Associations of HDL metrics with coronary artery calcium score and density among women traversing menopause

Samar R. El Khoudary, Alexis Nasr, Karen A. Matthews, Trevor J. Orchard, Maria M. Brooks, Jeffrey Billheimer, Dan McConnell, Imke Janssen, Susan A. Everson-Rose, Sybil Crawford, Daniel J. Rader

Research output: Contribution to journalArticlepeer-review

Abstract

The cardioprotective association of high-density lipoprotein cholesterol (HDL-C) may vary by menopause stage or estradiol level. We tested whether associations of comprehensive HDL metrics (HDL subclasses, phospholipid and triglyceride content, and HDL cholesterol efflux capacity [HDL-CEC]) with coronary artery calcium (CAC) score and density vary by menopause stage or estradiol level in women transitioning through menopause. Participants (N = 294; mean age [SD]: 51.3 [2.9]) had data on HDL metrics and CAC measures at one or two time points during the menopause transition. Generalized estimating equations were used for analyses. Effect modifications by menopause stage or estradiol level were tested in multivariable models. In adjusted models, menopause stage modified the associations of specific HDL metrics with CAC measures. Higher small HDL particles (HDL-P) concentrations (p-interaction = 0.008) and smaller HDL size (p-interaction = 0.02) were associated with greater odds of CAC presence in late perimenopause than in pre/early perimenopause stage. Women in the highest estradiol tertile, but not the lower tertiles, showed a protective association of small HDL-P with CAC presence (p-interaction = 0.007). Lower large HDL-P concentrations (p-interaction = 0.03) and smaller HDL size (p-interaction = 0.03) were associated with lower CAC density in late perimenopause than in postmenopause stage. Associations of HDL phospholipid and triglyceride content and HDL-CEC with CAC measures did not vary by menopause stage or estradiol level. We concluded that HDL subclasses may impact the likelihood of CAC presence and the stability of coronary plaque differently over the menopause transition. Endogenous estradiol levels may contribute to this observation.

Original languageEnglish (US)
Article number100098
JournalJournal of lipid research
Volume62
Issue number3
Early online dateJul 22 2021
DOIs
StatePublished - 2021

Bibliographical note

Funding Information:
The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), US Department of Health and Human Services (DHHS), through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women's Health (ORWH) (Grants U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, and U01AG012495) and the SWAN Repository (U01AG017719). The Study of Women's Health Across the Nation (SWAN) HDL ancillary study has Grant support (AG058690) from the NIA. SWAN Heart was supported by the National Heart, Lung, and Blood Institute (grants HL065581 and HL065591). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH, or the NIH.

Publisher Copyright:
© 2021 The Authors.

Keywords

  • Calcium density
  • Calcium score
  • Cardiovascular disease
  • Cholesterol/Efflux
  • Climacteric
  • HDL/structure
  • Hormones
  • Lipoproteins
  • Menopause
  • Women

PubMed: MeSH publication types

  • Journal Article

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