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Pathology of the Vulnerable Plaque

Renu Virmani, MD^_*,_*, Allen P. Burke, MD^_*, Andrew Farb, MD and Frank D. Kolodgie, PhD^_*

^_* CVPath, International Registry of Pathology, Gaithersburg, Maryland
U.S. Food and Drug Administration, CDRH-ODE-DCD-ICDB, Rockville, Maryland

Manuscript received June 16, 2005; revised manuscript received October 10, 2005, accepted October 24, 2005.

^_* Reprint requests and correspondence: Dr. Renu Virmani, CVPath, International Registry of Pathology, 19 Firstfield Road, Gaithersburg, Maryland 20878. (Email: rvirmani{at}cvpath.org).

The majority of patients with acute coronary syndromes (ACS) present with unstable angina, acute myocardial infarction, and sudden coronary death. The most common cause of coronary thrombosis is plaque rupture followed by plaque erosion, whereas calcified nodule is infrequent. If advances in coronary disease are to occur, it is important to recognize the precursor lesion of ACS. Of the three types of coronary thrombosis, a precursor lesion for acute rupture has been postulated. The non-thrombosed lesion that most resembles the acute plaque rupture is the thin cap fibroatheroma (TCFA), which is characterized by a necrotic core with an overlying fibrous cap measuring <65 µm, containing rare smooth muscle cells but numerous macrophages. Thin cap fibroatheromas are most frequently observed in patients dying with acute myocardial infarction and least common in plaque erosion. They are most frequently observed in proximal coronary arteries, followed by mid and distal major coronary arteries. Vessels demonstrating TCFA do not usually show severe narrowing but show positive remodeling. In TCFAs the necrotic core length is approximately 2 to 17 mm (mean 8 mm) and the underlying cross-sectional area narrowing in over 75% of cases is <75% (diameter stenosis <50%). The area of the necrotic core in at least 75% of cases is 3 mm². These lesions have lesser degree of calcification than plaque ruptures. Thin cap fibroatheromas are common in patients with high total cholesterol (TC) and high TC/high-density lipoprotein cholesterol ratio, in women >50 years, and in those patients with elevated high levels of high sensitivity C-reactive protein. It has only recently been recognized that their identification in living patients might help reduce the incidence of sudden coronary death.

Abbreviations and Acronyms   ACS = acute coronary syndromes   CRP = C-reactive protein   HDL = high-density lipoprotein   MPO = myeloperoxidase   TC = total cholesterol   TCFA = thin cap fibroatheroma

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