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Proteomic exploration of common pathophysiological pathways in diabetes and cardiovascular disease

Molvin, John LU ; Jujić, Amra LU ; Melander, Olle LU ; Pareek, Manan ; Råstam, Lennart LU ; Lindblad, Ulf LU ; Daka, Bledar ; Leósdóttir, Margrét LU ; Nilsson, Peter M LU and Olsen, Michael H , et al. (2020) In ESC Heart Failure
Abstract

AIMS: The epidemiological association between diabetes and cardiovascular disease is well established, but the pathophysiological link is complex and multifactorial. We investigated seven proteins, previously linked to incident diabetes mellitus, and their association with cardiovascular disease and mortality.

METHODS AND RESULTS: Plasma samples from 1713 individuals from the Swedish population-based Malmö Preventive Project (mean age 67.4 ± 6.0 years; 29.1% women) were analysed with a proximity extension assay panel. Seven proteins [scavenger receptor cysteine rich type 1 protein M130 (CD163), fatty acid-binding protein 4 (FABP4), plasminogen activator inhibitor 1 (PAI), insulin-like growth factor-binding protein 2 (IGFB2),... (More)

AIMS: The epidemiological association between diabetes and cardiovascular disease is well established, but the pathophysiological link is complex and multifactorial. We investigated seven proteins, previously linked to incident diabetes mellitus, and their association with cardiovascular disease and mortality.

METHODS AND RESULTS: Plasma samples from 1713 individuals from the Swedish population-based Malmö Preventive Project (mean age 67.4 ± 6.0 years; 29.1% women) were analysed with a proximity extension assay panel. Seven proteins [scavenger receptor cysteine rich type 1 protein M130 (CD163), fatty acid-binding protein 4 (FABP4), plasminogen activator inhibitor 1 (PAI), insulin-like growth factor-binding protein 2 (IGFB2), cathepsin D (CTSD), galectin-4 (GAL4), and paraoxonase-3 (PON3)] previously shown to be associated with incident diabetes were analysed for associations with all-cause mortality (ACM), cardiovascular mortality (CVM), incident coronary events (CEs), and incident heart failure (HF). After exclusion of prevalent cases of respective outcome, proteins that met Bonferroni-corrected significance were analysed in multivariable Cox regression models. Significant associations were identified between five proteins [GAL4 (hazard ratio; 95% confidence interval: 1.17-1.41), CTSD (1.15-1.37), CD163 (1.09-1.30), IGFBP2 (1.05-1.30), and FABP4 (1.04-1.29)] and ACM and four proteins [GAL4 (1.38-1.56), CTSD (1.14-1.43), CD163 (1.09-1.36), and IGFBP2 (1.03-1.35)] with CVM. Three proteins [GAL4 (1.14-1.57), CTSD (1.12-1.50), and FABP4 (1.05-1.55)] were significantly associated with incident CE and two [GAL4 (1.03-1.54) and CTSD (1.01-1.46)] were associated with incident HF after adjusting for traditional risk factors including N-terminal pro-brain natriuretic peptide.

CONCLUSIONS: In a general Swedish population, four proteins previously shown to be associated with diabetes were associated with ACM and CVM. Three proteins were associated with incident CE. Finally, GAL4 and CTSD displayed novel associations with incident HF and were the only proteins associated with all outcomes.

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Contribution to journal
publication status
published
subject
in
ESC Heart Failure
publisher
John Wiley and Sons
external identifiers
  • scopus:85092354386
  • pmid:33047884
ISSN
2055-5822
DOI
10.1002/ehf2.13036
language
English
LU publication?
yes
additional info
© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
id
abacf912-edac-4182-a428-ff6516a8be41
date added to LUP
2020-10-22 10:28:55
date last changed
2021-06-16 01:22:37
@article{abacf912-edac-4182-a428-ff6516a8be41,
  abstract     = {<p>AIMS: The epidemiological association between diabetes and cardiovascular disease is well established, but the pathophysiological link is complex and multifactorial. We investigated seven proteins, previously linked to incident diabetes mellitus, and their association with cardiovascular disease and mortality.</p><p>METHODS AND RESULTS: Plasma samples from 1713 individuals from the Swedish population-based Malmö Preventive Project (mean age 67.4 ± 6.0 years; 29.1% women) were analysed with a proximity extension assay panel. Seven proteins [scavenger receptor cysteine rich type 1 protein M130 (CD163), fatty acid-binding protein 4 (FABP4), plasminogen activator inhibitor 1 (PAI), insulin-like growth factor-binding protein 2 (IGFB2), cathepsin D (CTSD), galectin-4 (GAL4), and paraoxonase-3 (PON3)] previously shown to be associated with incident diabetes were analysed for associations with all-cause mortality (ACM), cardiovascular mortality (CVM), incident coronary events (CEs), and incident heart failure (HF). After exclusion of prevalent cases of respective outcome, proteins that met Bonferroni-corrected significance were analysed in multivariable Cox regression models. Significant associations were identified between five proteins [GAL4 (hazard ratio; 95% confidence interval: 1.17-1.41), CTSD (1.15-1.37), CD163 (1.09-1.30), IGFBP2 (1.05-1.30), and FABP4 (1.04-1.29)] and ACM and four proteins [GAL4 (1.38-1.56), CTSD (1.14-1.43), CD163 (1.09-1.36), and IGFBP2 (1.03-1.35)] with CVM. Three proteins [GAL4 (1.14-1.57), CTSD (1.12-1.50), and FABP4 (1.05-1.55)] were significantly associated with incident CE and two [GAL4 (1.03-1.54) and CTSD (1.01-1.46)] were associated with incident HF after adjusting for traditional risk factors including N-terminal pro-brain natriuretic peptide.</p><p>CONCLUSIONS: In a general Swedish population, four proteins previously shown to be associated with diabetes were associated with ACM and CVM. Three proteins were associated with incident CE. Finally, GAL4 and CTSD displayed novel associations with incident HF and were the only proteins associated with all outcomes.</p>},
  author       = {Molvin, John and Jujić, Amra and Melander, Olle and Pareek, Manan and Råstam, Lennart and Lindblad, Ulf and Daka, Bledar and Leósdóttir, Margrét and Nilsson, Peter M and Olsen, Michael H and Magnusson, Martin},
  issn         = {2055-5822},
  language     = {eng},
  month        = {10},
  publisher    = {John Wiley and Sons},
  series       = {ESC Heart Failure},
  title        = {Proteomic exploration of common pathophysiological pathways in diabetes and cardiovascular disease},
  url          = {http://dx.doi.org/10.1002/ehf2.13036},
  doi          = {10.1002/ehf2.13036},
  year         = {2020},
}