Plasma lipid profiles in early adulthood are associated with epigenetic aging in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Tao Gao, John T. Wilkins, Yinan Zheng, Brian T. Joyce, David R. Jacobs, Pamela J. Schreiner, Steve Horvath, Philip Greenland, Donald Lloyd-Jones, Lifang Hou

Research output: Contribution to journalArticlepeer-review

Abstract

Background: GrimAge acceleration (GAA), an epigenetic marker that represents physiologic aging, is associated with atherosclerotic cardiovascular disease. However, the associations between early adulthood lipid levels and GAA in midlife are unknown. Also, it is unknown whether GAA mediates the associations between lipid levels in young adults and subclinical atherosclerosis in midlife. Results: We estimated measures of epigenetic age acceleration in 1118 White and Black participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Study at examination years (Y) 15 and 20. We used multivariable regression models to examine associations of Y15 and Y20 GAA estimates with plasma lipid levels measured at prior examination years (Y0, Y5, and Y10) and concurrently: triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. Mediation analysis was used to assess the extent to which GAA may mediate associations between plasma lipids and coronary artery calcification (CAC). In our study each 1-SD higher cumulative TG level was associated with an average 0.73 ± 0.12 years older GAA. Each 1-SD higher cumulative HDL-C level was associated with an average 0.57 ± 0.17 years younger GAA. Stratified analyses showed that the associations between TG and GAA were stronger among female and Black participants and the associations between HDL-C and GAA were stronger among female and White participants. GAA statistically mediated 17.4% of the association of cumulative TG with CAC. Conclusions: High TG and low HDL-C in early adulthood are associated with accelerated epigenetic aging by midlife. Increased epigenetic age acceleration may partially mediate the associations between high TG levels and the presence of subclinical atherosclerosis.

Original languageEnglish (US)
Article number16
JournalClinical epigenetics
Volume14
Issue number1
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
This article has been reviewed by CARDIA (Coronary Artery Risk Development in Young Adults) for scientific content.

Funding Information:
The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I & HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005). The laboratory work and analytical component were funded by American Heart Association (17SFRN33700278 & 14SFRN20790000, Northwestern University, PI: Dr. Lifang Hou) and NHLBI (R01HL146844 PI: Dr. John T. Wilkins).

Publisher Copyright:
© 2022, The Author(s).

Keywords

  • Coronary artery calcification
  • GrimAge acceleration
  • Lipid

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

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