Published Online
on May 6, 2002

A more recent version of this article appeared on May 28, 2002

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Submitted on February 21, 2002
Accepted on March 22, 2002

Intimomedial Interface Damage and Adventitial Inflammation Is Increased Beneath Disrupted Atherosclerosis in the Aorta. Implications for Plaque Vulnerability

Pedro R. Moreno MD^*, K. Raman Purushothaman MD, Valentin Fuster MD, PhD, and William N. O'Connor MD

From the Linda and Jack Gill Heart Institute, University of Kentucky, Lexington (P.R.M., K.R.P., W.N.O.), and the Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY (V.F.).

^* To whom correspondence should be addressed. E-mail: pmoreno{at}pop.uky.edu.

Background—Atherosclerotic plaque progression is frequently accompanied by compensatory enlargement to preserve the lumen. These enlarging plaques develop features of vulnerability, however, leading to disruption and lumen obstruction. This complex transition from compensatory expansion to plaque disruption may not derive solely from progressive intimal disease. Concurrent changes at the intimomedial interface and within the tunica media and adventitia may play a role in plaque instability. We tested this hypothesis by investigating whether interface changes, including internal elastic lamina (IEL) rupture, and medial and adventitial changes, including inflammation, fibrosis, and atrophy, more frequently accompany disrupted than nondisrupted atherosclerotic plaques.

Methods and Results—Computerized planimetry and ocular micrometry were used for systematic quantification of intimal, medial, and adventitial histopathological features in 598 human aortic plaques according to the AHA classification. Disrupted plaques exhibited larger plaque and lipid pool areas (P=0.0001) and a higher incidence of rupture of the IEL (P=0.0001). Medial and adventitial inflammation (P=0.01), medial fibrosis (P=0.0001), and medial atrophy (P=0.0001) were also higher in disrupted plaques. Furthermore, medial thickness was reduced in disrupted plaques (P=0.0001). Logistic regression analysis identified rupture of the IEL as an independent predictor for fibrous cap disruption (P=0.0001).

Conclusions—Compared with nondisrupted plaques, disrupted plaques have an increased incidence of IEL rupture, medial and adventitial inflammation, medial fibrosis, and medial atrophy. These intimomedial interface and adventitial changes may play a role in the natural history of complex atherosclerotic lesions. The interaction between medial and adventitial pathology and the intimal atherosclerotic process deserves further investigation.

Key words: atherosclerosis • plaque • inflammation • aorta • remodeling

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