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Altered Acylcarnitine Metabolism Is Associated With an Increased Risk of Atrial Fibrillation

Smith, Einar LU ; Fernandez, Celine LU ; Melander, Olle LU orcid and Ottosson, Filip LU (2020) In Journal of the American Heart Association 9(21). p.016737-016737
Abstract

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, but the pathogenesis is not completely understood. The application of metabolomics could help in discovering new metabolic pathways involved in the development of the disease. Methods and Results We measured 112 baseline fasting metabolites of 3770 participants in the Malmö Diet and Cancer Study; these participants were free of prevalent AF. Incident cases of AF were ascertained through previously validated registers. The associations between baseline levels of metabolites and incident AF were investigated using Cox proportional hazard models. During 23.1 years of follow-up, 650 cases of AF were identified (incidence rate: 8.6 per 1000 person-years). In Cox... (More)

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, but the pathogenesis is not completely understood. The application of metabolomics could help in discovering new metabolic pathways involved in the development of the disease. Methods and Results We measured 112 baseline fasting metabolites of 3770 participants in the Malmö Diet and Cancer Study; these participants were free of prevalent AF. Incident cases of AF were ascertained through previously validated registers. The associations between baseline levels of metabolites and incident AF were investigated using Cox proportional hazard models. During 23.1 years of follow-up, 650 cases of AF were identified (incidence rate: 8.6 per 1000 person-years). In Cox regression models adjusted for AF risk factors, 7 medium- and long-chain acylcarnitines were associated with higher risk of incident AF (hazard ratio [HR] ranging from 1.09; 95% CI, 1.00-1.18 to 1.14, 95% CI, 1.05-1.24 per 1 SD increment of acylcarnitines). Furthermore, caffeine and acisoga were also associated with an increased risk (HR, 1.17; 95% CI, 1.06-1.28 and 1.08; 95% CI, 1.00-1.18, respectively), while beta carotene was associated with a lower risk (HR, 0.90; 95% CI, 0.82-0.99). Conclusions For the first time, we show associations between altered acylcarnitine metabolism and incident AF independent of traditional AF risk factors in a general population. These findings highlight metabolic alterations that precede AF diagnosis by many years and could provide insight into the pathogenesis of AF. Future studies are needed to replicate our finding in an external cohort as well as to test whether the relationship between acylcarnitines and AF is causal.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
acylcarnitines, atrial fibrillation, metabolomics
in
Journal of the American Heart Association
volume
9
issue
21
pages
016737 - 016737
publisher
Wiley-Blackwell
external identifiers
  • pmid:33076748
  • scopus:85095673554
ISSN
2047-9980
DOI
10.1161/JAHA.120.016737
language
English
LU publication?
yes
id
144d27ca-ca0b-4968-93ea-1a8ac8e2aa15
date added to LUP
2020-11-24 16:17:57
date last changed
2024-06-13 00:41:56
@article{144d27ca-ca0b-4968-93ea-1a8ac8e2aa15,
  abstract     = {{<p>Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, but the pathogenesis is not completely understood. The application of metabolomics could help in discovering new metabolic pathways involved in the development of the disease. Methods and Results We measured 112 baseline fasting metabolites of 3770 participants in the Malmö Diet and Cancer Study; these participants were free of prevalent AF. Incident cases of AF were ascertained through previously validated registers. The associations between baseline levels of metabolites and incident AF were investigated using Cox proportional hazard models. During 23.1 years of follow-up, 650 cases of AF were identified (incidence rate: 8.6 per 1000 person-years). In Cox regression models adjusted for AF risk factors, 7 medium- and long-chain acylcarnitines were associated with higher risk of incident AF (hazard ratio [HR] ranging from 1.09; 95% CI, 1.00-1.18 to 1.14, 95% CI, 1.05-1.24 per 1 SD increment of acylcarnitines). Furthermore, caffeine and acisoga were also associated with an increased risk (HR, 1.17; 95% CI, 1.06-1.28 and 1.08; 95% CI, 1.00-1.18, respectively), while beta carotene was associated with a lower risk (HR, 0.90; 95% CI, 0.82-0.99). Conclusions For the first time, we show associations between altered acylcarnitine metabolism and incident AF independent of traditional AF risk factors in a general population. These findings highlight metabolic alterations that precede AF diagnosis by many years and could provide insight into the pathogenesis of AF. Future studies are needed to replicate our finding in an external cohort as well as to test whether the relationship between acylcarnitines and AF is causal.</p>}},
  author       = {{Smith, Einar and Fernandez, Celine and Melander, Olle and Ottosson, Filip}},
  issn         = {{2047-9980}},
  keywords     = {{acylcarnitines; atrial fibrillation; metabolomics}},
  language     = {{eng}},
  number       = {{21}},
  pages        = {{016737--016737}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of the American Heart Association}},
  title        = {{Altered Acylcarnitine Metabolism Is Associated With an Increased Risk of Atrial Fibrillation}},
  url          = {{http://dx.doi.org/10.1161/JAHA.120.016737}},
  doi          = {{10.1161/JAHA.120.016737}},
  volume       = {{9}},
  year         = {{2020}},
}