Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy
Identifieur interne : 001106 ( Main/Exploration ); précédent : 001105; suivant : 001107Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy
Auteurs : Paul W. X. Foley [Royaume-Uni] ; Berthold Stegemann [Pays-Bas] ; Kelvin Ng [Royaume-Uni] ; Sud Ramachandran [Royaume-Uni] ; Anthony Proudler [Royaume-Uni] ; Michael P. Frenneaux [Royaume-Uni] ; Leong L. Ng [Royaume-Uni] ; Francisco Leyva [Royaume-Uni]Source :
- European Heart Journal [ 0195-668X ] ; 2009-11.
Abstract
Aims The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) predicts mortality and morbidity after cardiac resynchronization therapy (CRT). Growth differentiation factor-15, a transforming growth factor--related cytokine which is up-regulated in cardiomyocytes via multiple stress pathways, predicts mortality in patients with heart failure treated pharmacologically. Methods and results Growth differentiation factor-15 was measured before and 360 days (median) after implantation in 158 patients with heart failure [age 68 11 years (mean SD), left ventricular ejection fraction (LVEF) 23.1 9.8, New York Class Association (NYHA) class III (n 117) or IV (n 41), and QRS 153.9 28.2 ms] undergoing CRT and followed up for a maximum of 5.4 years for events. In a stepwise Cox proportional hazards model with bootstrapping, adopting log GDF-15, log NT pro-BNP, LVEF, and NYHA class as independent variables, only log GDF-15 [hazard ratio (HR), 3.76; P 0.0049] and log NT pro-BNP (HR, 2.12; P 0.0171) remained in the final model. In the latter, the bias-corrected slope was 0.85, the optimism (O) was 0.06, and the c-statistic was 0.74, indicating excellent internal validity. In univariate analyses, log GDF-15 [HR, 5.31; 95 confidence interval (CI), 2.3111.9; likelihood ratio (LR) 2 14.6; P < 0.0001], NT pro-BNP (HR, 2.79; 95 CI, 1.555.26; LR 2 10.4; P 0.0004), and the combination of both biomarkers (HR, 7.03; 95 CI, 2.9117.5; LR 2 19.1; P < 0.0001) emerged as significant predictors. The biomarker combination was associated with the highest LR 2 for all endpoints. Conclusion Pre-implant GDF-15 is a strong predictor of mortality and morbidity after CRT, independent of NT pro-BNP. The predictive value of these analytes is enhanced by combined measurement.
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DOI: 10.1093/eurheartj/ehp300
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Foley</name></author><author><name sortKey="Stegemann, Berthold" sort="Stegemann, Berthold" uniqKey="Stegemann B" first="Berthold" last="Stegemann">Berthold Stegemann</name></author><author><name sortKey="Ng, Kelvin" sort="Ng, Kelvin" uniqKey="Ng K" first="Kelvin" last="Ng">Kelvin Ng</name></author><author><name sortKey="Ramachandran, Sud" sort="Ramachandran, Sud" uniqKey="Ramachandran S" first="Sud" last="Ramachandran">Sud Ramachandran</name></author><author><name sortKey="Proudler, Anthony" sort="Proudler, Anthony" uniqKey="Proudler A" first="Anthony" last="Proudler">Anthony Proudler</name></author><author><name sortKey="Frenneaux, Michael P" sort="Frenneaux, Michael P" uniqKey="Frenneaux M" first="Michael P." last="Frenneaux">Michael P. Frenneaux</name></author><author><name sortKey="Ng, Leong L" sort="Ng, Leong L" uniqKey="Ng L" first="Leong L." last="Ng">Leong L. 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Foley</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiology, University of Birmingham, Good Hope Hospital, Heart of England NHS Trust, Rectory Road, Sutton Coldfield, West Midlands B75 7RR</wicri:regionArea><orgName type="university">Université de Birmingham</orgName><placeName><settlement type="city">Birmingham</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Midlands de l'Ouest</region></placeName></affiliation></author><author><name sortKey="Stegemann, Berthold" sort="Stegemann, Berthold" uniqKey="Stegemann B" first="Berthold" last="Stegemann">Berthold Stegemann</name><affiliation wicri:level="1"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Medtronic Inc., Maastricht</wicri:regionArea><wicri:noRegion>Maastricht</wicri:noRegion></affiliation></author><author><name sortKey="Ng, Kelvin" sort="Ng, Kelvin" uniqKey="Ng K" first="Kelvin" last="Ng">Kelvin Ng</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Medicine and Therapeutics, Leicester Royal Infirmary, Leicester</wicri:regionArea><wicri:noRegion>Leicester</wicri:noRegion></affiliation></author><author><name sortKey="Ramachandran, Sud" sort="Ramachandran, Sud" uniqKey="Ramachandran S" first="Sud" last="Ramachandran">Sud Ramachandran</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Biochemistry, Good Hope Hospital, Heart of England NHS Trust, Sutton Coldfield, West Midlands</wicri:regionArea><wicri:noRegion>West Midlands</wicri:noRegion></affiliation></author><author><name sortKey="Proudler, Anthony" sort="Proudler, Anthony" uniqKey="Proudler A" first="Anthony" last="Proudler">Anthony Proudler</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Biochemistry, Good Hope Hospital, Heart of England NHS Trust, Sutton Coldfield, West Midlands</wicri:regionArea><wicri:noRegion>West Midlands</wicri:noRegion></affiliation></author><author><name sortKey="Frenneaux, Michael P" sort="Frenneaux, Michael P" uniqKey="Frenneaux M" first="Michael P." last="Frenneaux">Michael P. Frenneaux</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Queen Elizabeth Hospital, University of Birmingham, Birmingham</wicri:regionArea><placeName><settlement type="city">Birmingham</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Midlands de l'Ouest</region></placeName><orgName type="university">Université de Birmingham</orgName></affiliation></author><author><name sortKey="Ng, Leong L" sort="Ng, Leong L" uniqKey="Ng L" first="Leong L." last="Ng">Leong L. Ng</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Medicine and Therapeutics, Leicester Royal Infirmary, Leicester</wicri:regionArea><wicri:noRegion>Leicester</wicri:noRegion></affiliation></author><author><name sortKey="Leyva, Francisco" sort="Leyva, Francisco" uniqKey="Leyva F" first="Francisco" last="Leyva">Francisco Leyva</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiology, University of Birmingham, Good Hope Hospital, Heart of England NHS Trust, Rectory Road, Sutton Coldfield, West Midlands B75 7RR</wicri:regionArea><orgName type="university">Université de Birmingham</orgName><placeName><settlement type="city">Birmingham</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Midlands de l'Ouest</region></placeName></affiliation><affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">European Heart Journal</title><idno type="ISSN">0195-668X</idno><idno type="eISSN">1522-9645</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2009-11">2009-11</date><biblScope unit="volume">30</biblScope><biblScope unit="issue">22</biblScope><biblScope unit="page" from="2749">2749</biblScope><biblScope unit="page" to="2757">2757</biblScope></imprint><idno type="ISSN">0195-668X</idno></series><idno type="istex">1C020A911A8260FE60E0782240E00700FE4B9828</idno><idno type="DOI">10.1093/eurheartj/ehp300</idno><idno type="ArticleID">ehp300</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0195-668X</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Aims The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) predicts mortality and morbidity after cardiac resynchronization therapy (CRT). Growth differentiation factor-15, a transforming growth factor--related cytokine which is up-regulated in cardiomyocytes via multiple stress pathways, predicts mortality in patients with heart failure treated pharmacologically. Methods and results Growth differentiation factor-15 was measured before and 360 days (median) after implantation in 158 patients with heart failure [age 68 11 years (mean SD), left ventricular ejection fraction (LVEF) 23.1 9.8, New York Class Association (NYHA) class III (n 117) or IV (n 41), and QRS 153.9 28.2 ms] undergoing CRT and followed up for a maximum of 5.4 years for events. In a stepwise Cox proportional hazards model with bootstrapping, adopting log GDF-15, log NT pro-BNP, LVEF, and NYHA class as independent variables, only log GDF-15 [hazard ratio (HR), 3.76; P 0.0049] and log NT pro-BNP (HR, 2.12; P 0.0171) remained in the final model. In the latter, the bias-corrected slope was 0.85, the optimism (O) was 0.06, and the c-statistic was 0.74, indicating excellent internal validity. In univariate analyses, log GDF-15 [HR, 5.31; 95 confidence interval (CI), 2.3111.9; likelihood ratio (LR) 2 14.6; P < 0.0001], NT pro-BNP (HR, 2.79; 95 CI, 1.555.26; LR 2 10.4; P 0.0004), and the combination of both biomarkers (HR, 7.03; 95 CI, 2.9117.5; LR 2 19.1; P < 0.0001) emerged as significant predictors. The biomarker combination was associated with the highest LR 2 for all endpoints. Conclusion Pre-implant GDF-15 is a strong predictor of mortality and morbidity after CRT, independent of NT pro-BNP. The predictive value of these analytes is enhanced by combined measurement.</div></front></TEI><affiliations><list><country><li>Pays-Bas</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Midlands de l'Ouest</li></region><settlement><li>Birmingham</li></settlement><orgName><li>Université de Birmingham</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Foley, Paul W X" sort="Foley, Paul W X" uniqKey="Foley P" first="Paul W. X." last="Foley">Paul W. X. Foley</name></region><name sortKey="Frenneaux, Michael P" sort="Frenneaux, Michael P" uniqKey="Frenneaux M" first="Michael P." last="Frenneaux">Michael P. Frenneaux</name><name sortKey="Leyva, Francisco" sort="Leyva, Francisco" uniqKey="Leyva F" first="Francisco" last="Leyva">Francisco Leyva</name><name sortKey="Ng, Kelvin" sort="Ng, Kelvin" uniqKey="Ng K" first="Kelvin" last="Ng">Kelvin Ng</name><name sortKey="Ng, Leong L" sort="Ng, Leong L" uniqKey="Ng L" first="Leong L." last="Ng">Leong L. Ng</name><name sortKey="Proudler, Anthony" sort="Proudler, Anthony" uniqKey="Proudler A" first="Anthony" last="Proudler">Anthony Proudler</name><name sortKey="Ramachandran, Sud" sort="Ramachandran, Sud" uniqKey="Ramachandran S" first="Sud" last="Ramachandran">Sud Ramachandran</name></country><country name="Pays-Bas"><noRegion><name sortKey="Stegemann, Berthold" sort="Stegemann, Berthold" uniqKey="Stegemann B" first="Berthold" last="Stegemann">Berthold Stegemann</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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