Intra-individual lipoprotein(a) variability and risk reclassification in patients with cardiovascular disease

Introduction Lipoprotein(a) (Lp(a)) is traditionally regarded as a genetically determined and stable cardiovascular risk factor, often assumed to require only a single lifetime measurement. However, emerging evidence suggests that intra-individual Lp(a) levels may fluctuate over time. In this study, we aim to investigate the magnitude and prevalence of intra-individual Lp(a) variability in patients with established cardiovascular disease (CVD). Methods We analyzed longitudinal Lp(a) measurements from 1,570 CVD individuals（69.3% male）with baseline and follow-up testing between 2020 and 2025 at University Hospital Basel. Intra-individual Lp(a) variability was defined as an absolute change ≥25 nmol/L or a relative change ≥25%. Baseline Lp(a) levels were categorized as low (<75 nmol/L), intermediate (75–124 nmol/L), or high (≥125 nmol/L), and transitions between categories were assessed. Associations between Lp(a) variability with age, sex, BMI, lipids parameters, renal function, and follow-up duration were examined. Results Baseline and follow-up Lp(a) levels were strongly correlated (Spearman ρ = 0.92, p < 0.001), indicating overall population-level stability. Nevertheless, 15.4% of individuals exhibited an absolute Lp(a) change ≥25 nmol/L and 34.6% demonstrated a relative change ≥25%. Notably, 36% of individuals with intermediate baseline Lp(a) transitioned to a different risk category at follow-up. Lp(a) variability was more pronounced in females aged between 42 and 80 years than males of the same age. Lp(a) variability occurred significantly more often when the interval between measurements exceeded 3.5 years. In multivariable logistic regression models incorporating restricted cubic splines, changes in LDL-C were independently associated with Lp(a) variability (P <0.01, nonlinear P < 0.01). Conclusions Intra-individual Lp(a) variability is substantial among CVD patients. Individuals with intermediate baseline Lp(a) levels are particularly prone to risk category reclassification. These findings challenge the concept of lifelong Lp(a) stability and support consideration of repeated Lp(a) measurements in selected patients.