الفهرس 
CORONARY ARTERY ATHEROSCLEROSISOnly 14 pages are availabe for public view
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Abstract
Cardiovascular disease, currently the leading cause of death and illness in developed countries, will soon become the pre-eminent health problem worldwide. Atherosclerosis a progressive disease characterized by the accumulation of lipids and fibrous elements in the large arteries constitutes the single most important contributor to this growing burden of cardiovascular disease. The views regarding the pathophysiology of this important malady have evolved over the past century. The link between lipids and atherosclerosis dominated our thinking until the 1970s, based on strong experimental and clinical relationships between hypercholesterolemia and atheroma. The emerging knowledge of vascular biology led to a focus on the role of inflammation in atherosclerosis.
Later on, laboratory and clinical evidence have demonstrated that atherosclerosis is not simply a disease of lipid deposits. Rather, systemic inflammation also plays a pivotal role in atherothrombotic growth and progression. Mononuclear cells, macrophages and T lymphocytes are prominent in atheromatous plaques in the arterial wall. Furthermore, the shoulder region of a plaque, the most vulnerable site for rupture in ACS, is heavily infiltrated with inflammatory cells.
The growing appreciation of the role of inflammation in atherogenesis, atheromatous plaque growth and plaque disruption has triggered interest as to whether circulating inflammatory biomarkers may help to identify subjects at risk of future cardiovascular events.
Atherosclerosis seems to be a chronic inflammatory process that can develop to an acute clinical event by the induction of plaque rupture. The risk of plaque rupture depends more on the number and the activation status of macrophages, the principal inflammatory cells in atherosclerotic plaques, than on plaque size. Inflammatory cells are capable of releasing lytic enzymes that may be responsible for the weakening of the fibrous cap and subsequent rupture of the atherosclerotic plaque. Neopterin, a by-product of the guanosine triphosphate pathway, is produced by activated macrophages and serves as a marker for the activation status of monocytes/macrophages.
In the view of the previous observations and postulations, the aim of this study is to determine neopterin levels in patients with ACS and to study its relationship with other inflammatory markers such as hs-CRP. This necessitated the studying of serum levels of neopterin and hs-CRP in 55 patients with ACS. These patients were divided into two groups, one group were patients with AMI (n=20) and the other group were patients with UA (n=35). The patients of the latter group underwent coronary angiography and were further subdivided according to the severity of atherosclerotic lesions into patients with mild-moderate atherosclerotic lesions (n=9), and patients with severe atherosclerotic lesions (n=26). The control group consisted of 25 subjects with angiograms showing normal coronaries. The adopted assay method was ELISA for both neopterin and hs-CRP.
Results of the present study revealed that levels of neopterin and hs-CRP were significantly higher in patients with AMI and UA as compared to controls. The high levels of neopterin and hs-CRP are due to the fact that inflammation and macrophage activation play a central role in atherogenesis and plaque vulnerability.
On the other hand, there was no statistical significant difference in the levels of neopterin and hs-CRP among patients with AMI and those with UA. This is because these markers are markers of inflammation and not markers of ischeamia.
A hallmark in the present study revealed that serum neopterin levels were significantly higher in patients with severe atherosclerotic lesions when compared to those with mild to moderate atherosclerotic lesions. This augments the theory that the high levels of neopterin reflect the higher degree of inflammation and immune activation among patients with severe CAD.
We also studied the percentage of cases with increased concentrations of hs-CRP and/or neopterin in patients with AMI and in patients with UA. Our results showed that performing neopterin with hs-CRP had achieved better results than performing either one of the parameters alone.
Our correlation study revealed a positive correlation between neopterin and hs-CRP concentrations in the whole patient groups. This shows that there is a positive association between the cellular inflammatory marker neopterin and the acute phase inflammatory marker CRP.
On the other hand neither neopterin nor hs-CRP were correlated with any of the routine lipid profile parameters. These findings were most probably to the lipid-lowering drugs which might be taken by these patients.
To summarize, the significant increase in serum levels of neopterin and hs-CRP that was present in all our patients’ groups, as well as the positive correlation between these indexes, allows us to conclude that inflammation has a pivotal role in the progression of CAD. Our data also suggest that neopterin may be a marker of inflammatory CAD activity and a measure of the extent of the coronary atheromatous process.