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Growth differentiation factor-15 is a biomarker for all-cause mortality but less evident for cardiovascular outcomes : A prospective study

Bao, Xue LU ; Borné, Yan LU ; Xu, Biao ; Orho-Melander, Marju LU ; Nilsson, Jan LU ; Melander, Olle LU orcid and Engström, Gunnar LU (2021) In American Heart Journal 234. p.81-89
Abstract

Background: Previous studies have proposed growth differentiation factor-15 (GDF-15) as a predictor of adverse cardiovascular outcomes and mortality. The present study aimed to determine if such associations remain after accounting for death as a competing risk, and if GDF-15 provides superior prediction performance than other biomarkers. Methods: Plasma GDF-15 levels and cardiovascular risk factors were measured in individuals without cardiovascular diseases (n = 4,143, aged 57.4 ± 5.96 years, 38.6 % men) from Malmö Diet and Cancer-Cardiovascular Cohort and were followed up for more than 20 years. Incidence of coronary events, ischemic stroke, cardiovascular mortality, and all-cause mortality was studied in relation to GDF-15 using Cox... (More)

Background: Previous studies have proposed growth differentiation factor-15 (GDF-15) as a predictor of adverse cardiovascular outcomes and mortality. The present study aimed to determine if such associations remain after accounting for death as a competing risk, and if GDF-15 provides superior prediction performance than other biomarkers. Methods: Plasma GDF-15 levels and cardiovascular risk factors were measured in individuals without cardiovascular diseases (n = 4,143, aged 57.4 ± 5.96 years, 38.6 % men) from Malmö Diet and Cancer-Cardiovascular Cohort and were followed up for more than 20 years. Incidence of coronary events, ischemic stroke, cardiovascular mortality, and all-cause mortality was studied in relation to GDF-15 using Cox proportional hazards regression, with adjustment for potential confounders. Confounding from death as competing risk was carefully checked using the Fine and Gray subdistribution hazard model. Predictive capabilities were further evaluated using C-statistics, continuous net reclassification improvement, and integrated discrimination improvement. Results: During follow-up, 424 coronary events, 327 ischemic stroke, 368 cardiovascular deaths, and 1,308 all-cause deaths occurred. After controlling for death from other causes as competing events, only all-cause mortality remained significantly related to GDF-15. The addition of GDF-15 significantly improved prediction for all-cause mortality in addition to the traditional risk factors, high-sensitive C-reactive protein and N-terminal prohormone of brain natriuretic peptide. Only N-terminal prohormone of brain natriuretic peptide improved prediction for CVD mortality. Conclusions: GDF-15 is a robust biomarker for all-cause mortality but less reliable for coronary event, ischemic stroke or cardiovascular mortality. Competing risk from death is an important consideration when interpreting the results.

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organization
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type
Contribution to journal
publication status
published
subject
in
American Heart Journal
volume
234
pages
9 pages
publisher
Mosby-Elsevier
external identifiers
  • pmid:33421373
  • scopus:85100397809
ISSN
0002-8703
DOI
10.1016/j.ahj.2020.12.020
language
English
LU publication?
yes
id
a38886b8-c166-48a1-82bd-7fa6d71c1542
date added to LUP
2021-02-16 11:14:12
date last changed
2024-06-13 07:05:51
@article{a38886b8-c166-48a1-82bd-7fa6d71c1542,
  abstract     = {{<p>Background: Previous studies have proposed growth differentiation factor-15 (GDF-15) as a predictor of adverse cardiovascular outcomes and mortality. The present study aimed to determine if such associations remain after accounting for death as a competing risk, and if GDF-15 provides superior prediction performance than other biomarkers. Methods: Plasma GDF-15 levels and cardiovascular risk factors were measured in individuals without cardiovascular diseases (n = 4,143, aged 57.4 ± 5.96 years, 38.6 % men) from Malmö Diet and Cancer-Cardiovascular Cohort and were followed up for more than 20 years. Incidence of coronary events, ischemic stroke, cardiovascular mortality, and all-cause mortality was studied in relation to GDF-15 using Cox proportional hazards regression, with adjustment for potential confounders. Confounding from death as competing risk was carefully checked using the Fine and Gray subdistribution hazard model. Predictive capabilities were further evaluated using C-statistics, continuous net reclassification improvement, and integrated discrimination improvement. Results: During follow-up, 424 coronary events, 327 ischemic stroke, 368 cardiovascular deaths, and 1,308 all-cause deaths occurred. After controlling for death from other causes as competing events, only all-cause mortality remained significantly related to GDF-15. The addition of GDF-15 significantly improved prediction for all-cause mortality in addition to the traditional risk factors, high-sensitive C-reactive protein and N-terminal prohormone of brain natriuretic peptide. Only N-terminal prohormone of brain natriuretic peptide improved prediction for CVD mortality. Conclusions: GDF-15 is a robust biomarker for all-cause mortality but less reliable for coronary event, ischemic stroke or cardiovascular mortality. Competing risk from death is an important consideration when interpreting the results.</p>}},
  author       = {{Bao, Xue and Borné, Yan and Xu, Biao and Orho-Melander, Marju and Nilsson, Jan and Melander, Olle and Engström, Gunnar}},
  issn         = {{0002-8703}},
  language     = {{eng}},
  pages        = {{81--89}},
  publisher    = {{Mosby-Elsevier}},
  series       = {{American Heart Journal}},
  title        = {{Growth differentiation factor-15 is a biomarker for all-cause mortality but less evident for cardiovascular outcomes : A prospective study}},
  url          = {{http://dx.doi.org/10.1016/j.ahj.2020.12.020}},
  doi          = {{10.1016/j.ahj.2020.12.020}},
  volume       = {{234}},
  year         = {{2021}},
}