**7. Evaluation of demographic, antropologic and epidemiologic results of the study**

In the discussion of the results of this study, we used every available data base, but most of all US National Library of Medicine National Institutes of Health (www.ncbi.nlm.nih.gov/pubmed), as well as other browsers for medical papers in MEDLINE and other indexed publications. Browsing bibliographic data was performed using relevant key words (races, aorta, CT, aortography, MDCT, aneurysm etc. )

Sex distribution in both groups of patients and controls in this study showed three basic features: there is no statistically significant difference in terms of sex in patients, that in control Caucasian subjects predominant group consisted of females and that in analyzed groups of patients predomination of males was statistically significant. Compared to the most citated epidemiologic studies considering the sex of patients, showing 4-6 times more frequent development of aneurysms in men, in this study we showed slight predominance of male patients in Caucasian group (around 72%), while in Asian group the number of male patients was smaller (around 50%). According to available data on the frequency of AAA in different races, it is generally accepted that the disease is most frequent in Caucasian population (12,14). In USA, for example, the incidence of AAA is significantly higher in white males than Afro-americans, while in female population, there is no statistically significant difference in the occurrence of the disease. Asian population (yellow race) is the least frequently affected by AAA (10,12). In Africa, aneurysm of thoracic aorta is more frequent, as well as in Carribean population. African males are three times less affected than Europeans (40). Interesting epidemiologic fact might be that in Britain, the morbidity ratio of Asian population is insignificantly lower than Caucasians, which is not applicable for non-emigrants (9). In China, AAA is a rare disease, as well as in population of Indonesia (9).

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**6. Evaluation of the metodology of imaging studies** 

preoccupation of inovators until now.

**the study** 

Generation of spiral CT units enabled the examination of large blood vessels for the first time as a substitute for the invasive conventional angiography, most importantly for aorta, extracranial arteries of the neck and skull base, main trunks of visceral arteries of thorax and abdomen and ilio-popliteal vessels. There have been numerous attempts to affirm spiral angiography for the exploration of 2nd and 3rd order arteries of parenchymatous organs, but diagnostic sensitivity was disappointing (33,39). Development of CT technology from the year 2000, enabled the start of new epoch with multidetector CT units, that brought amazing possibilities of image acquisition and spatial to temporal resolution ratio (30,31). In the same terms, a new postprocessing editing of transverse CT images was developed, offering faster, more detailed and accurate reconstruction possibilities in all planes. Definitely, MDCT examination established itself as diagnostically most sensitive in postprocedural evaluation of AAA and became method of choice in this field. In year 2007, exponential dose for the examination of infrarenal aorta using standard protocol at 64-slice unit, was approximatelly 6-8 mSv for both sexes. In obese patients it was somewhat higher (29). During the following 3 years, introducing new pulse generators and faster rotating tubes in clinical practice, exponential dose for CT exam of infrarenal aorta was lowered for 8-10 times, remaining the

**7. Evaluation of demographic, antropologic and epidemiologic results of** 

In the discussion of the results of this study, we used every available data base, but most of all US National Library of Medicine National Institutes of Health (www.ncbi.nlm.nih.gov/pubmed), as well as other browsers for medical papers in MEDLINE and other indexed publications. Browsing bibliographic data was performed

Sex distribution in both groups of patients and controls in this study showed three basic features: there is no statistically significant difference in terms of sex in patients, that in control Caucasian subjects predominant group consisted of females and that in analyzed groups of patients predomination of males was statistically significant. Compared to the most citated epidemiologic studies considering the sex of patients, showing 4-6 times more frequent development of aneurysms in men, in this study we showed slight predominance of male patients in Caucasian group (around 72%), while in Asian group the number of male patients was smaller (around 50%). According to available data on the frequency of AAA in different races, it is generally accepted that the disease is most frequent in Caucasian population (12,14). In USA, for example, the incidence of AAA is significantly higher in white males than Afro-americans, while in female population, there is no statistically significant difference in the occurrence of the disease. Asian population (yellow race) is the least frequently affected by AAA (10,12). In Africa, aneurysm of thoracic aorta is more frequent, as well as in Carribean population. African males are three times less affected than Europeans (40). Interesting epidemiologic fact might be that in Britain, the

using relevant key words (races, aorta, CT, aortography, MDCT, aneurysm etc. )

It remains unclear why AAA predominantly affects male population. Almost all the studies that tangle this question, insist on the fact that male population has higher incidence of etiopathogenetic risk factors: arteriosclerosis, smoking, hypertension and elevated blood cholesterol level. Generally speaking, the cause of this fact remains unclear, and as predisposing factors arise hormones, genetic disposition, disposition to atherosclerosis, more frequent risk factors or the combination of aforementioned factors. Singh K and Bønaa KH from famous University Hospital of Tromsø, Norway, in their study including 6.386 subjest of both sexes, established the diagnosis of AAA using sonographic screening , in 263 (8.9%) males and 74 (2.2%) females (9,20). Bearing in mind that subjects ranged in age (form 24-85 years), they compared the diameter of infrarenal aorta in terms of age and concluded that in male population there was a progressive growth in diameter of infrarenal aorta during the process of ageing. The effect of elevated plasma fibrinogen level in male population also remained unclear (8,11,44).

In terms of age distribution, Caucasian patients are statistically significantly younger than Asian patients (for 15 years). Compared to other studies, European patients are shown to be significantly younger than in other Caucasian populations (21,40). This data becomes interesting if we analyze distribution by age subgroups, where dominant incidence in white race population is found in the subgroup of patients younger than 64 (66%), while almost half of these patients are even younger than 54. The same distribution is shown in the control group of this population. On the other hand, in the Asian group of patients, AAA occurs in much older population- dominant incidence was found in the subgroup of older than 75 (54,8%). In the light of these results, we can analyze AAA as a primary disease (in white race) or in the setting of generalized atherosclerotic pathologic changes in the process of ageing (yellow race). Special attention must be paid to EVAR procedure in the group of elderly population, patients with cardiopulmonary and cerebrovascular insufficiency.

Definite conclusion is that the incidence of AAA increases with age, which is explained by prolonged impact of risk factors, long period between latency of risk factors and aneurysm development, and increased sensitivity of aorta to risk factors in the process of ageing. Hypothetically, changes in elastin structure cause increased mechanic stress on collagen which forms a strong fiber network. Experiment models of aneurysmatic blood vessels showed that isolated destruction of elastin led to dilatation of the vessel for 25-65%; also, following dilatation and possible rupture occur due to the alteration of collagen (6). Half-life of elastin is considered to be 75 years, and aorta of adult does not have the ability to produce functional elastin (6,7,42).

In terms of correlation patient height in study population and control groups, we obtained expected results. There is a statistically significant difference in the average height (Caucasian population is 17 cm taller than Asian population, dominant group in Asian

population are patients shorter than 160 cm, while in Caucasians dominant group consists of patients over 171 cm )(17,29).

Further, there is statistically significant difference in body weight in study populations-European patients weigh 25.6 kg more than the Asian population, on average. This might be explained by obesity as a modern social-medicine phenomenon in developed countries where there is an increase in AAA incidence. Body weight in this study arised as statistically significant risk factor for the development of AAA.

Considering the level of nutrition, in the yellow race the dominant group consisted of normal weighted (70,97%), while there was no obese subjects (with BMI over 30) in this population. On the other hand, in the white race population over 50% patients were overweighted and obese. BMI can be observed as a universal parameter nondependent of the race, and obtain valid results with the use of simple statistical models (21). This parameter excludes race constitutional features and heterogeneity of the subjects in terms of body weight and body height, since last two parameters in 20% of observed patients and control subjects showed no statistically significant difference. If we use BMI value of 23 (approximate height of 170cm and weight of 58kg-mean BMI value in both groups of patients BMI=22,04±3,77 for Asian group and BMI=25,38±3,19 for Caucasian group) as observation criterion, instead of race, and divide all the subjects in two subgroups, BMI-1 (BMI<23) and BMI-2 (BMI>23), a correlation of antropologic and morphologic parameters calculated by MDCT aortography can be obtained (21).

In this study, there was no statistically significant difference in the presence of risk factors in subjects of both groups. In the Asian population, only 3,2% showed no risk factors present, while in the Caucasian population this percentage was 3,3%. Since patients with no risk factors present represent statistically insignificant subgroup in both populations, we can consider the presence of risk factors as a leading impact factor on the pathogenesis of the development of AAA. Considering the number of present risk factors, in Caucasian population the dominant group consists of patient with 3 or 4 risk factors (40% + 30% = 70%), while in Asian population dominant group consists of patients with 2 or 3 risk facotrs present (45,2% + 19,4% = 64,6%). In terms of the presence and number of RF in patients of both races, there is statistically significant difference in development of the disease. In Asian population, AAA occurs most frequently in patients with 2 RF (with 1 or 2 RF: 64,6%) while in white race this percentage is almost 3 times lower, only 23,3%. As a conclusion, Asian population seems to be more prone to the development of this disease.

The number of associated risk factors in patients of Asian population is statistically significantly higher than in control subjects of the same population. Over 40% (41,54%) control subjects in this population showed no risk factors present, while 25,3% showed only 1 RF present. Number of subjects with 3 associated RF is insignificant (2,3%), while there were no subjects with all 4 RF present. In total, there was statistically significant difference in the presence of risk factors in the patients and controls of the Asian population. In the same term, there is a positive correlation in the presence of risk factors in the patients and controls in European population also, while it is especially applicable for the presence of 3 or 4 associated risk factors.

Tha analysis of the results considering smoking as risk factor in all the study subjects independently of race and smoking history, there was statistically significant number of smokers in both subgroups of patients compared to controls. The analysis of the results considering male and female populations showed that in patients of both populations smoking represents an extremely significant risk factor for the development of AAA. The results of multivariant logistic regresssion analysis were concordant.

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patients over 171 cm )(17,29).

or 4 associated risk factors.

significant risk factor for the development of AAA.

population are patients shorter than 160 cm, while in Caucasians dominant group consists of

Further, there is statistically significant difference in body weight in study populations-European patients weigh 25.6 kg more than the Asian population, on average. This might be explained by obesity as a modern social-medicine phenomenon in developed countries where there is an increase in AAA incidence. Body weight in this study arised as statistically

Considering the level of nutrition, in the yellow race the dominant group consisted of normal weighted (70,97%), while there was no obese subjects (with BMI over 30) in this population. On the other hand, in the white race population over 50% patients were overweighted and obese. BMI can be observed as a universal parameter nondependent of the race, and obtain valid results with the use of simple statistical models (21). This parameter excludes race constitutional features and heterogeneity of the subjects in terms of body weight and body height, since last two parameters in 20% of observed patients and control subjects showed no statistically significant difference. If we use BMI value of 23 (approximate height of 170cm and weight of 58kg-mean BMI value in both groups of patients BMI=22,04±3,77 for Asian group and BMI=25,38±3,19 for Caucasian group) as observation criterion, instead of race, and divide all the subjects in two subgroups, BMI-1 (BMI<23) and BMI-2 (BMI>23), a correlation of antropologic

and morphologic parameters calculated by MDCT aortography can be obtained (21).

population seems to be more prone to the development of this disease.

In this study, there was no statistically significant difference in the presence of risk factors in subjects of both groups. In the Asian population, only 3,2% showed no risk factors present, while in the Caucasian population this percentage was 3,3%. Since patients with no risk factors present represent statistically insignificant subgroup in both populations, we can consider the presence of risk factors as a leading impact factor on the pathogenesis of the development of AAA. Considering the number of present risk factors, in Caucasian population the dominant group consists of patient with 3 or 4 risk factors (40% + 30% = 70%), while in Asian population dominant group consists of patients with 2 or 3 risk facotrs present (45,2% + 19,4% = 64,6%). In terms of the presence and number of RF in patients of both races, there is statistically significant difference in development of the disease. In Asian population, AAA occurs most frequently in patients with 2 RF (with 1 or 2 RF: 64,6%) while in white race this percentage is almost 3 times lower, only 23,3%. As a conclusion, Asian

The number of associated risk factors in patients of Asian population is statistically significantly higher than in control subjects of the same population. Over 40% (41,54%) control subjects in this population showed no risk factors present, while 25,3% showed only 1 RF present. Number of subjects with 3 associated RF is insignificant (2,3%), while there were no subjects with all 4 RF present. In total, there was statistically significant difference in the presence of risk factors in the patients and controls of the Asian population. In the same term, there is a positive correlation in the presence of risk factors in the patients and controls in European population also, while it is especially applicable for the presence of 3 On the contrary, hypertension as a risk factor in this study was proven to be controversial. In both races, the number of patients with hypertension was not significantly different than the number of normotensive patients. Epidemiologically significant finding was that in Asian population the number of normotensive patients was for 17% higher than hypertensive, while in European population there was 20% more hypertensive than normotensive patients. Generally speaking, in patients of both populations, hypertension is more commonly found than in control subjects, especially in the European population.

One of the referring studies considering pathogenesis of peripheral vascular diseases (McConathy, Oklahoma Medical Research Foundation) showed that in AAA, the level of cholesterol in plasma is lower than in patients with stenotic-occlusive arterial diseases, as well as VLDL level and apolipoprotein B, C-III and E. Total cholesterol is shown to be a stastically significant factor in the study of Reed-a et al. performed in integrated clinicalautopsy study in the 20-year period on 8000 men living in Hawaii (9). This study predominantly addressed the question of atherosclerosis as a risk risk factor in the development of AAA. The results concordant to this study were obtained in the Whitehall study of Strachan, published in British Journal of Surgery in 2005 considering younger population. Integrated epidemiologic study included 18.403 men, aged 40-64, working as accountants, in the period of 18 years. There were 99 lethal cases of ruptured AAA, and smoking and elevated systolic presure were isolated. Considering type of cholesterol, LDL and less importantly VLDL, are considered the dominant risk factor by many previous studies on this subject.

The analysis of results considering diabetes melitus (DM) as a risk factor in this study showed some unexpected results. The first "paradoxal" finding was extremely low number of patients in both groups with DM (3 patients in each group), with no significant difference between groups. In control groups of both populations, the incidence of DM is lower than 30%, with no statistically significant difference between controls and patients in both poulations. The unexpected result is that higher incidence of DM is found not in patient, but in control group of both populations. The most stunning result is the correlation of the presence of DM in patients and controls of the white race, where disease is significantly more frequent in the control subjects. These results raise the question: Does DM have etiopathogenetic correlation with the development of AAA, or closer to the results of this study- is DM some kind of protective factor in the AAA development? Meta analysis of 11 relevant studies considering correlation of DM and etiopathogenesis of AAA shed light to this "paradox". Out of 11, 4 studies were excluded for no existing or inadequate control group. The rest of the studies showed that there is a small possibility of associated DM in

patients with AAA (OR=0.65, 0.60-0.70, p<0.001)(30). 3 referring studies found decreased prevalence of DM in patients with AAA (17,18,20).
