Statin Treatment, Carotid Atherosclerotic Plaque Macrophage Infiltration and Circulating Inflammatory Markers

Abstract

Abstract:Backround: Statin treatment is considered as first line therapy in patients with atherosclerotic disease. We evaluated the effect of pre-treatment with statins on carotid plaque infiltration by macrophages and on the circulating levels of proinflammatory cytokines in patients who underwent carotid endarterectomy. Patients and Methods:One hundred fourteen patients were enrolled; 89 men and 25 women (mean age 67±8 years; range 42-83 years). Fifty three patients (46%) were on statin treatment at least 3 months before endarterectomy and 61 (54%) had never received statin treatment. The serum levels of high sensitivity C reactive protein (hsCRP), serum amyloid A (SAA), tumor necrosis factor (TNF ), interleukin (IL)-1 and IL-6 were evaluated preoperatively. The intensity of macrophage infiltration was evaluated by immunochemistry, using the monoclonal antibody CD 68. The area of the plaque covered by macrophages was measured as a proportion of the whole plaque area, using a custom designed image tool analysis.Results: Patients on statins had lower serum total cholesterol levels (172±50 vs 194±35 mg/dl, p= 0.014), lower low density cholesterol levels (103±44 vs 123±31 mg/dl, p= 0.010) and lower serum hsCRP levels (1.8 [1.1-3.4] vs 3.4 [1.3-4.9] mg/l, p= 0.03), while SAA, TNF , IL-6 and IL-1 levels did not differ between the 2 groups. The infiltration of atherosclerotic plaque by macrophages was similar in statin treated patients and in controls (0.55±0.15% vs 0.49±0.19%, p= 0.21). Conclusion:Patients on statins have similar macrophage accumulation in their carotid atherosclerotic plaques compared with patients not on statins. Inflammatory markers were also similar in both groups except for hsCRP which was significantly lower in those taking statins.

Macrophage Infiltration and Smooth Muscle Cells Content Associated With Haptoglobin Genotype in Human Atherosclerotic Carotid Plaques

“…12 Moreover, we have recently shown that patients on statins have similar macrophage accumulation in their carotid atherosclerotic plaques compared with patients not on statins. 32 The high macrophage infiltration in the Hp 2-2 group suggests a potential role of Hp genotype in the evolution of carotid plaque and plaque instability. Proposed pathogenetic mechanisms involve the impaired clearance of Hb-derived iron in Hp 2-2 plaques and the increased oxidative stress.…”

Inflammation of carotid plaques and risk of cerebrovascular events

“…Similarly, also the study of Koutouzis and co-workers found a decrease of the hs-CRP level in patients treated with statins. However, the accumulation of macrophages in carotid plaques was not significantly lower in patients taking statins (51). Intensive lipid-lowering therapy, utilizing statin medication was more effective in the prevention of cardiovascular events in patients after a transient ischemic attack (TIA) and ischemic stroke than a moderate lowering of lipids.…”

Inflammation as a Marker for the Prediction of Internal Carotid Artery Restenosis Following Eversion Endarterectomy—Evidence From Clinical Studies

“…[65][66][67] Statin treatment is considered as first-line therapy in patients with atherosclerotic disease. Koutouzis et al 68 evaluated the effect of pretreatment with statins on carotid plaque infiltration by macrophages and on the circulating levels of proinflammatory cytokines in patients who underwent CEA. They concluded that patients on statins have similar macrophage accumulation in their carotid atherosclerotic plaques compared with patients not on statins.…”

“…Inflammatory markers were also similar in both groups except for hsCRP which was significantly lower in those taking statins. 68 The ability of statin agents to lower hsCRP in a cholesterolindependent manner was first described in the analyses of data from the Cholesterol and Recurrent Events (CARE) trial, 69,70 a randomized evaluation of pravastatin in the secondary prevention of acute coronary events conducted among 4159 patients with a prior history of MI who had LDL-C levels between 115 and 175 mg/dL (2.98 and 4.53 mmol/L). They concluded that relative risk reduction associated with statin therapy was significantly greater in the presence of inflammation and elevated hsCRP than in its absence.…”

“…Inflammatory markers were also similar in both groups except for hsCRP which was significantly lower in those taking statins. 68…”