Biological variation, reference change values and index of individuality of GDF-15

Sithiravel, Cindhya; Røysland, Ragnhild; Alaour, Bashir; Sylte, Marit Sverresdotter; Torsvik, Janniche; Strand, Heidi; Marber, Michael; Omland, Torbjørn; Aakre, Kristin Moberg

doi:10.1515/cclm-2021-0769

Cited by 8 publications

(4 citation statements)

References 10 publications

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“… 18 Moreover, reported low biological variation of GDF-15 (over repeated measurements in the same individual) supports that it may be useful for prognostication in individual subjects. 37 It is not known whether GDF-15 is useful in identifying groups of patients who will benefit from specific cardiac interventions. Although there was statistically significant heterogeneity in the HR for MI with higher GDF-15 levels in patients with ACS vs. in those without, it should be noted that there were only three ACS trials in this dataset and validation of this observation in additional data sets will be helpful.…”

Section: Discussionmentioning

confidence: 99%

Growth differentiation factor 15 and cardiovascular risk: individual patient meta-analysis

Kato

Morrow

Guo

et al. 2022

European Heart Journal

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Aims Levels of growth differentiation factor 15 (GDF-15), a cytokine secreted in response to cellular stress and inflammation, have been associated with multiple types of cardiovascular (CV) events. However, its comparative prognostic performance across different presentations of atherosclerotic cardiovascular disease (ASCVD) remains unknown. Methods and results An individual patient meta-analysis was performed using data pooled from eight trials including 53 486 patients. Baseline GDF-15 concentration was analyzed as a continuous variable and using established cutpoints (<1200 ng/L, 1200–1800 ng/L, > 1800 ng/L) to evaluate its prognostic performance for CV death/hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE), and their components using Cox models adjusted for clinical variables and established CV biomarkers. Analyses were further stratified on ASCVD status: acute coronary syndrome (ACS), stabilized after recent ACS, and stable ASCVD. Overall, higher GDF-15 concentration was significantly and independently associated with an increased rate of CV death/HHF and MACE (P < 0.001 for each). However, while GDF-15 showed a robust and consistent independent association with CV death and HHF across all presentations of ASCVD, its prognostic association with future myocardial infarction (MI) and stroke only remained significant in patients stabilized after recent ACS or with stable ASCVD [hazard ratio (HR): 1.24, 95% confidence interval (CI): 1.17–1.31 and HR: 1.16, 95% CI: 1.05–1.28 for MI and stroke, respectively] and not in ACS (HR: 0.98, 95% CI: 0.90–1.06 and HR: 0.87, 95% CI: 0.39–1.92, respectively). Conclusion Growth differentiation factor 15 consistently adds prognostic information for CV death and HHF across the spectrum of ASCVD. GDF-15 also adds prognostic information for MI and stroke beyond clinical risk factors and cardiac biomarkers but not in the setting of ACS.

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Section: Discussionmentioning

confidence: 99%

Growth differentiation factor 15 and cardiovascular risk: individual patient meta-analysis

Kato

Morrow

Guo

et al. 2022

European Heart Journal

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“…Like galectin-3 and ST2, GDF-15 has a low RCV. 19 Assays for these tests are not available within hospital or emergency department laboratories, but instead, from national reference laboratories. Diabetes is a major risk factor for the development of HF.…”

Section: Speakermentioning

confidence: 99%

Emerging Biomarkers in the Laboratory and in Practice: A Novel Approach to Diagnosing Heart Failure in Diabetes

Aaron,

Tian,

Fleming

et al. 2024

J Diabetes Sci Technol

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The Biomarkers for the Diagnosis of Heart Failure in Diabetes webinar was hosted by Diabetes Technology Society on September 20, 2023, with the objective to review current evidence and management practices of biomarker screening for heart failure in people with diabetes. The webinar discussed (1) the four stages of heart failure, (2) diabetes and heart failure, (3) natriuretic peptide and troponin for diagnosing heart failure in diabetes, (4) emerging composite and investigational biomarkers for diagnosing heart failure, and (5) prevention of heart failure progression. Experts in heart failure from the fields of clinical chemistry, cardiology, and diabetology presented data about the importance of screening for heart failure as an often-unnoticed complication of people with type 1 and type 2 diabetes.

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“…More importantly, GDF-15 undergoes various post-translational modifications such as glycosylation, phosphorylation, and lipid modification, which contribute to its increased stability and specific interactions with other biomolecules. [31][32][33][34] For instance, GDF-15 binds to its receptors to exert its effects leading to specific cellular responses, such as cellular growth, differentiation, and apoptosis. 26,29,35 Furthermore, GDF-15 can also block TGF-β receptors and downstream N-Myc signaling pathways, inhibiting apoptosis and collagen production in primary fibroblasts, thereby exerting anti-fibrotic effects on the kidneys.…”

Section: The Structure and Functions Of Gdf-15mentioning

confidence: 99%

Role and Mechanism of Growth Differentiation Factor 15 in Chronic Kidney Disease

Tang,

Liu,

Sun

et al. 2024

JIR

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GDF-15 is an essential member of the transforming growth factor-beta superfamily. Its functions mainly involve in tissue injury, inflammation, fibrosis, regulation of appetite and weight, development of tumor, and cardiovascular disease. GDF-15 is involved in various signaling pathways, such as MAPK pathway, PI3K/AKT pathway, STAT3 pathway, RET pathway, and SMAD pathway. In addition, several factors such as p53, ROS, and TNF-α participate the regulation of GDF-15. However, the specific mechanism of these factors regulating GDF-15 is still unclear and more research is needed to explore them. GDF-15 mainly improves the function of kidneys in CKD and plays an important role in the prediction of CKD progression and cardiovascular complications. In addition, the role of GDF-15 in the kidney may be related to the SMAD and MAPK pathways. However, the specific mechanism of these pathways remains unclear. Accordingly, more research on the specific mechanism of GDF-15 affecting kidney disease is needed in the future. In conclusion, GDF-15 may be a therapeutic target for kidney disease.

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Biological variation, reference change values and index of individuality of GDF-15

Cited by 8 publications

References 10 publications

Growth differentiation factor 15 and cardiovascular risk: individual patient meta-analysis

Growth differentiation factor 15 and cardiovascular risk: individual patient meta-analysis

Emerging Biomarkers in the Laboratory and in Practice: A Novel Approach to Diagnosing Heart Failure in Diabetes

Role and Mechanism of Growth Differentiation Factor 15 in Chronic Kidney Disease

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