Original Article

Serum Levels of Growth Differentiation Factor-15 as an Inflammatory Marker in Patients with Unstable Angina Pectoris


Background: Growth differentiation factor-15 (GDF-15), a member of transforming growth factors, is a stress-responsive marker whose levels may significantly increase in response to pathological stresses associated with inflammatory tissue injuries such as unstable angina pectoris (USAP). This study evaluated the diagnostic value of GDF-15 in patients with USAP.

Methods: The present cross-sectional study recruited 39 patients with USAP criteria and 30 patients with stable angina pectoris (SAP), referred to Shahid Beheshti Hospital, Kashan, Iran. All the patients with USAP had at least 1 coronary artery stenosis (>50%) in angiography. The control group comprised 42 healthy individuals. The serum levels of GDF-15 were measured in all the participants by ELISA. Also analyzed were the relationship between GDF-15 levels and thrombolysis in myocardial infarction (TIMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores in the patients with USAP to determine the severity of the disease.

Result: The study population consisted of 111 subjects, 62 women and 49 men, divided into 3 groups of USAP (n=39, mean age=60.07±14.10 y), SAP (n=30, mean age=67.56±9.88 y), and control (n=42, mean age=61.21±7.76 y). The mean serum level of GDF-15 in the USAP group was significantly different from the other 2 groups (P<0.001), while no significant difference was observed in this regard between the SAP and control groups (P=0.797). No correlation was found between the mean GDF-15 serum level and the GRACE (P=0.816) and TIMI (P=0.359) risk scores in the USAP group.

Conclusion:  The mean serum level of GDF-15 exhibited a rise in our patients with USAP. GDF-15 may be a diagnostic biomarker of USAP and its severity.

Silva FMF, Pesaro AEP, Franken M, Wajngarten M. Tratamento atual da síndrome coronária aguda sem supradesnivelamento do segmento ST. Einstein (16794508). 2015;13(3).

Bhatheja R, Mukherjee D. Acute coronary syndromes: unstable angina/non-ST elevation myocardial infarction. Critical care clinics. 2007;23(4):709-35.

Pokras R. Detailed diagnoses and procedures for patients discharged from short-stay hospitals, United States; 1985. 1987.

Amane HS, Burte N. A comparative study of dalteparin and unfractionated heparin in patients with unstable angina pectoris. Indian journal of pharmacology. 2011;43(6):703.

Théroux P, Fuster V. Acute coronary syndromes. Circulation. 1998;97(12):1195-206.

Zheng W, Lai Y, Jin P, Gu W, Zhou Q, Wu X. Association of Circulating IGFBP1 Level with the Severity of Coronary Artery Lesions in Patients with Unstable Angina. Disease markers. 2017;2017.

Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes. New England Journal of Medicine. 1992;326(4):242-50.

Salam RF, Nabeh M, Rashed L, Ahmed D. PROGNOSTIC VALUE OF PENTRAXIN3 IN ACUTE CORONARY SYNDROME. International Journal of Academic Research. 2014;6(5).

Kempf T, Sinning J-M, Quint A, Bickel C, Sinning C, Wild PS, et al. Growth-differentiation factor-15 for risk stratification in patients with stable and unstable coronary heart disease. Circulation: Cardiovascular Genetics. 2009;2(3):286-92.

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-β superfamily. Proceedings of the National Academy of Sciences. 1997;94(21):11514-9.

Hsiao EC, Koniaris LG, Zimmers-Koniaris T, Sebald SM, Huynh TV, Lee S-J. Characterization of growth-differentiation factor 15, a transforming growth factor β superfamily member induced following liver injury. Molecular and cellular biology. 2000;20(10):3742-51.

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.

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.

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.

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.

Silva FMF, Pesaro AEP, Franken M, Wajngarten M. Acute management of unstable angina and non-ST segment elevation myocardial infarction. Einstein (São Paulo). 2015;13(3):454-61.

Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, et al. The TIMI risk score for unstable angina/non–ST elevation MI: a method for prognostication and therapeutic decision making. Jama. 2000;284(7):835-42.

Tang EW, Wong C-K, Herbison P. Global Registry of Acute Coronary Events (GRACE) hospital discharge risk score accurately predicts long-term mortality post acute coronary syndrome. American heart journal. 2007;153(1):29-35.

Ambrose JA, Winters SL, Stern A, Eng A, Teichholz LE, Gorlin R, et al. Angiographie morphology and the pathogenesis of unstable angina pectoris. Journal of the American College of Cardiology; 1985.

Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT. Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture. Circulation. 1994;90(2):775-8.

DiSciascio G, Cowley MJ, Goudreau E, Vetrovec GW, Johnson DE. Histopathologic correlates of unstable ischemic syndromes in patients undergoing directional coronary atherectomy: in vivo evidence of thrombosis, ulceration, and inflammation. American heart journal. 1994;128(3):419-26.

Centurión OA. Serum biomarkers and source of inflammation in acute coronary syndromes and percutaneous coronary interventions. Cardiovascular Revascularization Medicine. 2016;17(2):119-28.

Bauskin AR, Brown DA, Kuffner T, Johnen H, Luo XW, Hunter M, et al. Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer. Cancer research. 2006;66(10):4983-6.

Secchiero P, Corallini F, Gonelli A, Dell’Eva R, Vitale M, Capitani S, et al. Antiangiogenic activity of the MDM2 antagonist nutlin-3. Circulation research. 2007;100(1):61-9.

Bermúdez B, López S, Pacheco YM, Villar J, Muriana FJ, Hoheisel JD, et al. Influence of postprandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coronary artery. Cardiovascular research. 2008;79(2):294-303.

Ding Q, Mracek T, Gonzalez-Muniesa P, Kos K, Wilding J, Trayhurn P, et al. Identification of macrophage inhibitory cytokine-1 in adipose tissue and its secretion as an adipokine by human adipocytes. Endocrinology. 2008;150(4):1688-96.

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.

Kempf T, Sinning J-M, Quint A, Bickel C, Sinning C, Wild PS, et al. Growth-Differentiation Factor-15 for Risk Stratification in Patients With Stable and Unstable Coronary Heart DiseaseCLINICAL PERSPECTIVE: Results From the AtheroGene Study. Circulation: Genomic and Precision Medicine. 2009;2(3):286-92.

Schaub N, Reichlin T, Twerenbold R, Reiter M, Steuer S, Bassetti S, et al. Growth differentiation factor-15 in the early diagnosis and risk stratification of patients with acute chest pain. Clinical chemistry. 2012;58(2):441-9.

Kempf T, von Haehling S, Peter T, Allhoff T, Cicoira M, Doehner W, et al. Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure. Journal of the American College of Cardiology. 2007;50(11):1054-60.

Kempf T, Horn-Wichmann R, Brabant G, Peter T, Allhoff T, Klein 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. Clinical chemistry. 2007;53(2):284-91.

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.

IssueVol 16 No 1 (2021): J Teh Univ Heart Ctr QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/jthc.v16i1.6595
Unstable angina Stable angina GDF-15 GRACE risks score TIMI risk score

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How to Cite
Raygan F, Etminan A, Mohammadi H, Akbari H, Nikoueinejad hassan. Serum Levels of Growth Differentiation Factor-15 as an Inflammatory Marker in Patients with Unstable Angina Pectoris. J Tehran Heart Cent. 16(1):15-19.