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Plasma Metabolome Predicts Aortic Stiffness and Future Risk of Coronary Artery Disease and Mortality After 23 Years of Follow-Up in the General Population

Ottosson, Filip LU ; Engström, Gunnar LU ; Orho-Melander, Marju LU ; Melander, Olle LU orcid ; Nilsson, Peter M LU and Johansson, Madeleine LU orcid (2024) In Journal of the American Heart Association p.1-13
Abstract

BACKGROUND: Increased aortic stiffness (arteriosclerosis) is associated with early vascular aging independent of age and sex. The underlying mechanisms of early vascular aging remain largely unexplored in the general population. We aimed to investigate the plasma metabolomic profile in aortic stiffness (vascular aging) and associated risk of incident cardiovascular disease and mortality.

METHODS AND RESULTS: We included 6865 individuals from 2 Swedish population-based cohorts. Untargeted plasma metabolomics was performed by liquid-chromatography mass spectrometry. Aortic stiffness was assessed directly by carotid-femoral pulse wave velocity (PWV) and indirectly by augmentation index (AIx@75). A least absolute shrinkage and... (More)

BACKGROUND: Increased aortic stiffness (arteriosclerosis) is associated with early vascular aging independent of age and sex. The underlying mechanisms of early vascular aging remain largely unexplored in the general population. We aimed to investigate the plasma metabolomic profile in aortic stiffness (vascular aging) and associated risk of incident cardiovascular disease and mortality.

METHODS AND RESULTS: We included 6865 individuals from 2 Swedish population-based cohorts. Untargeted plasma metabolomics was performed by liquid-chromatography mass spectrometry. Aortic stiffness was assessed directly by carotid-femoral pulse wave velocity (PWV) and indirectly by augmentation index (AIx@75). A least absolute shrinkage and selection operator (LASSO) regression model was created on plasma metabolites in order to predict aortic stiffness. Associations between metabolite-predicted aortic stiffness and risk of new-onset cardiovascular disease, cardiovascular mortality, and all-cause mortality were calculated. Metabolite-predicted aortic stiffness (PWV and AIx@75) was positively associated particularly with acylcarnitines, dimethylguanidino valeric acid, glutamate, and cystine. The plasma metabolome predicted aortic stiffness (PWV and AIx@75) with good accuracy (R 2=0.27 and R 2=0.39, respectively). Metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly correlated with age, sex, systolic blood pressure, body mass index, and low-density lipoprotein. After 23 years of follow-up, metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly associated with increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality.

CONCLUSIONS: Aortic stiffness is associated particularly with altered metabolism of acylcarnitines, cystine, and dimethylguanidino valeric acid. These metabolic disturbances predict increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality after more than 23 years of follow-up in the general population.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
keywords
cardiology, aortic stiffness, Biomarkers
in
Journal of the American Heart Association
article number
e033442
pages
1 - 13
publisher
Wiley-Blackwell
external identifiers
  • pmid:38639368
ISSN
2047-9980
DOI
10.1161/JAHA.123.033442
project
Vascular Ageing and Arterial Stiffness in the Swedish Population
language
English
LU publication?
yes
id
9e941d69-7350-4a01-883d-0f9c803e31ad
date added to LUP
2024-04-21 22:04:57
date last changed
2024-06-15 15:36:27
@article{9e941d69-7350-4a01-883d-0f9c803e31ad,
  abstract     = {{<p>BACKGROUND: Increased aortic stiffness (arteriosclerosis) is associated with early vascular aging independent of age and sex. The underlying mechanisms of early vascular aging remain largely unexplored in the general population. We aimed to investigate the plasma metabolomic profile in aortic stiffness (vascular aging) and associated risk of incident cardiovascular disease and mortality.</p><p>METHODS AND RESULTS: We included 6865 individuals from 2 Swedish population-based cohorts. Untargeted plasma metabolomics was performed by liquid-chromatography mass spectrometry. Aortic stiffness was assessed directly by carotid-femoral pulse wave velocity (PWV) and indirectly by augmentation index (AIx@75). A least absolute shrinkage and selection operator (LASSO) regression model was created on plasma metabolites in order to predict aortic stiffness. Associations between metabolite-predicted aortic stiffness and risk of new-onset cardiovascular disease, cardiovascular mortality, and all-cause mortality were calculated. Metabolite-predicted aortic stiffness (PWV and AIx@75) was positively associated particularly with acylcarnitines, dimethylguanidino valeric acid, glutamate, and cystine. The plasma metabolome predicted aortic stiffness (PWV and AIx@75) with good accuracy (R 2=0.27 and R 2=0.39, respectively). Metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly correlated with age, sex, systolic blood pressure, body mass index, and low-density lipoprotein. After 23 years of follow-up, metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly associated with increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality. </p><p>CONCLUSIONS: Aortic stiffness is associated particularly with altered metabolism of acylcarnitines, cystine, and dimethylguanidino valeric acid. These metabolic disturbances predict increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality after more than 23 years of follow-up in the general population.</p>}},
  author       = {{Ottosson, Filip and Engström, Gunnar and Orho-Melander, Marju and Melander, Olle and Nilsson, Peter M and Johansson, Madeleine}},
  issn         = {{2047-9980}},
  keywords     = {{cardiology; aortic stiffness; Biomarkers}},
  language     = {{eng}},
  month        = {{04}},
  pages        = {{1--13}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of the American Heart Association}},
  title        = {{Plasma Metabolome Predicts Aortic Stiffness and Future Risk of Coronary Artery Disease and Mortality After 23 Years of Follow-Up in the General Population}},
  url          = {{http://dx.doi.org/10.1161/JAHA.123.033442}},
  doi          = {{10.1161/JAHA.123.033442}},
  year         = {{2024}},
}