DISCUSSION

The present study has something important as follows: 1) The hs-CRP is correlated to the volume measures of total plaque; 2) The hs-CRP has a relationship with specific components of the plaque; FF and DC. The level of hs-CRP is related the magnitude of FF and DC; the volume and volume index of that components has stastical correlation with hs-CRP; 3) Any parametersregarding NC and presense of VH-TCFAs are not related with the level of hs-CRP. 4) The volume index of DC is best independent factor for hs-CRP on multivariate analysis.

The atherosclerosis is one of important mechanism for coronary artery disease. The natural history of the atherosclerosis is related to the composition of the plaque. Previous pathological studies suggested that plaque composition detremines plaque vulnerability;

large lipid core, a thin cap fibroatheroma, infiltration of inflammatory cells and less amount of smooth muscle cells (Kubo et al., 2009).

With the development of histologic studies for the plaque, there has been rapid expansion of coronary imaging, especially for vulnerable plaque in coronary arteries.One of them is IVUS; that can be possible to display structures of vessel and plaque. With advantages of IVUS, VH-IVUS adds the information about the plaque composition; that discriminates the plaque as 4 color codes, which help the analysis of plaque components in coronary artery andatheroscleorsis. In PROSPECT trial, VH-IVUS demonstrated plaque composition of the analyzed vessel affected clinical cardiac event, although that vessel had mild severity angiographically. In 697 patients in acutecoronary syndromes, nonculprit lesions associated with recurrent events were more likely characterized by 1) a plaque burden of 70% or greater or2) a minimal luminal area of 4.0 mm² or less or 3) to have more VH-TCFAs.(Stone et al., 2011).

Inflammation and inflammatory cells are involved in progression of the atherosclerosis.

After being recruited into the atherosclerotic plaque, inflammation affect degradation of fibrous cap, expression of adhesion molecule, promoting chemotaxis to enthelial cells and etc, which were related to hs-CRP.(Pasceri et al., 2000; Pasceri et al., 2001; Pepys and

16 Hirschfield, 2003).

Based on aforementioned theories and facts, some reports advert hs-CRP was associated with the atherosclerosis, specially for plaque vulnerability. There are some evidences that confirm an association with hs-CRP and plaque vulnerability by pathologic findings (Burke et al., 2002; Ishikawa et al., 2003).Coronary computed tomography angiography also proved hs-CRP was increased as mixed calcified plaque which was represented unstable plaque, grew up(Rubin et al., 2011).It could be found similar results from VH-IVUS studies.

Culprit plaque in patients with acute coronary syndrome had much NC than those in patients without, and there was an inverse relation between hs-CRP and NC ratio (Otake et al., 2008).

It can be established same connection with hs-CRP and NC in cases with stable angina (Kubo et al., 2009) and unstable angina (Ko et al., 2012). However, these studies have a concomitantfeature; they are limited in only one vessel: culprit vessel. It’s needed to be studied for whole coronary vessels forreinforcement of a connection between hs-CRP and vulnerable plaque compositions(Otake et al., 2008).

Our study was not only about culprit lesions, but also nonculprit lesions and non-target vessel and showed contrary outcomes compared to that of some reports as mentioned previously. The level of hs-CRP correlated, not to any parameters of NC and VH-TCFAs that were markers of plaque vulnerability, tothat of DC and FF.

It was known that NC was associated plaque vulnerability, which ultimately had high probability of acute cardiac events (Rodriguez-Granillo et al., 2006; Missel et al., 2008).

VH-TCFAs also showed similar results; patients with acute coronary event or plaque rupture had more VH-TCFAs than them with stable angina in pathologic study, and Rodriguez – Granillo et al. and Hong et al. reportedthere were more VH-TCFAs with acute coronary syndrome than with stable angina in VH-IVUS studies.(Kolodgie et al., 2001; Rodriguez-Granillo et al., 2005; Hong et al., 2008).

Therefore, in our study, the most popularinflammatory biomarker-hs-CRP -indicated rather the burden than the vulnerability of the plaque, that was supported by our resultwhich DC was most intimate composition tohs-CRP and other evidences were as follows. Coronary calcium reflected the burden and age of the atherosclerosis;in other words, the extent of calcification was closely associated with that of atherosclerosis (Rumberger et al., 1995;

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Schmermund et al., 1998; Schmermund et al., 1999; Falk, 2006). Because the progression of calcification affects the coronary tree in a systemic fashion, it would help

rather to identify subjects at increased risk than localized unstable plaque (Schmermund and Erbel, 2001).A few studies indicated what most importatnt thing in coronary calcificiation to determine plaque vulnerability was the character of distribution of calcium, not the absolute quantity. Fujii et alshowed that ruptured plaque had quantitatively less calcium but a larger number of small calcium deposits compared to with non-ruptured plaque(Fujii et al., 2005). The pattern of spotty calcification was a robust finding of plaque vulnerability (Ehara et al., 2004; Motoyama et al., 2007).

Additionally, coronary calcium could predict cardiac events (Pletcher et al., 2004; Church et al., 2007). The volume of DC in a 3-vessel VH-IVUS studywas also related to major adverse cardiac events (Shimizu et al., 2012).Although clinical outcomes didn’t descrbied in our study, hs-CRP and DC of VH-IVUS would be used to forecast cardiac disease, totally.

There were some limitation in our study.This study was a single center, retrospective study and based on a small patient population. The distribution of patients differentiated from clinical presentation was not even;more than a half of cases were unstable angina. This one would have affected not only the composition of plaque, but also relationship between hs-CRP and specific plaque compositions. Furthermore there are limited data on the reproducibility or the ability of VH-IVUS to predict future events because VH-IVUS have limitation in analyzing small vessel and in distinguishing from thrombus and other plaque component.

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