Macrophages are associated with lipid-rich carotid artery plaques, echolucency on B-mode imaging, and elevated plasma lipid levels.

OBJECTIVE Atherosclerosis may be regarded as an inflammatory disease dominated by macrophages. We tested whether macrophages in carotid artery atherosclerotic plaques are associated with echolucency on B-mode ultrasound imaging, lipid levels, inflammatory markers, and aspirin use. METHODS We studied 106 patients undergoing carotid endarterectomy having >/=50% carotid artery stenosis and previous ipsilateral hemispheric neurologic symptoms. RESULTS Macrophages were particularly common in plaques with a high content of lipid and hemorrhage and, conversely, rare in plaques dominated by calcification and fibrous tissue. Macrophage density in carotid artery plaques classified by B-mode ultrasound imaging as echolucent (n = 56), intermediate (n = 25), or echorich (n = 25) was 1.8% +/- 0.2%, 1.5% +/- 0.4%, and 1.0% +/- 0.2% (+/-SE), respectively (analysis of variance, P =.02). A computer-generated measure of plaque echolucency, gray-scale median, was associated with increased macrophage density (r = -0.31; P =.002). Furthermore, plasma and low-density lipoprotein cholesterol levels were associated with carotid artery macrophage density (r = 0.26, P =.008 and r = 0.23, P =.02); this was most pronounced in patients with lipid-rich plaques. Macrophage density was not associated with plasma levels of acute-phase reactants. Finally, macrophage density in carotid artery plaques of users (n = 55) and nonusers of aspirin (n = 51) was 1.2% +/- 0.2% and 1.8% +/- 0.2% (t test, P =.01). CONCLUSIONS Increased macrophage density in carotid atherosclerotic plaques was associated with lipid content, plaque echolucency, and increased plasma and low-density lipoprotein cholesterol levels. Furthermore, use of aspirin was associated with reduced macrophage density in carotid artery plaques.

[1]  Torben V. Schroeder,et al.  Ultrasonic Echolucent Carotid Plaques Predict Future Strokes , 2001, Circulation.

[2]  R. Virmani,et al.  Hyperfibrinogenemia is associated with specific histocytological composition and complications of atherosclerotic carotid plaques in patients affected by transient ischemic attacks. , 2000, Circulation.

[3]  A. Becker,et al.  Atherosclerosis, inflammation, and infection , 2000, The Journal of pathology.

[4]  P. Nihoyannopoulos,et al.  Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. , 1999, Circulation.

[5]  M. Pfeffer,et al.  Long-Term Effects of Pravastatin on Plasma Concentration of C-reactive Protein , 1999 .

[6]  C. Visser,et al.  C-reactive protein as a cardiovascular risk factor: more than an epiphenomenon? , 1999, Circulation.

[7]  R. Ross,et al.  Atherosclerosis is an inflammatory disease. , 1998, American heart journal.

[8]  M. Grønholdt,et al.  Ultrasound and lipoproteins as predictors of lipid-rich, rupture-prone plaques in the carotid artery. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[9]  J. Parodi,et al.  Carotid rupture and intraplaque hemorrhage: immunophenotype and role of cells involved. , 1998, American heart journal.

[10]  F M van den Berg,et al.  Distribution of inflammatory cells in atherosclerotic plaques relates to the direction of flow. , 1998, Circulation.

[11]  W. Brant,et al.  Hypoechoic plaque at US of the carotid artery: an independent risk factor for incident stroke in adults aged 65 years or older. Cardiovascular Health Study. , 1998, Radiology.

[12]  B Hillen,et al.  Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox. , 1998, Journal of the American College of Cardiology.

[13]  H. Steinmetz,et al.  Inflammation in high-grade carotid stenosis: a possible role for macrophages and T cells in plaque destabilization. , 1998, Stroke.

[14]  P. Libby,et al.  Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization. , 1998, Circulation.

[15]  R. Virmani,et al.  Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women. , 1998, Circulation.

[16]  R. Rosenson,et al.  Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. , 1998, JAMA.

[17]  R Peto,et al.  Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. , 1998, JAMA.

[18]  J. Wilhjelm,et al.  Echo-lucency of computerized ultrasound images of carotid atherosclerotic plaques are associated with increased levels of triglyceride-rich lipoproteins as well as increased plaque lipid content. , 1998, Circulation.

[19]  W. Erl,et al.  HMG-CoA reductase inhibitors decrease CD11b expression and CD11b-dependent adhesion of monocytes to endothelium and reduce increased adhesiveness of monocytes isolated from patients with hypercholesterolemia. , 1997, Journal of the American College of Cardiology.

[20]  R. Virmani,et al.  Activated inflammatory cells are associated with plaque rupture in carotid artery stenosis. , 1997, Surgery.

[21]  S. Glagov,et al.  Juxtalumenal location of plaque necrosis and neoformation in symptomatic carotid stenosis. , 1997, Journal of vascular surgery.

[22]  P. Ridker,et al.  Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. , 1997, The New England journal of medicine.

[23]  K. Schrör.  Aspirin and Platelets: The Antiplatelet Action of Aspirin and Its Role in Thrombosis Treatment and Prophylaxis , 1997, Seminars in thrombosis and hemostasis.

[24]  R. Virmani,et al.  Atherosclerotic plaque rupture in symptomatic carotid artery stenosis. , 1996, Journal of vascular surgery.

[25]  C. Serhan,et al.  Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[26]  T. Paavonen,et al.  Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction. , 1995, Circulation.

[27]  V. Fuster,et al.  Coronary plaque disruption. , 1995, Circulation.

[28]  W. Erl,et al.  Aspirin inhibits nuclear factor-kappa B mobilization and monocyte adhesion in stimulated human endothelial cells. , 1995, Circulation.

[29]  H. Hecker,et al.  Dose‐Dependent Effect of Aspirin on Carotid Atherosclerosis , 1993, Circulation.

[30]  V. Fuster,et al.  The pathogenesis of coronary artery disease and the acute coronary syndromes (2). , 1992, The New England journal of medicine.

[31]  C. Page.  Platelets as inflammatory cells. , 1989, Immunopharmacology.

[32]  G. Davı̀,et al.  Clinical pharmacology of platelet cyclooxygenase inhibition. , 1985, Circulation.

[33]  R. Lusby,et al.  Carotid plaque hemorrhage. Its role in production of cerebral ischemia. , 1982, Archives of surgery.

[34]  P. Huijgens,et al.  ASPIRIN AND PLATELETS , 1980, The Lancet.

[35]  Bridget Wilcken,et al.  Pathogenesis of coronary artery disease , 1969 .