Atherosclerotic Plaque Vulnerability as an Explanation for the Increased Risk of Stroke in Elderly Undergoing Carotid Artery Stenting

Abstract

Background and Purpose— Recent randomized trials showed an increased periprocedural risk for stroke with increasing age in patients undergoing carotid artery stenting. Manipulation of atherosclerotic plaques during carotid artery stenting can result in plaque rupture with subsequent superimposed thrombus formation, embolization, and cerebrovascular events. We hypothesized that atherosclerotic plaques become more unstable with increasing age and thereby might provide insight into the age-related increased risk of cerebrovascular events during carotid artery stenting. Methods— Carotid atherosclerotic plaques were harvested from 1385 consecutive patients undergoing carotid endarterectomy between 2002 and 2010. Carotid plaques were quantitatively analyzed for macrophages, smooth muscle cells, and microvessels; and semiquantitatively analyzed for collagen, calcifications lipid cores, and intraplaque hemorrhages. Patients were divided in 4 groups by age: <60, 60 to 69, 70 to 79, and ≥80 years. Measures of association between age as a continuous variable and histological characteristics were also calculated. Results— Increasing age was associated with a decrease in the amount of smooth muscle cells in the carotid plaque. More plaques with large atheroma and heavy plaque calcifications were observed among elderly patients. After correction for baseline differences, risk factors, and medication use, age was independently associated with a more vulnerable carotid plaque composition. Conclusion— Plaque stability decreases gradually with age. Older patients with carotid stenosis have relatively unstable plaques with low smooth muscle cell content, a high amount of large lipid cores, and more calcified plaques as compared with younger patients. The underlying vulnerable plaque composition in the elderly might be an important contributing factor to the increased risk of stroke for older patients undergoing carotid artery stenting.