A Pro-Inflammatory Biomarker-Profile Predicts Amputation-Free Survival in Patients with Severe Limb Ischemia
Patients with Severe Limb Ischemia (SLI) have a high risk of amputation and mortality. Here, we investigated a panel of serum biomarkers with the aim of identifying biomarkers for major events and mechanisms that contribute to disease progression in established SLI. A panel of biomarkers including G...
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| Veröffentlicht in: | Scientific reports 2019-07, Vol.9 (1), p.10740-10, Article 10740 |
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| description | Patients with Severe Limb Ischemia (SLI) have a high risk of amputation and mortality. Here, we investigated a panel of serum biomarkers with the aim of identifying biomarkers for major events and mechanisms that contribute to disease progression in established SLI. A panel of biomarkers including GROα, HGF, SCF, SCGFβ, SDF1α, TRAIL, IL-6, IL-8, FGFβ, GCSF, GMCSF, IP10, MCP1, PDGFbb, RANTES, TNFα, VEGF, sICAM, sVCAM, TM, and E-selectin was measured in serum samples from a subset (n = 108) of the JUVENTAS cohort. The primary outcome was major events, defined as major amputation or death. The inflammatory biomarkers IL-6, IL-8, GROα and IP-10 were significantly elevated in patients who reached a major endpoint. Results were validated in a secondary cohort (n = 146). Cox regression showed that adjusted hazard ratios were 1.40 (95% CI: 1.15–1.70, p = 0.0007) and 1.48 (95% CI 1.16–1.87, p = 0.001) for IL-6 and IP-10 in a fully adjusted model containing both biomarkers. A prediction model using IL-6 and IP-10 showed predictive accuracy with an AUC of ~ 78% in both discovery and validation cohorts, which is higher than previously published models. We conclude that inflammatory biomarkers predict major events in patients with SLI and allow the creation of biomarker-based risk-prediction models. |
| doi_str_mv | 10.1038/s41598-019-47217-1 |
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A. ; Pasterkamp, Gerard ; de Borst, Gert J. ; Verhaar, Marianne C.</creator><creatorcontrib>Gremmels, Hendrik ; Teraa, Martin ; de Jager, Saskia C. A. ; Pasterkamp, Gerard ; de Borst, Gert J. ; Verhaar, Marianne C.</creatorcontrib><description>Patients with Severe Limb Ischemia (SLI) have a high risk of amputation and mortality. Here, we investigated a panel of serum biomarkers with the aim of identifying biomarkers for major events and mechanisms that contribute to disease progression in established SLI. A panel of biomarkers including GROα, HGF, SCF, SCGFβ, SDF1α, TRAIL, IL-6, IL-8, FGFβ, GCSF, GMCSF, IP10, MCP1, PDGFbb, RANTES, TNFα, VEGF, sICAM, sVCAM, TM, and E-selectin was measured in serum samples from a subset (n = 108) of the JUVENTAS cohort. The primary outcome was major events, defined as major amputation or death. The inflammatory biomarkers IL-6, IL-8, GROα and IP-10 were significantly elevated in patients who reached a major endpoint. Results were validated in a secondary cohort (n = 146). Cox regression showed that adjusted hazard ratios were 1.40 (95% CI: 1.15–1.70, p = 0.0007) and 1.48 (95% CI 1.16–1.87, p = 0.001) for IL-6 and IP-10 in a fully adjusted model containing both biomarkers. A prediction model using IL-6 and IP-10 showed predictive accuracy with an AUC of ~ 78% in both discovery and validation cohorts, which is higher than previously published models. We conclude that inflammatory biomarkers predict major events in patients with SLI and allow the creation of biomarker-based risk-prediction models.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-47217-1</identifier><identifier>PMID: 31341203</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/21 ; 692/4019/592/75/593/1920 ; 692/53/2423 ; 82/1 ; Aged ; Amputation ; Amputation - statistics & numerical data ; Biomarkers ; Biomarkers - blood ; Chemokine CXCL1 - blood ; Chemokine CXCL10 - blood ; Chemokines - blood ; Cytokines - blood ; E-selectin ; Extremities - blood supply ; Extremities - surgery ; Female ; Humanities and Social Sciences ; Humans ; Inflammation ; Inflammation - blood ; Interleukin 6 ; Interleukin 8 ; Interleukin-6 - blood ; Interleukin-8 - blood ; IP-10 protein ; Ischemia ; Ischemia - blood ; Ischemia - mortality ; Ischemia - surgery ; Male ; Middle Aged ; multidisciplinary ; Peripheral Arterial Disease - blood ; Peripheral Arterial Disease - complications ; Peripheral Arterial Disease - surgery ; Prediction models ; Predictive Value of Tests ; Proportional Hazards Models ; RANTES ; Science ; Science (multidisciplinary) ; Survival Analysis ; Tumor necrosis factor-α ; Vascular endothelial growth factor</subject><ispartof>Scientific reports, 2019-07, Vol.9 (1), p.10740-10, Article 10740</ispartof><rights>The Author(s) 2019</rights><rights>2019. 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Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c522t-e32129f6e66795130ae01c76908729f1e1f533068ce299ac7e203913aec0db6f3</citedby><cites>FETCH-LOGICAL-c522t-e32129f6e66795130ae01c76908729f1e1f533068ce299ac7e203913aec0db6f3</cites><orcidid>0000-0002-3276-6428 ; 0000-0002-6751-6752 ; 0000-0002-7818-620X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656730/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656730/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31341203$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gremmels, Hendrik</creatorcontrib><creatorcontrib>Teraa, Martin</creatorcontrib><creatorcontrib>de Jager, Saskia C. A.</creatorcontrib><creatorcontrib>Pasterkamp, Gerard</creatorcontrib><creatorcontrib>de Borst, Gert J.</creatorcontrib><creatorcontrib>Verhaar, Marianne C.</creatorcontrib><title>A Pro-Inflammatory Biomarker-Profile Predicts Amputation-Free Survival in Patients with Severe Limb Ischemia</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Patients with Severe Limb Ischemia (SLI) have a high risk of amputation and mortality. Here, we investigated a panel of serum biomarkers with the aim of identifying biomarkers for major events and mechanisms that contribute to disease progression in established SLI. A panel of biomarkers including GROα, HGF, SCF, SCGFβ, SDF1α, TRAIL, IL-6, IL-8, FGFβ, GCSF, GMCSF, IP10, MCP1, PDGFbb, RANTES, TNFα, VEGF, sICAM, sVCAM, TM, and E-selectin was measured in serum samples from a subset (n = 108) of the JUVENTAS cohort. The primary outcome was major events, defined as major amputation or death. The inflammatory biomarkers IL-6, IL-8, GROα and IP-10 were significantly elevated in patients who reached a major endpoint. Results were validated in a secondary cohort (n = 146). Cox regression showed that adjusted hazard ratios were 1.40 (95% CI: 1.15–1.70, p = 0.0007) and 1.48 (95% CI 1.16–1.87, p = 0.001) for IL-6 and IP-10 in a fully adjusted model containing both biomarkers. A prediction model using IL-6 and IP-10 showed predictive accuracy with an AUC of ~ 78% in both discovery and validation cohorts, which is higher than previously published models. We conclude that inflammatory biomarkers predict major events in patients with SLI and allow the creation of biomarker-based risk-prediction models.</description><subject>13/21</subject><subject>692/4019/592/75/593/1920</subject><subject>692/53/2423</subject><subject>82/1</subject><subject>Aged</subject><subject>Amputation</subject><subject>Amputation - statistics & numerical data</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Chemokine CXCL1 - blood</subject><subject>Chemokine CXCL10 - blood</subject><subject>Chemokines - blood</subject><subject>Cytokines - blood</subject><subject>E-selectin</subject><subject>Extremities - blood supply</subject><subject>Extremities - surgery</subject><subject>Female</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - blood</subject><subject>Interleukin 6</subject><subject>Interleukin 8</subject><subject>Interleukin-6 - blood</subject><subject>Interleukin-8 - blood</subject><subject>IP-10 protein</subject><subject>Ischemia</subject><subject>Ischemia - blood</subject><subject>Ischemia - mortality</subject><subject>Ischemia - surgery</subject><subject>Male</subject><subject>Middle Aged</subject><subject>multidisciplinary</subject><subject>Peripheral Arterial Disease - blood</subject><subject>Peripheral Arterial Disease - complications</subject><subject>Peripheral Arterial Disease - surgery</subject><subject>Prediction models</subject><subject>Predictive Value of Tests</subject><subject>Proportional Hazards Models</subject><subject>RANTES</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Survival Analysis</subject><subject>Tumor necrosis factor-α</subject><subject>Vascular endothelial growth factor</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU9v1DAQxSNERavSL8ABWeLCxdQzTpz4grRUFFZaiUqFs-X1TrouSbzYyVb99njZ_j_gi62Zn9_M0yuKdyA-gZDNaSqh0g0XoHlZI9QcXhVHKMqKo0R8_eR9WJykdC3yqVCXoN8UhxJkCSjkUdHN2EUMfD60ne17O4Z4y7740Nv4myLPrdZ3lBFaeTcmNus302hHHwZ-HonY5RS3fms75gd2kes0ZOjGj2t2SVuKxBa-X7J5cmvqvX1bHLS2S3Rydx8Xv86__jz7zhc_vs3PZgvuKsSRk0RA3SpSqtYVSGFJgKuVFk2d60DQVlIK1ThCra2rKVvRIC05sVqqVh4Xn_e6m2nZ08rlraLtzCb67OvWBOvN887g1-YqbI1SlaqlyAIf7wRi-DNRGk3vk6OuswOFKRlEVSKiBMjohxfodZjikO3tKIlNBXWdKdxTLoaUIrUPy4AwuzzNPk-T8zT_8jQ76fdPbTx8uU8vA3IPpNwarig-zv6P7F8RwatO</recordid><startdate>20190724</startdate><enddate>20190724</enddate><creator>Gremmels, Hendrik</creator><creator>Teraa, Martin</creator><creator>de Jager, Saskia C. 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A. ; Pasterkamp, Gerard ; de Borst, Gert J. ; Verhaar, Marianne C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-e32129f6e66795130ae01c76908729f1e1f533068ce299ac7e203913aec0db6f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13/21</topic><topic>692/4019/592/75/593/1920</topic><topic>692/53/2423</topic><topic>82/1</topic><topic>Aged</topic><topic>Amputation</topic><topic>Amputation - statistics & numerical data</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Chemokine CXCL1 - blood</topic><topic>Chemokine CXCL10 - blood</topic><topic>Chemokines - blood</topic><topic>Cytokines - blood</topic><topic>E-selectin</topic><topic>Extremities - blood supply</topic><topic>Extremities - surgery</topic><topic>Female</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammation - blood</topic><topic>Interleukin 6</topic><topic>Interleukin 8</topic><topic>Interleukin-6 - blood</topic><topic>Interleukin-8 - blood</topic><topic>IP-10 protein</topic><topic>Ischemia</topic><topic>Ischemia - blood</topic><topic>Ischemia - mortality</topic><topic>Ischemia - surgery</topic><topic>Male</topic><topic>Middle Aged</topic><topic>multidisciplinary</topic><topic>Peripheral Arterial Disease - blood</topic><topic>Peripheral Arterial Disease - complications</topic><topic>Peripheral Arterial Disease - surgery</topic><topic>Prediction models</topic><topic>Predictive Value of Tests</topic><topic>Proportional Hazards Models</topic><topic>RANTES</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Survival Analysis</topic><topic>Tumor necrosis factor-α</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gremmels, Hendrik</creatorcontrib><creatorcontrib>Teraa, Martin</creatorcontrib><creatorcontrib>de Jager, Saskia C. A.</creatorcontrib><creatorcontrib>Pasterkamp, Gerard</creatorcontrib><creatorcontrib>de Borst, Gert J.</creatorcontrib><creatorcontrib>Verhaar, Marianne C.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gremmels, Hendrik</au><au>Teraa, Martin</au><au>de Jager, Saskia C. A.</au><au>Pasterkamp, Gerard</au><au>de Borst, Gert J.</au><au>Verhaar, Marianne C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Pro-Inflammatory Biomarker-Profile Predicts Amputation-Free Survival in Patients with Severe Limb Ischemia</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-07-24</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>10740</spage><epage>10</epage><pages>10740-10</pages><artnum>10740</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Patients with Severe Limb Ischemia (SLI) have a high risk of amputation and mortality. Here, we investigated a panel of serum biomarkers with the aim of identifying biomarkers for major events and mechanisms that contribute to disease progression in established SLI. A panel of biomarkers including GROα, HGF, SCF, SCGFβ, SDF1α, TRAIL, IL-6, IL-8, FGFβ, GCSF, GMCSF, IP10, MCP1, PDGFbb, RANTES, TNFα, VEGF, sICAM, sVCAM, TM, and E-selectin was measured in serum samples from a subset (n = 108) of the JUVENTAS cohort. The primary outcome was major events, defined as major amputation or death. The inflammatory biomarkers IL-6, IL-8, GROα and IP-10 were significantly elevated in patients who reached a major endpoint. Results were validated in a secondary cohort (n = 146). Cox regression showed that adjusted hazard ratios were 1.40 (95% CI: 1.15–1.70, p = 0.0007) and 1.48 (95% CI 1.16–1.87, p = 0.001) for IL-6 and IP-10 in a fully adjusted model containing both biomarkers. A prediction model using IL-6 and IP-10 showed predictive accuracy with an AUC of ~ 78% in both discovery and validation cohorts, which is higher than previously published models. We conclude that inflammatory biomarkers predict major events in patients with SLI and allow the creation of biomarker-based risk-prediction models.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31341203</pmid><doi>10.1038/s41598-019-47217-1</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-3276-6428</orcidid><orcidid>https://orcid.org/0000-0002-6751-6752</orcidid><orcidid>https://orcid.org/0000-0002-7818-620X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13/21 692/4019/592/75/593/1920 692/53/2423 82/1 Aged Amputation Amputation - statistics & numerical data Biomarkers Biomarkers - blood Chemokine CXCL1 - blood Chemokine CXCL10 - blood Chemokines - blood Cytokines - blood E-selectin Extremities - blood supply Extremities - surgery Female Humanities and Social Sciences Humans Inflammation Inflammation - blood Interleukin 6 Interleukin 8 Interleukin-6 - blood Interleukin-8 - blood IP-10 protein Ischemia Ischemia - blood Ischemia - mortality Ischemia - surgery Male Middle Aged multidisciplinary Peripheral Arterial Disease - blood Peripheral Arterial Disease - complications Peripheral Arterial Disease - surgery Prediction models Predictive Value of Tests Proportional Hazards Models RANTES Science Science (multidisciplinary) Survival Analysis Tumor necrosis factor-α Vascular endothelial growth factor |
| title | A Pro-Inflammatory Biomarker-Profile Predicts Amputation-Free Survival in Patients with Severe Limb Ischemia |
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