Published Online
on May 1, 2006

A more recent version of this article appeared on May 16, 2006

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Submitted on September 15, 2005
Revised on February 9, 2006
Accepted on March 10, 2006

Histological Assessment of 526 Symptomatic Carotid Plaques in Relation to the Nature and Timing of Ischemic Symptoms. The Oxford Plaque Study

J. N.E. Redgrave MRCP, J. K. Lovett MRCP, P. J. Gallagher PhD, and P. M. Rothwell PhD^*

From the Stroke Prevention Research Unit (J.N.E.R., J.K.L., P.M.R.), Department of Clinical Neurology, Radcliffe Infirmary, Oxford, United Kingdom; and Department of Pathology (P.J.G.), Southampton General Hospital, Southampton, United Kingdom.

^* To whom correspondence should be addressed. E-mail: peter.rothwell{at}clneuro.ox.ac.uk.

Background--Atherosclerotic plaque at the carotid bifurcation is often associated with transient ischemic attack (TIA) and ischemic stroke, but the mechanisms are not completely understood. Previous histological studies have been too small or insufficiently detailed to reliably determine the temporal course of features of plaque instability or to stratify analyses by the nature of presenting symptoms.

Methods and Results--We performed the largest-ever histological study of symptomatic carotid plaques from consecutive patients (n=526) undergoing endarterectomy and related detailed reproducible histological assessments to the nature and timing of presenting symptoms. There was a high prevalence of many features of coronary-type plaque instability. Dense plaque inflammation (especially infiltration with macrophages) was the feature most strongly associated with both cap rupture (odds ratio 3.39, 95% confidence interval 2.31 to 4.98, P<0.001) and time since stroke (P=0.001). Strong negative associations with time since stroke were also seen for cap rupture (P=0.02), overall plaque inflammation (P=0.003), and "unstable plaque" (P=0.001). Although plaques removed 60 days after the most recent event were more unstable after a stroke than after a TIA, the instability persisted after a TIA, and plaques removed >180 days after most recent event were less unstable after a stroke than after a TIA (plaque inflammation: 60 days, odds ratio 2.33 [95% confidence interval 0.76 to 7.19]; >180 days, 0.36 [0.16 to 0.84]; P=0.008; unstable plaque: odds ratio 3.27 [95% confidence interval 0.93 to 11.50] versus 0.74 [0.33 to 1.69], P=0.05).

Conclusions--Pathology of recently symptomatic carotid plaques is similar to that of culprit coronary plaques, with strong correlations between macrophage infiltration and plaque instability. The tendency for plaque inflammation and overall instability to persist with time after a TIA but to decrease with time after a stroke suggests that the nature of the underlying pathology may differ.

Key words: stroke • pathology • carotid arteries • atherosclerosis • plaque

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