Increases In Low-density Lipoprotein Subclasses During The Menopause Transition Are Associated With Greater Risk Of Coronary Calcification And Carotid Atherosclerosis: The SWAN HDL Study

Objectives: Increase in LDL-C occurs within 1 year of the final menstrual period (FMP), and this increase has been linked to a greater plaque risk. LDL subclasses have been linked to CAD beyond LDL-C, promising a better risk stratification. We aim to characterize changes in LDL subclasses over the menopause transition (MT) and assess associations of these changes with presence of coronary artery calcification (CAC Agatston score ≥10) and carotid intima-media thickness (cIMT), and test the effect modification of time relative to FMP on these associations. Design: Midlife women with nuclear magnetic resonance spectroscopy LDL subclasses measured over the MT for a maximum of 5 timepoints were included (n=471; baseline age 50.19 ± 2.7 years; 81.0% Pre-/Early perimenopausal). A subset of women had CAC and cIMT measured for a maximum of 2 timepoints (n=221). LOESS plots were used to characterize changes in LDL subclasses over the MT in the full sample. Inflection points identified from the LOESS plots suggested timing of changes in slope (Figure). Linear mixed effect models or generalized estimating equation was used for analysis. Effect modification by time relative to FMP was tested. Results: All LDL metrics increased around the FMP except for Intermediate LDL Particles (IDL-P), which declined (Figure). Higher total LDL particles (LDL-P) and greater ApoB independently associated with higher CAC prevalence and greater cIMT. Although none of the associations of LDL metrics with cIMT or CAC were modified by time relative to FMP, higher LDL-C, ApoB and total LDL-P were associated with higher cIMT during peri- or postmenopausal stages (Table), while higher LDL-C, small LDL-P and large LDL-P were associated with greater CAC prevalence, mainly during perimenopause stage in adjusted models (Table). Conclusions: During the MT women experience significant increases in LDL subclasses found to be related to greater cIMT levels and CAC prevalence. Monitoring LDL subclasses over the MT may help in identifying women at greater risk for future CAD.