Enlargement of peripheral arteries – an indicator of cardiovascular risk

Background

There is growing evidence that different stimuli can modify the diameter of arteries, including

• haemodynamic stress
• inflammation
• injury(1)

Recent findings have indicated that the process of vascular remodelling is

• an important stage in the development of atherosclerosis

It seems that remodelling of the arterial diameter during the development of atherosclerosis is

• a compensatory process

by preserving the lumen diameter and blood flow and may influence the clinical presentation of atherosclerotic vascular disease. However, the data have also shown that remodelling of the arterial wall and enlargement of the arterial diameter also affect undiseased vascular segments. Thus the process of remodelling of the arterial wall is not completely understood (2-4).

I - Mechanisms of enlargement of the arterial diameter

The biological and physiological significance of enlargement of the arterial diameter during the atherosclerotic process and the mechanisms that are involved in this process are not fully comprehended. Labropoulos et al have found that all arteries dilate in the stage of early atherosclerotic plaque formation and they concluded that dilation of the artery occurs to preserve luminal area (5). Therefore the increase in arterial diameter in subjects with atherosclerosis is usually discussed in terms of compensatory enlargement to preserve luminal area.

However the results of the investigations of Jensen - Urstadt et al have suggested that the mechanisms behind the increase in artery diameter may be related to regulatory mechanisms present before compensatory enlargement of the lumen (6). It is possible that the vessel diameter in itself is a measure of vascular regulatory function. In advanced stages of atherosclerosis the increased diameter is probably a consequence of the long term harmful effects of risk factors that initiate the inflammatory process, with the accumulation of macrophages in the arterial wall. Activated macrophages produce metalloproteinases (MMPs) and increased activity of MMPs is probably associated with pathological remodelling. MMPs probably cause vessel enlargement with a break down of the structure of the elastic lamellae (7).

II - Arterial diameter and atherosclerosis

Various studies have shown that arterial diameter enlarges during the atherosclerotic process. In animal experimental studies various types of arteries have been shown to enlarge in response to diet - induced atherogenesis with a normal lumen preserved early in the course of the disease (8, 9). The importance of the remodelling process in human coronary arteries was first proposed by Glagov and co-workers, based on post-mortem evaluation (10). Steinke and co-workers investigated dilation of the carotid arteries and revealed a strong relation between plaque growth and consequent dilation of the carotid arteries (3). Therefore, changes in the diameter of arteries were represented as a compensatory remodelling response to local atherosclerotic lesions.

The relationship between the diameter of peripheral arteries and atherosclerosis supports findings on the correlation between arterial diameter and different risk factors of atherosclerosis. Holewijn and co-workers has shown that the diameter of the brachial artery is significantly related to smoking, diastolic blood pressure, diabetes mellitus, body mass index, age and male gender (11). In a number of studies an interrelationship between arterial diameter and preclinical or clinical atherosclerosis was also found. In the Atherosclerosis Risk in Communities (ARIC) cohort study the diameter of the carotid arteries was related to atherosclerotic lesions in the investigated arteries (2). Recent findings also confirmed that the diameter of the carotid artery is an indicator of cardiovascular risk and is associated with cardiovascular events, particularly with myocardial infarction (12). It was also reported that increased common carotid artery diameter is positively related to coronary artery disease (13) and to acute coronary syndrome  (14). Studies also showed that arterial diameter enlargement occurs in early atherosclerosis and is aggravated in the presence of vulnerable plaques (15). Further, a relationship between common carotid artery diameter and the burden of severity of atherosclerotic deterioration of the investigated arteries was found (16).

An interrelationship between the diameter of peripheral arteries and asymptomatic-preclinical atherosclerotic lesions was also indicated. In the EVA study intima media thickness and the presence of plaques were accompanied with increased lumen diameter of the carotid arteries (17). Holewijn showed that brachial artery diameter is related to intima- media thickness. This may indicate that arterial remodelling in atherosclerosis may be a systemic process (11).

Eigenbrodt et al confirmed that there is an interrelationship between carotid artery diameter and IMT. In this study it was shown that the diameter is an IMT-independent indicator of cardiovascular events.

In one of our studies we also showed that in patients with idiopathic venous thrombosis who have more frequent atherosclerotic lesions than healthy subjects’ the carotid and femoral artery diameters are increased. Enlargement of the diameter was not related to the presence of classical risk factors of atherosclerosis, but was most significantly influenced by the presence of venous thrombosis. As enlargement of the arterial diameter represents a risk for atherosclerosis, it could mean that venous thrombosis represents a risk for atherosclerosis and that both diseases are interrelated (data not yet published).

III - Clinical usefulness of the determination of arterial diameter

The diameter of the carotid or brachial artery is easily

• assessed by B-mode ultrasound

and is related to risk factors of atherosclerosis and as such helps in identification of persons at higher risk of cardiovascular events.

However, the question arises as to whether it adds to risk estimation based on the presence of risk factors of atherosclerosis. In the study done by Eigenbrodt and co-workers it was shown that carotid artery diameter adds little to overall risk discrimination after risk factor adjustment. Nevertheless, the prevailing opinion is that determination of the arterial diameter

• improves the prediction of cardiovascular events

It may be

• useful in subjects without risk factors of atherosclerosis, a low risk score for atherosclerosis and a positive family history of cardiovascular events

Determination of preclinical atherosclerosis including arterial diameter is not only useful for prediction of the statistical probability for development of atherosclerosis, but also

• helps to identify individuals in whom the atherosclerotic process is already present.