Markers of Preclinical Atherosclerosis and their Clinical Relevance

ABSTRACT

The estimation of risk for atherosclerotic and cardiovascular events based only on the presence of classical risk factors is often insufficient. Therefore, efforts have been made to find markers that indicate the presence of preclinical disease in individual subjects like blood markers of atherosclerosis and preclinical deterioration of the arterial wall.

Elevated levels of several inflammatory mediators have been found in subjects with atherosclerosis. Prospective epidemiological studies have found increased vascular risk in association with increased basal levels of cytokines, the cell adhesion molecules P-selectin and E-selectin; and acute-phase reactants such as high sensitive C-reactive protein (hsCRP), fibrinogen, and serum amyloid A. For clinical purposes, the most promising inflammatory biomarker appears to be hsCRP.

In the last decade, markers of plaque stability and unstable coronary artery disease have been sought such as myeloperoxidase, soluble CD40 ligand, pregnancy-associated plasma protein A, free fatty acids and placental growth factor.

Further, markers of endothelial dysfunction (ED), like circulating molecules as well as indicators of functional deterioration of the arterial wall, that represent a common denominator of harmful effects of risk factors on the vessel wall were identified. It was show that endothelial dysfunction is closely related to different risk factors of atherosclerosis, and to their intensity and duration.

Measurement of the intima-media thickness (IMT) using high resolution B-mode ultrasonography has emerged as one of the methods of choice for determining the anatomic extent of preclinical atherosclerosis and for assessing cardiovascular risk. A strong correlation between carotid IMT and several cardiovascular risk factors was shown and it has also been found to be associated with the extent of atherosclerosis and end-organ damage of high risk patients.

Determination of markers of preclinical atherosclerosis could influence the decision of a clinician to intervene with medication and to use more aggressive treatment of risk factors in primary prevention, and in patients with atherosclerotic disease.

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