Level of the growth differentiation factor-15 in patients with acute myocardial infarction

Aim To reveal relationships between growth differentiation factor-15 (GDF-15) and laboratory and instrumental indexes in patients with myocardial infarction in acute phase.
Material and methods The study included 118 patients younger than 70 years with ST-segment elevation or non-ST segment elevation myocardial infarction (MI). For these patients, GDF-15 was measured by enzyme immunoassay within 48 h of MI clinical onset along with a routine examination. Statistical significance of differences in qualitative variables was assessed by the Student’s t-test for normal distribution and by the nonparametric Mann-Whitney U-test; significance of differences in quantitative variables was assessed by the Pearson’s chi-squared test. The presence of a relationship between quantitative variables was assessed with the Pearson’s correlation coefficient and the Spearman’s rank correlation coefficient.
Results For patients with MI, mean GDF-15 concentration was 2.25±1.0 ng/ml. Moderate correlations were found for GDF-15 and levels of natriuretic peptide (r=0.36, p<0.01), white blood cells (r=0.32, p<0.01), and ejection fraction (Simpson rule) (r=-0.32, p<0.01); weak correlations were found with levels of troponin I (r=0.21, p=0.02) and urea (r=0.20, p=0.04), and interventricular septal thickness by echocardiography (r= -0.26, p<0.01). GDF-15 was higher in patients with ST-segment elevation MI (2.36±1.02 vs 1.99±0.96, p<0.05) and in the presence of hypo- or akinetic areas (2.35±1.05 vs 1.85±0.70, p<0.05). No dependence of GDF-15 on the presence of traditional cardiovascular risk factors was observed.
Conclusion GDF-15 correlates with major markers of myocardial injury; its level is higher in patients with ST-segment elevation MI regardless of the infarct location.

1. Bootcov MR, Bauskin AR, Valenzuela SM, Moore AG, Bansal M, He XY et al. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF- superfamily. Proceedings of the National Academy of Sciences. 1997;94(21):11514–9. DOI: 10.1073/pnas.94.21.11514

2. Kempf T, Eden M, Strelau J, Naguib M, Willenbockel C, Tongers J et al. The Transforming Growth Factor-β Superfamily Member Growth-Differentiation Factor-15 Protects the Heart from Ischemia/Reperfusion Injury. Circulation Research. 2006;98(3):351–60. DOI: 10.1161/01.RES.0000202805.73038.48

3. Kempf T, Zarbock A, Widera C, Butz S, Stadtmann A, Rossaint J et al. GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nature Medicine. 2011;17(5):581–8. DOI: 10.1038/nm.2354

4. Bonaca MP, Morrow DA, Braunwald E, Cannon CP, Jiang S, Breher S et al. Growth Differentiation Factor-15 and Risk of Recurrent Events in Patients Stabilized After Acute Coronary Syndrome: Observations from PROVE IT-TIMI 22. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31(1):203–10. DOI: 10.1161/ATVBAHA.110.213512

5. Wollert KC, Kempf T, Lagerqvist B, Lindahl B, Olofsson S, Allhoff T et al. Growth Differentiation Factor 15 for Risk Stratification and Selection of an Invasive Treatment Strategy in Non–ST-Elevation Acute Coronary Syndrome. Circulation. 2007;116(14):1540–8. DOI: 10.1161/CIRCULATIONAHA.107.697714

6. Wollert KC, Kempf T, Peter T, Olofsson S, James S, Johnston N et al. Prognostic Value of Growth-Differentiation Factor-15 in Patients with Non–ST-Elevation Acute Coronary Syndrome. Circulation. 2007;115(8):962–71. DOI: 10.1161/CIRCULATIONAHA.106.650846

7. Kempf T, Bjorklund E, Olofsson S, Lindahl B, Allhoff T, Peter T et al. Growth-differentiation factor-15 improves risk stratification in STsegment elevation myocardial infarction. European Heart Journal. 2007;28(23):2858–65. DOI: 10.1093/eurheartj/ehm465

8. Dinh W, Füth R, Lankisch M, Hess G, Zdunek D, Scheffold T et al. Growth-differentiation factor-15: a novel biomarker in patients with diastolic dysfunction? Arquivos Brasileiros de Cardiologia. 2011;97(1):65–75. DOI: 10.1590/S0066-782X2011005000058

9. Lok DJ, Klip IjT, Lok SI, Bruggink-André de la Porte PW, Badings E, van Wijngaarden J et al. Incremental Prognostic Power of Novel Biomarkers (Growth-Differentiation Factor-15, High-Sensitivity C-Reactive Protein, Galectin-3, and High- Sensitivity Troponin-T) in Patients with Advanced Chronic Heart Failure. The American Journal of Cardiology. 2013;112(6):831– 7. DOI: 10.1016/j.amjcard.2013.05.013

10. Wallentin L, Hijazi Z, Andersson U, Alexander JH, De Caterina R, Hanna M et al. Growth Differentiation Factor 15, a Marker of Oxidative Stress and Inflammation, for Risk Assessment in Patients With Atrial Fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial. Circulation. 2014;130(21):1847–58. DOI: 10.1161/CIRCULATIONAHA.114.011204

11. Hijazi Z, Oldgren J, Lindbäck J, Alexander JH, Connolly SJ, Eikelboom JW et al. The novel biomarker-based ABC (age, biomarkers, clinical history) – bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet. 2016; 387: 2302–11. DOI: 0.1016/S0140-6736(16)00741-8

12. Khan SQ, Ng K, Dhillon O, Kelly D, Quinn P, Squire IB et al. Growth differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction. European Heart Journal. 2009;30(9):1057–65. DOI: 10.1093/eurheartj/ehn600

13. Daniels LB, Clopton P, Laughlin GA, Maisel AS, Barrett-Connor E. Growth-Differentiation Factor-15 Is a Robust, Independent Predictor of 11-Year Mortality Risk in Community- Dwelling Older Adults: The Rancho Bernardo Study. Circulation. 2011;123(19):2101–10. DOI: 10.1161/CIRCULATIONAHA.110.979740

14. Lew J, Sanghavi M, Ayers CR, McGuire DK, Omland T, Atzler D et al. Sex-Based Differences in Cardiometabolic Biomarkers. Circulation. 2017;135(6):544–55. DOI: 10.1161/CIRCULATIONAHA.116.023005

15. Lind L, Wallentin L, Kempf T, Tapken H, Quint A, Lindahl B et al. Growth-differentiation factor-15 is an independent marker of cardiovascular dysfunction and disease in the elderly: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study. European Heart Journal. 2009;30(19):2346–53. DOI: 10.1093/eurheartj/ehp261

16. Ho JE, Mahajan A, Chen M-H, Larson MG, McCabe EL, Ghorbani A et al. Clinical and Genetic Correlates of Growth Differentiation Factor 15 in the Community. Clinical Chemistry. 2012;58(11):1582–91. DOI: 10.1373/clinchem.2012.190322

17. Xu J, Kimball TR, Lorenz JN, Brown DA, Bauskin AR, Klevitsky R et al. GDF15/MIC-1 Functions As a Protective and Antihypertrophic Factor Released From the Myocardium in Association with SMAD Protein Activation. Circulation Research. 2006;98(3):342–50. DOI: 10.1161/01.RES.0000202804.84885.d0