Evidence of a chronic systemic cause of instability of atherosclerotic plaques

Background Major thrombotic and embolic complications of atherosclerosis ar e closely associated with irregularity and rupture of atheromatous plaques in both the carotid and coronary arteries. Plaque instability is partly det ermined by local factors, but systemic factors, such as infection, autoimmu nity, or genes, may also be important. If plaque stability is influenced by systemic factors that are present in only a proportion of patients, some i ndividuals should be more prone to rupture of plaques than others-ie, irreg ular plaques should occur in multiple vascular beds in some individuals mor e frequently than would be expected by chance alone. Methods We studied 5393 carotid bifurcation angiograms from 3007 patients w ith a recently symptomatic carotid stenosis. We assessed the extent to whic h plaque-surface irregularity at the symptomatic carotid artery was associa ted with irregularity at a distant site, the contralateral carotid artery, and the extent to which plaque irregularity at these sites was associated w ith 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 symptoma tic carotid artery were more likely than those with smooth plaque (n=110) t o have irregularity in the contralateral carotid artery (odds ratio 2.21 [9 5% CI 1.62-3.01], p<0.001). Patients with irregular plaques in both arterie s were more likely to have had a previous myocardial infarction than patien ts with smooth plaques (hazard ratio 1.82 [1.23-2.64], p<0.001), and were m ore 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 associatio ns were not explicable on the basis of differences in traditional vascular risk factors. Interpretation These data suggest that some individuals have a systemic pre disposition 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 plaqu e instability.