Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease

Wollert, Kai C.; Kempf, Tibor; Wallentin, Lars

doi:10.1373/clinchem.2016.255174

Cited by 419 publications

(425 citation statements)

References 78 publications

Supporting

Mentioning

367

Contrasting

Unclassified

Order By: Relevance

“…Both NT-proBNP and GDF15 are established markers of CV risk. 13,14 Notably, NT-proBNP only predicted CV events in 7 subjects with established CVD in the present study, irrespective of diabetes status. Other studies have identified elevated NT-proBNP as a CV risk factor in subjects with T2DM, 15 but to our knowledge it has previously not been shown that this primarily is the case for T2DM subjects with prevalent CVD.…”

Section: Discussionmentioning

confidence: 46%

Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes: The SUMMIT VIP Study

et al. 2018

View full text Add to dashboard Cite

OBJECTIVE Cardiovascular disease (CVD) risk prediction represents an increasing clinical challenge in the treatment of diabetes. We used a panel of vascular imaging, functional assessments, and biomarkers reflecting different disease mechanisms to identify clinically useful markers of risk for cardiovascular (CV) events in subjects with type 2 diabetes (T2D) with or without manifest CVD. RESEARCH DESIGN AND METHODS The study cohort consisted of 936 subjects with T2D recruited at four European centers. Carotid intima-media thickness and plaque area, ankle-brachial pressure index, arterial stiffness, endothelial function, and circulating biomarkers were analyzed at baseline, and CV events were monitored during a 3-year follow-up period. RESULTS The CV event rate in subjects with T2D was higher in those with (n = 440) than in those without (n = 496) manifest CVD at baseline (5.53 vs. 2.15/100 life-years, P < 0.0001). New CV events in subjects with T2D with manifest CVD were associated with higher baseline levels of inflammatory biomarkers (interleukin 6, chemokine ligand 3, pentraxin 3, and hs-CRP) and endothelial mitogens (hepatocyte growth factor and vascular endothelial growth factor A), whereas CV events in subjects with T2D without manifest CVD were associated with more severe baseline atherosclerosis (median carotid plaque area 30.4 mm2 [16.1–92.2] vs. 19.5 mm2 [9.5–40.5], P = 0.01). Conventional risk factors, as well as measurements of arterial stiffness and endothelial reactivity, were not associated with CV events. CONCLUSIONS Our observations demonstrate that markers of inflammation and endothelial stress reflect CV risk in subjects with T2D with manifest CVD, whereas the risk for CV events in subjects with T2D without manifest CVD is primarily related to the severity of atherosclerosis.

show abstract

Section: Discussionmentioning

confidence: 46%

Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes: The SUMMIT VIP Study

et al. 2018

View full text Add to dashboard Cite

show abstract

“…22 In response to tissue injury like MI, there is a further elevation of GDF- 15 that might be related to further activation of inflammatory activity and myocardial stress. 23,24 With regard to the more recently discovered bleeding association, the mechanism might still be related to frailty and cellular aging. 24 However, GDF-15 knockout mice show accelerated thrombus formation compared with wild type, and, in vitro, GDF-15 has been shown to inhibit platelet integrin activation, 25 which provides a possible pathophysiological link between the observed association between GDF-15 levels and bleeding in patients treated with antithrombotic and/or anticoagulant therapies.…”

Section: Discussionmentioning

confidence: 99%

“…23,24 With regard to the more recently discovered bleeding association, the mechanism might still be related to frailty and cellular aging. 24 However, GDF-15 knockout mice show accelerated thrombus formation compared with wild type, and, in vitro, GDF-15 has been shown to inhibit platelet integrin activation, 25 which provides a possible pathophysiological link between the observed association between GDF-15 levels and bleeding in patients treated with antithrombotic and/or anticoagulant therapies. Currently, there is intense discussion on the duration and intensity of DAPT and/or the combination of platelet inhibition with oral anticoagulation in patients with coronary artery disease.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

Self Cite

View full text Add to dashboard Cite

Background--Growth differentiation factor-15 (GDF-15) is related to major bleeding when measured at initial presentation in patients with acute coronary syndromes (ACSs) treated with dual antiplatelet therapy. It is unknown whether follow-up measurements provide additional information. The objective of this study was to investigate whether GDF-15 measured 1 month after an ACS provides additional information beyond the baseline levels with regard to the risk of major bleeding.

show abstract

“…For instance, serum galectin 3 has been reported to be a good predictor of dismal events and mortality in HF patients 26. Similarly, soluble ST2 has been reported to be independently associated with cardiovascular mortality in HF patients,27 and growth differentiation factor 15 with mortality and non‐fatal events in HF with preserved or reduced ejection fraction 28…”

Section: Selection Of Biomarkers Of Interestmentioning

confidence: 99%

Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis

et al. 2017

View full text Add to dashboard Cite

AimsMyocardial fibrosis alters the cardiac architecture favouring the development of cardiac dysfunction, including arrhythmias and heart failure. Reducing myocardial fibrosis may improve outcomes through the targeted diagnosis and treatment of emerging fibrotic pathways. The European‐Commission‐funded ‘FIBROTARGETS’ is a multinational academic and industrial consortium with the main aims of (i) characterizing novel key mechanistic pathways involved in the metabolism of fibrillary collagen that may serve as biotargets, (ii) evaluating the potential anti‐fibrotic properties of novel or repurposed molecules interfering with the newly identified biotargets, and (iii) characterizing bioprofiles based on distinct mechanistic phenotypes involving the aforementioned biotargets. These pathways will be explored by performing a systematic and collaborative search for mechanisms and targets of myocardial fibrosis. These mechanisms will then be translated into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure.Methods and resultsThe FIBROTARGETS consortium has merged data from 12 patient cohorts in a common database available to individual consortium partners. The database consists of >12 000 patients with a large spectrum of cardiovascular clinical phenotypes. It integrates community‐based population cohorts, cardiovascular risk cohorts, and heart failure cohorts.ConclusionsThe FIBROTARGETS biomarker programme is aimed at exploring fibrotic pathways allowing the bioprofiling of patients into specific ‘fibrotic’ phenotypes and identifying new therapeutic targets that will potentially enable the development of novel and tailored anti‐fibrotic therapies for heart failure.

show abstract

Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease

Abstract: GDF-15 captures distinct aspects of CV disease development, progression, and prognosis, which are not represented by clinical risk predictors and other biomarkers. The usefulness of GDF-15 to guide management decisions and discover new treatment targets should be further explored.

Cited by 419 publications

References 78 publications

Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes: The SUMMIT VIP Study

Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes: The SUMMIT VIP Study

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

Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis

Contact Info

Product

Resources

About