Serum YKL-40 predicts long-term mortality in patients with stable coronary disease: A prognostic study within the CLARICOR trial

Abstract Objective We investigated whether the inflammatory biomarker YKL-40 could improve the long-term prediction of death made by common risk factors plus high-sensitivity C-reactive protein (hs-CRP) and N-terminal-pro-B natriuretic peptide (NT-proBNP) in patients with stable coronary artery dise...

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Veröffentlicht in:Immunobiology (1979) 2013-07, Vol.218 (7), p.945-951
Hauptverfasser: Harutyunyan, Marina, Gøtze, Jens P, Winkel, Per, Johansen, Julia S, Hansen, Jørgen Fischer, Jensen, Gorm Boje, Hilden, Jørgen, Kjøller, Erik, Kolmos, Hans J, Gluud, Christian, Kastrup, Jens
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container_end_page 951
container_issue 7
container_start_page 945
container_title Immunobiology (1979)
container_volume 218
creator Harutyunyan, Marina
Gøtze, Jens P
Winkel, Per
Johansen, Julia S
Hansen, Jørgen Fischer
Jensen, Gorm Boje
Hilden, Jørgen
Kjøller, Erik
Kolmos, Hans J
Gluud, Christian
Kastrup, Jens
description Abstract Objective We investigated whether the inflammatory biomarker YKL-40 could improve the long-term prediction of death made by common risk factors plus high-sensitivity C-reactive protein (hs-CRP) and N-terminal-pro-B natriuretic peptide (NT-proBNP) in patients with stable coronary artery disease (CAD). Background Non-hospitalized CAD patients are usually followed in general practice. There is a need for identify biomarkers which could help to foresee the prognoses of these patients. Elevated serum YKL-40 is a short-term predictor for myocardial infarction, cardiovascular mortality and all-cause mortality in patients with stable CAD. Methods Serum YKL-40, hs-CRP, and NT-proBNP were measured in 4265 (97.6%) of the 4372 patients with stable CAD included in the CLARICOR trial, and death was registered in a 6-years follow-up period. Results The median serum YKL-40 was 110 μg/L [IQR = 93], hs-CRP 2.8 mg/L [IQR = 4.74], and NT-proBNP 203 ng/L [IQR = 407]. During 6 years follow-up period 923 (21.1%) patients died. After adjustment for type of intervention, risk factors (age, sex, hypertension, diabetes, smoking status, and previous myocardial infarction) and medical treatment (diuretics, digoxin, and statin) serum YKL-40 (transformed as ln(max(82, YKL-40/μg/L)) was significantly associated with all-cause mortality [hazard ratio (HR) = 1.55, 95% CI = 1.39–1.73, p < 0.001]. After additional adjustment for ln(hs-CRP) and ln(NT-proBNP) this was still true [HR = 1.38, 95% CI = 1.21–1.53, p < 0.001]. Conclusions Serum YKL-40 is a predictor of long-term mortality in patients with stable CAD independent of common risk factors and ln(hs-CRP) and ln(NT-proBNP). Serum YKL-40 can be used for prognostication in these patients.
doi_str_mv 10.1016/j.imbio.2012.10.015
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Background Non-hospitalized CAD patients are usually followed in general practice. There is a need for identify biomarkers which could help to foresee the prognoses of these patients. Elevated serum YKL-40 is a short-term predictor for myocardial infarction, cardiovascular mortality and all-cause mortality in patients with stable CAD. Methods Serum YKL-40, hs-CRP, and NT-proBNP were measured in 4265 (97.6%) of the 4372 patients with stable CAD included in the CLARICOR trial, and death was registered in a 6-years follow-up period. Results The median serum YKL-40 was 110 μg/L [IQR = 93], hs-CRP 2.8 mg/L [IQR = 4.74], and NT-proBNP 203 ng/L [IQR = 407]. During 6 years follow-up period 923 (21.1%) patients died. After adjustment for type of intervention, risk factors (age, sex, hypertension, diabetes, smoking status, and previous myocardial infarction) and medical treatment (diuretics, digoxin, and statin) serum YKL-40 (transformed as ln(max(82, YKL-40/μg/L)) was significantly associated with all-cause mortality [hazard ratio (HR) = 1.55, 95% CI = 1.39–1.73, p &lt; 0.001]. After additional adjustment for ln(hs-CRP) and ln(NT-proBNP) this was still true [HR = 1.38, 95% CI = 1.21–1.53, p &lt; 0.001]. Conclusions Serum YKL-40 is a predictor of long-term mortality in patients with stable CAD independent of common risk factors and ln(hs-CRP) and ln(NT-proBNP). Serum YKL-40 can be used for prognostication in these patients.</description><identifier>ISSN: 0171-2985</identifier><identifier>EISSN: 1878-3279</identifier><identifier>DOI: 10.1016/j.imbio.2012.10.015</identifier><identifier>PMID: 23294528</identifier><language>eng</language><publisher>Netherlands: Elsevier GmbH</publisher><subject>Adipokines - blood ; Advanced Basic Science ; Aged ; Allergy and Immunology ; Biomarker ; Biomarkers - blood ; C-Reactive Protein - metabolism ; Cardiotonic Agents - therapeutic use ; Case-Control Studies ; Chitinase-3-Like Protein 1 ; Coronary artery disease ; Coronary Artery Disease - blood ; Coronary Artery Disease - diagnosis ; Coronary Artery Disease - drug therapy ; Coronary Artery Disease - mortality ; Female ; Follow-Up Studies ; hs-CRP ; Humans ; Inflammation ; Lectins - blood ; Male ; Middle Aged ; Mortality ; Natriuretic Peptide, Brain - blood ; NT-proBNP ; Peptide Fragments - blood ; Predictive Value of Tests ; Prognosis ; Risk Factors ; Survival Analysis ; YKL-40</subject><ispartof>Immunobiology (1979), 2013-07, Vol.218 (7), p.945-951</ispartof><rights>Elsevier GmbH</rights><rights>2012 Elsevier GmbH</rights><rights>Copyright © 2012 Elsevier GmbH. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c447t-d62364f68387b514baf768886d77507bb82c2752f4ec977cd1c9ea21a52f18513</citedby><cites>FETCH-LOGICAL-c447t-d62364f68387b514baf768886d77507bb82c2752f4ec977cd1c9ea21a52f18513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.imbio.2012.10.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23294528$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Harutyunyan, Marina</creatorcontrib><creatorcontrib>Gøtze, Jens P</creatorcontrib><creatorcontrib>Winkel, Per</creatorcontrib><creatorcontrib>Johansen, Julia S</creatorcontrib><creatorcontrib>Hansen, Jørgen Fischer</creatorcontrib><creatorcontrib>Jensen, Gorm Boje</creatorcontrib><creatorcontrib>Hilden, Jørgen</creatorcontrib><creatorcontrib>Kjøller, Erik</creatorcontrib><creatorcontrib>Kolmos, Hans J</creatorcontrib><creatorcontrib>Gluud, Christian</creatorcontrib><creatorcontrib>Kastrup, Jens</creatorcontrib><title>Serum YKL-40 predicts long-term mortality in patients with stable coronary disease: A prognostic study within the CLARICOR trial</title><title>Immunobiology (1979)</title><addtitle>Immunobiology</addtitle><description>Abstract Objective We investigated whether the inflammatory biomarker YKL-40 could improve the long-term prediction of death made by common risk factors plus high-sensitivity C-reactive protein (hs-CRP) and N-terminal-pro-B natriuretic peptide (NT-proBNP) in patients with stable coronary artery disease (CAD). Background Non-hospitalized CAD patients are usually followed in general practice. There is a need for identify biomarkers which could help to foresee the prognoses of these patients. Elevated serum YKL-40 is a short-term predictor for myocardial infarction, cardiovascular mortality and all-cause mortality in patients with stable CAD. Methods Serum YKL-40, hs-CRP, and NT-proBNP were measured in 4265 (97.6%) of the 4372 patients with stable CAD included in the CLARICOR trial, and death was registered in a 6-years follow-up period. Results The median serum YKL-40 was 110 μg/L [IQR = 93], hs-CRP 2.8 mg/L [IQR = 4.74], and NT-proBNP 203 ng/L [IQR = 407]. During 6 years follow-up period 923 (21.1%) patients died. After adjustment for type of intervention, risk factors (age, sex, hypertension, diabetes, smoking status, and previous myocardial infarction) and medical treatment (diuretics, digoxin, and statin) serum YKL-40 (transformed as ln(max(82, YKL-40/μg/L)) was significantly associated with all-cause mortality [hazard ratio (HR) = 1.55, 95% CI = 1.39–1.73, p &lt; 0.001]. After additional adjustment for ln(hs-CRP) and ln(NT-proBNP) this was still true [HR = 1.38, 95% CI = 1.21–1.53, p &lt; 0.001]. Conclusions Serum YKL-40 is a predictor of long-term mortality in patients with stable CAD independent of common risk factors and ln(hs-CRP) and ln(NT-proBNP). Serum YKL-40 can be used for prognostication in these patients.</description><subject>Adipokines - blood</subject><subject>Advanced Basic Science</subject><subject>Aged</subject><subject>Allergy and Immunology</subject><subject>Biomarker</subject><subject>Biomarkers - blood</subject><subject>C-Reactive Protein - metabolism</subject><subject>Cardiotonic Agents - therapeutic use</subject><subject>Case-Control Studies</subject><subject>Chitinase-3-Like Protein 1</subject><subject>Coronary artery disease</subject><subject>Coronary Artery Disease - blood</subject><subject>Coronary Artery Disease - diagnosis</subject><subject>Coronary Artery Disease - drug therapy</subject><subject>Coronary Artery Disease - mortality</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>hs-CRP</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Lectins - blood</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Natriuretic Peptide, Brain - blood</subject><subject>NT-proBNP</subject><subject>Peptide Fragments - blood</subject><subject>Predictive Value of Tests</subject><subject>Prognosis</subject><subject>Risk Factors</subject><subject>Survival Analysis</subject><subject>YKL-40</subject><issn>0171-2985</issn><issn>1878-3279</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUk1v1DAUtBCILoVfgIR85JLFH3FsI4G0WkGpWKlSCwdOluO8bb0k8dZ2QHvjp9fpFg5cerI0npn3NPMQek3JkhLavNst_dD6sGSEsoIsCRVP0IIqqSrOpH6KFoRKWjGtxAl6kdKOEKqZVM_RCeNM14KpBfpzBXEa8I-vm6omeB-h8y4n3IfxusoQBzyEmG3v8wH7Ee9t9jCW_98-3-CUbdsDdiGG0cYD7nwCm-A9XhWjcD2GlL0rrKk73AuKQb4BvN6sLs_XF5c4R2_7l-jZ1vYJXj28p-j750_f1l-qzcXZ-Xq1qVxdy1x1DeNNvW0UV7IVtG7tVjZKqaaTUhDZtoo5JgXb1uC0lK6jToNl1BaIKkH5KXp79C2r3U6Qshl8ctD3doQwJUMFIVJTycTjVF5rrrWoeaHyI9XFkFKErdlHP5QwDCVmbsnszH1LZm5pBktLRfXmYcDUDtD90_ytpRA-HAlQEvnlIZrkSvCutBPBZdMF_8iAj__pXe9H72z_Ew6QdmGKYwnbUJOYIeZqPpT5TigjRDDR8DsvNLhk</recordid><startdate>20130701</startdate><enddate>20130701</enddate><creator>Harutyunyan, Marina</creator><creator>Gøtze, Jens P</creator><creator>Winkel, Per</creator><creator>Johansen, Julia S</creator><creator>Hansen, Jørgen Fischer</creator><creator>Jensen, Gorm Boje</creator><creator>Hilden, Jørgen</creator><creator>Kjøller, Erik</creator><creator>Kolmos, Hans J</creator><creator>Gluud, Christian</creator><creator>Kastrup, Jens</creator><general>Elsevier GmbH</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>7T5</scope><scope>H94</scope></search><sort><creationdate>20130701</creationdate><title>Serum YKL-40 predicts long-term mortality in patients with stable coronary disease: A prognostic study within the CLARICOR trial</title><author>Harutyunyan, Marina ; Gøtze, Jens P ; Winkel, Per ; Johansen, Julia S ; Hansen, Jørgen Fischer ; Jensen, Gorm Boje ; Hilden, Jørgen ; Kjøller, Erik ; Kolmos, Hans J ; Gluud, Christian ; Kastrup, Jens</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c447t-d62364f68387b514baf768886d77507bb82c2752f4ec977cd1c9ea21a52f18513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adipokines - blood</topic><topic>Advanced Basic Science</topic><topic>Aged</topic><topic>Allergy and Immunology</topic><topic>Biomarker</topic><topic>Biomarkers - blood</topic><topic>C-Reactive Protein - metabolism</topic><topic>Cardiotonic Agents - therapeutic use</topic><topic>Case-Control Studies</topic><topic>Chitinase-3-Like Protein 1</topic><topic>Coronary artery disease</topic><topic>Coronary Artery Disease - blood</topic><topic>Coronary Artery Disease - diagnosis</topic><topic>Coronary Artery Disease - drug therapy</topic><topic>Coronary Artery Disease - mortality</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>hs-CRP</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Lectins - blood</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Natriuretic Peptide, Brain - blood</topic><topic>NT-proBNP</topic><topic>Peptide Fragments - blood</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Risk Factors</topic><topic>Survival Analysis</topic><topic>YKL-40</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Harutyunyan, Marina</creatorcontrib><creatorcontrib>Gøtze, Jens P</creatorcontrib><creatorcontrib>Winkel, Per</creatorcontrib><creatorcontrib>Johansen, Julia S</creatorcontrib><creatorcontrib>Hansen, Jørgen Fischer</creatorcontrib><creatorcontrib>Jensen, Gorm Boje</creatorcontrib><creatorcontrib>Hilden, Jørgen</creatorcontrib><creatorcontrib>Kjøller, Erik</creatorcontrib><creatorcontrib>Kolmos, Hans J</creatorcontrib><creatorcontrib>Gluud, Christian</creatorcontrib><creatorcontrib>Kastrup, Jens</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Immunobiology (1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Harutyunyan, Marina</au><au>Gøtze, Jens P</au><au>Winkel, Per</au><au>Johansen, Julia S</au><au>Hansen, Jørgen Fischer</au><au>Jensen, Gorm Boje</au><au>Hilden, Jørgen</au><au>Kjøller, Erik</au><au>Kolmos, Hans J</au><au>Gluud, Christian</au><au>Kastrup, Jens</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum YKL-40 predicts long-term mortality in patients with stable coronary disease: A prognostic study within the CLARICOR trial</atitle><jtitle>Immunobiology (1979)</jtitle><addtitle>Immunobiology</addtitle><date>2013-07-01</date><risdate>2013</risdate><volume>218</volume><issue>7</issue><spage>945</spage><epage>951</epage><pages>945-951</pages><issn>0171-2985</issn><eissn>1878-3279</eissn><abstract>Abstract Objective We investigated whether the inflammatory biomarker YKL-40 could improve the long-term prediction of death made by common risk factors plus high-sensitivity C-reactive protein (hs-CRP) and N-terminal-pro-B natriuretic peptide (NT-proBNP) in patients with stable coronary artery disease (CAD). Background Non-hospitalized CAD patients are usually followed in general practice. There is a need for identify biomarkers which could help to foresee the prognoses of these patients. Elevated serum YKL-40 is a short-term predictor for myocardial infarction, cardiovascular mortality and all-cause mortality in patients with stable CAD. Methods Serum YKL-40, hs-CRP, and NT-proBNP were measured in 4265 (97.6%) of the 4372 patients with stable CAD included in the CLARICOR trial, and death was registered in a 6-years follow-up period. Results The median serum YKL-40 was 110 μg/L [IQR = 93], hs-CRP 2.8 mg/L [IQR = 4.74], and NT-proBNP 203 ng/L [IQR = 407]. During 6 years follow-up period 923 (21.1%) patients died. After adjustment for type of intervention, risk factors (age, sex, hypertension, diabetes, smoking status, and previous myocardial infarction) and medical treatment (diuretics, digoxin, and statin) serum YKL-40 (transformed as ln(max(82, YKL-40/μg/L)) was significantly associated with all-cause mortality [hazard ratio (HR) = 1.55, 95% CI = 1.39–1.73, p &lt; 0.001]. After additional adjustment for ln(hs-CRP) and ln(NT-proBNP) this was still true [HR = 1.38, 95% CI = 1.21–1.53, p &lt; 0.001]. Conclusions Serum YKL-40 is a predictor of long-term mortality in patients with stable CAD independent of common risk factors and ln(hs-CRP) and ln(NT-proBNP). Serum YKL-40 can be used for prognostication in these patients.</abstract><cop>Netherlands</cop><pub>Elsevier GmbH</pub><pmid>23294528</pmid><doi>10.1016/j.imbio.2012.10.015</doi><tpages>7</tpages></addata></record>
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subjects Adipokines - blood
Advanced Basic Science
Aged
Allergy and Immunology
Biomarker
Biomarkers - blood
C-Reactive Protein - metabolism
Cardiotonic Agents - therapeutic use
Case-Control Studies
Chitinase-3-Like Protein 1
Coronary artery disease
Coronary Artery Disease - blood
Coronary Artery Disease - diagnosis
Coronary Artery Disease - drug therapy
Coronary Artery Disease - mortality
Female
Follow-Up Studies
hs-CRP
Humans
Inflammation
Lectins - blood
Male
Middle Aged
Mortality
Natriuretic Peptide, Brain - blood
NT-proBNP
Peptide Fragments - blood
Predictive Value of Tests
Prognosis
Risk Factors
Survival Analysis
YKL-40
title Serum YKL-40 predicts long-term mortality in patients with stable coronary disease: A prognostic study within the CLARICOR trial
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