Associations of HDL subclasses and lipid content with complement proteins over the menopause transition: The SWAN HDL ancillary study: HDL and complement proteins in women

J Clin Lipidol. 2022 Sep-Oct;16(5):649-657. doi: 10.1016/j.jacl.2022.07.015. Epub 2022 Jul 31.


Background: The menopause transition (MT) could trigger low-grade chronic inflammation which may modify high-density lipoproteins (HDL) and lead to additional inflammatory responses contributing to atherosclerosis development.

Objective: To test whether complement proteins C3 and C4 increase around the final menstrual period (FMP), and whether changes in HDL subclasses and lipid content associate with C3 and C4 levels over time in midlife women.

Methods: The study included 471 women (at baseline: age 50.2(2.7) years; 87.3% pre or peri-menopausal) who had nuclear magnetic resonance spectroscopy HDL subclasses, lipid content, and C3 and C4 measured up to 5 times over the MT.

Results: Adjusted annual changes in C3 and C4 varied by time segments relative to FMP with significant increases, steeper for C3, only observed within 1 year before to 2 years after the FMP. Greater decreases in large HDL particles (HDL-P), HDL size, and HDL-phospholipids, and greater increases in small HDL-P and HDL-Triglycerides were associated with higher C3 and C4 over time, although associations with C4 were weaker than those with C3.

Conclusion: Complement proteins C3 and C4 significantly rise around menopause with C3 showing the steepest rise. Changes in HDL subclasses, overall size, and lipid content, over the MT may play a role in modulating inflammation responses known to be related to atherosclerosis. These results raise the possibility that novel therapeutic agents focusing on HDL might contribute to CVD protection by modulating inflammation.

Keywords: Complement; Estradiol; High-density lipoproteins; Lipid; Menopause.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Atherosclerosis*
  • Complement System Proteins
  • Female
  • Humans
  • Inflammation
  • Lipoproteins, HDL*
  • Menopause
  • Middle Aged


  • Lipoproteins, HDL
  • Complement System Proteins