Skip to main content
SpringerLink
Log in

Growth differentiation factor-15 as a negative predictor for microvascular obstruction in ST-segment elevation myocardial infarction after primary percutaneous coronary intervention

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

Growth differentiation factor-15 (GDF-15) is an anti-inflammatory cytokine with cardioprotective effects, but circulating GDF-15 concentration predicts adverse cardiovascular outcomes in clinical settings. Microvascular obstruction (MVO) formation contributed to poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (pPCI). We aimed to investigate GDF-15 concentration in relation to cardiac magnetic resonance (CMR)-derived MVO in STEMI patients after pPCI, which might help better understand the role of GDF-15 in STEMI. GDF-15 levels at 6 h after pPCI and MVO extent at day 5 ± 2 after pPCI were measured in 74 STEMI patients (mean age 60.3 ± 12.8 years, 86.5% men). The adjusted association of GDF-15 with MVO was analyzed with MVO treated as a categorized variable (extensive MVO, defined as MVO extent ≥ 2.6% of left ventricular (LV)) and a continuous variable (MVO mass, % of LV), respectively, in multivariate logistic and linear regression models. 41.9% of the patients developed extensive MVO after pPCI. In multivariate analysis, the odds ratio (95% confidential interval (CI)) of each standard deviation (SD) increase in GDF-15 for developing extensive MVO was 0.46 (0.21, 0.82), p = 0.02). Consistently, when MVO was used a continuous variable, each SD increase in GDF-15 was associated with a substantially lower MVO mass (β − 0.42, standard error 0.19, p = 0.03). GDF-15 was a negative predictor for MVO in STEMI patients after pPCI. The observation was consistent with results from experiment studies, suggesting a potential protective effect of GDF-15 against cardiac injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

References

  1. Ibanez B et al (2018) 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 39(2):119–177

    Article  PubMed  Google Scholar 

  2. de Waha S et al (2017) Relationship between microvascular obstruction and adverse events following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: an individual patient data pooled analysis from seven randomized trials. Eur Heart J 38(47):3502–3510

    Article  PubMed  Google Scholar 

  3. Niccoli G et al (2016) Coronary microvascular obstruction in acute myocardial infarction. Eur Heart J 37(13):1024–1033

    Article  PubMed  Google Scholar 

  4. Unsicker K, Spittau B, Krieglstein K (2013) The multiple facets of the TGF-beta family cytokine growth/differentiation factor-15/macrophage inhibitory cytokine-1. Cytokine Growth Factor Rev 24(4):373–384

    Article  CAS  PubMed  Google Scholar 

  5. Kempf T et al (2006) The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury. Circ Res 98(3):351–360

    Article  CAS  PubMed  Google Scholar 

  6. Kempf T et al (2011) GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nat Med 17(5):581–588

    Article  CAS  PubMed  Google Scholar 

  7. Xu J et al (2006) GDF15/MIC-1 functions as a protective and antihypertrophic factor released from the myocardium in association with SMAD protein activation. Circ Res 98(3):342–350

    Article  CAS  PubMed  Google Scholar 

  8. Wollert KC, Kempf T, Wallentin L (2017) Growth differentiation factor 15 as a biomarker in cardiovascular disease. Clin Chem 63(1):140–151

    Article  CAS  PubMed  Google Scholar 

  9. Li M et al (2020) Growth differentiation factor-15 is associated with cardiovascular outcomes in patients with coronary artery disease. Cardiovasc Diabetol 19(1):120

    Article  PubMed  PubMed Central  Google Scholar 

  10. Xie S, Lu L, Liu L (2019) Growth differentiation factor-15 and the risk of cardiovascular diseases and all-cause mortality: a meta-analysis of prospective studies. Clin Cardiol 42(5):513–523

    Article  PubMed  PubMed Central  Google Scholar 

  11. Wu E et al (2001) Visualisation of presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction. Lancet 357(9249):21–28

    Article  CAS  PubMed  Google Scholar 

  12. Ibanez B et al (2019) Cardiac MRI endpoints in myocardial infarction experimental and clinical trials: JACC scientific expert panel. J Am Coll Cardiol 74(2):238–256

    Article  PubMed  PubMed Central  Google Scholar 

  13. Symons R et al (2018) Long-term incremental prognostic value of cardiovascular magnetic resonance after ST-segment elevation myocardial infarction: a study of the collaborative registry on CMR in STEMI. JACC Cardiovasc Imaging 11(6):813–825

    Article  PubMed  Google Scholar 

  14. Desquilbet L, Mariotti F (2010) Dose-response analyses using restricted cubic spline functions in public health research. Stat Med 29(9):1037–1057

    Article  PubMed  Google Scholar 

  15. No author (1991) Troponin T and myocardial damage. Lancet 338(8758):23–24

    Article  Google Scholar 

  16. Garcia R et al (2019) VEGF-A plasma levels are associated with microvascular obstruction in patients with ST-segment elevation myocardial infarction. Int J Cardiol 291:19–24

    Article  PubMed  Google Scholar 

  17. Arcari L et al (2015) Impact of heart rate on myocardial salvage in timely reperfused patients with ST-segment elevation myocardial infarction: new insights from cardiovascular magnetic resonance. PLoS ONE 10(12):e0145495

    Article  PubMed  PubMed Central  Google Scholar 

  18. Eitel I et al (2011) Growth-differentiation factor 15 as predictor of mortality in acute reperfused ST-elevation myocardial infarction: insights from cardiovascular magnetic resonance. Heart 97(8):632–640

    Article  PubMed  Google Scholar 

  19. Zhang M et al (2016) Growth differentiation factor 15 may protect the myocardium from no-reflow by inhibiting the inflammatory-like response that predominantly involves neutrophil infiltration. Mol Med Rep 13(1):623–632

    Article  CAS  PubMed  Google Scholar 

  20. Taddei S, Virdis A (2010) Growth differentiation factor-15 and cardiovascular dysfunction and disease: malefactor or innocent bystander? Eur Heart J 31(10):1168–1171

    Article  CAS  PubMed  Google Scholar 

  21. Thiele, H. et al. (2010) Impact of high-dose N-acetylcysteine versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: the LIPSIA-N-ACC (Prospective, single-blind, placebo-controlled, randomized Leipzig Immediate PercutaneouS coronary intervention acute myocardial infarction N-ACC) trial. J Am Coll Cardiol 55(20): 2201–2209

  22. McLeod SL, Iansavichene A, Cheskes S (2017) Remote ischemic Perconditioning to reduce reperfusion injury during acute ST-segment-elevation myocardial infarction: a systematic review and meta-analysis. J Am Heart Assoc. https://doi.org/10.1161/JAHA.117.005522

    Article  PubMed  PubMed Central  Google Scholar 

  23. Davidson SM et al (2019) Multitarget strategies to reduce myocardial ischemia/reperfusion injury: JACC review topic of the week. J Am Coll Cardiol 73(1):89–99

    Article  PubMed  Google Scholar 

  24. Hausenloy DJ, Yellon DM (2004) New directions for protecting the heart against ischaemia-reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway. Cardiovasc Res 61(3):448–460

    Article  CAS  PubMed  Google Scholar 

  25. Wang J et al (2020) Intravenously delivered mesenchymal stem cells prevent microvascular obstruction formation after myocardial ischemia/reperfusion injury. Basic Res Cardiol 115(4):40

    Article  CAS  PubMed  Google Scholar 

  26. Artz A, Butz S, Vestweber D (2016) GDF-15 inhibits integrin activation and mouse neutrophil recruitment through the ALK-5/TGF-betaRII heterodimer. Blood 128(4):529–541

    Article  CAS  PubMed  Google Scholar 

  27. Hayiroglu MI et al (2019) Predictors of in-hospital mortality in patients with ST-segment elevation myocardial infarction complicated with cardiogenic shock. Heart Lung Circ 28(2):237–244

    Article  PubMed  Google Scholar 

  28. Cinar T et al (2019) The predictive value of age, creatinine, ejection fraction score for in-hospital mortality in patients with cardiogenic shock. Coron Artery Dis 30(8):569–574

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all the participants in this study and the staff of the department of Clinical Laboratory at Nanjing Drum Tower Hospital.

Funding

This work was supported by the Natural Science Foundation of China (Grant Number 81970296) and Funds for Distinguished Young Scientists in Nanjing (Grant Number: JQX20006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Author notes

  1. Xiang Wu, Jian Bai, and Ying Tan are Co-first authors and have contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, China

    Xiang Wu, Jian Bai, Ying Tan, Zhonghai Wei, Qing Dai, Lina Kang, Lian Wang, Jianzhou Chen, Kun Wang & Han Wu

  2. Department of Echocardiography, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China

    Yining Yang

Authors
  1. Xiang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhonghai Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qing Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lina Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lian Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jianzhou Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yining Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Han Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HW and KW designed the study. XW, JB and YT wrote the manuscript. ZHW, QD, LNK, LW, JZC, KW and HW performed primary PCI. YNY analyzed the data and edited the manuscript. YT performed the data analysis. All the authors read and approved the final manuscript.

Corresponding authors

Correspondence to Kun Wang or Han Wu.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, X., Bai, J., Tan, Y. et al. Growth differentiation factor-15 as a negative predictor for microvascular obstruction in ST-segment elevation myocardial infarction after primary percutaneous coronary intervention. Int J Cardiovasc Imaging 40, 863–871 (2024). https://doi.org/10.1007/s10554-024-03055-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-024-03055-5

Keywords

Search

Navigation