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 atherosclero...
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| Veröffentlicht in: | Journal of vascular surgery 2008-03, Vol.47 (3), p.513-522 |
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| description | 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. |
| doi_str_mv | 10.1016/j.jvs.2007.11.045 |
| format | Article |
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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.</description><identifier>ISSN: 0741-5214</identifier><identifier>EISSN: 1097-6809</identifier><identifier>DOI: 10.1016/j.jvs.2007.11.045</identifier><identifier>PMID: 18295103</identifier><identifier>CODEN: JVSUES</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>Aged ; Anti-Inflammatory Agents - pharmacology ; Anti-Inflammatory Agents - therapeutic use ; Biological and medical sciences ; Biomarkers - analysis ; Carotid Artery, Internal - drug effects ; Carotid Artery, Internal - enzymology ; Carotid Artery, Internal - pathology ; Carotid Artery, Internal - surgery ; Carotid Stenosis - complications ; Carotid Stenosis - drug therapy ; Carotid Stenosis - enzymology ; Carotid Stenosis - pathology ; Carotid Stenosis - surgery ; Cerebrovascular Disorders - enzymology ; Cerebrovascular Disorders - etiology ; Cerebrovascular Disorders - pathology ; Cerebrovascular Disorders - prevention & control ; Endarterectomy, Carotid ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use ; Immunohistochemistry ; Inflammation Mediators - analysis ; Macrophages - drug effects ; Macrophages - pathology ; Male ; Matrix Metalloproteinase 9 - analysis ; Medical sciences ; Middle Aged ; Neurology ; Odds Ratio ; Reproducibility of Results ; Retrospective Studies ; Risk Assessment ; Rupture ; Surgery ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Time Factors ; Vascular diseases and vascular malformations of the nervous system ; Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels</subject><ispartof>Journal of vascular surgery, 2008-03, Vol.47 (3), p.513-522</ispartof><rights>The Society for Vascular Surgery</rights><rights>2008 The Society for Vascular Surgery</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c545t-25f3dc2b9bb2c44949fc8cc3db41904ecd46ebf61c4b0ddae98fc0b9cb319cb43</citedby><cites>FETCH-LOGICAL-c545t-25f3dc2b9bb2c44949fc8cc3db41904ecd46ebf61c4b0ddae98fc0b9cb319cb43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jvs.2007.11.045$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,778,782,3539,27911,27912,45982</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20137056$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18295103$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kunte, Hagen, MD</creatorcontrib><creatorcontrib>Amberger, Nicola, MD</creatorcontrib><creatorcontrib>Busch, Markus Alexander, MD, MPH</creatorcontrib><creatorcontrib>Rückert, Ralph-Ingo, MD, PhD</creatorcontrib><creatorcontrib>Meiners, Silke, PhD</creatorcontrib><creatorcontrib>Harms, Lutz, MD</creatorcontrib><title>Markers of instability in high-risk carotid plaques are reduced by statins</title><title>Journal of vascular surgery</title><addtitle>J Vasc Surg</addtitle><description>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.</description><subject>Aged</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - analysis</subject><subject>Carotid Artery, Internal - drug effects</subject><subject>Carotid Artery, Internal - enzymology</subject><subject>Carotid Artery, Internal - pathology</subject><subject>Carotid Artery, Internal - surgery</subject><subject>Carotid Stenosis - complications</subject><subject>Carotid Stenosis - drug therapy</subject><subject>Carotid Stenosis - enzymology</subject><subject>Carotid Stenosis - pathology</subject><subject>Carotid Stenosis - surgery</subject><subject>Cerebrovascular Disorders - enzymology</subject><subject>Cerebrovascular Disorders - etiology</subject><subject>Cerebrovascular Disorders - pathology</subject><subject>Cerebrovascular Disorders - prevention & control</subject><subject>Endarterectomy, Carotid</subject><subject>Female</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>Immunohistochemistry</subject><subject>Inflammation Mediators - analysis</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - pathology</subject><subject>Male</subject><subject>Matrix Metalloproteinase 9 - analysis</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Odds Ratio</subject><subject>Reproducibility of Results</subject><subject>Retrospective Studies</subject><subject>Risk Assessment</subject><subject>Rupture</subject><subject>Surgery</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Time Factors</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><subject>Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels</subject><issn>0741-5214</issn><issn>1097-6809</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0EotvCD-CCcoFbwoztbGIhIVUVFFARB-Bs-WNCnc0mi51U2n-Po12BxIHLeA7POx49w9gLhAoBt2_6qn9IFQdoKsQKZP2IbRBUU25bUI_ZBhqJZc1RXrDLlHoAxLptnrILbLmqEcSGff5i4o5iKqauCGOajQ1DmI-5L-7Dz_syhrQrnInTHHxxGMyvhVJhIhWR_OLIF_ZY5NScs8_Yk84MiZ6f3yv248P77zcfy7uvt59uru9KV8t6LnndCe-4VdZyJ6WSqnOtc8JbiQokOS-3ZLstOmnBe0Oq7RxY5azAXKS4Yq9Pcw9xWteZ9T4kR8NgRpqWpBsQAgSvM4gn0MUppUidPsSwN_GoEfQqUPc6C9SrQI2os8CceXkevtg9-b-Js7EMvDoDJjkzdNGMLqQ_HAcUDdTbzL09cZRVPASKOrlAY1YWIrlZ-yn8d413_6TdEMaQP9zRkVI_LXHMjjXqxDXob-ul10NDA9gq3ojfJtSjzA</recordid><startdate>20080301</startdate><enddate>20080301</enddate><creator>Kunte, Hagen, MD</creator><creator>Amberger, Nicola, MD</creator><creator>Busch, Markus Alexander, MD, MPH</creator><creator>Rückert, Ralph-Ingo, MD, PhD</creator><creator>Meiners, Silke, PhD</creator><creator>Harms, Lutz, MD</creator><general>Mosby, Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20080301</creationdate><title>Markers of instability in high-risk carotid plaques are reduced by statins</title><author>Kunte, Hagen, MD ; Amberger, Nicola, MD ; Busch, Markus Alexander, MD, MPH ; Rückert, Ralph-Ingo, MD, PhD ; Meiners, Silke, PhD ; Harms, Lutz, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c545t-25f3dc2b9bb2c44949fc8cc3db41904ecd46ebf61c4b0ddae98fc0b9cb319cb43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Aged</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - analysis</topic><topic>Carotid Artery, Internal - drug effects</topic><topic>Carotid Artery, Internal - enzymology</topic><topic>Carotid Artery, Internal - pathology</topic><topic>Carotid Artery, Internal - surgery</topic><topic>Carotid Stenosis - complications</topic><topic>Carotid Stenosis - drug therapy</topic><topic>Carotid Stenosis - enzymology</topic><topic>Carotid Stenosis - pathology</topic><topic>Carotid Stenosis - surgery</topic><topic>Cerebrovascular Disorders - enzymology</topic><topic>Cerebrovascular Disorders - etiology</topic><topic>Cerebrovascular Disorders - pathology</topic><topic>Cerebrovascular Disorders - prevention & control</topic><topic>Endarterectomy, Carotid</topic><topic>Female</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</topic><topic>Immunohistochemistry</topic><topic>Inflammation Mediators - analysis</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - pathology</topic><topic>Male</topic><topic>Matrix Metalloproteinase 9 - analysis</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Odds Ratio</topic><topic>Reproducibility of Results</topic><topic>Retrospective Studies</topic><topic>Risk Assessment</topic><topic>Rupture</topic><topic>Surgery</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Time Factors</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><topic>Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kunte, Hagen, MD</creatorcontrib><creatorcontrib>Amberger, Nicola, MD</creatorcontrib><creatorcontrib>Busch, Markus Alexander, MD, MPH</creatorcontrib><creatorcontrib>Rückert, Ralph-Ingo, MD, PhD</creatorcontrib><creatorcontrib>Meiners, Silke, PhD</creatorcontrib><creatorcontrib>Harms, Lutz, MD</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of vascular surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kunte, Hagen, MD</au><au>Amberger, Nicola, MD</au><au>Busch, Markus Alexander, MD, MPH</au><au>Rückert, Ralph-Ingo, MD, PhD</au><au>Meiners, Silke, PhD</au><au>Harms, Lutz, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Markers of instability in high-risk carotid plaques are reduced by statins</atitle><jtitle>Journal of vascular surgery</jtitle><addtitle>J Vasc Surg</addtitle><date>2008-03-01</date><risdate>2008</risdate><volume>47</volume><issue>3</issue><spage>513</spage><epage>522</epage><pages>513-522</pages><issn>0741-5214</issn><eissn>1097-6809</eissn><coden>JVSUES</coden><abstract>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.</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>18295103</pmid><doi>10.1016/j.jvs.2007.11.045</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Anti-Inflammatory Agents - pharmacology Anti-Inflammatory Agents - therapeutic use Biological and medical sciences Biomarkers - analysis Carotid Artery, Internal - drug effects Carotid Artery, Internal - enzymology Carotid Artery, Internal - pathology Carotid Artery, Internal - surgery Carotid Stenosis - complications Carotid Stenosis - drug therapy Carotid Stenosis - enzymology Carotid Stenosis - pathology Carotid Stenosis - surgery Cerebrovascular Disorders - enzymology Cerebrovascular Disorders - etiology Cerebrovascular Disorders - pathology Cerebrovascular Disorders - prevention & control Endarterectomy, Carotid Female Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Immunohistochemistry Inflammation Mediators - analysis Macrophages - drug effects Macrophages - pathology Male Matrix Metalloproteinase 9 - analysis Medical sciences Middle Aged Neurology Odds Ratio Reproducibility of Results Retrospective Studies Risk Assessment Rupture Surgery Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Time Factors Vascular diseases and vascular malformations of the nervous system Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels |
| title | Markers of instability in high-risk carotid plaques are reduced by statins |
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