Lipoprotein(a) [Lp(a)] is a major cardiovascular risk factor. In contrast to the genetic regulation of apo(a) and its effect on Lp(a) levels, the lipidomic and proteomic properties of Lp(a) have attracted far less attention. Lp(a) is the main carrier of oxidized phospholipids (OxPL), the major portion being phosphatidylcholine residues, in particular PONPC or ALDO-PC. While Lp(a) levels increase with a reduction in saturated fat intake, findings regarding Lp(a)-OxPL concentrations have varied, some studies finding an increase and others a decrease. Lp(a)-TG levels vary substantially depending on the individual triglyceridemia status. More than 440 lipid species have been identified in Lp(a) lipidomic analyses, and 20% of these change during dietary modification, suggesting a high degree of variability in the Lp(a) lipid composition and that it is impacted by metabolic conditions. The proteomic properties of Lp(a) have been reported in several studies and while much variation in protein content is evident, a consensus Lp(a) proteome of 46 proteins can be derived. A functional network analysis of these proteins showed two major clusters, one of “plasma lipoprotein particle” proteins, and another of “complement and coagulation cascade” proteins with a third minor cluster containing “complement activation pathway” proteins. A significant number of proteins across all three clusters were classified as proinflammatory. Comparisons between the LDL and Lp(a) proteomes show Lp(a) to have a more diverse protein makeup. The Lp(a) lipidomic and proteomic properties found to date offer unique avenues to explore properties contributing to its risk factor role.

Aims: To determine whether menopausal status, menopausal hormone therapy (MHT), or oral contraceptive (OCP) use modifies the association between elevated Lp(a) and prevalent coronary artery disease (CAD).

Aims: To determine whether menopausal status, menopausal hormone therapy (MHT), or oral contraceptive (OCP) use modifies the association between elevated Lp(a) and prevalent coronary artery disease (CAD).

Methods: We conducted a cross-sectional study of 6,314 U.S. Women Veterans with Lp(a) testing from 1999-2025 to evaluate whether menopausal status, MHT use, or OCP use modify the association between elevated Lp(a) (≥ 125 nmol/L) and prevalent CAD. Logistic regression was used to estimate adjusted odds ratios (aOR), with interaction terms evaluated by likelihood ratio tests. Restricted cubic splines were used to model the continuous association between Lp(a) and prevalent CAD.

Results: Elevated Lp(a) was present in 31.6% of Women Veterans and was independently associated with increased odds of prevalent CAD (aOR 1.24, 95% confidence interval 1.06-1.44, p = 0.0079). We observed a continuous increase in prevalent CAD with rising Lp(a) levels (aOR 1.023 per 25 nmol/L increase, 95% confidence interval 1.010-1.040, p = 0.0033). No effect modification was detected for menopausal status (p-value for interaction = 1.0), MHT use in postmenopausal women (p-value for interaction = 0.20), or OCP use in premenopausal women (p-value for interaction = 0.32).

Conclusion: Elevated Lp(a) is common and associated with prevalent CAD in Women Veterans. We did not detect modification of the association between elevated Lp(a) and prevalent CAD based on menopausal status or hormonal therapy. These findings support systematic Lp(a) screening across the full female reproductive spectrum.