Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Plasma Protein Profiling of Incident Cardiovascular Diseases : A Multisample Evaluation

Lind, Lars ; Titova, Olga ; Zeng, Rui ; Zanetti, Daniela ; Ingelsson, Martin ; Gustafsson, Stefan ; Sundström, Johan ; Arnlov, Johan ; Elmståhl, Sölve LU and Assimes, Themistocles , et al. (2023) In Circulation: Genomic and Precision Medicine 16(6).
Abstract

BACKGROUND: Proteomic profiling could potentially disclose new pathophysiological pathways for cardiovascular diseases (CVD) and improve prediction at the individual level. We therefore aimed to study the plasma protein profile associated with the incidence of different CVDs. METHODS: Plasma levels of 245 proteins suspected to be linked to CVD or metabolism were measured in 4 Swedish prospective population-based cohorts (SIMPLER [Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research], ULSAM (Uppsala Longitudinal Study of Adult Men), EpiHealth, and POEM [Prospective Investigation of Obesity, Energy Production, and Metabolism]) comprising 11 869 individuals, free of CVD diagnoses at baseline. Our... (More)

BACKGROUND: Proteomic profiling could potentially disclose new pathophysiological pathways for cardiovascular diseases (CVD) and improve prediction at the individual level. We therefore aimed to study the plasma protein profile associated with the incidence of different CVDs. METHODS: Plasma levels of 245 proteins suspected to be linked to CVD or metabolism were measured in 4 Swedish prospective population-based cohorts (SIMPLER [Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research], ULSAM (Uppsala Longitudinal Study of Adult Men), EpiHealth, and POEM [Prospective Investigation of Obesity, Energy Production, and Metabolism]) comprising 11 869 individuals, free of CVD diagnoses at baseline. Our primary CVD outcome was defined by a combined end point that included either incident myocardial infarction, stroke, or heart failure. RESULTS: Using a discovery/validation approach, 42 proteins were associated with our primary composite end point occurring in 1163 subjects. In separate meta-analyses for each of the 3 CVD outcomes, 49 proteins were related to myocardial infarction, 34 to ischemic stroke, and 109 to heart failure. Thirteen proteins were related to all 3 outcomes. Of those, urokinase plasminogen activator surface receptor, adrenomedullin, and KIM-1 (kidney injury molecule 1) were also related to several markers of subclinical CVD in Prospective Investigation of Obesity, Energy production and Metabolism, reflecting myocardial or arterial pathologies. In prediction analysis, a lasso selection of 11 proteins in ULSAM improved the discrimination of CVD by 3.3% (P<0.0001) in SIMPLER when added to traditional risk factors. CONCLUSIONS: Protein profiling in multiple samples disclosed several new proteins to be associated with subsequent myocardial infarction, stroke, and heart failure, suggesting common pathophysiological pathways for these diseases. KIM-1, urokinase plasminogen activator surface receptor, and adrenomedullin were novel early markers of CVD. A selection of 11 proteins improved the discrimination of CVD.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biomarkers, cardiovascular diseases, heart failure, ischemic stroke, myocardial infarction
in
Circulation: Genomic and Precision Medicine
volume
16
issue
6
article number
E004233
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:38014560
  • scopus:85180352483
ISSN
2574-8300
DOI
10.1161/CIRCGEN.123.004233
language
English
LU publication?
yes
id
42e2e16f-b668-4627-96bf-136a88bc9504
date added to LUP
2024-01-03 12:04:32
date last changed
2024-04-18 09:20:15
@article{42e2e16f-b668-4627-96bf-136a88bc9504,
  abstract     = {{<p>BACKGROUND: Proteomic profiling could potentially disclose new pathophysiological pathways for cardiovascular diseases (CVD) and improve prediction at the individual level. We therefore aimed to study the plasma protein profile associated with the incidence of different CVDs. METHODS: Plasma levels of 245 proteins suspected to be linked to CVD or metabolism were measured in 4 Swedish prospective population-based cohorts (SIMPLER [Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research], ULSAM (Uppsala Longitudinal Study of Adult Men), EpiHealth, and POEM [Prospective Investigation of Obesity, Energy Production, and Metabolism]) comprising 11 869 individuals, free of CVD diagnoses at baseline. Our primary CVD outcome was defined by a combined end point that included either incident myocardial infarction, stroke, or heart failure. RESULTS: Using a discovery/validation approach, 42 proteins were associated with our primary composite end point occurring in 1163 subjects. In separate meta-analyses for each of the 3 CVD outcomes, 49 proteins were related to myocardial infarction, 34 to ischemic stroke, and 109 to heart failure. Thirteen proteins were related to all 3 outcomes. Of those, urokinase plasminogen activator surface receptor, adrenomedullin, and KIM-1 (kidney injury molecule 1) were also related to several markers of subclinical CVD in Prospective Investigation of Obesity, Energy production and Metabolism, reflecting myocardial or arterial pathologies. In prediction analysis, a lasso selection of 11 proteins in ULSAM improved the discrimination of CVD by 3.3% (P&lt;0.0001) in SIMPLER when added to traditional risk factors. CONCLUSIONS: Protein profiling in multiple samples disclosed several new proteins to be associated with subsequent myocardial infarction, stroke, and heart failure, suggesting common pathophysiological pathways for these diseases. KIM-1, urokinase plasminogen activator surface receptor, and adrenomedullin were novel early markers of CVD. A selection of 11 proteins improved the discrimination of CVD.</p>}},
  author       = {{Lind, Lars and Titova, Olga and Zeng, Rui and Zanetti, Daniela and Ingelsson, Martin and Gustafsson, Stefan and Sundström, Johan and Arnlov, Johan and Elmståhl, Sölve and Assimes, Themistocles and Michaëlsson, Karl}},
  issn         = {{2574-8300}},
  keywords     = {{biomarkers; cardiovascular diseases; heart failure; ischemic stroke; myocardial infarction}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Circulation: Genomic and Precision Medicine}},
  title        = {{Plasma Protein Profiling of Incident Cardiovascular Diseases : A Multisample Evaluation}},
  url          = {{http://dx.doi.org/10.1161/CIRCGEN.123.004233}},
  doi          = {{10.1161/CIRCGEN.123.004233}},
  volume       = {{16}},
  year         = {{2023}},
}