scholarly journals Growth Differentiation Factor 15 Provides Prognostic Information Superior to Established Cardiovascular and Inflammatory Biomarkers in Unselected Patients Hospitalized With COVID-19

Circulation ◽  
2020 ◽  
Vol 142 (22) ◽  
pp. 2128-2137 ◽  
Author(s):  
Peder L. Myhre ◽  
Christian Prebensen ◽  
Heidi Strand ◽  
Ragnhild Røysland ◽  
Christine M. Jonassen ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Troponin T ◽  
Inflammatory Biomarkers ◽  
Receiver Operating Curve ◽  
Prognostic Information ◽  
Unique Identifier ◽  
Growth Differentiation Factor 15 ◽  
End Point ◽  
Differentiation Factor ◽  
Lower Oxygen

Background: Growth differentiation factor 15 (GDF-15) is a strong prognostic marker in sepsis and cardiovascular disease (CVD). The prognostic value of GDF-15 in coronavirus disease 2019 (COVID-19) is unknown. Methods: Consecutive, hospitalized patients with laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and symptoms of COVID-19 were enrolled in the prospective, observational COVID Mechanisms Study. Biobank samples were collected at baseline, day 3 and day 9. The primary end point was admission to the intensive care unit or death during hospitalization, and the prognostic performance of baseline and serial GDF-15 concentrations were compared with that of established infectious disease and cardiovascular biomarkers. Results: Of the 123 patients enrolled, 35 (28%) reached the primary end point; these patients were older, more often had diabetes, and had lower oxygen saturations and higher National Early Warning Scores on baseline. Baseline GDF-15 concentrations were elevated (>95th percentile in age-stratified healthy individuals) in 97 (79%), and higher concentrations were associated with detectable SARS-CoV-2 viremia and hypoxemia (both P <0.001). Patients reaching the primary end point had higher concentrations of GDF-15 (median, 4225 [IQR, 3197–5972] pg/mL versus median, 2187 [IQR, 1344–3620] pg/mL, P <0.001). The area under the receiver operating curve was 0.78 (95% CI, 0.70–0.86). The association between GDF-15 and the primary end point persisted after adjusting for age, sex, race, body mass index, estimated glomerular filtration rate, previous myocardial infarction, heart failure, and atrial fibrillation ( P <0.001) and was superior and incremental to interleukin-6, C-reactive protein, procalcitonin, ferritin, D-dimer, cardiac troponin T, and N-terminal pro-B-type natriuretic peptide. Increase in GDF-15 from baseline to day 3 was also greater in patients reaching the primary end point (median, 1208 [IQR, 0–4305] pg/mL versus median, –86 [IQR, –322 to 491] pg/mL, P <0.001). Conclusions: GDF-15 is elevated in the majority of patients hospitalized with COVID-19, and higher concentrations are associated with SARS-CoV-2 viremia, hypoxemia, and worse outcome. The prognostic value of GDF-15 was additional and superior to established cardiovascular and inflammatory biomarkers. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04314232.

Abstract 5016: Growth-Differentiation Factor-15 is an Independent Predictor of Cardiovascular Events and Mortality in Patients with Stable Coronary Artery Disease

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Tibor Kempf ◽  
Jan-Malte Sinning ◽  
Anja Quint ◽  
Christoph Bickel ◽  
Christoph Sinning ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Independent Predictor ◽  
Troponin T ◽  
Receiver Operating Curve ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
All Cause Mortality ◽  
Artery Disease ◽  
Stable Cad

Circulating levels of the TGF β-related cytokine, growth-differentiation factor-15 (GDF-15), provide independent prognostic information in patients with unstable coronary artery disease (CAD). To explore the prognostic utility of GDF-15 in patients with stable CAD, we analyzed the relation of GDF-15 to mortality and cardiovascular (CV) events in the AtheroGene registry which enrolled consecutive patients with stable angina and at least one stenosis >30% in a larger coronary artery. Patients were followed for a median of 3.6 years. Serum samples for measurement of GDF-15 along with other biomarkers were available from 1352 patients. Two pre-specified cutoff points (1200 and 1800 ng/L) were used to identify different risk groups. 55.9%, 26.4%, and 17.7% of the patients presented with GDF-15 values <1200 ng/L, between 1200 and 1800 ng/L, and >1800 ng/L, respectively. Increasing levels of GDF-15 were related to age (P<0.001), hypertension (P=0.01), diabetes mellitus (P<0.001), low HDL cholesterol (P<0.001), and the extent of CAD (P=0.001). Moreover, significant relations to hsCRP, troponin T, NT-proBNP, and reduced renal function (GFR) were observed (all P<0.001). Increasing levels of GDF-15 were associated with an increased risk of all-cause mortality (P<0.001, log-rank test), CV mortality (P<0.001), and CV events (P<0.001). Receiver operating curve analyses confirmed GDF-15 as a strong marker of 2-year adverse outcomes (area under the curve for all-cause mortality, 0.79; CV mortality, 0.81; CV events, 0.70). By multiple Cox regression analysis, GDF-15 emerged as an independent predictor of all-cause mortality (HR 2.1 per one standard deviation of lnGDF-15 [95% CI 1.6 –2.8], P<0.001), CV mortality (HR 2.2 [95% CI 1.5–3.3], P<0.001), and CV events (HR 1.7 [95% CI 1.3–2.4], P=0.001) after adjustment for baseline characteristics, clinical variables, LDL/HDL ratio, hsCRP, troponin T, NT-proBNP, and GFR. Patients with a GDF-15 level above 1800 ng/L had a highly elevated risk of CV mortality even in the fully adjusted model (HR 5.2 [95% CI 1.6 –16.1], P=0.005). These data identify GDF-15 as a powerful and independent biomarker of mortality and CV events in patients with stable CAD.

scholarly journals Growth Differentiation Factor 15 Predicts All-Cause Morbidity and Mortality in Stable Coronary Heart Disease

2017 ◽  
Vol 63 (1) ◽  
pp. 325-333 ◽  
Author(s):  
Emil Hagström ◽  
Claes Held ◽  
Ralph A H Stewart ◽  
Philip E Aylward ◽  
Andrzej Budaj ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Troponin T ◽  
High Sensitivity ◽  
Prognostic Biomarkers ◽  
Morbidity And Mortality ◽  
Growth Differentiation Factor 15 ◽  
End Point ◽  
Differentiation Factor ◽  
Stable Coronary Heart Disease

Abstract BACKGROUND Higher growth differentiation factor 15 (GDF-15) concentrations are associated with cardiovascular (CV) and non-CV morbidity and mortality. However, information on associations between GDF-15 and the risk of specific CV and non-CV events in stable coronary heart disease (CHD) patients is limited. METHODS In 14 577 patients with stable CHD participating in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY), GDF-15 and other prognostic biomarkers (N-terminal pro–B-type natriuretic peptide, high-sensitivity troponin T, cystatin C, and high-sensitivity C-reactive protein) were measured. In adjusted Cox regression models, the associations between GDF-15 and the composite CV end point [CV death, myocardial infarction (MI), and stroke], as well as other CV and non-CV events, were assessed. RESULTS The median concentration (interquartile range) of GDF-15 at baseline was 1253 (915–1827) ng/L. The hazard ratio for the composite end point for the highest compared to the lowest quartile of GDF-15 was 1.8 (95% CI, 1.5–2.2); for CV death, 2.63 (1.9–3.6); for sudden death, 3.06 (1.9–4.8); for heart failure (HF) death, 4.3 (1.3–14); for cancer death, 2.5 (1.3–4.7); for hospitalization for HF, 5.8 (3.2–10); for MI 1.4 (95% CI, 1.1–1.9); and for stroke, 1.8 (95% CI, 1.1–2.8). After adjustment for other prognostic biomarkers, GDF-15 remained significantly associated with all outcomes except for MI. CONCLUSIONS In stable CHD, GDF-15 was independently associated with CV, non-CV, and cancer mortality, as well as with MI and stroke. When also adjusting for other prognostic biomarkers, the associations to all fatal and nonfatal events were maintained except for MI. Information on GDF-15, therefore, might be helpful when assessing the risk of adverse outcomes in patients with stable CHD. ClinicalTrials.gov Identifier: NCT00799903

scholarly journals PROGNOSTIC VALUE OF GROWTH DIFFERENTIATION FACTOR 15(GDF-15) IN MYOCARDIAL INFARCTION

2021 ◽  
Vol 14 (2) ◽  
pp. 52-55
Author(s):  
ALEXANDRA A. SABIRZYANOVA ◽  
◽  
ALBERT S. GALYVICH ◽  
Keyword(s):  
Myocardial Infarction ◽  
Risk Stratification ◽  
Prognostic Value ◽  
Practical Medicine ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

Determining the prognosis of a disease and risk stratification are significant issues in practical medicine. Aim.The aim of the study was to estimate the prognostic value of growth differentiation factor 15 (GDF-15) in myocardial infarction according to the literature.

Abstract P009: Growth Differentiation Factor 15 And The Subsequent Risk Of Atrial Fibrillation: The Atherosclerosis Risk In Communities Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Mengkun Chen ◽  
Ning Ding ◽  
Lena Mathews ◽  
Ron C Hoogeveen ◽  
Christie M Ballantyne ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Proportional Hazards ◽  
Troponin T ◽  
Cox Proportional Hazards ◽  
Atherosclerosis Risk In Communities ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Cox Proportional Hazards Models ◽  
Increased Risk ◽  
Icd 10

Introduction: Growth differentiation factor 15 (GDF-15) is a marker of oxidative stress and inflammation and has been associated with several cardiovascular disease (CVD) phenotypes. However, conflicting results have been reported regarding the association of GDF-15 with incident atrial fibrillation (AF) in the general population. Hypotheses: Higher GDF-15 level is associated with increased risk of incident AF independent of potential confounders. Methods: In 10,101 White and Black ARIC participants (mean age 60 years and 20.9% Blacks) free of AF at baseline (1993-95), we quantified the association of GDF-15 and incident AF using three Cox proportional hazards models. GDF-15 was measured by SOMA scan assay. AF was defined by hospitalizations with AF diagnosis or death certificates (ICD-9 codes: 427.31-427.32; ICD-10 codes: I48.x) or AF diagnosis by ECG at subsequent ARIC visits. Results: There were 2165 cases of incident AF over a median follow-up of 20.7 years (incidence rate 12.1 cases/1,000 person-years). After adjusting for demographic characteristics and cardiovascular risk factors, log GDF-15 was significantly associated with incident AF (hazard ratio 1.42 (1.25-1.63) for top vs. bottom quartile) (Model 1 in Table ). The result was robust even further adjusting for history of other CVD phenotypes and cardiac markers (Models 2 and 3 in Table ). In Model 3, quartiles of high-sensitive cardiac troponin T (hs-cTnT) did not demonstrate significant associations with incident AF. Conclusions: In community-based population, elevated GDF-15 level was independently and robustly associated with incident AF (even more strongly than troponin). These results suggest the involvement of GDF-15 in the development of AF and the potential of GDF-15 as a risk marker to identify individuals at high risk of AF.

Growth Differentiation Factor-15 in Patients with Light Chain (AL) Amyloidosis Has Independent Prognostic Significance and Adds Prognostic Information Related to Risk of Early Death and Renal Outcomes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 306-306 ◽  
Author(s):  
Efstathios Kastritis ◽  
Ioannis Papassotiriou ◽  
Evangelos Terpos ◽  
Athanassios Akalestos ◽  
Erasmia Psimenou ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Significance ◽  
Early Death ◽  
Cardiac Biomarkers ◽  
Al Amyloidosis ◽  
Prognostic Information ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Hematological Response ◽  
Independent Prognostic Significance

Abstract Growth differentiation factor-15 (GDF-15) is a member of the TGF-beta family, which is involved in several pathological conditions, including inflammation, cancer, cardiovascular, pulmonary and renal diseases. GDF-15 has prognostic value in patients with cardiovascular disorders and adds prognostic information to conventional prognostic factors, such as NT-proBNP and high-sensitivity troponin (hs-TnT). Cardiac involvement is the most important determinant of prognosis in patients with AL amyloidosis and cardiac biomarkers have major prognostic importance in AL. The aim of the study was to explore the value of GDF-15 in patients with AL amyloidosis. We measured the circulating levels of GDF-15, NT-proBNP and hs-TnT in 77 patients with newly diagnosed AL amyloidosis, before and 3 months post frontline treatment. GDF-15 was measured by a novel pre-commercial immunoassay (Roche Diagnostics). Patients' median age was 68 years; most patients had cardiac (61%) or renal involvement (74%); 61% had NT-proBNP >1284 pg/ml and 46% had hsTnT>54 ng/ml. Median eGFR was 57 ml/min/1.73m2, 52% had eGFR <60 ml/min/1.73m2, while 12% required dialysis at the time of treatment initiation. All patients received primary therapy with bortezomib- (49%) or lenalidomide-based regimens (51%). Median levels of GDF-15 were 3594 pg/ml (range 626-71,475pg/ml); 95% of patients with AL had GDF-15 levels >1200 pg/ml (the upper limit of normal for individuals without cardiovascular disease). GDF-15 correlated with NT-proBNP (r=0.538, p<0.001), hs-TnT (r=0.447, p=0.02) and eGFR (r=-0.570, p<0.001). Patients with GDF-15 levels within the upper quartile (>7575 pg/ml) had a very poor outcome (median overall survival (OS) 3 months) compared to patients with GDF-15 levels below the upper quartile (p=0.01; see the Figure). Among other cardiac markers, hs-TnT >54 ng/ml (12 vs >48 months, p=0.001) and NT-proBNP >1284 pg/ml (11 vs >48 months, p<0.001) were also associated with shorter OS. Higher cut-off levels for NT-proBNP and hs-TnT did not discriminate patients at high risk for early death more accurately. In a multiple logistic regression model which included GDF-15, NT-proBNP and hs-TnT, only GDF-15 in the upper quartile (HR: 8.427, 95% CI 1.73-41.1, p=0.008) was independently predictive of early death at 3 months. Similar results were obtained when these biomarkers were treated as continuous variables. Regarding OS, GDF-15 had independent prognostic significance in a multivariate model that included both NT-proBNP and hs-TnT. We also evaluated changes in the levels of GDF-15, NT-proBNP and hs-TnT in patients who received lenalidomide after 3 months of treatment. In these patients NT-proBNP often increases without obvious deterioration of cardiac function, thus complicating the assessment of cardiac response early, during the course of therapy. GDF-15 levels did not change significantly either in patients with hematological response (p=0.998) or those without hematological response (p=0.774). However, NT-proBNP levels increased substantially both in those with hematological response (p=0.05) and in those without hematological responses (p=0.013). Similarly, hs-TnT levels increased in non-responders (p=0.006) and did not change in patients with hematological response (p=0.251). As GDF-15 reflects heart and renal defects, we further evaluated whether GDF-15 could be associated with the risk of progression to ESRD and need for dialysis. Using ROC analysis, GDF-15 >median was identified to better discriminate patients which had a shorter time to dialysis (29 months vs not reached, p=0.001, see the Figure; with 38% vs. 8% progressing to ESRD, respectively). eGFR< 60 ml/min/m2 was also a strong predictor of ESRD (p=0.004). However, in multivariate analysis which included GDF-15 >median, eGFR <60 ml/min/m2 and proteinuria >5 g/day, only GDF-15 was independently associated with a higher risk of ESRD requiring dialysis (HR: 4.25, 95% CI 1.01-18, p=0.045). In conclusion, GDF-15 is a novel biomarker with prognostic implications for different outcomes in patients with AL; it is associated with a high risk of early death, with OS and also with renal outcome. More importantly GDF-15 adds prognostic information independent of the traditional cardiac biomarkers and thus, its measurement in larger series of patients is recommended. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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