Age , gender and hypertension as major risk factors in development of subclinical atherosclerosis

© 2013 Rahimiæ – Èatiæ et al.; licensee University of Sarajevo Faculty of Health Studies. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES ABSTRACT


INTRODUCTION
Cardiovascular disease (CVD) remains the leading cause of death worldwide, coronary heart disease being more common than stroke in the Western coun-tries (1).Early detection of atherosclerosis and its associated risk factors is important to prevent stroke and heart diseases.Atherosclerosis in the carotid arteries can be easily and non-invasively detected by carotid ultrasound.Carotid ultrasound measurement is highly reliable and reproducible (2).Intima-media thickness (IMT) measurements of the common carotid artery (CCA) is considered as useful indicator of carotid atherosclerosis (1,3).
Th e aim of the present study was to investigate which risk factors are better determinants of subclinical atherosclerosis, measured by common carotid artery intima media thickness (CCA-IMT).

Study design and patients
A total of 74 subjects were randomly selected in this cross -sectional study, which was carried out on patients who underwent Color Doppler Sonography at the Clinic of Radiology, Clinical Center University of Sarajevo.All participants provided informed consent, and the study protocol was approved by the institutional Ethics Committee of the Clinical Center University of Sarajevo.Subjects younger than 18 and the ones who did not want to participate in the study were excluded.

Cardiovascular risk factors
Information on the patient's medical history and laboratory fi ndings were obtained from their clinical records.Risk factors relevant to this study were age, gender, cigarette smoking status, diabetes, hypertension and dyslipidemia.Participants were categorized into those who never smoked, former smokers and current smokers.Subjects were classifi ed as having diabetes mellitus if they used anti-diabetic medication or had a fasting venous blood glucose ≥ 6.1 mmol/ L (4).Patients were considered to have arterial hypertension if they had a systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic pressure (DBP) ≥ 90 mmHg, or if they were taking antihypertensive drugs (5).Dyslipidemia was defi ned by the values of cholesterol greater than 5.2 mmol/L and/or triglycerides greater than 1.7 mmol/L, or by usage of antilipemic medication.

Intima media thickness (IMT) measurement
Ultrasound scanning of carotid arteries was performed with a 7.5 MHz linear array transducer (GE Voluson 730 pro).All measurements were performed with subjects in a supine position.We measured IMT at the far wall of each common carotid artery.Th e highest value of six common carotid artery measurements was taken as the fi nal IMT.Carotid IMT was defi ned as the distance from the leading edge of the fi rst echogenic line to the leading edge of the second echogenic line on the scans, with the fi rst line representing the lumen-intimal interface and the second line representing the collagen-containing upper layer of the adventitia (6).Increased CCA-IMT was defi ned when it was > 1 mm.To diff erentiate plaques from increased IMT, a plaque was defi ned as a focal structure that encroaches into the arterial lumen at least 0.5 mm or 50% of the surrounding IMT value, or demonstrates a thickness > 1.5 mm as measured from the media -adventitia interface to the intima lumen interface (7,8).Th e measurement of CCA-IMT was made without knowledge of laboratory results.

Statistical analysis
Statistical analysis was performed using SPSS 20, with the Mann-Whitney test used for comparing continuous variables and the chi-square test used for categorical variables.Th e level of statistical significance was set at P<0.05.

RESULTS
Th e study population had a mean age of 56.20 ± 2.78 years.36 patients (48.6%) were male and 38 patients (51.4%) were female.Of the 74 subjects, there were 34 (45.9%) with diabetes mellitus, 50 (67.6%)with dyslipidemia and 53 (71.6%) with hypertension.31 patients (41.9%) were current smokers, 18 patients (24.3%) were former smokers and 25 patients (33.8%) were never smoking.Carotid atherosclerosis was present with a prevalence of 47.3% (35 patients) for increased CCA-IMT and 54.1% (40 patients) for carotid plaques.55 patients (74.3%) had combination of risk factors, at least two of them.Patients had mean blood glucose level, mean plasma lipid levels and mean blood pressure values as shown in Table 1.Data in this study showed that 62.9% of male patients and 37.1% of female patients had increased CCA-IMT; the diff erence was statistically significant (P=0.035).Increased CCA-IMT was found in 37.1% patients who are current smokers, 28.6% patients who are former smokers and 34.3% patients who were never smoking; the diff erence was not statistically signifi cant (P=0.652).In patients with history of hypertension 85.7% had increased CCA-IMT compared with 14.3% in normotensive patients; the diff erence was statistically signifi cant (P=0.019).In patients with history of diabetes, the prevalence of increased CCA-IMT was 51.4% compared with 48.6% in non-diabetic patients; the difference was not statistically signifi cant (P=0.484).In patients with history of dyslipidemia 62.9% had increased CCA-IMT compared with 37.1% in nondyslipidemic patients; the diff erence was not statistically signifi cant (P=0.463).Increased CCA-IMT was the most closely related to age (P<0.001),followed by systolic blood pressure (P=0.001),diastolic blood pressure (P=0.003) and glucose blood level (P=0.048),but was not statistically associated with total triglyceride (P=0.914) and cholesterol (P=0.486)blood level.Signifi cant correlation was also found between CCA-IMT values and age (P<0.001),systolic blood pressure (P=0.001) and diastolic blood pressure (P<0.001),butnot with glucose blood level (P=0.215),triglyceride (P=0.243) and cholesterol (P=0.997),Pearson correlation coeffi cient and Pvalue showed in Table 2.

DISCUSSION
Th e results of our above mentioned study indicate that age, gender and hypertension are the most important risk factors in development of carotid atherosclerosis.Other studies also observed that hypertension infl uences the carotid IMT (6,9) and fi nd it the most prominent risk factor for thicker IMT and for the development of carotid stenosis (9,10).Mechanisms by which hypertension predisposes to atherosclero-sis may include endothelial dysfunction, hyperinsulinemia, hemodynamic stress, and multiple metabolic alterations.Impaired production of endothelium derived relaxing factors and increased activity of endothelium-derived contractile substances have been demonstrated in hypertensive patients, preceding overt atherosclerotic disease.In addition, enhanced smooth muscle cell proliferation with intimal wall thickening and proteoglycan accumulation accelerates atherosclerosis.Hypertension increases the wall shear stress and barotrauma to the arterial intima.Increased fl ow velocity and wall shear stress are considered to be the important factors that caused hypertension-induced intima-media hypertrophy and thickness (10).Cross-sectional analyses suggest that age is related to carotid wall thickening in all carotid beds, and carotid wall IMT is greater in men than in women 27 (2,10), because atherosclerosis develops in men at an earlier stage (1).Our study also showed that increased CCA-IMT was related to glucose blood level, but not with history of diabetes mellitus.Various literature fi ndings support the idea that glucose is a risk factor for atherosclerosis, but possibly of minor importance than traditional CVD risk factors.Stern et al. developed a model for the prediction of cardiovascular diseases which included age, sex, and ethnicity, lipids, blood pressure, BMI, family history and smoking as traditional CVD risk factors.Accordingly, Meigs et al. found that fasting glucose was not an independent risk factor for CVD (11).(12).Dyslipidemia is one of the important risk factors for atherosclerosis.Even though many studies detected the increase of IMT in patients with dyslipidemia (13,14), there are still some that fi nd no signifi cant correlation between carotid IMT and dyslipidemia (15,16).
Limitations of this study were its cross-sectional nature and a relatively small sample size.

CONCLUSION
Carotid sonography is recommended as a screening tool for future cardiovascular events among highrisk populations, especially for patients with hypertension, which we proved to be the most important risk factor for carotid atherosclerosis.Blood pressure measurement also should be performed routinely for every adult in clinical practice.Appropriate antihypertensive therapy should be used in order to lower blood pressure and to prevent hypertensive complications such as carotid atherosclerosis.

TABLE 1 .
Baseline characteristics of the study population

TABLE 2 .
Correlation coeffi cient between CCA-IMT values and quantifi ed variables of the study population