Lp(a) does not predict long-term cardiometabolic risk in healthy women despite its lipid links, 387-woman cohort (Metabolites 2026)

Background/Objectives: Lipoprotein(a) [Lp(a)] is an established risk-enhancing biomarker for atherosclerotic cardiovascular disease (ASCVD) and is increasingly incorporated into preventive risk assessment. However, whether Lp(a) predicts long-term cardiometabolic disease (CMD) beyond its associations with lipid parameters in apparently healthy women remains unclear.

Methods: We retrospectively analyzed 559 women (median age 41 [36-46] years) who underwent comprehensive health check-ups with baseline Lp(a) measurements. After excluding those with baseline CMD, ASCVD, or insufficient follow-up, 387 women formed the primary longitudinal cohort. Participants were stratified by Lp(a) level (<50 vs. ≥50 mg/dL). Incident composite CMD, defined as new-onset hypertension, diabetes mellitus, or dyslipidemia, was assessed using Kaplan-Meier analysis, Cox proportional hazards models, and sensitivity analyses treating Lp(a) as a continuous variable and restricting the analysis to participants with ≥10 years of follow-up.

Results: At baseline, elevated Lp(a) (≥50 mg/dL) was associated with higher total cholesterol and LDL-C and a greater prevalence of dyslipidemia, with a modest Lp(a)-LDL-C correlation (ρ = 0.24, p < 0.001). Over a median follow-up of 12.6 years, CMD incidence did not differ between Lp(a) groups (33.3% vs. 35.3%, p = 0.907). Lp(a) was not associated with incident CMD in multivariable Cox models (adjusted HR 0.81, 95% CI 0.49-1.34), with consistent findings in the ≥10-year follow-up subgroup (n = 224) and in continuous-variable sensitivity analyses.

Conclusions: In apparently healthy women, elevated Lp(a) reflects an adverse baseline lipid phenotype but does not independently predict long-term incident CMD. These findings suggest that the clinical utility of Lp(a) may be context-dependent, with its predictive value primarily limited to ASCVD risk assessment rather than broader cardiometabolic risk prediction in this population.