ReviewAssociation of inflammatory markers with angiographic severity and extent of coronary artery disease
Introduction
Cardiovascular disease is the leading cause of morbidity and mortality in the western world and atherosclerosis is the major common underlying disease [1]. The pathogenesis of atherosclerosis involves a number of local inflammatory mechanisms, including endothelial dysfunction, leukocyte migration, extracellular matrix degradation, and platelet activation [2], [3]. Several systemic inflammatory markers may reflect different degrees of coronary inflammation and especially in acute coronary syndromes (ACS), they may provide unique information, not related with the biomarkers of myocyte necrosis and hemodynamic stress [4].
Angiography, the most commonly performed invasive procedure for the illustration of arterial anatomy and luminal narrowing, is not an established surrogate measure of coronary atherosclerosis. Moreover, the association between inflammatory markers and severity and extent of coronary artery disease (CAD) remains controversial, although a more consistent relationship between systemic inflammatory markers and major adverse cardiac events has been observed [3], [5], [6].
Currently there is no consensus if increased inflammatory levels may predict the presence of atherosclerosis. The question of how to use these biomarkers as part of a broader risk stratification strategy is still an issue of debate. The aim of this manuscript is to review the literature for the evaluation of the relationship of inflammatory markers with the presence and extent of coronary atherosclerosis, as assessed by coronary angiography in order to evaluate the potential utility of these markers in identifying patients with higher levels of coronary atherosclerosis and predicting the atheromatic burden. Thus, we performed a computerized search, using the keywords coronary angiography and inflammation, to identify relevant English language articles published in Pub Med until November 2008. Individual articles had to meet the following criteria to be included: (1) articles examining the relationship between C-reactive protein (CRP) and coronary angiography and (2) articles or reviews relating atherosclerosis to local and systemic inflammation. We also examined the references of all the studies from our initial search to locate additional references that would be useful for this review. To ensure the quality of our data we limited our review to the studies published as full text in peer-reviewed journals.
Section snippets
Angiographic classification of coronary atheromatic lesions
The classic angiographic features of lesions associated with the ACS, including irregular ragged borders and intraluminal lucency, have been previously demonstrated [7], [8]. Ambrose et al., has shown that concentric lesions are symmetrical and usually smooth, whereas eccentric are asymmetrical. Eccentric lesions of type I are smooth, whereas lesions of type II, are either smooth with a narrow neck, due to overhanging edges, or have irregular borders. Lesions with multiple irregularities are
Limitations of angiography
Although angiography is one of the most commonly performed invasive procedures for the illustration of arterial anatomy and luminal narrowing and has been characterized as the “gold standard”, it is not an established a surrogate measure of coronary atherosclerosis. It only provides information about the vessel lumen, and does not provide direct information on plaque composition, plaque burden and plaque changes within the vessel wall. In addition, visual assessment of the degree of stenosis is
Correlation between inflammation and atherosclerosis
Evidence supports a pivotal role of inflammation in all phases of atherosclerosis from the initiation of the fatty streak to the culmination in ACS [5], [10]. The earliest event in atherogenesis appears to be endothelial cell dysfunction. Endothelial dysfunction manifests itself primarily as nitric oxide and prostacyclin deficiency and increased circulating levels of endothelin-1, angiotensin II, and plasminogen activator inhibitor-1. Attachment of mononuclear cells such as monocytes and T
C-reactive protein as a direct mediator of plaque inflammation
Among the numerous circulating inflammatory markers of atherosclerotic process, CRP received the greatest attention mostly because of its easy measurement as an analyte. Beyond its role as an inflammatory marker, CRP has also been considered as a mediator of atherosclerosclerosis [13]. There are two issues regarding the pro-atherogenic effect of CRP. Firstly, the site of CRP production and secondly the direct effect of CRP on the arterial wall.
Recent data challenge the hypothesis that CRP is
Inflammatory markers and burden of atherosclerosis
Several studies have shown that the association between inflammatory markers and the extent of CAD is weak and is mostly explained by concomitant burden of cardiovascular risk factors (Table 1). Previous studies, reported no correlations between inflammatory markers and any of the applied scores [24], [25]. However, all patients had known CAD whereas patients with normal angiograms and consecutively low levels of inflammatory markers were not included. In addition, some patients were on statin
The impact of new imaging modalities
The need of improved diagnostic accuracy and superior visualization of atheromatic burden has resulted in the development of newer imaging techniques that minimize the limitations of conventional angiography and has promoted interest in alternative invasive or catheter-based techniques to directly visualize the arterial wall and to characterize plaque. Most of the studies have used intravascular ultrasound for the quantitative and qualitative assessment of atheromatic burden. Several studies
Conclusions
Currently there is no consensus if increased inflammatory levels may predict presence and increased burden of atherosclerosis. Further research efforts should be directed at investigating the effect of CRP on other atherogenic mediators and at elucidating the proinflammatory, prothrombotic molecular mechanisms of atherosclerosis.
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