Growth-differentiation factor-15 improves risk stratification in ST-segment elevation myocardial infarction

Kempf, Tibor; Björklund, Erik; Olofsson, Sylvia; Lindahl, Bertil; Allhoff, Tim; Peter, Timo; Tongers, Jörn; Wollert, Kai C.; Wallentin, Lars

doi:10.1093/eurheartj/ehm465

Cited by 204 publications

(171 citation statements)

References 27 publications

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“…Increased levels of GDF15/MIC-1 have been reported in several studies related to CVD or CV events, particularly in women 27,40,41 . A number of SNP have been analyzed for the GDF15/MIC-1 gene, and in particular SNP associated with promoter activity were associated with GDF15 protein level.…”

Section: Rheumatologymentioning

confidence: 87%

Polymorphisms of the Genes EncodingCD40and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease

Ärlestig¹,

Rantapää-Dahlqvist²

2012

J Rheumatol

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Objective.Genes or gene products associated with coronary artery disease in the general population were analyzed in rheumatoid arthritis (RA) patients with atherothrombotic manifestations (ATM).Methods.A cross-sectional study of 681 individuals (498 women; 183 men) with RA (American College of Rheumatology criteria), a mean age of 60.6 ± 13.2 years, and mean disease duration of 15.5 ± 12.6 years who were consecutively recruited and followed for 6 years. The prevalence of ATM [i.e., myocardial infarction, angina pectoris with intervention, deep vein thrombosis/pulmonary embolism (DVT/PE), and/or stroke/transient ischemic attack (TIA)] was recorded. Polymorphisms were analyzed in the genes coding for growth differentiation factor 15 (GDF15)/monocyte inhibitory cytokine-1 (MIC-1; rs1058587),CD40(rs1535045 and rs3765459), and the 9p21.3 locus (rs1333049). Controls were randomly selected (n = 687; matched for age and sex).Results.The distribution of genotypes ofGDF15/MIC-1differed significantly between patients with RA and controls (chi-squared = 6.40, 2 df, p = 0.041). ATM were associated with polymorphism of theGDF15/MIC-1G allele (OR 2.21, 95% CI 1.17–4.18), and with CC genotype of the 9p21.3 locus (rs1333049; OR 1.92, 95% CI 1.15–3.19). Stroke/TIA in women was associated withGDF15/MIC-1GG genotype (OR 3.75, 95% CI 1.06–13.33), while stroke/TIA in men was associated withCD40homozygous major alleles (OR 6.48, 95% CI 1.31–32.0 and OR 2.78, 95% CI 0.78–9.91, respectively). DVT/PE was associated with polymorphism in theGDF15/MIC-1gene (rs1058587) minor allele (OR 3.53, 95% CI 1.30–9.58).Conclusion.The gene polymorphisms analyzed were associated with different ATM in RA. TheGDF15/MIC-1gene polymorphism was also associated with RAper se, suggesting a common etiology for RA and ATM.

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Section: Rheumatologymentioning

confidence: 87%

Polymorphisms of the Genes EncodingCD40and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease

Ärlestig¹,

Rantapää-Dahlqvist²

2012

J Rheumatol

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“…[9][10][11][12][13][14][15][16] In clinically stable patients with acute decompensated heart failure, high levels of B-type natriuretic peptide (BNP) at the end of a hospitalization are strong, independent markers of CV events compared with levels during the acute phase.…”

Section: )mentioning

confidence: 99%

“…8) High-sensitivity C reactive protein (hs-CRP); growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-β superfamily; and ST2, a member of the interleukin-1 receptor family, are strongly associated with CV events in AMI patients. [9][10][11][12][13][14][15][16] In clinically stable patients with acute decompensated heart failure, high levels of B-type natriuretic peptide (BNP) at the end of a hospitalization are strong, independent markers of CV events compared with levels during the acute phase. 17) Secondary prevention of CV events is a crucial factor for the prognostic improvement in patients with AMI, and novel biomarkers provide important information about patient management if the biomarkers contribute to the risk stratification in these patients.…”

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confidence: 99%

Comparison of Inflammatory Biomarkers in Outpatients With Prior Myocardial Infarction

et al. 2016

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SummaryInflammatory biomarkers have been proposed for use in the risk stratification of patients with acute myocardial infarction (AMI). We examined the value of inflammatory biomarkers over clinical features for predicting cardiovascular (CV) events in stable outpatients with MI. We enrolled 430 post-MI patients and measured their levels of high-sensitivity C reactive protein (hs-CRP), growth differentiation factor-15 (GDF-15), and the interleukin-1 receptor family member called ST2 (ST2), one month after AMI. Patients were prospectively followed for 3 years. In our study cohort (mean age, 66 ± 12 years; left ventricular ejection fraction, 55 ± 13%), CV events were observed in 39 patients (9.1%). KaplanMeier analysis revealed that patients with high levels of GDF-15 (≥ 1221.0 ng/L) showed poorer prognoses than those with low levels of GDF-15 (< 1221.0 ng/L) (20.4% versus 3.6%, P < 0.001); hs-CRP and ST2 did not show a similar correlation with prognoses. GDF-15 remained associated with CV events after adjusting for age, chronic kidney disease, and B-type natriuretic peptide (hazard ratio, 1.001; 95% confidence interval, 1.000 -1.001; P = 0.046). GDF-15 provided an incremental predictive value for CV events over clinical features (incremental value in global χ 2 = 43.81, P < 0.001). In outpatients with prior MI, GDF-15 was an independent indicator of CV events, unlike hs-CRP and ST2. GDF-15 provided an incremental prognostic value over clinical features. (Int Heart J 2016; 57: 11-17) Key words: Coronary artery disease, Growth differentiation factor-15, Prognosis I nflammatory biomarkers have been proposed for use in the risk stratification of patients with cardiovascular (CV) disease. 1-7) Patients with acute myocardial infarction (AMI) are at significant risk for recurrent CV events, such as death, recurrent MI, and heart failure. Novel biomarkers for patients with AMI are of interest because they may reveal pivotal disease mechanisms and potential therapeutic targets. 8)High-sensitivity C reactive protein (hs-CRP); growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-β superfamily; and ST2, a member of the interleukin-1 receptor family, are strongly associated with CV events in AMI patients. [9][10][11][12][13][14][15][16] In clinically stable patients with acute decompensated heart failure, high levels of B-type natriuretic peptide (BNP) at the end of a hospitalization are strong, independent markers of CV events compared with levels during the acute phase.17) Secondary prevention of CV events is a crucial factor for the prognostic improvement in patients with AMI, and novel biomarkers provide important information about patient management if the biomarkers contribute to the risk stratification in these patients. However, the prognostic significance of inflammatory biomarkers for risk stratification in stable post-MI outpatients is poorly understood. Editorial p.1The aims of this study were to 1) compare the prognostic significance of inflammatory biomarkers for predicting C...

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“…158 In prospective trials of ACS [the Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV non-ST-elevation acute coronary syndrome trial 159 and the PRavastatin OR atorVastatin Evaluation and Infection Therapy -Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial 160 ] GDF15 has been shown to be a prognostic marker. GDF15 has been shown to be a long-term prognostic marker in patients admitted with NSTEMI 161 and a prognostic marker in STEMI 162,163 and in the general AMI population. 164 Measurement of GDF15 has been shown to be prognostic in the chest pain population 165 and to add to conventional risk scores such as the Global Registry of Acute Coronary Events (GRACE) score.…”

Section: Growth Differentiation Factor 15mentioning

confidence: 99%

Randomised Assessment of Treatment using Panel Assay of Cardiac markers – Contemporary Biomarker Evaluation (RATPAC CBE)

Collinson

Gaze²,

Thokala³

et al. 2013

Health Technol Assess

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Reports are published in Health Technology Assessment (HTA) if (1) they have resulted from work for the HTA programme, and (2) they are of a sufficiently high scientific quality as assessed by the reviewers and editors.Reviews in Health Technology Assessment are termed 'systematic' when the account of the search appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others. HTA programmeThe HTA programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care.The journal is indexed in NHS Evidence via its abstracts included in MEDLINE and its Technology Assessment Reports inform National Institute for Health and Care Excellence (NICE) guidance. HTA research is also an important source of evidence for National Screening Committee (NSC) policy decisions.For more information about the HTA programme please visit the website: http://www.hta.ac.uk/ This reportThe research reported in this issue of the journal was funded by the HTA programme as project number 09/22/16. The contractual start date was in August 2010. The draft report began editorial review in February 2012 and was accepted for publication in June 2012. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors' report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health. Published by the NIHR Journals Library, produced by Prepress Projects Ltd, Perth, Scotland (www.prepress-projects.co.uk). Objectives: To test the diagnostic accuracy for detecting an acute myocardial infarction (AMI) using highly sensitive troponin assays and a range of new cardiac biomarkers of plaque destabilisation, myocardial ischaemia and necrosis; to test the prognostic accuracy for detecting adverse cardiac events using highly sensitive troponin assays and this range of new cardiac biomarkers; and to estimate the cost-effectiveness of using highly sensitive troponin assays or this range of new cardiac biomarkers instead of an admission and 10-to 12-hour troponin measurement. NIHR Journals LibraryDesign: Substudy of the point-of-care arm of the RATPAC (Randomised Assessment ...

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Growth-differentiation factor-15 improves risk stratification in ST-segment elevation myocardial infarction

Abstract: GDF-15 is a new biomarker in STEMI that provides prognostic information beyond established clinical and biochemical markers.

Cited by 204 publications

References 27 publications

Polymorphisms of the Genes EncodingCD40and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease

Polymorphisms of the Genes EncodingCD40and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease

Comparison of Inflammatory Biomarkers in Outpatients With Prior Myocardial Infarction

Randomised Assessment of Treatment using Panel Assay of Cardiac markers – Contemporary Biomarker Evaluation (RATPAC CBE)

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