Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events?
Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to no...
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| Veröffentlicht in: | PLoS medicine 2009-06, Vol.6 (6), p.e1000099-e1000099 |
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| creator | Sattar, Naveed Murray, Heather M Welsh, Paul Blauw, Gerard J Buckley, Brendan M Cobbe, Stuart de Craen, Anton J M Lowe, Gordon D Jukema, J Wouter Macfarlane, Peter W Murphy, Michael B Stott, David J Westendorp, Rudi G J Shepherd, James Ford, Ian Packard, Chris J |
| description | Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI) and stroke.
In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70-82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44-2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04-1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p |
| doi_str_mv | 10.1371/journal.pmed.1000099 |
| format | Article |
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In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70-82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44-2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04-1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p<0.0001) improved by inclusion of IL-6 but not so for nonfatal CVD events (p = 0.20).
In PROSPER, inflammatory markers, in particular IL-6 and CRP, are more strongly associated with risk of fatal vascular events than nonfatal vascular events. These novel observations may have important implications for better understanding aetiology of CVD mortality, and have potential clinical relevance.</description><identifier>ISSN: 1549-1676</identifier><identifier>ISSN: 1549-1277</identifier><identifier>EISSN: 1549-1676</identifier><identifier>DOI: 10.1371/journal.pmed.1000099</identifier><identifier>PMID: 19554082</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Aged, 80 and over ; Anticholesteremic Agents - therapeutic use ; Biomarkers - blood ; C-Reactive Protein - metabolism ; Cardiovascular Disorders/Myocardial Infarction ; Cardiovascular Disorders/Vascular Biology ; Female ; Fibrinogen - metabolism ; Humans ; Inflammation - complications ; Inflammation - mortality ; Interleukin-6 - blood ; Kaplan-Meier Estimate ; Male ; Myocardial Infarction - etiology ; Myocardial Infarction - mortality ; Pravastatin - therapeutic use ; Public Health and Epidemiology/Epidemiology ; Risk Factors ; Stroke - etiology ; Stroke - mortality</subject><ispartof>PLoS medicine, 2009-06, Vol.6 (6), p.e1000099-e1000099</ispartof><rights>Sattar et al. 2009</rights><rights>2009 Sattar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Sattar N, Murray HM, Welsh P, Blauw GJ, Buckley BM, et al. (2009) Are Markers of Inflammation More Strongly Associated with Risk for Fatal Than for Nonfatal Vascular Events? PLoS Med 6(6): e1000099. doi:10.1371/journal.pmed.1000099</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-101e4fa69cafdd71e9d2de5484b9fcc3d71a2a65600202d44707088f00264cb23</citedby><cites>FETCH-LOGICAL-c496t-101e4fa69cafdd71e9d2de5484b9fcc3d71a2a65600202d44707088f00264cb23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694359/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694359/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19554082$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sattar, Naveed</creatorcontrib><creatorcontrib>Murray, Heather M</creatorcontrib><creatorcontrib>Welsh, Paul</creatorcontrib><creatorcontrib>Blauw, Gerard J</creatorcontrib><creatorcontrib>Buckley, Brendan M</creatorcontrib><creatorcontrib>Cobbe, Stuart</creatorcontrib><creatorcontrib>de Craen, Anton J M</creatorcontrib><creatorcontrib>Lowe, Gordon D</creatorcontrib><creatorcontrib>Jukema, J Wouter</creatorcontrib><creatorcontrib>Macfarlane, Peter W</creatorcontrib><creatorcontrib>Murphy, Michael B</creatorcontrib><creatorcontrib>Stott, David J</creatorcontrib><creatorcontrib>Westendorp, Rudi G J</creatorcontrib><creatorcontrib>Shepherd, James</creatorcontrib><creatorcontrib>Ford, Ian</creatorcontrib><creatorcontrib>Packard, Chris J</creatorcontrib><creatorcontrib>Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) Study Group</creatorcontrib><creatorcontrib>for the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) Study Group</creatorcontrib><title>Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events?</title><title>PLoS medicine</title><addtitle>PLoS Med</addtitle><description>Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI) and stroke.
In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70-82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44-2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04-1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p<0.0001) improved by inclusion of IL-6 but not so for nonfatal CVD events (p = 0.20).
In PROSPER, inflammatory markers, in particular IL-6 and CRP, are more strongly associated with risk of fatal vascular events than nonfatal vascular events. These novel observations may have important implications for better understanding aetiology of CVD mortality, and have potential clinical relevance.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Anticholesteremic Agents - therapeutic use</subject><subject>Biomarkers - blood</subject><subject>C-Reactive Protein - metabolism</subject><subject>Cardiovascular Disorders/Myocardial Infarction</subject><subject>Cardiovascular Disorders/Vascular Biology</subject><subject>Female</subject><subject>Fibrinogen - metabolism</subject><subject>Humans</subject><subject>Inflammation - complications</subject><subject>Inflammation - mortality</subject><subject>Interleukin-6 - blood</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Myocardial Infarction - etiology</subject><subject>Myocardial Infarction - mortality</subject><subject>Pravastatin - therapeutic use</subject><subject>Public Health and Epidemiology/Epidemiology</subject><subject>Risk Factors</subject><subject>Stroke - etiology</subject><subject>Stroke - mortality</subject><issn>1549-1676</issn><issn>1549-1277</issn><issn>1549-1676</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNpVUsluFDEQbSEQCYE_QOATtxm8tbt9AUURS6RIXOBsVXuZ8YzbHuzuifL3OJkGEl_sqnr1avFrmrcErwnryMddmnOEsD6M1qwJrkfKZ805ablcEdGJ54_eZ82rUnYYU4klftmcEdm2HPf0vNlfZotGyHubC0oO-egCjCNMPkU0phosU05xE-4QlJK0h8kadOunLcq-7JFLGTmYIKBpC_HBjCmePEcoeg6QkT3aOJXPr5sXDkKxb5b7ovn19cvPq--rmx_frq8ub1aaSzGtCCaWOxBSgzOmI1YaamzLez5IpzWrLqAgWlHnwdRw3uEO972rpuB6oOyieX_iPYRU1LKnogjt-4rrcFsR1yeESbBTh-zrBu5UAq8eHClvFOTJ62AVNh1jA6GMCcoJa3siBTNmMIK0lnNXuT4t1eahfoWuo2YIT0ifRqLfqk06KiokZ62sBB8Wgpx-z7ZMavRF2xAg2jQXJTpOBKakAvkJqHMqJVv3rwjB6l4Tf2dV95pQiyZq2rvHDf5PWkTA_gDypbav</recordid><startdate>20090623</startdate><enddate>20090623</enddate><creator>Sattar, Naveed</creator><creator>Murray, Heather M</creator><creator>Welsh, Paul</creator><creator>Blauw, Gerard J</creator><creator>Buckley, Brendan M</creator><creator>Cobbe, Stuart</creator><creator>de Craen, Anton J M</creator><creator>Lowe, Gordon D</creator><creator>Jukema, J Wouter</creator><creator>Macfarlane, Peter W</creator><creator>Murphy, Michael B</creator><creator>Stott, David J</creator><creator>Westendorp, Rudi G J</creator><creator>Shepherd, James</creator><creator>Ford, Ian</creator><creator>Packard, Chris J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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><scope>5PM</scope><scope>DOA</scope><scope>CZK</scope></search><sort><creationdate>20090623</creationdate><title>Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events?</title><author>Sattar, Naveed ; Murray, Heather M ; Welsh, Paul ; Blauw, Gerard J ; Buckley, Brendan M ; Cobbe, Stuart ; de Craen, Anton J M ; Lowe, Gordon D ; Jukema, J Wouter ; Macfarlane, Peter W ; Murphy, Michael B ; Stott, David J ; Westendorp, Rudi G J ; Shepherd, James ; Ford, Ian ; Packard, Chris J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c496t-101e4fa69cafdd71e9d2de5484b9fcc3d71a2a65600202d44707088f00264cb23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Anticholesteremic Agents - therapeutic use</topic><topic>Biomarkers - blood</topic><topic>C-Reactive Protein - metabolism</topic><topic>Cardiovascular Disorders/Myocardial Infarction</topic><topic>Cardiovascular Disorders/Vascular Biology</topic><topic>Female</topic><topic>Fibrinogen - metabolism</topic><topic>Humans</topic><topic>Inflammation - complications</topic><topic>Inflammation - mortality</topic><topic>Interleukin-6 - blood</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Myocardial Infarction - etiology</topic><topic>Myocardial Infarction - mortality</topic><topic>Pravastatin - therapeutic use</topic><topic>Public Health and Epidemiology/Epidemiology</topic><topic>Risk Factors</topic><topic>Stroke - etiology</topic><topic>Stroke - mortality</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sattar, Naveed</creatorcontrib><creatorcontrib>Murray, Heather M</creatorcontrib><creatorcontrib>Welsh, Paul</creatorcontrib><creatorcontrib>Blauw, Gerard J</creatorcontrib><creatorcontrib>Buckley, Brendan M</creatorcontrib><creatorcontrib>Cobbe, Stuart</creatorcontrib><creatorcontrib>de Craen, Anton J M</creatorcontrib><creatorcontrib>Lowe, Gordon D</creatorcontrib><creatorcontrib>Jukema, J Wouter</creatorcontrib><creatorcontrib>Macfarlane, Peter W</creatorcontrib><creatorcontrib>Murphy, Michael B</creatorcontrib><creatorcontrib>Stott, David J</creatorcontrib><creatorcontrib>Westendorp, Rudi G J</creatorcontrib><creatorcontrib>Shepherd, James</creatorcontrib><creatorcontrib>Ford, Ian</creatorcontrib><creatorcontrib>Packard, Chris J</creatorcontrib><creatorcontrib>Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) Study Group</creatorcontrib><creatorcontrib>for the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) Study Group</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Medicine</collection><jtitle>PLoS medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sattar, Naveed</au><au>Murray, Heather M</au><au>Welsh, Paul</au><au>Blauw, Gerard J</au><au>Buckley, Brendan M</au><au>Cobbe, Stuart</au><au>de Craen, Anton J M</au><au>Lowe, Gordon D</au><au>Jukema, J Wouter</au><au>Macfarlane, Peter W</au><au>Murphy, Michael B</au><au>Stott, David J</au><au>Westendorp, Rudi G J</au><au>Shepherd, James</au><au>Ford, Ian</au><au>Packard, Chris J</au><aucorp>Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) Study Group</aucorp><aucorp>for the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events?</atitle><jtitle>PLoS medicine</jtitle><addtitle>PLoS Med</addtitle><date>2009-06-23</date><risdate>2009</risdate><volume>6</volume><issue>6</issue><spage>e1000099</spage><epage>e1000099</epage><pages>e1000099-e1000099</pages><issn>1549-1676</issn><issn>1549-1277</issn><eissn>1549-1676</eissn><abstract>Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI) and stroke.
In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70-82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44-2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04-1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p<0.0001) improved by inclusion of IL-6 but not so for nonfatal CVD events (p = 0.20).
In PROSPER, inflammatory markers, in particular IL-6 and CRP, are more strongly associated with risk of fatal vascular events than nonfatal vascular events. These novel observations may have important implications for better understanding aetiology of CVD mortality, and have potential clinical relevance.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19554082</pmid><doi>10.1371/journal.pmed.1000099</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Aged, 80 and over Anticholesteremic Agents - therapeutic use Biomarkers - blood C-Reactive Protein - metabolism Cardiovascular Disorders/Myocardial Infarction Cardiovascular Disorders/Vascular Biology Female Fibrinogen - metabolism Humans Inflammation - complications Inflammation - mortality Interleukin-6 - blood Kaplan-Meier Estimate Male Myocardial Infarction - etiology Myocardial Infarction - mortality Pravastatin - therapeutic use Public Health and Epidemiology/Epidemiology Risk Factors Stroke - etiology Stroke - mortality |
| title | Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events? |
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