Cor Vasa 2026, 68(4):503-508 | DOI: 10.33678/cor.2026.012

Growth Differentiation Factor-15 and Cardiovascular Diseases: Biology, Clinical Implications, and Future Outlook.

Lutfu Askina, Okan Tanriverdib, Husna Sengul Askinc
a Department of Cardiology, Gaziantep Islam Science and Technology University, Gaziantep, Turkey
b Department of Cardiology, Adiyaman Education and Research Hospital, Adiyaman, Turkey
c Department of Infectious Disease, Gaziantep City Hospital, Gaziantep, Turkey

Growth Differentiation Factor-15 (GDF-15) is a cytokine responsive to stress, linked to inflammation, oxidative stress, metabolic dysfunction, and tissue damage. In the past twenty years, it has become a significant biomarker in several cardiovascular diseases (CVDs), such as heart failure (HF), coronary artery disease, acute coronary syndromes, pulmonary vascular disease, arrhythmias, and cardiometabolic disorders. Increased circulating GDF-15 levels forecast mortality, hospitalisation due to HF, repeated ischaemic incidents, and the likelihood of haemorrhage. This review consolidates GDF-15 biology, pathophysiology, diagnostic and prognostic applications, and therapeutic implications and offers a critical evaluation of existing evidence gaps and future research requirements.

© 2026, ČKS.

Keywords: Cardiovascular diseases, Growth Differentiation Factor-15, Oxidative stress

Received: December 11, 2025; Revised: December 11, 2025; Accepted: February 6, 2026; Prepublished online: August 25, 2026; Published: August 31, 2026  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Askin L, Tanriverdi O, Askin HS. Growth Differentiation Factor-15 and Cardiovascular Diseases: Biology, Clinical Implications, and Future Outlook. Cor Vasa. 2026;68(4):503-508. doi: 10.33678/cor.2026.012.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • PDF will be unlocked 1.10.2026

    References

    1. Kempf T, Zarbock A, Widera C, et al. GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nat Med 2011;17:581-588. Table 2 - The main topic points of recent studies Reference no. Authors Subjects Main theme Ref [54] Li et al. Patients with "lone" atrial fibrillation In AF of unknown aetiology (UeAF), plasma GDF-15 was higher than sinus rhythm and lower than paroxysmal AF (PAF). Left atrial diameter and age substantially influence GDF-15. Ref [55] Chen et al. Patients with atrial fibrillation In this community-based biracial group, greater GDF-15 concentrations independently predicted incident AF. Ref [56] Carballo-Casla et al. Older adults The metabolic syndrome raised elderly GDF-15 levels. Abdominal obesity, hyperglycemia, low HDL-cholesterol, and inflammation caused this link. Ref [57] García-Esquinas et al. Non-smoking older adults Cd exposure raises CVD risk. CD may boost GDF-15. Ref [58] Zang et al. Ischemic Stroke patients GDF-15 levels independently predicted poststroke depression (PSD) in acute ischemic stroke, suggesting it may be a PSD biomarker. Ref [59] Sendur et al. Patients with diabetic foot ulcer Diabetic foot ulcer patients have elevated GDF-15. Advanced lesions are more common. GDF-15 measurement may help treat diabetic foot ulcers. Ref [60] Paneitz et al. Children with Congenital Heart Disease GDF-15 is an important growth indicator in congenital cardiac disease (CHD) children, especially those under 2 with HF. Prealbumin has no long-term growth biomarker. Ref [61] May et al. Patients with nonischemic dilated cardiomyopathy Serum GDF-15 independently predicted major arrhythmic episodes and mortality in nonischemic HF patients on optimal medication treatment. This biomarker may stratify sudden death risk in this population. Ref [62] Asrih et al. Patients with metabolic syndrome Preclinical animal studies show that GDF15 mimics lower food intake and weight. Thus, GDF15 might fight global obesity. Ref [63] Tridamayanti et al. Acute myocardial Infarction Patients At 3 months, MI patients with elevated GDF-15 risked major cardiac adverse events (MACE). Ref [64] Royston et al. People living with and without HIV GDF-15 and smoking synergistically increase coronary plaque volume in people living with HIV (PLWH). GDF-15 levels independently predicted coronary artery plaques in HIV-negative individuals. Ref [65] Deng et al. Patients With Chronic Obstructive Pulmonary Disease Chronic obstructive pulmonary disease (COPD) patients may readily assess sarcopenia using serum GDF15 levels. Ref [66] Mei et al. Patients with type 2 diabetes mellitus CAD and diabetic patients exhibited differing GDF-15 and ApoB/ ApoA1 levels. Diabetics may predict CAD using ApoB/ApoA1 and GDF-15. Ref [67] Duceppe et al. Patients 45 years or older having major noncardiac surgery GDF-15 accurately predicts 30-day major cardiovascular events and cardiac risk in noncardiac surgery patients. 508 Growth Differentiation Factor-15 and Cardiovascular Diseases
    2. Artz A, Butz S, Vestweber D. GDF-15 inhibits integrin activation and Mouse neutrophil recruitment through the ALK-5/TGF-RII heterodimer. Blood 2016;128:529 -41. Go to original source...
    3. Kempf T, Horn-Wichmann R, Brabant G, et al. Circulating concentrations of growthdifferentiation 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. Go to original source...
    4. Ding Q, Mracek T, Gonzalez-Muniesa P, et al. Identification of macrophage inhibitory cytokine-1 in adipose tissue and its secretion as an adipokine by human adipocytes. Endocrinology 2009;150:1688-1696. Go to original source...
    5. Lok SI, Winkens B, Goldschmeding R, et al. Circulating growth differentiation factor-15 correlates with myocardial fibrosis in patients with non-ischaemic dilated cardiomyopathy and decreases rapidly after left ventricular assist device support. Eur J Heart Fail 2012;14:1249-1256. Go to original source... Go to PubMed...
    6. Schaub N, Reichlin T, Twerenbold R, et al. Growth differentiation factor-15 in the early diagnosis and risk stratification of patients with acute chest pain. Clin Chem 2012;58:441-449. Go to original source... Go to PubMed...
    7. Daniels LB, Clopton P, Laughlin GA, et al. Growthdifferentiation 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. Go to original source...
    8. Wiklund FE, Bennet AM, Magnusson PK, et al. Macrophage inhibitory cytokine-1 (MIC-1/GDF15): a new marker of all-cause mortality. Aging Cell 2010;9:1057-1064. Go to original source... Go to PubMed...
    9. 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. Go to original source...
    10. 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. Go to original source...
    11. Koene RJ, Prizment AE, Blaes A, Konety SH. Shared risk factors in cardiovascular disease and cancer. Circulation 2016;133:1104-1114. Go to original source...
    12. Rasmussen-Torvik LJ, Shay CM, et al. Ideal cardiovascular health is inversely associated with incident cancer: the Atherosclerosis Risk In Communities study. Circulation 2013;127:1270-1275. Go to original source...
    13. Rothwell PM, Price JF, Fowkes FG, et al. Short-term effects of Daily aspirin on cancer incidence, mortality, and nonvascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet 2012;379:1602-1612. Go to original source...
    14. Fuchs T, Trollor JN, Crawford J, et al. Macrophage inhibitory cytokine-1 is associated with cognitive impairment and predicts cognitive decline - the Sydney Memory and Aging Study. Aging Cell 2013;12:882-889. Go to original source...
    15. 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. Go to original source... Go to PubMed...
    16. Bonaca MP, Morrow DA, Braunwald E, et al. Growth differentiation factor-15 and risk of recurrent events in patients stabilized after acute coronary syndrome: observations from PROVE ITTIMI 22. Arterioscler Thromb Vasc Biol 2011;31:203- Go to original source...
    17. Schopfer DW, Ku IA, Regan M, Whooley MA. 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.e1-192.e1. Go to original source... Go to PubMed...
    18. Fuernau G, Poenisch C, EitelI, et al. Growth- differentiation factor 15 and osteoprotegerin in acute myocardial infarction complicated by cardiogenic shock: a biomarker substudy of the IABP-SHOCK IItrial. Eur J Heart Fail 2014;16:880-887. Go to original source...
    19. Wallentin L, Lindhagen L, Ärnström E, et al. Early invasive versus non-invasive treatment in patients with non-STelevation acute coronary syndrome (FRISC-II): 15 year followup of a prospective, randomised, multicentre study. Lancet 2016;388:1903-1911. Go to original source...
    20. Wallentin L, Lindholm D, Siegbahn A, et al. Biomarkers in relation to the effects of ticagrelor in comparison with clopidogrel in non-ST-elevation acute coronary syndrome patients managed with or without in- hospital revascularization: a substudy from the Prospective Randomized Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation 2014;129:293-303. Go to original source...
    21. 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. Go to original source...
    22. Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 2013;62:263-271. Go to original source...
    23. Brassard P, Jensen AS, Nordsborg N, et al. Central and peripheral blood flow during exercise with a continuous-flow left ventricular assistdevice: constant versus increasing pump speed: a pilot study. Circ Heart Fail 2011;4:554-560. Go to original source...
    24. Kato TS, Chokshi A, Singh P, et al. Effects of continuousflow versus pulsatile-flow left ventricular assist devices on myocardial unloading andremodeling. Circ Heart Fail 2011;4:546-553. Go to original source... Go to PubMed...
    25. Cotter G, Voors AA, Prescott MF, et al. Growth differentiation factor 15 (GDF-15) in patients admitted for acute heart failure: results from the RELAX-AHF study. Eur J Heart Fail 2015;17:1133-1143. Go to original source... Go to PubMed...
    26. Wollert KC, Kempf T, Wallentin L. Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease. Clin Chem 2017;63:140-151. Go to original source... Go to PubMed...
    27. Abu-Assi E, Raposeiras-Roubin S, et al. Bleeding risk stratification in an era of aggressive management of acute coronary syndromes. World J Cardiol 2014;6:1140-1148. Go to original source...
    28. 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. Go to original source...
    29. Omar M, Jensen J, Kistorp C, et al. The effect of empagliflozin on growth differentiation factor 15 in patients with heart failure: a randomized controlled trial (Empire HF Biomarker). Cardiovasc Diabetol 2022;21:34. Go to original source...
    30. Li N, Feng Q, Yu F, et. Plasma growth differentiation factor-15 in patients with "lone" atrial fibrillation. J Clin Lab Anal 2022;36:e24373. Go to original source...
    31. Carballo-Casla A, García-Esquinas E, et al. Metabolic syndrome and Growth Differentiation Factor 15 in older adults. Geroscience 2022;44:867-880. Go to original source... Go to PubMed...
    32. García-Esquinas E, Ortolá R, Buño A, et al. Cadmium exposure and growth differentiation factor-15 (GDF-15) levels in nonsmoking older adults. Environ Res 2022;206:112250. Go to original source...
    33. Zang Y, Zhu Z, Xie Y, et al. Serum Growth Differentiation Factor 15 Levels Are Associated With Depression After Ischemic Stroke. J Am Heart Assoc 2022;11:e022607. Go to original source... Go to PubMed...
    34. Sendur SN, Firlatan B, Baykal G, et al. Serum growth differentiation factor-15 levels are associated with the severity of diabetic foot ulcer. Hormones (Athens) 2022;21:719-728. Go to original source...
    35. Paneitz DC, Zhou A, Yanek L, et al. Growth Differentiation Factor 15: A Novel Growth Biomarker for Children With Congenital Heart Disease. World J Pediatr Congenit Heart Surg 2022;13:745-751. Go to original source... Go to PubMed...
    36. Royston L, Isnard S, Perrin N, et al. Growth differentiation factor-15 as a biomarker of atherosclerotic coronary plaque: Value in people living with and without HIV. Front Cardiovasc Med 2022;9:964650. Go to original source... Go to PubMed...
    37. Mei Y, Zhao Z, Lyu Y, Li Y. Circulating growth differentiation factor 15 levels and apolipoprotein B to apolipoprotein A1 ratio in coronary artery disease patients with type 2 diabetes mellitus. Lipids Health Dis 2022;21:59. Go to original source...

    This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0), which permits non-comercial use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.


    Return to the content