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Associations of Arachidonic Acid Synthesis with Cardiovascular Risk Factors and Relation to Ischemic Heart Disease and Stroke: A Univariable and Multivariable Mendelian Randomization Study.

Authors
  • Zhang, Ting1
  • Au Yeung, Shiu-Lun1
  • Schooling, C Mary1, 2
  • 1 School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. , (China)
  • 2 School of Public Health and Health Policy, City University of New York, New York, NY 10027, USA.
Type
Published Article
Journal
Nutrients
Publisher
MDPI AG
Publication Date
Apr 28, 2021
Volume
13
Issue
5
Identifiers
DOI: 10.3390/nu13051489
PMID: 33924871
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Arachidonic acid (AA), a major long-chain omega-6 polyunsaturated fatty acid, is associated with ischemic heart disease (IHD) and stroke. We assessed bi-directional associations of AA synthesis reflected by plasma phospholipid AA with CVD risk factors, and identified mediators of associations of AA with IHD and stroke using Mendelian randomization (MR). We used two-sample MR to assess bi-directional associations of AA synthesis with lipids, blood pressure, adiposity, and markers of inflammation and coagulation. We used multivariable MR to assess mediators of associations of AA with IHD and stroke. Genetically predicted AA (% of total fatty acids increase) was positively associated with apolipoprotein B (ApoB, 0.022 standard deviations (SD), 95% confidence interval (CI) 0.010, 0.034), high-density (0.030 SD, 95% CI 0.012, 0.049) and low-density lipoprotein cholesterol (LDL-C, 0.016 SD, 95% CI 0.004, 0.027) and lower triglycerides (-0.031 SD, 95% CI -0.049, -0.012) but not with other traits. Genetically predicted these traits gave no association with AA. The association of AA with IHD was attenuated adjusting for ApoB or LDL-C. Genetically predicted AA was associated with lipids but not other traits. Given ApoB is thought to be the key lipid in IHD, the association of AA with IHD is likely mediated by ApoB.

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