The Prognostic Potential of Growth Differentiation Factor-15 on Bleeding Events and Patient Outcome after Cardiac Surgery—A Prospective Cohort Study

Abstract

Background: GDF-15 (growth/differentiation factor 15) is induced by myocardial stretch, volume overload, inflammation and oxidative stress. Its expression is tightly linked with cardiovascular events as well as the risk for major bleeding and all-cause mortality. The present study aimed to elucidate the prognostic potential of GDF-15 in patients after cardiac surgery. Methods: 504 patients undergoing elective cardiac valve and/or coronary artery bypass graft surgery were prospectively enrolled. GDF-15 levels were measured prior surgery to evaluate the impact on bleeding events, thromboembolic events and mortality. Results: Preoperative GDF-15 was associated with the primary endpoint of intra- and postoperative red blood cell transfusion (for bleeding risk factors adjusted [adj] OR [odds ratio] per 1-SD [standard deviation] of 1.62 [95%CI:1.31-2.00]; p<0.001). Higher concentrations of GDF-15 were observed in patients reaching the secondary endpoint of major or clinically relevant minor bleeding (for bleeding risk factors adj. OR per 1-SD of 1.70 [95%CI:1.05-2.75]; p=0.030) during the 1st postoperative year, but not for thromboembolic events. GDF-15 was a predictor for cardiovascular mortality (for comorbidities adj. HR [hazard ratio] per 1-SD of 1.67 [95%CI:1.23-2.27]; p=0.001) and all-cause mortality (for comorbidities adj. HR per 1-SD of 1.55 [95%CI:1.19-2.01]; p=0.001). A combined risk model of GDF-15 and EuroSCORE II outperformed the EuroSCORE II alone for long-term survival (c-index: 0.75 [95%CI: 0.70-0.80], p=0.046; net reclassification improvement: 33.6%, p<0.001). Conclusion: Preoperative GDF-15 concentration is an independent predictor for intra- and postoperative major bleeding, major bleeding during the first year and for long-term cardiovascular or all-cause mortality after cardiac surgery.

Association of Preoperative Growth Differentiation Factor-15 Concentrations and Postoperative Cardiovascular Events after Major Noncardiac Surgery

“…In a cohort of 504 patients undergoing elective coronary artery bypass surgery and/or cardiac valve repair, Kazem et al found that preoperative GDF-15 was associated with 1-year all-cause mortality and cardiovascular mortality. 21 The addition of GDF-15 to the European System of Cardiac Operative Risk Evaluation (EuroSCORE II; i.e., a risk score used in cardiac surgery to predict postoperative mortality) improved prediction of long-term survival (i.e., net reclassification improvement, 33.6%). A study by Heringlake et al looked at preoperative GDF-15 in 1,458 patients undergoing cardiac surgery and found that patients who died at 30 days had significantly higher median preoperative GDF-15 than survivors (2,537 pg/ ml vs. 1,057 pg/ml).…”

“…In a cohort of 504 patients undergoing elective coronary artery bypass surgery and/or cardiac valve repair, Kazem et al found that preoperative GDF-15 was associated with 1-year all-cause mortality and cardiovascular mortality. 21 The addition of GDF-15 to the European System of Cardiac Operative Risk Evaluation (EuroSCORE II; i.e. , a risk score used in cardiac surgery to predict postoperative mortality) improved prediction of long-term survival ( i.e.…”

“…19 In cardiac surgery, GDF-15 was independently associated with postoperative morbidity and mortality and significantly improved risk stratification in addition to preoperative risk score and NT-proBNP. 20,21 The study hypotheses were that GDF-15 could also have incremental predictive value when added to a preoperative risk score and NT-proBNP in a noncardiac surgery population. The aim of this study was to determine in patients undergoing noncardiac surgery if GDF-15 was associated with postoperative cardiovascular events and improved risk stratification in addition to Revised Cardiac Risk Index and NT-proBNP.…”

Growth Differentiation Factor 15 in Cardiovascular Diseases: Predicting Bleeding after Cardiac Surgery and Beyond That!

“…In this issue of Thrombosis and Haemostasis , Kazem and colleagues reported the outcomes of 504 prospective patients undergoing cardiac valve and/or coronary artery bypass graft surgery. 20 In brief, preoperative GDF-15 levels strongly associated with any intra- and postoperative red blood cell transfusion (adjusted odds ratio [aOR]: 1.62, 95% CI: 1.31–2.00) and ≥2 intra- and postoperative red blood cell transfusions (aOR: 1.75, 95% CI: 1.39–2.21). Importantly, preoperative GDF-15 levels were also related with the risk of composite of bleeding events (aOR: 1.33, 95% CI: 1.01–1.76), major or clinically relevant minor bleeding (aOR: 1.69, 95% CI: 1.08–4.46), and ≥2 red blood cell transfusions (aOR: 4.07, 95% CI: 1.78–9.28) during the first postoperative year.…”

“…The authors therefore concluded that the preoperative GDF-15 level was an independent predictor for intra- and postoperative major bleeding, and major bleeding during the first year after cardiac surgery. 20…”