Growth differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction

Khan, Sohail Q.; Ng, Kelvin; Dhillon, Onkar S.; Kelly, Dominic; Quinn, Paulene A.; Squire, Iain B.; Davies, Joan E.; Ng, Leong L.

doi:10.1093/eurheartj/ehn600

Cited by 195 publications

(137 citation statements)

References 18 publications

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“…Increased levels of GDF15/MIC-1 have been reported in several studies related to CVD or CV events, particularly in women 27,40,41 . A number of SNP have been analyzed for the GDF15/MIC-1 gene, and in particular SNP associated with promoter activity were associated with GDF15 protein level.…”

Section: Rheumatologymentioning

confidence: 86%

Polymorphisms of the Genes EncodingCD40and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease

Ärlestig¹,

Rantapää-Dahlqvist²

2012

J Rheumatol

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Objective.Genes or gene products associated with coronary artery disease in the general population were analyzed in rheumatoid arthritis (RA) patients with atherothrombotic manifestations (ATM).Methods.A cross-sectional study of 681 individuals (498 women; 183 men) with RA (American College of Rheumatology criteria), a mean age of 60.6 ± 13.2 years, and mean disease duration of 15.5 ± 12.6 years who were consecutively recruited and followed for 6 years. The prevalence of ATM [i.e., myocardial infarction, angina pectoris with intervention, deep vein thrombosis/pulmonary embolism (DVT/PE), and/or stroke/transient ischemic attack (TIA)] was recorded. Polymorphisms were analyzed in the genes coding for growth differentiation factor 15 (GDF15)/monocyte inhibitory cytokine-1 (MIC-1; rs1058587),CD40(rs1535045 and rs3765459), and the 9p21.3 locus (rs1333049). Controls were randomly selected (n = 687; matched for age and sex).Results.The distribution of genotypes ofGDF15/MIC-1differed significantly between patients with RA and controls (chi-squared = 6.40, 2 df, p = 0.041). ATM were associated with polymorphism of theGDF15/MIC-1G allele (OR 2.21, 95% CI 1.17–4.18), and with CC genotype of the 9p21.3 locus (rs1333049; OR 1.92, 95% CI 1.15–3.19). Stroke/TIA in women was associated withGDF15/MIC-1GG genotype (OR 3.75, 95% CI 1.06–13.33), while stroke/TIA in men was associated withCD40homozygous major alleles (OR 6.48, 95% CI 1.31–32.0 and OR 2.78, 95% CI 0.78–9.91, respectively). DVT/PE was associated with polymorphism in theGDF15/MIC-1gene (rs1058587) minor allele (OR 3.53, 95% CI 1.30–9.58).Conclusion.The gene polymorphisms analyzed were associated with different ATM in RA. TheGDF15/MIC-1gene polymorphism was also associated with RAper se, suggesting a common etiology for RA and ATM.

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Section: Rheumatologymentioning

confidence: 86%

Polymorphisms of the Genes EncodingCD40and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease

Ärlestig¹,

Rantapää-Dahlqvist²

2012

J Rheumatol

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“…8). In cardiovascular research, GDF-15 has emerged as an independent predictor of mortality (9,10). From this perspective, elevated GDF-15 levels are considered an endogenous protective mechanism for limiting cardiovascular damage (11).…”

mentioning

confidence: 99%

Growth Differentiation Factor 15, a Marker of Lung Involvement in Systemic Sclerosis, Is Involved in Fibrosis Development but Is not Indispensable for Fibrosis Development

Lambrecht

Smith

Wilde

et al. 2014

Arthritis & Rheumatology

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ObjectiveTransforming growth factor β superfamily members are involved in the pathogenesis of systemic sclerosis (SSc). Growth differentiation factor 15 (GDF‐15) is a distant member of this family. We undertook this study to evaluate the role of GDF‐15 in SSc pathogenesis.MethodsA longitudinal prospective cohort of SSc patients was screened for serum GDF‐15 levels using enzyme‐linked immunosorbent assay, and associations with clinical data were analyzed. In vitro stimulation experiments were performed on lung fibroblasts. The role of GDF‐15 in fibrosis development in vivo was evaluated in the bleomycin lung fibrosis model in GDF‐15–deficient mice.ResultsGDF‐15 was measured at baseline in serum samples from 119 SSc patients. An increase in GDF‐15 levels was observed in patients classified as having no skin involvement, those with limited cutaneous SSc, and those with diffuse cutaneous SSc. Moreover, baseline serum GDF‐15 levels correlated strongly with disease activity and extent of organ involvement, particularly clinical symptoms of lung fibrosis, including impact on lung function at prospective followup. This was mimicked in the bleomycin model of SSc, in which animals exposed to bleomycin had elevated expression levels of GDF‐15 in lung tissue. Lung fibroblasts isolated from GDF‐15–deficient mice showed reduced induction of interleukin‐6 and CCL2 upon bleomycin stimulation. Surprisingly, no differences in fibrosis development were observed between wild‐type and GDF‐15–deficient animals.ConclusionAn intriguing profile of serum GDF‐15 levels was found in SSc patients. GDF‐15 expression is induced during fibrosis development and markedly correlates with lung function impairment in this disease. The protein may participate in fibrosis initiation, but is not indispensable in the course of fibrosis development in vivo.

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“…Dodanie GDF-15 do skali ryzyka GRACE (Global Registry Of Acute Cardiac Events) poprawiało stratyfikację ryzyka (wystąpie-nia) zgonu i ponownego zawału niezakończonego zgonem [4]. W innej pracy GDF-15 okazał się także istotnym czynnikiem predykcyjnym zgonu i pozawałowej HF u chorych z przebytym zawałem serca [7]. Istotna klinicznie jest również ostatnio uznana rola GDF-15 jako predyktora dużych krwawień u pacjentów z migotaniem przedsionków leczonych przeciwzakrzepowo [8].…”

Section: Znaczenie Biologiczne Gdf-15unclassified

Czynnik różnicowania wzrostu 15 jako biomarker w niewydolności serca

Piechota

Krzesiński

2018

Folia Cardiologica

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Growth differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction

Cited by 195 publications

References 18 publications

Polymorphisms of the Genes EncodingCD40and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease

Polymorphisms of the Genes EncodingCD40and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease

Growth Differentiation Factor 15, a Marker of Lung Involvement in Systemic Sclerosis, Is Involved in Fibrosis Development but Is not Indispensable for Fibrosis Development

Czynnik różnicowania wzrostu 15 jako biomarker w niewydolności serca

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