growth differentiation factor 15
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Author(s):  
Lingxiao He ◽  
Philipe de Souto Barreto ◽  
Juan Luis Sánchez Sánchez ◽  
Yves Rolland ◽  
Sophie Guyonnet ◽  
...  

Abstract Background Growth differentiation factor 15 (GDF15) has been associated with several age-related disorders, but its associations with functional abilities in community-dwelling older adults are not well studied. Methods The study was a secondary analysis on 1096 community-dwelling older adults (aged 69 to 94 years) recruited from the Multidomain Alzheimer’s Preventive Trial. Plasma GDF15 was measured one year after participants’ enrolment. Annual data of physical performance (grip strength and short physical performance battery [SPPB]) and global cognitive functions (mini-mental state examination [MMSE] and a composite cognitive score) were measured for four years. Adjusted mixed-effects linear models were performed for cross-sectional and longitudinal association analyses. Results A higher GDF15 was cross-sectionally associated with a weaker grip strength (β = -1.1E-03, 95%CI [-2.0E-03, -1.5E-04]), a lower SPPB score (β = -3.1E-04, 95%CI [-5.4E-04, -9.0E-05]) and worse cognitive functions (β = -2.4E-04, 95%CI [-3.3E-04, -1.6E-04] for composite cognitive score; β = -4.0E-04, 95%CI [-6.4E-04, -1.6E-04] for MMSE). Participants with higher GDF15 demonstrated greater longitudinal declines in SPPB (β = -1.0E-04, 95%CI [-1.7E-04, -2.0E-05]) and composite cognitive score (β = -2.0E-05, 95%CI [-4.0E-05, -3.6E-06]). The optimal initial GDF15 cutoff values for identifying participants with minimal clinically significant decline after one year were 2189 pg/mL for SPPB (AUC: 0.580) and 2330 pg/mL for composite cognitive score (AUC: 0.587). Conclusions Plasma GDF15 is cross-sectionally and longitudinally associated with lower-limb physical performance and global cognitive function in older adults. Circulating GDF15 alone has limited capacity of discriminating older adults who will develop clinically significant functional declines.


Author(s):  
Yuhan Zang ◽  
Zhengbao Zhu ◽  
Yi Xie ◽  
Zhen Liu ◽  
Jieyun Yin ◽  
...  

Background The effect of serum growth differentiation factor 15 (GDF‐15) on poststroke depression (PSD) remains unknown. This study aimed to investigate the association between serum GDF‐15 and PSD among patients with ischemic stroke. Methods and Results This study was based on a random sample from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). A total of 572 patients from 7 participating hospitals with GDF‐15 levels were included in this analysis. The study outcome was depression (Hamilton Depression Rating Scale score ≥8) at 3 months after ischemic stroke. A total of 231 (40.4%) patients with stroke experienced PSD within 3 months. The multivariate‐adjusted odds ratio of PSD associated with the highest tertile of serum GDF‐15 was 2.92 (95% CI, 1.36–6.27) compared with the lowest tertile. Each SD increase in log‐transformed GDF‐15 was associated with a 42% (95% CI, 2%–97%) increased risk of PSD, and a linear association between serum GDF‐15 and the risk of PSD was observed ( P for linearity=0.006). Conclusions Elevated serum GDF‐15 levels in the acute phase of ischemic stroke were independently associated with PSD, suggesting that GDF‐15 may be a valuable prognostic biomarker for PSD.


2021 ◽  
Author(s):  
Susanna Lemmela ◽  
Eleanor M Wigmore ◽  
Christian Benner ◽  
Aki Havulinna ◽  
Rachel MY Ong ◽  
...  

Growth differentiation factor 15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6,610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across 3 different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant rs1058587 in GDF15, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine-mapping identified 4 independent putative causal signals at the locus. Mendelian randomisation (MR) analysis did not find evidence of a causal relationship between GDF15 concentration and cardiometabolic traits. Using reverse MR, we identified a potential causal association of body mass index on GDF15 (IVW pFDR=0.0072). Taken together, our data do not support a role for elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.


Author(s):  
Keita Negishi ◽  
Satoshi Hoshide ◽  
Masahisa Shimpo ◽  
Hiroshi Kanegae ◽  
Kazuomi Kario

Background Growth differentiation factor‐15 (GDF‐15) has emerged as a novel biomarker to predict all‐cause death in community‐dwelling individuals and patients with cardiovascular disease. We evaluated the prognostic value of GDF‐15 in outpatients with cardiovascular risk factors. Methods and Results GDF‐15 levels were measured in 3562 outpatients with cardiovascular risk factors in the J‐HOP (Japan Morning Surge‐Home Blood Pressure) study, a nationwide prospective study. Participants were stratified according to tertiles of GDF‐15 and followed up for all‐cause death and cardiovascular disease. During a mean follow‐up period of 6.6 years, there were 155 all‐cause deaths, 81 stroke events including cerebral infarction and intracranial hemorrhage, and 141 cardiac events including cardiac artery disease and heart failure. Patients with higher GDF‐15 levels were associated with risks of all‐cause death and stroke events (except for cardiac events) after adjustment for traditional risk factors and other prognostic biomarkers (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], high‐sensitivity troponin T; all‐cause death, hazard ratio, 2.38; 95% CI, 1.26–4.48; P =0.007; stroke events, hazard ratio, 2.93; 95% CI, 1.31–6.56, P =0.009; compared with the lowest tertile). Furthermore, incorporating GDF‐15 to the predictive models for all‐cause death improved discrimination and reclassification significantly. For stroke events, GDF‐15 showed similar diagnostic accuracy to NT‐proBNP and high‐sensitivity troponin T. Conclusions In Japanese outpatients with cardiovascular risk factors, GDF‐15 improves risk stratification for all‐cause death when compared with NT‐proBNP and high‐sensitivity troponin T. GDF‐15 was associated with increased risks of stroke events beyond conventional risk factors and other prognostic markers; however, the predictive ability for stroke events was equivalent to NT‐proBNP and high‐sensitivity troponin T. Registration URL: http://www.umin.ac.jp/ctr .; Unique identifier: UMIN000000894.


2021 ◽  
Vol 11 (12) ◽  
pp. 1612
Author(s):  
Ting Sun ◽  
Rui Peng ◽  
Xiaojun Sun ◽  
Yan Li

The interaction between the endocrine system and inflammation is crucial pathogenesis of depression. Our study aimed at exploring the possible relationship between sex hormones and growth differentiation factor-15 (GDF-15), a common indicator of inflammation in male patients with major depressive disorder (MDD). Methods: GDF-15 levels of 121 male MDD patients were compared with 105 healthy subjects with the help of a Cobas 8000 automatic chemiluminescence immunoanalyzer. Results: (1) MDD patients showed higher GDF-15 levels, a lower testosterone (T) level and testosterone/estradiol ratio (T/E2 ratio) than healthy subjects (all p < 0.05). (2) Serum T levels and the T/E2 ratio were inversely associated with GDF-15 serum levels (all p < 0.05). (3) HAMD-24 scores were positively correlated with the levels of GDF-15 (p < 0.01), but not with T levels, estradiol (E2) levels, and the T/E2 ratio (all p > 0.05). Conclusion: The high level of GDF-15 was correlated with a low T/E2 ratio and T deficiency in male MDD patients. The above results demonstrate that up-regulation of serum GDF-15 and down-regulation of T and T/E2 ratio may be correlated with the occurrence and severity of depression. So, changing the level of GDF-15 by regulating the proportion of sex hormones may play a key role in the prognosis and treatment of depression.


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