Carotid Intima-Media Thickness Correlation with Metabolic Syndrome Parameters in Military Pilots

Introduction: Metabolic syndrome is one of the important risk factors in increasing the risk of cardiovascular disease. Recent studies have shown that increasing the thickness of the intima-medial layer of the carotid artery can be a risk factor associated with metabolic syndrome. Methods: This was a cross-sectional analytical study. All individuals underwent ultrasound of the carotid arteries. In the presence of stenosis, the stenosis caused by the plaque by North American symptomatic carotid endarterectomy trial (NASCET) was considered as a decrease in the diameter of the lumen compared to the diameter of the normal lumbar distal lobe and was expressed as a percentage. Statistical analysis of chi-square tests, independent t-test, ANOVA, and regression analysis were performed. Results: This study was performed on 112 male pilots (average age of 41.3 years, average ight time 2435 hours). There was no statistically signicant relationship between the mean thickness of intima media carotid and metabolic syndrome (no versus with metabolic syndrome: 0.62 versus 0.64 mm p = 0.355). The average thickness of the intima media carotid was signicantly statistically different between the three groups of ight types (transport aircraft: 01.61 against ghter: 0.70 and helicopter: 0.59 mm p = 0.004). There is also a signicant correlation between ight time and carotid thickness (p = 0.001, r = 0.380). In addition, there was a signicant correlation between the age of the pilots and the thickness of the carotid artery (p = 0.001, r = 0.033) as well as the age of the pilots and the ight time (p = 0.001, r = 0.713). Conclusion: Based on the results, there was no signicant relationship between carotid thickness and metabolic syndrome and metabolic syndrome components in the studied pilots. at This rate is be Other show the of in the group of of the Force is 18%, the is 9.9%, the is the is 9.0%, the Force is 5.28% and the Force than 28 , which shows a lower prevalence of the syndrome in countries that have stricter protocols in their pilots'


Introduction
Metabolic syndrome (MetS) is a combination of multiple factors including visceral obesity, hypertension, prediabetes, and atherogenic dyslipidemia 1 . Although there are still some Contradictory comments about the pathophysiologic nature of the MetS, insulin resistance is thought to be the primary cause of MetS.
Studies have shown that metabolic syndrome is a risk factor for cardiovascular disease 39 .
Subclinical atherosclerosis develops several years before the clinical manifestation of coronary artery disease (CAD). This process begins in early childhood and progresses into adulthood. An early manifestation of begins in early childhood the atherosclerotic process is the accumulation of lipid in the intimal layer of arteries forming fatty streaks 4 , leading to morphological changes 5 , a potential impact on vascular function, and eventually leading to coronary artery disease and stroke 6 . The development of atherosclerosis is accelerated in the presence of risk factors in youth, such as obesity [7][8][9] hypertension, dyslipidemia 10 and insulin resistance 7,10 . If the patients are diagnosed at subclinical stages, preventive measures can be implemented. Carotid artery stenosis, which is a common vascular disorder, is asymptomatic in many cases and increases with age.
Coronary artery angiography is the gold standard for diagnosing coronary artery disease 13 . But there are a variety of less invasive and non-invasive methods for diagnosing atherosclerosis in coronary arteries.
Carotid intima media thickness (CIMT) is a well-known noninvasive independent predictor of subclinical atherosclerosis 2,3 . In various studies, increasing the thickness of the intima media carotid artery has been identi ed as a useful predictive factor for coronary artery disease as well as cerebrovascular disease [14][15][16][17] .
Given today's lifestyle, sedentary lifestyle, high-calorie diets, and the presence of concomitant underlying diseases, cardiovascular disease is of paramount importance. The aviation community is no exception.
From an aeromedical point of view, cardiovascular disease is the leading cause of disquali cation and loss of pilot certi cation in ghter and transport pilots 12 and CAD is a signi cant cause of potential inight incapacitation and the most common reason for permanent ying incapacitation of military pilots 40,41 . The risk of developing coronary artery disease after age 40 is 49% in men and 32% in women in general population 11 . Accurate statistics are not available in the aviation community. Sudden cardiac death, as reported by different authors, in 20% to even 80% of military pilots has been found to be the initial presentation of CAD 40,41 . About 75% of these cases are due to coronary artery disease, which is often detected in pilots by observing cardiac tapes without clinical signs in routine examinations 18 . In transport pilots, if the risk of sudden incapacitation is only slightly increased, the ight will continue to be licensed only with quali ed pilots who do not have any problems, and in ghter pilots, any level of heart attack means that will not be allowed to y permanently 19 . Coronary artery disease is of particular importance in aviation for the following reasons: 1) Knowing about coronary artery disease and risk factors can affect the strategy of pilot routine examinations, 2) Coronary artery disease is a common cause of pilots grounding and losing pilots' licenses, 3) The high probability of a sudden incapacitation may jeopardize safety in aviation context and nally 4) It is a disease that requires primary and secondary prevention. Because most of the risk factors for coronary artery disease (such as hypertension, obesity, etc.) can be corrected and can be reduced with timely medication and lifestyle modi cations, identifying these risk factors in primary prevention is of particular importance, especially in jobs that are sensitive.
It has been shown that individual MetS components are associated with measures of carotid subclinical atherosclerosis; however, MetS is a better predictor of cardiovascular risk, possibly through higher atherosclerosis burden 42 . In this study, our goal is to examine CIMT as a predictor of cardiovascular disease and to compare its association with the components of metabolic syndrome.

Materials And Methods
This study was an analytical cross-sectional survey, it was performed on 112 pilots in 2019 and all subjects were male. Exclusion Criteria for the study included the following: clinical evidence of cardiovascular disease or clinical evidence of other atherosclerotic diseases (such as peripheral vascular disease, abdominal aortic aneurysm, and coronary artery disease), diabetes mellitus, malignancies, use of antihypertensive and lipid lowering drugs. It should be noted that all the pilots studied were active in terms of ight duties. This study was reviewed by the National Committee on Ethics in Research of the Army University of Medical Sciences of the Islamic Republic of Iran and approved with the identi cation of ethics.

Background information
Pilots' background information, including age, ight pro le (including ight status, type of aircraft and ight hours) and the year they entered service, were collected from their les. A questionnaire including: medical and pharmaceutical records, family history of diseases and tobacco use was prepared and answered by the participants. In the case of a recent blood test (less than 3 months), including the results of a fasting blood sugar test, fat pro le, and liver enzymes, the cases were extracted from the individual's annual examination le, otherwise re-examination was requested for the subjects. Measurements of height, weight, waist circumference, and blood pressure were performed on the same day of ultrasonography examination.
The steps of conducting the examinations and its general objectives were explained to the participants and the form of the informed consent of the Participate in the research plan was signed by them.

Sonography
Ultrasonography of the carotid arteries was performed when the patient was supine position and the experimenter was sitting next to the patient's head. The neck area was made as low as possible by lowering the shoulder on the same side. Ultrasonography was performed with a linear transducer with a frequency of 5.5-5 MHz. The distance between the rst echogenic intima and the second echogenic related to adventitia was considered as intima media. This measurement was measured at three separate points at a distance of one centimeter in the distal wall of the common carotid arteries on both sides. The average of these three measurements on each side was considered as the thickness of the Intima Media. Atherosclerotic plaque was ultrasound detected as echogenic material that thickened the intimal re ex and penetrated into the lumen. Increasing the focal thickness of Intima Media by twice the adjacent areas was considered as a plaque. If there was a stenosis, the stenosis caused by the plaque was considered as a decrease in the diameter of the narrow lumen compared to the diameter of normal distal lumen by using North American Symptomatic Carotid Endarterectomy Trial method and was expressed as a percentage.

Data analysis
Data analysis was performed using SPSS statistical software, version 24, and for quantitative variables, the mean and standard variables were recorded, and for qualitative variables, abundance and percentage were recorded. Analytical analysis was performed with the Kai Square and Fisher and T-independent tests and logistic regression and P was considered signi cant less than 0.05.

Results
The results consist of two parts, descriptive statistics and inferential statistics. The study was performed on 112 pilots with an average ight time 2345.98 hours (minimum of 300 and maximum of 14,000 hours). The type of aircraft was an 82-transport aircraft, 18 ghter jet and 12 helicopters. The mean age of the subjects was 41/33 years. The oldest person in the study was 65 years old and the youngest was 29 years old. Most of the subjects in the study age range were 35 to less than 45 years. 22 pilots (19.6%) were given positive history of smoking. The average height of the participants in the study was177.7 cm, the tallest person was 189 cm and the shortest was 165 cm. Average weight of participants was 83 kg (65 kg minimum, 127 kg maximum) and average body mass index (BMI)26.3 kg/m2 (maximum 41.5 cm2 and minimum 20.1 kg/m2) were obtained. Also, the mean waist circumference in the subjects under study was 95.4 cm (130 cm maximum and 79 cm minimum).
The mean systolic and diastolic blood pressures were 113.1-and 70.9-mm Hg, respectively. The maximum systolic and diastolic blood pressure obtained was 130-and 85-mm Hg, and the minimum systolic and diastolic blood pressure was 90-and 60-mm Hg. The mean serum fasting blood sugar level among the subjects was 91.1 mg/dl. The maximum fasting blood sugar in the people studied is 112 and the minimum is 74 mg/dl recorded. In 3 patients (67.2%), fasting blood sugar was more than or equal to 110 mg/dl. Average serum levels reported for total cholesterol (173.5 mg / dL, maximum 271 and minimum 98) and for triglycerides (43.7 mg/dL, minimum 43 and maximum 294). Also, the mean serum level of LDL 91.6 mg/dl (minimum 45 and maximum 146) was and HDL was 44.1 mg/dl (minimum 26 and maximum73). An examination of the status of liver enzymes showed an average serum level of ALT 29.8 IU/L the mean serum level of AST was 25.1 IU/L and alkaline phosphatase was 170.6 IU/L. In all participants, serum levels of liver enzymes were in normal range. All information is given in Table 1. The prevalence of metabolic syndrome in the subjects under our study was 8% (9 participants). Of these, 4 had four components of metabolic syndrome and 5 had three components.

Ultrasound Findings
The mean Carotid Intima Media thickness was 0.6 on the right and 0.65 mm on the left. Also, the total Carotid Intima Media thickness (average thickness of Intima Media Carotid right and left) was calculated to be 0.625 mm. Measurements above normal (> 0.8 mm) of left carotid artery were measured in 16 subjects and for right carotid artery in 9 subjects. In 3 people, the thickness was higher than normal on both sides. Carotid plaque was observed in 5 patients (4.4%). In 3 patients, there was a left isolation plaque and in one patient there was a right isolation plaque. One patient had a plaque on both side. None of these individuals were in the metabolic syndrome group. In one patient (0.9%), some degree of carotid stenosis was observed. In this patient, there was simultaneous right (less than 30%) and left (more than 30%) carotid stenosis.
Comparison of mean intima-mediated thickness of right and left carotid arteries in people with or without metabolic syndrome showed no signi cant statistical relationship between thickness values and metabolic syndrome. The relationship between the CIMT and the components of the metabolic syndrome is shown in Table 2. Pearson correlation analysis showed that there was a signi cant correlation between ight time and carotid thickness (P = 0.001, r = 0.380). In addition, there was a signi cant correlation between the increase in the age of the pilots and the thickness of the carotid (P = 0.001, r = 0.033), as well as the age of the pilots and the ight time (P = 0.001, r = 0.713).

Discussion
Cardiovascular disease (CVD) was ranked as the leading global cause of death in 1990 and 2010. The global death rate associated with CVD for individuals aged 15 to 49 was 10.7% in female patients and 12.8% in male patients in 2010 20 . Fortunately, cardiovascular disease (CVD) is a relatively infrequent cause of sudden incapacitation in aircrew, but it accounts for 50% of all pilot licences declined or withdrawn for medical reasons in Western Europe [21][22][23] . Aircrew is medically screened more intensively than many other professions; however, despite this, cardiovascular conditions such as acute coronary syndromes remain a causative factor in commercial aircraft accidents and fatalities 24,25 .
The metabolic syndrome is one of the major public health problems worldwide 29 , the prevalence of MetS are continuously increasing and aircrews are not spared from this high prevalence. Military and civilian aircrew is held to stringent physical standards in order to be considered quali ed for ight. While MetS itself can be a medical condition which causes ight disquali cation if it's associated with another cardiovascular disease like hypertension, diabetes, coronary disease or sleep apnea syndrome. The presence of the MetS is associated with a signi cant increase in cardiovascular mortality (12% vs. 2%) 30 and all-cause of mortality 31 . it's also associated with a high risk of cardiovascular disease (CVD). In ight MetS can cause sudden or subtle incapacitation by the occurrence of acute myocardial infarction, stroke or by a sudden death 32 . These complications can be decompensated by altitude and ight conditions including altitude hypoxia, stress and + Gz acceleration in ghter pilot in a high-performance aircraft. Non-diabetic people with the MetS are at a very high risk for developing type 2 diabetes, the risk for diabetes is up to vefold higher in patients with the syndrome 31 In aircrew member, diabetes may have an impact on the ight safety through its complications (ocular, cardiovascular, stroke, etc.), and through the glycemic disorder which may cause hypoglycemia in ight 33 . Obesity is rising rapidly in many parts of the world 34 , and the high prevalence of the MetS is mainly related to the obesity epidemic 35 .
The aim of this study was to investigate the intima media thickness of the carotid artery and compare with the criteria of metabolic syndrome in pilots. The main results included a lack of association between increased carotid intima media thickness and metabolic syndrome and metabolic syndrome components, a higher carotid thickness in ghter pilots, and a correlation between carotid intima media thickness and age and ight time.
In our study, no signi cant statistical or clinical association was found between CIMT and metabolic syndrome and its components, perhaps most importantly due to the low number of people in the metabolic syndrome group and the consequent low prevalence of metabolic syndrome in the pilot population. In our study, the prevalence of metabolic syndrome was 8%, which is much lower than the reported global values, the Middle East region and the Iranian population in the general population.
Currently, the global prevalence and prevalence in the Middle East is estimated at about 25% 26 . This rate is reported to be 29% for men in Iran 27 . Other studies show that the prevalence of metabolic syndrome in the group of pilots of the Jordanian Air Force is 18%, the Korean Air Force is 9.9%, the Taiwan Air Force is 5.32%, the German Air Force is 9.0%, the Serbian Air Force is 5.28% and the US Air Force Less than 1% 28 , which shows a lower prevalence of the syndrome in countries that have stricter protocols in their pilots' health.
However, the results of this study showed that none of the known risk factors, despite having a relatively high prevalence in the subjects, were not signi cantly associated with the thickness of the carotid artery. This was con rmed both in intergroup analyzes using chi-square and t-test analyzes and in regression models. However, the ndings of our study are different from the ndings of a single study that was similar in design to our study.
In addition, due to the proven link between high blood pressure, dyslipidemia and high body mass index with coronary syndromes, cardiac arrhythmias, and heart attack, and the high prevalence of these risk factors, individually in the subjects studied, Precautions must be taken to ensure that pilots are closely monitored 36 . Although a person is not diagnosed with one or two positive criteria as metabolic syndrome, with age, the risk of metabolic syndrome, cardiovascular disease, and diabetes will be higher than in people without symptoms.
High blood pressure, diabetes mellitus, smoking, dyslipidemia, old age, as well as metabolic syndrome have been identi ed as common risk factors for atherosclerosis of the carotid and cardiac arteries. Although the possible underlying mechanisms of the causes of metabolic syndrome and carotid damage are not yet well understood and are not the subject of this study, some studies have shown that all metabolic components of the syndrome alone can accelerate vascular endothelial disorders and, as a result, progressive arterial damage, and increase the chances of developing carotid disorders as the number of metabolic syndrome components increases 37 .
Although the diagnosis of metabolic syndrome does not in itself cause the pilot to be disquali ed, some of its components, such as hyperglycemia, hypertension, and fat pro le disorder, can cause at least a temporary loss of a pilot's license. This is important in the sense that in our study, about 60% of pilots were overweight, more than 40% had triglyceride abnormalities, and about 20% smoked, once again demonstrates the importance of controlling and minimizing risk factors in order to reduce the risk of vascular disorders 38 .
The study was accompanied by limitations. This study was conducted cross-sectionally in one center, so there were all the limitations of cross-sectional studies, such as the inability to fully control distorting interventions in this study. Due to the time allotted for the project, it was not possible to examine more people, so it is recommended that the project be continued in a larger population of pilots and in multiple centers.

Conclusion
Based on the results, no signi cant relationship was found between carotid thickness and metabolic syndrome and the components of metabolic syndrome in the Iranian pilots studied. The study found that the thickness of the carotid artery in ghter pilots was signi cantly increased compared to the commercial pilots. Also, a signi cant correlation was shown between carotid thickness with age and ight time. Given the relatively high prevalence of metabolic syndrome in the population of Iranian pilots (about 8%) compared to other countries, it seems that more preventive strategies should be considered to control the risk of cardiovascular factors. To do this research, we obtained the necessary permits from the ethics committee of AJA University of Medical Sciences. Consent was obtained from the participants to participate in the study, and each of the participants at any stage of the study could leave the study if they wished.

Consent for publication
We, the authors of the article, express our consent to the publication of the article.

Availability of data and materials
All study data are available.

Competing interests
Not applicable Funding Not applicable Authors' contributions All authors played an active role in reading and compiling the article.