Influence of Age and Gender on Asymptomatic Carotid Disease

Introduction: Stroke is one of the most severe and the most common diseases of modern man. Prevention is necessary in order to detect people who have risk factors for it. Objective: To determine the frequency of asymptomatic carotid disease in people of different ages. Subjects and methods: The project encompassed the part of population, that is, groups at high risk for stroke from the Republic of Srpska. 20 240 patients were examined there were 12797 (63.23%) females and 7443 (36.77%) males. The study protocol was created, as well as adequate software products to support all phases of project implementation such as preparation of marketing materials, doctors’ appointments, building of application for doctors and nurses to record patients’ data, reports, analysis and conclusion. Upon completion of the project, data were statistically processed and the analysis of obtained results was conducted. Discussion: Pathological changes in blood vessels were noticed through the ultrasound examination of the aforementioned blood vessels of the neck and head, and the degree of narrowing of the blood vessels was determined. Furthermore, adequate measures and treatment to prevent progression of the aforementioned as well as the occurrence of stroke were applied. On the basis of the obtained data, it was concluded that the age was one of the most significant predisposing factors for the development of asymptomatic carotid disease. It was also noted that females were, more than men, prone to developing carotid asymptomatic disease. Conclusion: Average stenosis of all respondents was 18.36% (in females, stenosis was approximately 3.92% lower and it was 16.92%, when compared to males 20.84% ). Overall median was 16% (in females 15% and it was 5% lower than in men 20%).


Introduction
Stroke is one of the most difficult and the most common diseases of modern man and it is the cause of death in over 4.5 million people.[4][5][6][7] Approximately 40 -60% of strokes occur due to pathological changes in the blood vessels of the head and neck, 8 and therefore, an early detection and beforehand treatment of the same is necessary.The aforementioned changes can be detected by auscultation of blood vessels, ultrasound examination, CT angiography, NMR angiography, and conventional angiography.[11] Ultrasound examination of blood vessels is of high importance in detection of asymptomatic carotid disease which implies a state in which pathological changes in blood vessels are expressed while subjective obstructions and neurologic disorders are absent. 12,13The annual risk of stroke ranges from 2 to 5% for patients with significant asymptomatic carotid lumen stenosis (greater than 70%). 14,15Early detection of patients with asymptomatic carotid stenosis allows the application of carotid endarterectomy and carotid stenting. 16According to various authors, data on the prevalence of asymptomatic carotid occlusive disease vary.High-grade asymptomatic carotid stenosis causes a disturbance in cognitive functioning of the patient.In the study conducted by Balestrini, 210 patients who had hi gh-grade stenosis were examined.[19][20][21] In the Republic of Srpska there is a large number of people with commonly called risk factors for stroke and they are not in the position to do the ultrasonic testing.This project enabled the residents to have a chargeless and fast ultrasound screening of the blood vessels of the neck and head, and therefore, the prevention of stroke.

Aim
The aim of this study is to detect pathological changes in the blood vessels of the head and neck and to prevent stroke in people who have risk factors for it (high blood pressure, diabetes, heart disease, high blood lipids, smokers, obese people, people whose family members had a stroke, and people exposed to stress), i.e. to determine the frequency of asymptomatic carotid disease in the population based on a random sample of patients who have undergone the ultrasound examination of the blood vessels of the neck.Furhtermore, the aitm is to determine the influence of age and gender on the frequency of asymptomatic carotid disease.

Patients and methods
This prospective study was conducted on the whole teritory of the Republic of Srpska.From 2012 to 2014, 20 240 patients were tested.There were 12 797 (63.23%) females and 7443 (36.77%) males.All respondents who had asymptomatic stroke (AS) and transient ischemic attack (TIA) were not included in the project.Before the examination, each patient completed standardized questionnaire with data on marital status, education, personal and family history of previous stroke or TIA, heart disease, diabetes, hypertension, smoking and alcohol.After completing the questionnaire, the ultra sound examination of the blood vessels of the neck on both sides was done.All the procedures were standardized and performed by particularly trained researchers.
Ultrasound examination was performed in patients in the supine position -on the back.This way we were able to review the common carotid artery, bifurcation and the internal and external carotid artery in all patients.Ultrasound machine vivid 5 with a probe of 7 MHz was used.IMK was measured on the basis of the adopted IMK definitions, and, if it was greater than 1 mm, it was indicated as pathological.In the case of the plaque occurrence, the same was measured according to NASCET criteria.

Results
During three-year period, 20240 patients were examined -there were 12797 (63.23%) females and 7443 (36.77%) males.The youngest respondent was 18 year-old (both genders), while the eldest respondent, a female, was 93 years old (Table 1.).By using the Mann-Whitney U test, there was a highly, statistically significant difference (z = -13.368,p = 0.000) in the age of the respondents in relation to the gender of the respondents.
Bearing in mind that 63.23% of the examined respondents were female and observing the age of the respondents according to groups, it was noticed that the female respondents were over-represented in the following age groups: 21 to 30 years (63.25%), 31 to 40 years (65.40%),41 to 50 years (68.67%) and 51 to 60 years (66.27%).
The degree of stenosis was present from 0 to 100% (both sexes).The average stenosis of the respondents was 18.36% (stenosis in females was on average 3.92% lower, that is, 16.92% when compared to males -20.84% ).Overall median was 16% (15% in females and it decreased by 5% when compared to males -20%).
By using the Mann-Whitney U test, there was a highly statistically significant difference in the degree of stenosis in females (Md = 15.00,N = 12797) and males (Md = 20.00,N = 7443); z = -19147, p = 0.000.The examination of the degree of stenosis of the carotid basin in groups showed that the majority of patients (11 747 or 58.0%) referred to the group of 0% to 19% of blockage, out of which 3716 (49.9% of all male respondents) were males and 8031 (62.8% of all female respondents) females.Based on frequency, the succeeding group was that of 20% to 49% of blockage -7740 (38.2%) patients, that is, 3315 males (44.5% of all male respondents) and 4425 females (34.6% of all female respondents).
The degree of stenosis of the carotid area less than 50% occurred in a total of 19 487 (96.3%) patients, 7031 males (94.5% of all male respondents) and 12456 females (97.3% of all female respondents).Over 50% of blockage occurred in 753 (3.7%) respondents, i.e. 412 males (5.5% of all male respondents) and 341 females (2.7% of all female respondents) -Table 2. ).In the presence of stenosis, more than 50% higher prevalence was in males (53.27% in the presence of stenosis of 50% to 69%, 57.53% in the presence of stenosis from 70% to 99%, and in the occlusion -61.40%).
At the percentage of stenosis from 0% to 19%, by testing all the patients, there was a highly statistically significant difference (p = 0.000) of the presence of stenosis in relation to gender (greater representation in female respondents).By monitoring the age groups in relation to gender, there was highly statistically significant difference in the following age groups -from 41 to 50 years (higher prevalence in females, p = 0.000); from 51 to 60 years (higher prevalence in females, p = 0.000) and from 71 to 80 years (higher prevalence in males, p = 0.001).However, there was a statistically significant difference in the following age groups -from 31 to 40 years (higher prevalence in females, p = 0.020); from 61 to 70 years (higher prevalence in females, p = 0.013) and more than 80 year (higher prevalence in males, p = 0.030).(Table 3.).By monitoring all the patients, in the case of the degree of stenosis from 20 to 49%, there was a highly statistically significant difference (p = 0.000) in the presence of stenosis in relation to gender (greater representation in male respondents).By monitoring the age groups with respect to gender, there was highly statistically significant difference for all age groups over 50 years (higher prevalence in males, p = 0.000), as well as statistically significant difference in the age groups from 31 to 40 years (higher prevalence in males, p = 0.012) (Table 3.).
By monitoring all the patients, in the case of the degree of stenosis of 50% to 69%, there was a highly statistically significant difference (p = 0.000) in the presence of stenosis in relation to gender (higher representation in male respondents).By monitoring the age groups with respect to gender, there was a highly statistically significant difference in the age groups from 51 to 60 years (higher prevalence in males, p = 0.001); from 61 to 70 years (higher prevalence in males, p = 0.000), and from 71 to 80 years (higher prevalence in males, p = 0.000), as well as a statistically significant difference in the age group above 40 years old (higher prevalence in males, p = 0.027) (Table 3).
By monitoring all the patients, in the case of the degree of stenosis of 70% to 99%, there was a highly statistically significant difference (p = 0.000) in presence of stenosis in relation to gender (higher representation in male respondents).Throughout monitoring the age groups with respect to gender, a highly statistically significant difference was noticed in the following age groups: from 61 to 70 years (higher prevalence in males, p = 0.000); from 71 to 80 years (higher prevalence in males, p = 0.008).
In the case of complete blockage of the carotid arteries (occlusion) and throughout monitoring all the patients, there was a highly statistically significant difference (p = 0.000) in the presence of occlusion in relation to gender (higher representation in male respondents).Throughout monitoring the age groups with respect to gender, a highly statistically significant difference was noticed for the age group of 61 to 70 years (higher prevalence in males, p = 0.000).Regarding the lower degrees of stenosis, more than expected number of cases occurred in females, while at the higher degree of stenosis, more than expected number of cases occurred in males, as well as in age groups -at lower age groups (younger), more than expected number of cases occurred in females, and in the higher age groups (older), more than expected number of cases occurred in males.

Discussion
Stroke is the leading cause of death and hospitalization in both males and females in almost every European country and the third cause of death in the United States.][3][4] Studies have shown that the annual risk of stroke in patients with asymptomatic carotid disease varies from 2 to 5% in the case of patients with severe asymptomatic carotid stenosis.[6][7] The prevalence of severe stenosis was noticed in males, more than in females, at the age of 70.In the case of patients older than 70 years, the difference is higher.The prevalence of males in that age was 12.5% and of females 6.9%.In Beks and associates' study, 22 the prevalence of any detectable lesions in males was 25.4%, and 26.6% in females.The degree of stenosis increased with age. 22.The analysis of the frequency of carotid disease by gender showed that before the sixth decade of life, there was almost doubled prevalence of carotid disease in females than in males.However, after the seventh decade, the difference was almost balanced. 22 Fabris and associates' study 18 , on the sample of 457 patients aged 18-97 years, a positive findings of the existence of atherosclerotic plaques in 178 patients, or 38.9% of the patients were noticed.According to this author, the prevalence of carotid disease was 45.4% in males and 32.3% in females. 18Also, this author recognized a higher prevalence in males than in females which increased with age (prevalence in the group of patients 65-74 years was 59.9% , and in the group over 75 years, 76.7%). 18The abovementioned author also recognized post-menopausal hormonal changes that led to increased atherosclerosis in females as the most probable cause for that phenomenon. 18ot only did the frequency, but the severity of carotid disease progressed with age as well. 18Average percentage of stenosis at the point of maximum stenosis was 9.1% in the age group from 45 to 64 years, 17.3% in the age group of 65-74 years and 27.1% in patients aged over 75 years. 18milar results were obtained in our study.The average stenosis of all the respondents was 18.36% (stenosis was 3.92% less in females and was 16.92%, when compared to males -20.84%).Considering the presence of stenosis / group / according to gender, a greater presence of low levels of stenosis in females was evident.In the presence of stenosis, more than 50% higher prevalence was in males.The presence of significant stenosing plaque in the carotid increased in accordance with the age.

Conclusion
The incidence of moderately severe carotid artery stenosis increases with age, more frequently in males than in females women.
By establishing the ultrasound examination as required screening method for patients of certain age range, the occurrence of stroke in elderly people could be prevented.

Figure 1 .
Figure 1.The statistical significance of the presence of stenosis according to groups, age groups and gender

Table 1 .
Age of the respondents according to gender

Table 2 .
The degree of stenosis/group according to gender

Table 3 .
Statistical significance and the presence of the degree of stenosis according to groups, age groups and gender