1 - Cardiovascular risk factors
Cardiovascular diseases remain today the first cause of death in the world. Understandably, the knowledge and the prevention of cardiovascular risk factors have attracted particular attention.
Beyond “traditional” risk factors such as age, gender, family history of CV disease, hypertension, hyperlipidemia, smoking and diabetes, very important as well, are “emerging” risk factors such as fibrinogen, metabolic syndrome (MS), hsCRP, Lp-(a), hyperhomocysteinemia and instrumental markers such as Ankle Brachial Index (ABI) and carotid Intima-Media Thickness (IMT).
Particularly, IMT is a non invasive low cost and highly reproducible procedure.
Carotid Artery IMT is measured with laser Doppler velocimetry: the ultrasonographic assessment of carotid arteries is operated while the subject is in a supine position with his head turned to the sonographer at an angle of 45°.
The scan head is kept perpendicular to the arterial walls. The Doppler mode permits the visualisation of vessels and an evaluation of flow disturbances. It measures the intima-media thickness (IMT) and the size and number of atheromatous plaques. IMT is defined as the distance between the media-adventitia interface and the intima-media interface.
IMT is measured at five locations on each side and, in particular, it is measured at internal carotid artery (ICA) about 1 cm distal from the flow divider, at bifurcation enlargement (BIF) and at proximal, middle and distal segment of the common carotid artery (CCA) is measured.
2 - Increased IMT as instrumental marker of vascular damage : Relation to cardiovascular risk factors (RF)
Cardiovascular RF are associated with an impaired endothelial function and an increased IMT, and the presence of carotid IMT is significantly related with endothelial dysfunction (p < 0.01).
In a study of our group impaired flow mediated vasodilatation (FMD) and values of carotid IMT have been found to be higher among patients with cardiovascular risk factors than among patients without RF.
Age (p < 0.005) and diabetes (p < 0.05) and levels oh hsCRP were directly related to carotid IMT. An inverse linear correlation was shown between systolic blood pressure (p < 0.005), smoking (p < 0.05), total cholesterol (p < 0.05), LDL-C plasma levels (p < 0.005), hsCRP levels and FMD. Finally, we showed a lower FMD in patients with carotid and femoral IMT in comparison with patients without peripheral atherosclerosis (p = 0.01) (1).
Another study showed the major prevalence of endothelial dysfunction in hypertensive patients and in normotensive offspring of subjects with essential hypertension, proving the importance of genetic predisposition (2).
Clinical studies have shown an important relation between smoking and IMT: non smokers had lower IMT values than smokers (p < 0.01) and smoking was associated with dose-related increases in intima-media thickness and endothelial dysfunction (3).
Furthermore, there is an interrelationship between total risk and IMT: IMT depends on the presence and a number of risk factors, duration and their intensity. In fact IMT increases with age and hypertension, hyperlipidemia and non-insulin-dependent diabetes mellitus are related to a higher IMT (4).
A relation between IMT and the cluster of risk factors of the Metabolic Syndrome has also been shown: in fact, a number of MS components and IMT value increases proportionately and in patients with manifest vascular disease, the presence of metabolic syndrome is associated with advanced vascular damage (5).
3 - Relation to the extent and severity of atherosclerosis in different arterial beds
Another study examined the relation between IMT and a number of arterial beds with significant (> 50%) stenoses, including coronary, supra-aortic, renal and iliac/femoral arteries. It showed that IMT was significantly correlated to the number of coronary vessels with stenoses (p<0.001). So, IMT has been shown to be an independent predictor of significant multifocal atherosclerosis, showing high sensitivity and specificity for indicating more advanced atherosclerotic involvement (6, 7).
4 - Prediction of cardiovascular events
Previous observational studies have shown a relationship between carotid intima-media thickness (IMT) and coronary artery disease (CAD).
Many studies such as the “Prospective Finnish Study”, “Atherosclerotic Risk in Communities (ARIC)”, the “Rotterdam Study” and the “Cardiovascular Health Study” showed a significant relation between IMT and cardiovascular risk and provided evidence that carotid IMT is related to future cerebrovascular and cardiovascular events (8-12).
The ACSRS study determined the risk of ipsilateral ischaemic neurological events in relation to the degree of asymptomatic carotid stenosis and other risk factors. It showed linearity between stenosis and risk, and provided a new approach to risk stratification (13).
In a study of our group, performed in asymptomatic high risk subjects followed for 5 years, a significant increase of fatal and non fatal cerebro- and cardiovascular events in those subjects that at baseline present IMT or asymptomatic carotid plaques in comparison to subjects with normal carotid arteries at baseline was shown (14).
Moreover, in this study, beyond traditional cardiovascular risk factors, markers of inflammation and previous infections to Cytomegalovirus, Chlamydia pneumoniae, Helicobacter pylori e Cytotoxic Helicobacter pylori seem to significantly influence the occurrence of cerebrovascular and cardiovascular events in patients with baseline asymptomatic carotid lesions (p<0.0001) (14).
5 - Therapeutic aspects concerning carotid IMT
In the Multiple Risk Factor Intervention Trial (MRFIT) it has been demonstrated that multiple risk factor intervention reduces cardiovascular risk in high-risk hypertensive men, and that this effect is confined to patients with carotid artery plaques and, in particular, to those patients with echolucent plaques (15).
The Atorvastatin versus Simvastatin on Atherosclerosis Progression (ASAP study) studied the long-term effects of statins on femoral IMT. It demonstred an increased efficacy of atorvastatin 80 mg in delaying the progression of atherosclerosis in the femoral artery (16).
Some antihypertensive agents influence experimental models of atherosclerosis through mechanisms independent of blood pressure lowering, as shown in the European Lacidipine Study on Atherosclerosis (ELSA), a randomised, double-blind, long-term trial, comparing the effects of a 4-year treatment based on either lacidipine or atenolol on an index of carotid atherosclerosis. The antihypertensive treatment with lacidipine slowed down progression of carotid atherosclerosis significantly more than atenolol treatment. Clinic blood pressure reductions were identical with both treatments, even if 24-hour ambulatory systolic/diastolic blood pressure decreased more with atenolol (-10/-9 mm Hg) than with lacidipine (-7/-5 mm Hg).
However, the ELSA study showed the greater efficacy of lacidipine on carotid IMT progression. These results, despite a smaller ambulatory blood pressure reduction, indicated an anti-atherosclerotic action of lacidipine independent of its antihypertensive action (17).
Data from our study (14) and other data from a recent paper on the evaluation of patients with apparently moderate risk using the Framingham score (18), demonstrate that patients with a cluster of risk factors and IMT have a cardiovascular risk at ten years > 20%; consequently these patients should have applied the concept that “lower cholesterol is better” and be treated with statins to reach a target of LDL-C < 100 mg%.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
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