ce7d3bd5cc915defd9f501c618bd020e  pmc_9312922.pdf
1b06670a96c8617c3325e1df0d81f304434a68ae  pmc_9312922.pdf
b22abefe9b8b5e91d1b6ab924e14089ea96e79c46d81dbfa568fcc7d910ef41a  pmc_9312922.pdf

Title:           Major Adverse Cardiovascular Events and Mortality Prediction by Circulating GDF-15 in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
Subject:         Background: Growth differentiation factor 15 (GDF-15) is a homeostatic cytokine that regulates neural and cardio-metabolic functions, and its release is increased in response to stress, injury, and inflammation. In patients with coronary artery disease and heart failure (HF), three separate meta-analyses have found that elevated circulating GDF-15 was predictive of major adverse cardiovascular events (MACE), but none has evaluated its effects on incident MACE including HF and mortality hazard in type 2 diabetes. Methods: MEDLINE, EMBASE, and Scopus databases were queried. Articles that met the predefined eligibility criteria, including prospective studies that reported adjusted hazard ratios (aHRs), were selected according to the Cochrane Handbook and PRISMA guidelines. Study endpoints were (1) MACE including HF, and (2) all-cause mortality. Different GDF-15 concentration measurements were harmonized using a validated mathematical approach to express log2-transformed values in per standard deviation (SD). Study heterogeneity (I2), quality, and bias were assessed. Results: 19354 patients in 8 prospective studies were included. In 7 studies that reported 4247 MACE among 19200 participants, the incident rate was 22.1% during a median follow-up of 5.6 years. It was found that four of eight studies included HF decompensation or hospitalization as a component of MACE. In 5 studies that reported all-cause mortality, 1893 of 13223 patients died, at an incidence rate of 15.1% over 5.0 years. Of note, each 1 SD increase of log2[GDF-15] was associated with aHRs of 1.12 (1.09–1.15, I2 = 5%, p < 0.000001) and 1.27 (1.11–1.46, I2 = 86%, p = 0.00062) and for MACE and all-cause mortality, respectively. Conclusion: Elevated circulating level of GDF-15 was robustly predictive of MACE in patients with T2D but its prognostic significance in the prediction of mortality requires further studies.
Keywords:        growth differentiation factor 15; adverse cardiovascular outcomes; coronary artery disease; heart failure; type 2 diabetes; mortality
Author:          Suyi Xie, Qi Li, Andrea O. Y. Luk, Hui-Yao Lan, Paul K. S. Chan, Antoni Bayés-Genís, Francis K. L. Chan and Erik Fung
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     Item: 
      Title: Introduction 
      Destination: section.1
     Item: 
      Title: Materials and Methods 
      Destination: section.2
      Children: 
       Item: 
        Title: Data Sources and Search Strategy 
        Destination: subsection.2.1
       Item: 
        Title: Eligibility Criteria 
        Destination: subsection.2.2
       Item: 
        Title: Definition of Study Endpoints 
        Destination: subsection.2.3
       Item: 
        Title: Data Extraction 
        Destination: subsection.2.4
       Item: 
        Title: Data Harmonization and Statistical Analysis 
        Destination: subsection.2.5
       Item: 
        Title: Assessment of Publication Bias and Study Quality 
        Destination: subsection.2.6
     Item: 
      Title: Results 
      Destination: section.3
      Children: 
       Item: 
        Title: Characteristics of the Included Prospective Studies 
        Destination: subsection.3.1
       Item: 
        Title: Elevated GDF-15 and Risks of Future MACE 
        Destination: subsection.3.2
       Item: 
        Title: Elevated GDF-15 and Hazard of All-Cause Mortality 
        Destination: subsection.3.3
       Item: 
        Title: Ascertainment of Quality of Study and Publicaiton Bias 
        Destination: subsection.3.4
     Item: 
      Title: Discussion 
      Destination: section.4
     Item: 
      Title: Conclusions 
      Destination: section.5
     Item: 
      Title: References
      Destination: section.5
   Info: 
    Title: Major Adverse Cardiovascular Events and Mortality Prediction by Circulating GDF-15 in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
    Author: Suyi Xie, Qi Li, Andrea O. Y. Luk, Hui-Yao Lan, Paul K. S. Chan, Antoni Bayés-Genís, Francis K. L. Chan and Erik Fung
    Subject: Background: Growth differentiation factor 15 (GDF-15) is a homeostatic cytokine that regulates neural and cardio-metabolic functions, and its release is increased in response to stress, injury, and inflammation. In patients with coronary artery disease and heart failure (HF), three separate meta-analyses have found that elevated circulating GDF-15 was predictive of major adverse cardiovascular events (MACE), but none has evaluated its effects on incident MACE including HF and mortality hazard in type 2 diabetes. Methods: MEDLINE, EMBASE, and Scopus databases were queried. Articles that met the predefined eligibility criteria, including prospective studies that reported adjusted hazard ratios (aHRs), were selected according to the Cochrane Handbook and PRISMA guidelines. Study endpoints were (1) MACE including HF, and (2) all-cause mortality. Different GDF-15 concentration measurements were harmonized using a validated mathematical approach to express log2-transformed values in per standard deviation (SD). Study heterogeneity (I2), quality, and bias were assessed. Results: 19354 patients in 8 prospective studies were included. In 7 studies that reported 4247 MACE among 19200 participants, the incident rate was 22.1% during a median follow-up of 5.6 years. It was found that four of eight studies included HF decompensation or hospitalization as a component of MACE. In 5 studies that reported all-cause mortality, 1893 of 13223 patients died, at an incidence rate of 15.1% over 5.0 years. Of note, each 1 SD increase of log2[GDF-15] was associated with aHRs of 1.12 (1.09 1.15, I2 = 5%, p < 0.000001) and 1.27 (1.11 1.46, I2 = 86%, p = 0.00062) and for MACE and all-cause mortality, respectively. Conclusion: Elevated circulating level of GDF-15 was robustly predictive of MACE in patients with T2D but its prognostic significance in the prediction of mortality requires further studies.
    Keywords: growth differentiation factor 15; adverse cardiovascular outcomes; coronary artery disease; heart failure; type 2 diabetes; mortality
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  Checksum: dbdc68d8
   Type: CRC32
  Checksum: ce7d3bd5cc915defd9f501c618bd020e
   Type: MD5
  Checksum: 1b06670a96c8617c3325e1df0d81f304434a68ae
   Type: SHA-1
  Checksum: b22abefe9b8b5e91d1b6ab924e14089ea96e79c46d81dbfa568fcc7d910ef41a
   Type: SHA-256