Predicting Value of Growth Differentiation Factor 15 and Its Correlations With Atrial Fibrillation
Keywords:GDF-15, atrial fibrillation, major bleeding, death
Aims: Despite several clinical risk factors for atrial fibrillation (AF), some newly identified biomarkers may also potentially serve as risk factors for AF. However, none of these factors so far have been adopted in clinical practice. Recently, a number of studies with an attempt to identify the role of growth differentiation factor 15 (GDF-15) in AF have obtained ambiguous results. We try to identify the predicting role of GDF-15 in AF and AF-related complications with meta-analysis or systematic analysis.
Methods and results: We enrolled 10 studies, looking at the predicting role of GDF-15 in non-valvular AF using meta-analysis, summarized its role in AF-related major complications, and discussed whether it was dependable to forecast postoperative AF. It turned out that GDF-15 is an independent factor to predict occurrence of AF, while it remains obscure to directly demonstrate its relationship with postoperative AF. For AF patients on anti-platelet treatment, GDF-15 plays a critical role in predicting major bleeding, cardiovascular death and overall death, and improves the current predicting model.
Conclusions: Circulating GDF-15 greatly associates with AF and AF-related complications. It should be applied clinically.
Adam O, Zimmer C, Hanke N, Hartmann RW, Klemmer B, Bohm M, and Laufs U. 2015. Inhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice. Journal of molecular and cellular cardiology. 85(140-50.
Anand IS, Kempf T, Rector TS, Tapken H, Allhoff T, Jantzen F, Kuskowski M, Cohn JN, Drexler H, and Wollert KC. 2010. Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial. Circulation. 122(14):1387-95.
Andrade J, Khairy P, Dobrev D, and Nattel S. 2014. The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms. Circulation research. 114(9):1453-68.
Bouchot O, Guenancia C, Kahli A, Pujos C, Malapert G, Vergely C, and Laurent G. 2015. Low Circulating Levels of Growth Differentiation Factor-15 Before Coronary Artery Bypass Surgery May Predict Postoperative Atrial Fibrillation. Journal of cardiothoracic and vascular anesthesia. 29(5):1131-9.
Chan MM, Santhanakrishnan R, Chong JP, Chen Z, Tai BC, Liew OW, Ng TP, Ling LH, Sim D, Leong KT, et al. 2016. Growth differentiation factor 15 in heart failure with preserved vs. reduced ejection fraction. European journal of heart failure. 18(1):81-8.
Cleophas TJ, and Zwinderman AH. 2007. Meta-analysis. Circulation. 115(22):2870-5.
DerSimonian R, and Laird N. 1986. Meta-analysis in clinical trials. Controlled clinical trials. 7(3):177-88.
Doulamis IP, Samanidis G, Tzani A, Antoranz A, Gkogkos A, Konstantopoulos P, Pliaka V, Minia A, Alexopoulos LG, Perrea DN, et al. 2018. Proteomic profile of patients with atrial fibrillation undergoing cardiac surgery. Interactive cardiovascular and thoracic surgery.
Duval S, and Tweedie R. 2000. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 56(2):455-63.
Fan LY, Jin ZG, Zong M, Wang QZ, Ju Y, Sun LS, Gu YY, Yu P, Zhang DF, and Liu ZM. 2014. Growth differentiation factor 15, ischemia modified albumin and pregnancy-associated plasma protein A in patients with coronary artery disease. Clinical laboratory. 60(6):973-82.
Fuernau G, Poenisch C, Eitel I, de Waha S, Desch S, Schuler G, Adams V, Werdan K, Zeymer U, and Thiele H. 2014. Growth-differentiation factor 15 and osteoprotegerin in acute myocardial infarction complicated by cardiogenic shock: a biomarker substudy of the IABP-SHOCK II-trial. European journal of heart failure. 16(8):880-7.
Hijazi Z, Oldgren J, Andersson U, Connolly SJ, Eikelboom JW, Ezekowitz MD, Reilly PA, Yusuf S, Siegbahn A, and Wallentin L. 2017. Growth-differentiation factor 15 and risk of major bleeding in atrial fibrillation: Insights from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. American heart journal. 190(94-103.
Hijazi Z, Oldgren J, Lindback J, Alexander JH, Connolly SJ, Eikelboom JW, Ezekowitz MD, Held C, Hylek EM, Lopes RD, et al. 2016. The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet. 387(10035):2302-11.
Hijazi Z, Oldgren J, Lindback J, Alexander JH, Connolly SJ, Eikelboom JW, Ezekowitz MD, Held C, Hylek EM, Lopes RD, et al. 2018. A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score. European heart journal. 39(6):477-85.
Hijazi Z, Oldgren J, Siegbahn A, and Wallentin L. 2017. Application of Biomarkers for Risk Stratification in Patients with Atrial Fibrillation. Clinical chemistry. 63(1):152-64.
Hirsh BJ, Copeland-Halperin RS, and Halperin JL. 2015. Fibrotic atrial cardiomyopathy, atrial fibrillation, and thromboembolism: mechanistic links and clinical inferences. Journal of the American College of Cardiology. 65(20):2239-51.
Hu XF, Zhan R, Xu S, Wang J, Wu J, Liu X, Li Y, and Chen L. 2018. Growth differentiation factor 15 is associated with left atrial/left atrial appendage thrombus in patients with nonvalvular atrial fibrillation. Clinical cardiology. 41(1):34-8.
Izumiya Y, Hanatani S, Kimura Y, Takashio S, Yamamoto E, Kusaka H, Tokitsu T, Rokutanda T, Araki S, Tsujita K, et al. 2014. Growth differentiation factor-15 is a useful prognostic marker in patients with heart failure with preserved ejection fraction. The Canadian journal of cardiology. 30(3):338-44.
Kahli A, Guenancia C, Zeller M, Grosjean S, Stamboul K, Rochette L, Girard C, and Vergely C. 2014. Growth differentiation factor-15 (GDF-15) levels are associated with cardiac and renal injury in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. PloS one. 9(8):e105759.
Kempf T, Zarbock A, Widera C, Butz S, Stadtmann A, Rossaint J, Bolomini-Vittori M, Korf-Klingebiel M, Napp LC, Hansen B, et al. 2011. GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nature medicine. 17(5):581-8.
Lind L, Sundstrom J, Stenemo M, Hagstrom E, and Arnlov J. 2017. Discovery of new biomarkers for atrial fibrillation using a custom-made proteomics chip. Heart. 103(5):377-82.
McManus DD, Rienstra M, and Benjamin EJ. 2012. An update on the prognosis of patients with atrial fibrillation. Circulation. 126(10):e143-6.
Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, and Stroup DF. 1999. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet. 354(9193):1896-900.
Montoro-Garcia S, Hernandez-Romero D, Jover E, Garcia-Honrubia A, Vilchez JA, Casas T, Martinez P, Climent V, Caballero L, Valdes M, et al. 2012. Growth differentiation factor-15, a novel biomarker related with disease severity in patients with hypertrophic cardiomyopathy. European journal of internal medicine. 23(2):169-74.
Rienstra M, Yin X, Larson MG, Fontes JD, Magnani JW, McManus DD, McCabe EL, Coglianese EE, Amponsah M, Ho JE, et al. 2014. Relation between soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I and incident atrial fibrillation. American heart journal. 167(1):109-15 e2.
Schlittenhardt D, Schober A, Strelau J, Bonaterra GA, Schmiedt W, Unsicker K, Metz J, and Kinscherf R. 2004. 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 and tissue research. 318(2):325-33.
Shiran A, and Sagie A. 2009. Tricuspid regurgitation in mitral valve disease incidence, prognostic implications, mechanism, and management. Journal of the American College of Cardiology. 53(5):401-8.
Vergara P, and Della Bella P. 2014. Management of atrial fibrillation. F1000Prime Rep. 6(22.
Wallentin L, Hijazi Z, Andersson U, Alexander JH, De Caterina R, Hanna M, Horowitz JD, Hylek EM, Lopes RD, Asberg S, et al. 2014. 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. 130(21):1847-58.
Wollert KC, Kempf T, and Wallentin L. 2017. Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease. Clinical chemistry. 63(1):140-51.
Zhang L, Huang B, Scherlag BJ, Ritchey JW, Embi AA, Hu J, Hou Y, and Po SS. 2015. Structural changes in the progression of atrial fibrillation: potential role of glycogen and fibrosis as perpetuating factors. International journal of clinical and experimental pathology. 8(2):1712-8.
Zhou YM, Li MJ, Zhou YL, Ma LL, and Yi X. 2015. Growth differentiation factor-15 (GDF-15), novel biomarker for assessing atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease. International journal of clinical and experimental medicine. 8(11):21201-7.
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