Markers of instability in high-risk carotid plaques are reduced by statins

Background: Macrophage infiltration and expression of matrix metalloproteinase-9 (MMP-9) are markers of high-risk atherosclerotic carotid plaques and strong indicators of plaque instability. Use of statins is associated with a decreased risk of stroke and reportedly improves stability of atherosclerotic plaques, but available data addressing the mechanism of this effect are conflicting. Methods: We retrospectively analyzed data from 94 consecutive patients with internal carotid artery stenosis who underwent carotid endarterectomy. Excised plaques underwent systematic quantitative immunohistochemical analysis to determine the percentage of macrophage area and the percentage of MMP-9 area. Associations between percentage of macrophage area and percentage of MMP-9 area and use of statins and cerebrovascular disease were examined by univariate and multivariate analysis. Results: We found significantly higher values of percentage of macrophage area and of MMP-9 area in recently symptomatic (n = 26) compared with asymptomatic (n = 68) internal carotid artery stenoses: median (IQR) percentage of macrophage area was 2.29 (1.53-4.129) vs 0.53 (0.27-0.96) and percentage of MMP-9 area was 0.61 (0.36-0.89) vs 0.08 (0.02-0.27; both P < .0005). Patients treated with statins (n = 49) showed lower percentage values of macrophage area and MMP-9 area than untreated patients: the percentage of macrophage area was 0.54 (0.31-1.18) vs 1.03 (0.57-2.08; P = .01) and percentage of MMP-9 area was 0.06 (0.02-0.22) vs 0.36 (0.16-0.62; P < .0005). These associations between statin treatment and percentages of macrophage area and MMP-9 area did not change after controlling for symptomatic cerebrovascular disease and the effects of other potential confounders in multivariable analysis. Conclusions: Our results confirm the value of percentage of macrophage area and percentage of MMP-9 area as markers of plaque instability and provide further evidence to support the hypothesis that statins reduce inflammatory responses and thereby stabilize carotid atherosclerotic plaques.