Evidence of a chronic systemic cause of instability of atherosclerotic plaques.

BACKGROUND: Major thrombotic and embolic complications of atherosclerosis are closely associated with irregularity and rupture of atheromatous plaques in both the carotid and coronary arteries. Plaque instability is partly determined by local factors, but systemic factors, such as infection, autoimmunity, or genes, may also be important. If plaque stability is influenced by systemic factors that are present in only a proportion of patients, some individuals should be more prone to rupture of plaques than others--ie, irregular plaques should occur in multiple vascular beds in some individuals more frequently than would be expected by chance alone. METHODS: We studied 5393 carotid bifurcation angiograms from 3007 patients with a recently symptomatic carotid stenosis. We assessed the extent to which plaque-surface irregularity at the symptomatic carotid artery was associated with irregularity at a distant site, the contralateral carotid artery, and the extent to which plaque irregularity at these sites was associated with previous myocardial infarction or subsequent non-stroke vascular death (due mainly to coronary-artery disease). FINDINGS: Patients with plaque-surface irregularity (n=1897) in the symptomatic carotid artery were more likely than those with smooth plaque (n=110) to have irregularity in the contralateral carotid artery (odds ratio 2.21 [95% CI 1.62-3.01], p<0.001). Patients with irregular plaques in both arteries were more likely to have had a previous myocardial infarction than patients with smooth plaques (hazard ratio 1.82 [1.23-2.64], p<0.001), and were more likely to have a non-stroke vascular death on follow-up (hazard ratio 1.67 [1.15-2.44], p=0.007). However, there was no difference in the risk of non-vascular death (hazard ratio 0.92 [0.57-1.45], p=0.5). These associations were not explicable on the basis of differences in traditional vascular risk factors. INTERPRETATION: These data suggest that some individuals have a systemic predisposition to irregularity and rupture of atherosclerotic plaques that is independent of traditional vascular risk factors. This finding supports the hypothesis that other systemic factors are important in the cause of plaque instability.