Czynnik różnicowania wzrostu 15 (GDF-15) w ocenie ryzyka sercowo-naczyniowego

• Authors: Wiesław Piechota , Paweł Krzesiński

Title variants

EN

Growth differentiation factor-15 (GDF-15) for cardiovascular risk assessment

• Languages of publication: PL EN

Abstracts

PL

Choroby układu sercowo-naczyniowego, mimo postępu w ich leczeniu i zauważalnego spadku częstości ich występowania, są nadal główną przyczyną zgonów w krajach rozwiniętych cywilizacyjnie, w tym także w Polsce. Zatem poszukiwanie biomarkerów do wczesnego określania ryzyka tych chorób zarówno w prewencji pierwotnej, jak i wtórnej jest zadaniem pierwszoplanowym. Spośród nowych markerów białkowych o dużym potencjale predykcyjnym chorób układu sercowo- -naczyniowego i ich powikłań na czoło wysuwa się czynnik różnicowania wzrostu 15 (GDF-15). Jego podwyższone stężenie we krwi wiąże się ze zwiększonym ryzykiem wielu chorób układu sercowo-naczyniowego, ich obecnością w postaci subklinicznej, a także ich powikłaniami, łącznie ze zgonami. Siła predykcyjna GDF-15 jest niezależna od innych czynników ryzyka i addytywna w stosunku do nich. Czynnik ten może być wykorzystywany w strategii wielomarkerowej do poprawienia stratyfikacji ryzyka, chociaż do oceny ryzyka zgonu może być także stosowany samodzielnie. Czynnik różnicowania wzrostu 15 nie jest swoisty dla mięśnia sercowego – w niektórych chorobach układu sercowo-naczyniowego jego zwiększona ekspresja może występować także w innych tkankach. Podwyższone stężenie GDF-15 we krwi stwierdza się w chorobach nowotworowych. Wzrost stężenia tego markera obserwuje się również w stanach upośledzenia czynności nerek. Ze względu na silny związek GDF-15 z umieralnością ogólną określa się go niekiedy mianem „markera śmierci”. Wzrost jego stężenia często poprzedza o wiele miesięcy czy nawet lat wystąpienie dużych zdarzeń klinicznych. Otwiera to pole do intensywniejszej prewencji zarówno pierwotnej, jak i wtórnej.

EN

Cardiovascular diseases remain the primary cause of death in developed countries, including Poland, despite the progress in their treatment and a noticeable decrease in their prevalence. For this reason, the search for biomarkers for early disease risk assessment in primary as well as secondary prevention is the main task. Growth differentiation factor-15 (GDF-15) is becoming a leader among the new protein markers with a high predictive potential for cardiovascular diseases and their complications. An elevated GDF-15 blood level is associated with an increased risk of many cardiovascular diseases, their subclinical presence and their complications, including death. The predictive strength of GDF-15 is independent of and additive to other risk factors. GDF-15 can be used as part of a multimarker strategy to improve risk stratification, although it can also be used alone for death risk assessment. GDF-15 is not heart-specific: in some cardiovascular diseases its expression can be increased in other tissues as well. Elevated GDF-15 blood levels are found in cancer. They are also observed in renal impairment. Due to the strong relationship between GDF-15 and general mortality it is sometimes called “the marker of death.” Its increase often precedes serious clinical events by many months or even years. This provides opportunities for more intensive prevention, both primary and secondary.

Keywords

EN

biomarker; czynnik różnicowania wzrostu 15; ryzyko sercowo-naczyniowe

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Pediatria i Medycyna Rodzinna
• Year: 2018
• Volume: 14
• Issue: 1
• Pages: 9–19

Contributors

author

Wiesław Piechota

• Zakład Diagnostyki Laboratoryjnej, Wojskowy Instytut Medyczny, Warszawa, Polska

author

Paweł Krzesiński

• Klinika Kardiologii i Chorób Wewnętrznych, Wojskowy Instytut Medyczny, Warszawa, Polska

References

• 1. Wallentin L, Zethelius B, Berglund L et al.: GDF-15 for prognostication of cardiovascular and cancer morbidity and mortality in men. PLoS ONE 2013; 8: e78797.
• 2. Wang TJ, Wollert KC, Larson MG et al.: Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study. Circulation 2012; 126: 1596–1604.
• 3. Wollert K, Kempf T, Peter T et al.: Prognostic value of growthdifferentiation factor-15 in patients with non–ST-elevation acute coronary syndrome. Circulation 2007; 115: 962–971.
• 4. Widera C, Pencina M, Bobadilla M et al.: Incremental prognostic value of biomarkers beyond the GRACE (Global Registry of Acute Coronary Events) score and high-sensitivity cardiac troponin T in non–ST-elevation acute coronary syndrome. Clin Chem 2013; 59: 1497–1505.
• 5. Kempf T, von Haehling S, Peter T et al.: Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure. J Am Coll Cardiol 2007; 50: 1054–1060.
• 6. Kempf T, Horn-Wichmann R, Brabant G et al.: Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay. Clin Chem 2007; 53: 284–291.
• 7. Sinning C, Kempf T, Schwarzl M et al.: Biomarkers for characterization of heart failure – distinction of heart failure with preserved and reduced ejection fraction. Int J Cardiol 2017; 227: 272–277.
• 8. Santhanakrishnan R, Chong JP, Ng TP et al.: Growth differentiation factor 15, ST2, high-sensitivity troponin T, and N-terminal pro brain natriuretic peptide in heart failure with preserved vs. reduced ejection fraction. Eur J Heart Fail 2012; 14: 1338–1347.
• 9. Bootcov MR, Bauskin AR, Valenzuela SM et al.: MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-β superfamily. Proc Natl Acad Sci USA 1997; 94: 11514–11519.
• 10. Bauskin AR, Zhang HP, Fairlie WD et al.: The propeptide of macrophage inhibitory cytokine (MIC-1), a TGF-β superfamily member, acts as a quality control determinant for correctly folded MIC-1. EMBO J 2000; 19: 2212–2220.
• 11. Hsiao EC, Koniaris LG, Zimmers-Koniaris T et al.: Characterization of growth-differentiation factor 15, a transforming growth factor-β superfamily member induced following liver injury. Mol Cell Biol 2000; 20: 3742–3751.
• 12. Kempf T, Eden M, Strelau J et al.: The transforming growth factor-β superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury. Circ Res 2006; 98: 351–360.
• 13. Schlittenhardt D, Schober A, Strelau et al.: Involvement of growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in oxLDL-induced apoptosis of human macrophages in vitro and in arteriosclerotic lesions. Cell Tissue Res 2004; 318: 325–333.
• 14. Wollert KC, Kempf T, Giannitsis E et al.: An automated assay for growth differentiation factor 15. JALM 2017; 1: 510–521.
• 15. Corre J, Hébraud B, Bourin P: Concise review: growth differentiation factor 15 in pathology: a clinical role? Stem Cells Transl Med 2013; 2: 946–952.
• 16. Xanthakis V, Enserro DM, Murabito JM et al.: Ideal cardiovascular health: associations with biomarkers and subclinical disease and impact on incidence of cardiovascular disease in the Framingham Offspring Study. Circulation 2014; 130: 1676–1683.
• 17. Nair V, Robinson-Cohen C, Smith MR et al.: Growth differentiation factor-15 and risk of CKD progression. J Am Soc Nephrol 2017; 28: 2233–2240.
• 18. Ago T, Sadoshima J: GDF15, a cardioprotective TGF-β superfamily protein. Circ Res 2006; 98: 294–297.
• 19. Shin MY, Kim JM, Kang YE et al.: Association between growth differentiation factor 15 (GDF15) and cardiovascular risk in patients with newly diagnosed type 2 diabetes mellitus. J Korean Med Sci 2016; 31: 1413–1418.
• 20. Kempf T, Guba-Quint A, Torgerson J et al.: Growth differentiation factor 15 predicts future insulin resistance and impaired glucose control in obese nondiabetic individuals: results from the XENDOS trial. Eur J Endocrinol 2012; 167: 671–678.
• 21. Wollert KC, Kempf T, Wallentin L: Growth differentiation factor 15 as a biomarker in cardiovascular disease. Clin Chem 2017; 63: 140–151.
• 22. Daniels LB, Clopton P, Laughlin GA et al.: 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: 2101–2110.
• 23. Brown DA, Breit SN, Buring J et al.: Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women: a nested case-control study. Lancet 2002; 359: 2159–2163.
• 24. Tomaschitz A, Pilz S, März W: GDF-15, soluble ST2 and troponin-I: biomarkers of subclinical vascular disease? Atherosclerosis 2016; 248: 255–256.
• 25. Andersson C, Enserro D, Sullivan L et al.: Relations of circulating GDF-15, soluble ST2, and troponin-I concentrations with vascular function in the community: the Framingham Heart Study. Atherosclerosis 2016; 248: 245–251.
• 26. Xanthakis V, Larson MG, Wollert KC et al.: Association of novel biomarkers of cardiovascular stress with left ventricular hypertrophy and dysfunction: implications for screening. J Am Heart Assoc 2013; 2: e000399.
• 27. Wiklund FE, Bennet AM, Magnusson PK et al.: Macrophage inhibitory cytokine-1 (MIC-1/GDF15): a new marker of allcause mortality. Aging Cell 2010; 9: 1057–1064.
• 28. Rohatgi A, Patel P, Das SR et al.: Association of growth differentiation factor-15 with coronary atherosclerosis and mortality in a young, multiethnic population: observations from the Dallas Heart Study. Clin Chem 2012; 58: 172–182.
• 29. Khavinson VKh, Kuznik BI, Linkova NS et al.: [The role of cytokines MIC-1/GDF15 in development of the old age disease]. Usp Fiziol Nauk 2015; 46: 38–52.
• 30. Fujita Y, Taniguchi Y, Shinkai S et al.: Secreted growth differentiation factor 15 as a potential biomarker for mitochondrial dysfunctions in aging and age-related disorders. Geriatr Gerontol Int 2016; 16 Suppl 1: 17–29.
• 31. Jiang J, Wen W, Sachdev PS: Macrophage inhibitory cytokine-1/ growth differentiation factor 15 as a marker of cognitive ageing and dementia. Curr Opin Psychiatry 2016; 29: 181–186.
• 32. Kempf T, Björklund E, Olofsson S et al.: Growth-differentiation factor-15 improves risk stratification in ST-segment elevation myocardial infarction. Eur Heart J 2007; 28: 2858–2865.
• 33. Wollert K, Kempf, Lagerqvist B 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: 1540–1548.
• 34. Lindholm D, James SK, Bertilsson M et al.; PLATO Investigators: Biomarkers and coronary lesions predict outcomes after revascularization in non–ST-elevation acute coronary syndrome. Clin Chem 2017; 63: 573–584.
• 35. Eggers KM, Kempf T, Allhoff T et al.: Growth-differentiation factor-15 for early risk stratification in patients with acute chest pain. Eur Heart J 2008; 29: 2327–2335.
• 36. Damman P, Kempf T, Windhausen F et al.: Growth-differentiation factor 15 for long-term prognostication in patients with non–ST-elevation acute coronary syndrome: an Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy. Int J Cardiol 2014; 172: 356–363.
• 37. Hagström E, James SK, Bertilsson M et al.: Growth differentiation factor-15 level predicts major bleeding and cardiovascular events in patients with acute coronary syndromes: results from the PLATO study. Eur Heart J 2016; 37: 1325–1333.
• 38. Heringlake M, Charitos EI, Gatz N et al.: Growth differentiation factor 15: a novel risk marker adjunct to the EuroSCORE for risk stratification in cardiac surgery patients. J Am Coll Cardiol 2013; 61: 672–681.
• 39. Khan SQ, Ng K, Dhillon O et al.: Growth differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction. Eur Heart J 2009; 30: 1057–1065.
• 40. Kempf T, Sinning JM, Quint A et al.: Growth-differentiation factor-15 for risk stratification in patients with stable and unstable coronary heart disease: results from the AtheroGene study. Circ Cardiovasc Genet 2009; 2: 286–292.
• 41. Schopfer DW, Ku IA, Regan M et al.: Growth differentiation factor 15 and cardiovascular events in patients with stable ischemic heart disease (The Heart and Soul Study). Am Heart J 2014; 167: 186–192.e1.
• 42. Hagström E, Held C, Stewart RAH et al.: Growth differentiation factor 15 predicts all-cause morbidity and mortality in stable coronary heart disease. Clin Chem 2017; 63: 325–333.
• 43. Dallmeier D, Brenner H, Mons U et al.: Growth differentiation factor 15, its 12-month relative change, and risk of cardiovascular events and total mortality in patients with stable coronary heart disease: 10-year follow-up of the KAROLA study. Clin Chem 2016; 62: 982–992.
• 44. Farhan S, Freynhofer MK, Brozovic I et al.: Determinants of growth differentiation factor 15 in patients with stable and acute coronary artery disease. A prospective observational study. Cardiovasc Diabetol 2016; 15: 60.
• 45. Lankeit M, Kempf T, Dellas C et al.: Growth differentiation factor-15 for prognostic assessment of patients with acute pulmonary embolism. Am J Respir Crit Care Med 2008; 177: 1018–1025.
• 46. Duran L, Kayhan S, Guzel A et al.: The prognostic values of GDF-15 in comparison with NT-proBNP in patients with normotensive acute pulmonary embolism. Clin Lab 2014; 60: 1365–1371.
• 47. Wallentin L, Hijazi Z, Andersson U 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: 1847–1858.
• 48. Hijazi Z, Oldgren J, Lindback J et al.; ARISTOTLE and RE-LY Investigators: 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: 2302–2311.
• 49. Ezekowitz MD, Connolly S, Parekh A et al.: Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran. Am Heart J 2009; 157: 805–810.
• 50. Pisters R, Lane DA, Nieuwlaat R et al.: A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation. The Euro Heart Survey. Chest 2010; 138: 1093–1100.
• 51. O’Brien EC, Simon DN, Thomas LE et al.: The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation. Eur Heart J 2015; 36: 3258–3264.
• 52. Kirchhof P, Benussi S, Kotecha D et al.: 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37: 2893–2962.
• 53. Xu XY, Nie Y, Wang FF et al.: Growth differentiation factor (GDF)-15 blocks norepinephrine-induced myocardial hypertrophy via a novel pathway involving inhibition of epidermal growth factor receptor transactivation. J Biol Chem 2014; 289: 10084–10094.
• 54. Xue H, Fu Z, Chen Y et al.: The association of growth differentiation factor-15 with left ventricular hypertrophy in hypertensive patients. PLoS One 2012; 7: e46534.
• 55. Hanatani S, Izumiya Y, Takashio S et al.: Growth differentiation factor 15 can distinguish between hypertrophic cardiomyopathy and hypertensive hearts. Heart Vessels 2014; 29: 231–237.
• 56. Chow SL, Maisel AS, Anand I et al.; American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology; Council on Basic Cardiovascular Sciences; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Epidemiology and Prevention; Council on Functional Genomics and Translational Biology; and Council on Quality of Care and Outcomes Research: Role of biomarkers for the prevention, assessment, and management of heart failure. A scientific statement from the American Heart Association. Circulation 2017; 135: e1054–e1091.
• 57. Li G, Li Y, Tan XQ et al.: Plasma growth differentiation factor-15 is a potential biomarker for pediatric pulmonary arterial hypertension associated with congenital heart disease. Pediatr Cardiol 2017; 38: 1620–1626.
• 58. Hess G, Horsch A, Zdunek D: Natriuretic peptide/GDF-15 ratio for diagnosis of cardiac disorders. United States Patent Application Publication. Pub. No.: US 2010/0248259 A1. Pub. Date: Sep. 30, 2010.
• 59. Demissei BG, Cotter G, Prescott MF et al.: A multimarker multitime point-based risk stratification strategy in acute heart failure: results from the RELAX-AHF trial. Eur J Heart Fail 2017; 19: 1001–1010.

• Document Type: article