Variation in collagen in the caps of human coronary lipid-core plaque autopsy specimens: A possible measure of cap weakness

BACKGROUND The cap over a coronary lipid core plaque (LCP) protects the plaque from rupture and causation of a coronary event. Cap thickness has been considered the primary measure of likelihood of plaque rupture. However, caps of equal thickness may contain different amounts of collagen and be at various risks of rupture. Collagen depletion at sites of LCP may provide additional valuable information regarding plaque vulnerability. This study assessed the correlation of dimensional cap thickness vs. a semi-quantitative measure of collagen in human coronary autopsy specimens. METHODS Seven coronary segments from 5 human autopsy hearts were used in this study. Arterial segments were fixed and divided into a total of thirty-two 2mm blocks for picrosirius red (PR) and Movat's (MP) staining. Pathological contouring of the lipid was performed on the unpolarized PR stain, using the MP as a histology reference. Cap thickness was assessed in the regions of histology-verified LCPs in 1° increments from the lumen center. Collagen was quantified in the same locations using co-registered polarized PR images. The data collected in this study are a part of a larger autopsy study of 40 hearts (n=103 artery segments) designed to build an algorithm for detecting weak LCP caps in patients using a commercial intravascular NIRSIVUS catheter. RESULTS A modest correlation (r=0.49) was found between caps <200μm and associated collagen content. However, for lipid-rich necrotic cores with much thicker caps (i.e. >200μm), the amount of collagen in the fibrous cap was not well correlated to its thickness, as measured on MP images. The correlation in 200μm ranges (e.g. 200- 400μm) was no better than r=0.23, and as poor as r=0.18. Large caps were found to have variable collagen content and, often a non-uniform distribution throughout the cap (Figure 1D vs 1B). CONCLUSIONS Caps of equal thickness can contain markedly different amounts of collagen. A thick cap may be low in collagen suggesting possible cap weakness. Poor correlation between cap thickness and collagen for caps above 200μm suggests that the clinical relevance of a dimensional measurement of cap thickness for detecting vulnerable plaques might be enhanced by assessing the amount of collagen in the plaque cap. Application of the aforementioned algorithm to patients in ongoing prospective clinical trials could increase the accuracy of vulnerable plaque detection. (Figure Presented).