LAUSR

Objective: High density lipoprotein (HDL) is emerging as a key player in modulating inflammation-related response impacting atherosclerosis development. HDL carries multiple proteins with direct roles in complement system activation including C3 and C4. Postmenopausal women have higher levels of C3 than premenopausal women suggesting a role of the menopause transition (MT) in modulating complement proteins. Preliminary work showed significant declines in large HDL particles (HDL-P) and overall HDL particle size, but increases in small HDL-P during the MT. Whether these changes contribute to higher levels of C3 reported after menopause is not known. Our objectives were to test whether C3 and C4 increase around the final menstrual period (FMP) and whether changes in HDL subclasses over the MT associate with C3 and C4 levels in midlife women. Design: We evaluated 558 women (at baseline: age 49.9(2.8) years; 86.6% perimenopausal) who had nuclear magnetic resonance spectroscopy HDL subclasses, C3 and C4 measured up to 5 times over the MT. Piecewise linear mixed-effects models were used to estimate and compare yearly changes in C3 and C4 at 3 time segments relative to the FMP. Linear mixed effect models were used to test associations between changes in each HDL subclass and overall HDL particle size with C3 and C4 separately. Results: Adjusted annual changes in C3 and C4 varied by time segments relative to FMP with significant increases only observed within 1 year before to 2 years after the FMP ( Figure ). These changes were significantly greater than changes in the other 2 time segments. Greater decreases in large and increases in small HDL-P concentrations and decreases in the overall size of HDL-P were independently associated with higher levels of C3 and C4 over time ( Table ). Conclusions: Complement proteins C3 and C4 significantly rise around menopause with C3 showing the steepest rise. Changes in HDL subclasses and overall size over the MT may play role in modulating inflammation responses known to be related to atherosclerosis.