Heterogeneity in Lipoprotein(a) Profile Changes Across the Menopausal Transition

AIM: Assess changes in Lp(a) levels and transitions across ASCVD risk-thresholds by menopausal trajectory to inform risk stratification and testing recommendations. . METHODS: We examined changes in Lp(a) between visits 1 and 2 among UK Biobank women. Analyses were examined by menopausal trajectory: those who underwent menopause (N=415), those who remained premenopausal (N=532), and those who remained postmenopausal (N=3,615) between visits. Change in Lp(a) between visits was also stratified by visit 1 Lp(a). The primary outcome was incident Lp(a) ≥125 nmol/L at visit 2, estimated using Poisson regression. RESULTS: Data were available for 4,562 women (mean visit 1 age = 57 years; median visit 1 Lp(a) = 22 nmol/L; median time between visits = 4 years). At visit 1, median Lp(a) was 23 nmol/L in postmenopausal women and 19 nmol/L in premenopausal women. Overall, median changes in Lp(a) between visits were modest. Among women with intermediate visit 1 Lp(a) (75-125 nmol/L), those who transitioned through menopause experienced a median increase of 34.9 nmol/L, approximately fourfold greater than women who remained pre- or postmenopausal. Further, 22 of 39 (56%) of women with intermediate visit 1 Lp(a) who had menopause between visits had incident Lp(a) ≥125 nmol/L at visit 2, compared with 29% and 28% of women who remained pre- or postmenopausal, representing a risk ratio of 2.27 (95% CI: 1.36, 3.78) after adjustment for visit 1 age and continuous Lp(a). CONCLUSIONS: Relying on a single lifetime Lp(a) measurement may miss reclassification across risk-enhancing thresholds during menopause, particularly for women with intermediate premenopausal levels.