Long-term lipoprotein (a) category stability and transitions in patients with cardiovascular disease

Background and Aims Lipoprotein(a) [Lp(a)] concentrations are considered largely genetically determined and stable over time. However, the frequency and clinical correlates of long-term transitions across clinically relevant Lp(a) categories in patients with cardiovascular disease remain unclear. Methods We retrospectively studied 467 patients with cardiovascular disease who underwent repeat Lp(a) measurements at least five years apart. Lp(a) concentrations were categorized as <30, 30-49.9, and ≥50 mg/dL. Patients were classified as having stable, upward, or downward category transitions. Associations with category changes were evaluated using multivariable logistic regression, with least absolute shrinkage and selection operator (LASSO) regression as a supplementary exploratory approach. Results During a median follow-up of 9.5 years, 372 patients remained within the same Lp(a) category, whereas 32 showed upward and 63 downward transitions. Baseline and follow-up Lp(a) concentrations were strongly correlated. Downward transition was independently associated with acute coronary syndrome (odds ratio [OR]: 2.58, 95% confidence interval [CI]: 1.09-6.07; P=0.03), persistent estimated glomerular filtration rate reduction (OR: 2.45, 95% CI: 1.15-5.30; P=0.02), persistent homeostasis model assessment of insulin resistance elevation (OR: 5.14, 95% CI: 1.69-15.55; P=0.004), and lower baseline Lp(a) concentration (OR: 0.97 per 1 mg/dL, 95% CI: 0.96-0.99; P=0.001). Conclusions In patients with cardiovascular disease, Lp(a) categories remained stable in most cases during long-term follow-up. However, a clinically meaningful minority of patients crossed established Lp(a) thresholds. Downward transitions were associated with acute coronary syndrome and persistent metabolic or cardiorenal abnormalities, suggesting that selective repeat Lp(a) measurements may provide additional clinical information in patients with unstable clinical profiles.