CORRELATION BETWEEN CAROTID INTIMAL MEDIA THICKNESS AND ANKLE BRACHIAL INDEX: COMPARISON WOMEN VERSUS MEN
Received for publication: 25th of June, 2007
Revised: 14th of August, 2007
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Introduction. Risk factors for atherosclerosis have been extensively studied but few studies included women or they were underrepresented. Aim. The purpose of our work was to evaluate atherosclerotic risk factors, carotid intimal media thikness (IMT) and ankle brachial index (ABI) in coronary postmenopausal women compared with men. Methods. From 1290 patients hospitalised during 6 months in our clinic we recruited 41 coronary patients (26 women, 15 men) with average age of 66.92 ±?9.1. Clinical measures included IMT, ABI, systolic blood pressure (SBP), diastolic blood pressure (DBP), body-mass index, fasting glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, tryglicerides, C-reactive protein (CRP), history of cerebrovascular disease (CVD), diabetes mellitus (DM), smoking, premature CAD in family. Results. After adjustment of the model by eliminating the features that do not have influence on IMT we obtained a significant regression model (F-statistic: 5.879 on 3 and 37 DF, p=0.0021). We found a low ABI (<0.9) in 30,66% women and 60% men and significant IMT (≥1.0 mm) in 53,84% women and 60% men. In women the linear regression showed a statistically significant relation between ABI and smoking (p=0.032), DBP (p=0.012) and DM (p=0.0049). In men a significant correllation was obtained for CRP (p=0.032), smoking (p=0.013) and DBP (p=0.015). Linear correlation between ABI and IMT was slightly significant (Pearson r = - 0.157). Conclusions. Coronary patients have concomitant carotid and peripheral artey involvment; those with low ABI had increased IMT; there were no statistical differences between postmenopausal women and men concerning values of IMT and ABI.
atherosclerosis, women, IMT
Risk factors for atherosclerosis have been extensively studied but few of the studies included women or they were underrepresented. Early detection of atherosclerosis either in carotid, coronary or peripheral localization may predict the risk of cardiovascular complications and lead to appropriate management therapy. There are some non-invasive methods easy to perfom for detection of subclinical and clinical atherosclerosis. Carotid intima-media thickness (IMT) is considered a marker of early atherosclerosis and it is demonstrated that can predict future risk of cardiovascular disease in coronary patients(Schott). The ankle brachial index (ABI) is a noninvasive method too, for assessing the atherosclerosis in lower extremities and also for establishing the severity of peripheral artery disease.
The purpose of our work was to evaluate atherosclerotic risk factors, carotid IMT and ABI in coronary postmenopausal women compared with men.
From 1290 patients hospitalised during 6 months in our clinic we recruited 41 coronary patients (26 women, 15 men) with average age of 66.92 ± 9.16. All the patiens had coronary artery disease documented by coronary angiography with significant stenosis, positive exercise test or typical ischemic lesions on 12 leads rest electrocardiogram. The patients had any kind of coronary artery disease: stable angina, unstable angina, myocardial infarction or silent ischemia.
Clinical measures and classical risk factors
In every patients baseline clinical measures included systolic blood pressure (SBP), diastolic blood pressure (DBP), body-mass index (kg/m2), fasting glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, tryglicerides and C- reactive protein as a marker of inflammation.
We also noted the characteristics of menopause (normally or early – surgical or not), hystory of ischemic stroke (including transient attaks), diabetes mellitus, smoking (non-smoker, former smoker or current smoker), premature coronary disease in first degree relatives, treatment with statins.
Diabetes mellitus was defined as a fasting plasma glucose level ³ 126 mg/dl or taking specific medication; hypertension was defined as systolic BP > 140 mmHg or diastolic BP> 90 mmHg or taking hypotensive treatment. Patients with total cholesterol > 200 mg/dl, LDLc > 100 mg/dl, HDLc< 40 mg/dl in men and 45 mg/dl in women, tryglicerides > 150 mg/dl or taking lipid lowering medication were classified as hypercholesterolemic or hypertrigliceridemic. Abnormal values of CRP were considered over 1 mg/dl.
Carotid ultrasound measures
Carotid arteries were examined using an ultrasound scanner (Vivid 4) with a 8 and 10 MHz linear probe by a single trained echographist. The patient was examined in supine position and comon carotid artery (CCA) was viewed in transversal and longitudinal sections. CCA was examined 2 cm proximal the bifurcation, where the walls are almost paralell, both near and far walls. Carotid wall is characterised in ultrasound B – mode by presence of two echogenic lines separated by an anechogen space. The external line corresponds to adventice-media interface and the internal one to intima-lumen interface. The distance between the two lines represent intima-media thikness. IMT was computerised calculated by marking the limit between adventice-media and lumen-intima on a 1 cm distance or using calliper, for the right and left carotids. For every carotid it has been made two measures an we noted the medium value. We considered wall thikness as abnormal if it was greater than or equal to 1.00 mm. The transversal section was used only in cases with difficult visualisation of walls in longitudinal section and for study of atheroma plaques on anterior wall, too.
The plaque is an echogenic structure localised on vascular wall.
ABI was measured with the patient in supine position after 5 minutes of rest. Systolic blood pressure was measured in each arm (brachial artery) and leg (posterior tybial artery). The ABI was calculated for each leg taking the highest upper-extremity SBP. The lowest of these two measures was used to clasify the severity of peripheral artery disease. Accordingly to Consensus on Intermitent Claudication the severity of peripheral artery disease could be stratify into three grades, taking into account the value of ABI: mild (ABI=0.9-0.7), moderate (ABI=0.7-0.5) and severe (ABI<0.5). In healthy people values of ABI ranges between 0.9-1.3.
For statistical analysis we used GraphPad InStat version 3.05. We used correlation and regression tests. Two-sided test with p values £ 0.05 were considered significant.
The baseline characteristics of the patients are represented in table 1. The age of the patients was not statistically significant (p=0.82) Concerning the type of coronary artery disease, we found that myocardial infarction was more prevalent in men and silent myocardial ischemia in women . 80% were hypertensive and 27% had diabetes mellitus, regardless the gender.
Women had more frequent hypercholesterolemia (p=0.0004). We found high levels of CRP in 15,38% women and 33,37% men. (table 1.)
Clinical peripheral artery disease was found in 26,92% coronary women and in 46,67% of men and clinical cerebrovascular disease in 19,23% coronary women and in 20% of men.
In order to study the statistical features we used correlation and regression tests. We tried to study the relationship between IMT and other risk factors (SBP, DBP, total cholesterol, HDL-cholasterol, LDL-cholesterol, tryglicerides, smoking, early menopause, obesity, premature coronary disease, statin tratment). Regression model used was multiple linear regression. After adjustment of the model by eliminating the features that do not have influence in IMT we obtained a significant regression model (F-statistic: 5.879 on 3 and 37 DF, p-value: 0.002182) and remanined as a predictive factors only premature CAD (p-value: 0.04341), diabetes mellitus (p-value: 0.11460) and cerebrovascular disease (p-value: 0.00516). The statistical relevance is disputable in diabetes mellitus and between acceptance limits in the case of premature CAD and cerebrovascular disease. Intima media thickness was > 1 mm in 54% of women and 60 % of coronary men. The presence of aterom plaques was higher in men vs women. A low ankle brachial index was found in 30.76% of women (11.53% with severe peripheral artery disease) and 60% of men (26.67% with very low ABI). More men were treated with statins
The same analysis was performed concerning relationship between ABI and the risk factors but it wasn’t found a significance. That is why we analysed this relationship in groups: women vs. men. In women the linear regression model was statisticaly sigificant (F-statistic: 4.54 on 6 and 19 DF, p-value: 0.005117) and showed a statisticaly sigificant relation between ABI and smoking (p-value: 0.032125), DBP (p-value: 0.012673) and diabetes metllitus (p-value: 0.004933). We study also some possible influencing factors: HDL-cholesterol (p-value: 0.157299) , tryglicerides (p-value: 0.097904) and obesity (p-value: 0.111659). In men a significant correlation was obtained for C-reactive protein (p-value: 0.0325), smoking (p-value: 0.0131) and DBP (p-value: 0.0157).
In linear correlation between ABI and IMT we obtained the Pearson coefficient of r = -0.15723. There is a weak negative correlation between these two parameters; the pathologic values are defined being greater than a prague value (10.0 mm) for IMT and less than a value prag (0.9) for ABI.
Other statistical analysis tried to find differences between coronary women and men when studying ABI and IMT. We used unpaired t test with a statistical prague of 0.05. The null hypothesis affirmed that there are no significant differences but the alternative billateral hypothesis found some differences: p=0.426061 for IMT and p=0.256631 for ABI. In both cases the null hypothesis couldn’t be rejected.
Coronary angiography can be used only in specific cases, but carotid ultrasound, as a non-invasive method can be used in a larger number of patients. Measuring of IMT allows detection of wall abnormalities before clinical hemodinamic consequences appear. Patients with increased IMT had a greater vascular risk that those without any lesion. ABI also is a simple non-invasive method for assesing the extent of significant atherosclerosis in the lower extremities.
The present study demonstrates that in coronary patients carotid and/or peripheral aterosclerotic involvement is present and significant statistically (Figure 2.). Both peripheral and cerebral vascular disease are present more frequent in coronary men vs women. In both genders subclinical aterosclerosis (thick intima-media with IMT > 1mm and a low ankle brachial index without clincal manifestation of arteriopathy) was more frequent in coronary patients (figure 3 and 4.).
IMT is correlated with age, gender (greater in men) (Gariepy), smoking, high LDL, low in both genders and with hypercholesterolemia, low HDL, hormon replacement therapy, smoking in women and hypertension and diabetes mellitus in men.
In our study a small ABI was significantly associated with a large carotid IMT, but the correlation is not so strong because of the common cause of the parameters, atherosclerosis. This results are similar with other studies (Allison). Men had a higher incidence of peripheral artery and of carotid subclinical aterosclerosis and more carotid aterosclerotic plaques than women. It seems that aterosclerotic disease is more extensive in men vs women at same similary age.
Concerning the correlation between ABI and IMT (figure 7.) we did not find a significant statistical difference between women and men. This result could be explained statisticaly beacuse the lower power of the test (small groups) but in the same time we have to take into account that all the women were in menopause, without hormonal protector effect.
Coronary patients have concomitant carotid and peripheral artey involvment; those with low ankle brachial-index had increased intima-media thickness. Patients with low ankle brachial-index were more frequent smokers and with diabetes mellitus in both genders. Women had increased plasma levels of total cholesterol, LDLc and tryglicerides. Intima-media thickness and carotid plaques were more frequent in men, in spite of statin treatment vs women. Peripheral artery disease is more frequent in men. There were no statistical differences between postmenopausal women and men concerning values of ankle brachial-index and intima-media thickness.
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