Growth‐differentiation factor 15 and osteoprotegerin in acute myocardial infarction complicated by cardiogenic shock: a biomarker substudy of the IABP‐SHOCK II‐trial

Abstract

Aims This study investigates the role of osteoprotegerin (OPG) and growth‐differentiation factor 15 (GDF‐15) as predictors of outcome in cardiogenic shock (CS) complicating acute myocardial infarction. The novel biomarkers OPG and GDF‐15 have shown prognostic impact in various cardiovascular diseases including myocardial infarction. In acute myocardial infarction complicated by CS, the diagnostic and prognostic impact of these biomarkers has not been investigated yet. OPG and GDF‐15 may have additional prognostic impact on early prognosis assessment, being potentially useful for decision‐making in CS. Methods and results In the randomized Intra‐aortic Balloon Pump in cardiogenic Shock II (IABP‐SHOCK II)‐trial, 600 patients with CS complicating acute myocardial infarction undergoing early revascularization were assigned to therapy with or without IABP. Within a pre‐defined substudy, blood samples were collected from 190 patients during PCI. GDF‐15 and OPG serum levels were measured with standard enzyme‐linked immunosorbent assay kits. Patients with GDF‐15 and OPG levels greater than the median showed higher rates of death at 30 days by χ2 testing (OPG, 51% vs. 32%, P = 0.01; GDF‐15, 52% vs. 31%, P = 0.005) and log rank testing [GDF‐15, hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.21–2.94; P = 0.005; OPG, HR 1.74, 95% CI 1.11–2.71; P = 0.01]. Both markers were significantly predictive of 30‐day mortality in univariable logistic regression analysis. In a multivariable logistic stepwise regression model, GDF‐15, TIMI (Thrombolysis In Myocardial Infarction) flow grade <3 after PCI, age, LVEF, and serum lactate remained significant predictors of 30‐day mortality. Conclusion GDF‐15 on admission is a significant independent predictor of short‐term mortality in infarct‐related CS. Trail registration: NCT00491036

The association of admission blood glucose level with the clinical picture and prognosis in cardiogenic shock – Results from the CardShock Study

“…Many novel biomarkers have been studied in myocardial infarction and heart failure [29,30]. In CS, data on angiopoetin-2, FGF-23 and GDF-15 have been published, but so far these biomarkers have not been incorporated in clinical decision making [31][32][33].…”

Serum Concentrations of Osteogenesis/Osteolysis-Related Factors and Micro-RNA Expression in ST-Elevation Myocardial Infarction

“…Moreover, Erkol et al showed that, in STEMI patients undergoing PCI complicated with a no-reflow phenomenon, OPG serum concentrations were much higher in comparison to individuals with optimal myocardial reperfusion [10]. Thus, in regard to the study results, we presume that the increase of OPG serum level reflects extensiveness of the myocardial necrotic process [11]. In patients with STEMI, OPG levels correlate with a viable myocardium area when evaluated by SPECT [12].…”

Protein-based cardiogenic shock patient classifier

“…More recent studies have explored cardiac and extra-cardiac predictive biomarkers in CS. [8][9][10][11]20 However, most of these studies are small or not validated by external cohorts or did not assess the incremental predictive value of such biomarkers combined with current clinical practice. Particularly, novel renal biomarkers, including cystatin C, plasma neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1, have not performed better than conventional creatinine.…”

“…7 Accumulating evidence indicates that CS is not only a pump failure problem but is rather a systemic inflammatory status within the context of multiorgan failure. [8][9][10][11] Therefore, comprehensive proteomics may enable the discovery of novel protein biomarkers that can be used to acquire pathophysiological knowledge, improve risk stratification accuracy, and identify therapeutic targets. 12 In the present study, we used quantitative proteomics to identify and cross-validate a protein-based biomarker combination (the Cardiogenic Shock 4 Proteins-CS4P) as a new CS risk assessment score model for short-term mortality.…”