66%) 1 (33%) Dyslipidemia 46 (82%) 18 (6%) Diabetes Mellitus 19 (34%) 1 (33%) History of heart disease 39 (7%) 16 (53%) Table 1. Study population and clinical characteristics 4. RESULTS The study involved a total of 86 patients. Men 56 (age from years) and women 3 (age from years). Among all the patients referred for Dobutamine stress echocardiography (DSE) 86 entered the study. Baseline characteristics of the population are depicted in Table 1. Hemodynamic behavior of our patients is shown in Table 2. In our study, DSE total of 86 patients according to the perceived deterioration of regional abnormalities or development of new regional abnormalities of certain segments of the left ventricle and in accordance with the equivalent distribution of coronary artery flow for all 17 LV segments and established the existence of single vessel coronary heart disease in 33 patients (38%), and multiple coronary disease in 41 patients (48%), while normal findings were found in 12 patients (14%). The involvement of coronary arteries during DSE are shown in Figure 1 and Figure 2. Coronary angiography confirmed normal finding in 12 patients (14%), single vessel disease in 34 patients (4%) and multiple vessel disease in 4 patients (47%). The involvement of coronary arteries by coronary angiography are shown in Figure 3. The results of the interpretation of echocardiographic findings Vs. Coronary angiography Among all the patients referred for dobutamine stress echocardiography (DSE) 86 entered the study. Baseline characteristics of the population are depicted in Table 1. In our study, DSE total of 86 patients according to the perceived deterioration of regional abnormalities or development of new regional abnormalities of certain segments of the left ventricle and in accordance with the equivalent distribution of coronary artery flow for all 17 LV segments and established the existence of single vessel coronary heart disease in 33 patients (38%), AIM, 11; 19(2): 1-14 Original paper vol 19 no 2 JUNE 11

3 12 (Comparison of Dobutamine Stress Echocardiography and Coronary Angiography) and multiple coronary disease in 41 patients (48%), while normal findings were found in 12 patients (14%). The involvement of coronary arteries during DSE are shown in figure 1 and figure 2. Coronary angiography confirmed normal finding in 12 patients (14%), single vessel disease in 34 patients (4%) and multiple vessel disease in 4 patients (47%). The involvement of coronary arteries by coronary angiography are shown in figure 3. The study results obtained indicate a high degree of sensitivity (97%), specificity (83%) and accuracy (95%) of the dobutamine stress echocardiography as a non-invasive diagnostic method compared to invasive diagnostics i.e. coronary angiography, which is the gold standard for the detection and evaluation of coronary artery diseases, 5. DISCUSSION Effect of gender and other risk factors on the development of coronary artery disease Wang Shu et all (7) 3 pointed out that despite the dramatic decline in mortality in recent years, coronary heart disease is the leading cause of death and disability worldwide. Simultaneously with Figure 3. Involvment of coronary arteries obtained by dobutamine stress ehocardiography (DSE) in all patients. Legend: LM: Main left coronary artery LAD: Left frontal descendent artery Cx: Circumflex artery RCA: Right coronary artery angiography in all pateints 1 12 Single vessel Multiple ves disease Jednosudovna Višesudovn disease na sel Normalee Uredan findings nalazs koronarna bolest koronarna bolest Figure 4. Interpretation of results obtained by coronary angiography in all pateints 4 12 the major advances in the development of medical sciences on the rise and populations of patients with a history of heart attack, and heart failure. Furthermore, in the whole world are evident increases in cigarette smoking, obesity, hypertension and metabolic syndrome. All of the above risk factors contribute to increasing incidence of diseases such as ischemic heart disease in men and women. In our study, were included 86 patients: 56 men (39-73 yr. age) and 3 women (42-72 yr. age). In the sample we found that the development of coronary artery disease play an important role of risk factors listed in the study Wang Shu et al.: cigarette smoking, obesity, hypertension, diabetes mellitus, dyslipoproteinemia and metabolic syndrome. Also Coronary heart disease in the family is present in 64% of respondents of both sexes. So 55 patients had positive family history of cardiovascular disease and 39 men (7% males) and 16 women (53% females). It can are concluded that the hereditary component, and genetic predisposition play a very important role in the development of ischemic heart disease. In recent years, the risk factors for coronary artery disease or ischemic heart disease are divided into fixed and variable risk factors. In the fixed risk factors include gender, age and genetic predisposition, and as their name says, these risk factors can not be modified or affected. In variable classify risk factors cigarette smoking, obesity, hypertension, hyperlipoproteinemia, diabetes mellitus and physical inactivity, these risk factors can be significantly affected and modified. We must emphasize that special attention is given to statistical analysis of risk factors that can significantly affect the aim of defining some conclusions of our study. In our sample, we analyzed how the presence of previously treated variable risk factors (smoking, obesity, diabetes mellitus, hypertension, hyperlipoproteinemia) and we concluded that of 86 patients: 5 patients (6%) had 1 risk factor, 9 patients (1%) had 2 risk factors, and 8 patients (9%) had 3 risk factors, 18 patients (21%) had 4 risk factors, 29 patients (34%) had 5 risk factors, and only 17 patients there was no variable risk factors. So 69 of our respondents of both sexes, or 8% have one or more risk factors for coronary heart disease. Regarding the fixed risk factors can clearly see that 64% of patients have a genetic predisposition and a positive family history for coronary artery disease and that man as a gender significantly leading (7%). Percentage distribution of coronary disease among men more significant than in women. Median age of men 57.5 and women 57.2 median age, and that they are not significantly different, so that age in our sample> 55 years. Shaw LJ et al. (5) 2 In their published paper about the Impact of gender on risk stratification by exercise and Dobutamine stress echocardiography: long-term mortality in 4234 women and 6898 men who underwent stress echocardiography or dobutamine stress testing in three hospitals., they analyzed the impact of gender on risk stratification of risk factors and mortality within 5 years. The conclusions of the study are: From a total of male patients had more positive history of coronary disease including a greater frequency of echocardiographic wall motion abnormalities. Within five years of monitoring 13 women and 226 men died from ischemic heart disease. Five-year survival among women who underwent stress test with normal findings was 99.4%, single vessel 97.6% of coronary artery disease and multiple coronary disease 95%. vol 19 no 2 JUNE 11 Original paper AIM, 11; 19(2): 1-14

4 (Comparison of Dobutamine Stress Echocardiography and Coronary Angiography) 13 Five-year survival rate for women undergoing dobutamine stress test, test, with normal findings was 95%, single vessel 89% of coronary heart disease and multiple vessels coronary disease 86.6%. Generally, women in this study had a lower rate of risk and higher survival rates. Echocardiographic measures of inducible wall motion abnormalities and left ventricular function are highly predictive of long-term outcome for women and men, alike. Diabetes mellitus (DM) with its complications is a very significant risk factor in contemporary society in the development of ischemic heart disease. In our study, special attention was devoted to the processing of the above factors as the identification of diabetic patients with high risk of heart disease or myocardial infarction is a necessary step for planning appropriate further treatment strategies. Specifically, Thomas H. Marwick et al. (2) 15 the authors examined whether stress echocardiography using dobutamine stress or can be used as a predictor of mortality in patients with diabetes. The study included 937 patients with diabetes mellitus aged 59±13 years. Stress echocardiography using load was used in 333 patients, dobutamine stress echocardiography using a standard dobutamine stress test in 64 patients. Patients were followed for a period of 9 years for all causes of mortality. During this period, revascularization was performed in 13 patients (11%) while 275 patients (29%) died in the first 5 years of monitoring 226 patients (24%) died before revascularization. The study indicates that the results of stress echocardiography independent predictors of death in diabetic patients with known or suspected coronary artery disease. The study results also indicate that the occurrence of ischemia during stress test, an independent predictor of death, which gives added value to other factors; so that this study supports the findings of previous smaller studies stress echocardiography in patients with diabetes mellitus who have not examined mortality as an endpoint. Geleijnse Author Stenosis (CAD) No. of patients Sensitivity Specificity PPV ML. et al. (), Senior R. et al. (1), Sicari R. et al. (3). Mancia G, De Backer G, Dominiczak A, et al (7) 12 The task for the management of arterial hypertension of the European Society of Hypertension, The task force for the management of arterial hypertension of the European Society of Cardiology (7). 7 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). The authors conclude in their paper that hypertension as a risk factor for habitual twice increases the risk of developing coronary heart disease. Eugenio Pican in his book echocardiography Picano Eugenio et al. Stress Echocardiography 5th edition Springer, 9; 31: in the chapter Hypertension points out that uncontrolled hypertension as a risk factor, can lead to various changes myocardial structure, coronary vasculature and the heart conductive system. These changes may lead to the development of left ventricular hypertrophy, coronary artery disease, various diseases of the processing system, and systolic and diastolic myocardial dysfunction that are clinically manifested as angina pectoris, myocardial infarction, cardiac arrhythmia (especially atrial fibrillation) and congestive heart failure. Shaw et al. (5) 2 in their paper state that the prognostic value of stress echocardiography or SPECT reveals that a high risk scan is associated with a 1-fold increased risk of cardiac death or myocardial infarction. Hence, these cardiac imaging tests could be aapplied for prognosis assessment purposes. The study results obtained indicate a high degree of sensitivity (97%), specificity (83%) and accuracy (95%) of the dobutamine stress echocardiography as a non-invasive diagnostic method compared to invasive diagnostics i.e. coronary angiography, which is the gold standard for the detection and evaluation of coronary artery diseases. Our results are similar to that reported on previous published studies with DSE shown in Table 2. 19,,21,22,23,24,25 6. CONCLUSIONS NPV Sawada et al. 5% Previtali et al. 5% Cohen et al. 7% Mazeika et al. 5% Marcovitz and Armstrong 5% Marwick et al. 5% Forster et al. 7% Segar et al. 5% Marwick et al. 5% Hoffmann et al. 7% Cohen et al. 7% Ostojic et al. 5% Ho et al. 5% Daoud et al. 5% Dagianti et al. 5% Pingitore et al. 5% Schroder et al. 5% Anthopoulos et al. 5% Ling et al. 5% Takeuchi et al. 5% Dionisopoulos et al. 5% Elhendy et all. 5% Ho et al. 5% Table 2. Sensitivity and specificity of DSE for detection of coronary artery disease Accuracy AIM, 11; 19(2): 1-14 Original paper vol 19 no 2 JUNE 11

5 14 (Comparison of Dobutamine Stress Echocardiography and Coronary Angiography) The epidemiology of the ischemic heart disease depends on fixed risk factors, such as sex, age and genetic predisposition, and on multiple risk factors that can be addressed, such as elevated lipid levels, arterial hypertension, diabetes mellitus, obesity, lifestyle (physical inactivity and stress), smoking, and alcohol consumption. Echocardiographic measures of inducible wall motion abnormalities and global and regional left ventricular function are highly accurate in detecting CAD in women and men alike. The safety and costeffectiveness of the dobutamine stress echocardiography as a diagnostic procedure has been proved. In modern cardiology, the DSE occupies a significant place in the evaluation of patients with known or suspected coronary artery disease, which has contributed to its accessibility and availability in a great number of centers. Dobutamine stress echocardiography (DSE) is an adjustable, comfortable non-invasive tool that provides information on the presence, position and degree of ischemia based on the reaction of regional wall motion to stress, and on the basis of such information, it provides diagnostic and prognostic information on various states of the disease. The DSE enables the evaluation of the severity, affected area and anatomical location of coronary lesion. REFERENCES 1. Picano E, Molinaro S, Pasanisi E. The diagnostic accuracy of pharmacological stress echocardiography for the detection of coronary artery disease: a meta-analysis. Cardiovasc Ultrasound, 8; 6:3. 2. Shaw LJ, Vasey C, Sawada S, Rimmerman C, Marwick H. T. Impact of gender on risk stratification by exercise and dobutamine stress echocardiography: long term mortality in 4234 women and 6898 men. Eur Heart J, 5; 26: Wang Shu, Wang Lei, Song Peng. Recent development of ischemic heart disease in sex difference. 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