Predictors of high lipoprotein(a) variability: A multicenter study and implications for risk stratification

초록

Background and Aims: Lipoprotein(a) [Lp(a)] is a emerging cardiovascular risk factor, but the clinical significance of its variability over time is unclear. This study aimed to identify clinical and biochemical predictors of high Lp(a) variability and explore its implications for cardiovascular risk stratification. Methods: This multicenter retrospective cohort study included 5,305 patients from three tertiary hospitals in Korea between January 2019 and June 2024. Eligible patients had at least two Lp(a) measurements taken with a minimum interval of 90 days. High Lp(a) variability was defined as an absolute change of ≥10 mg/dL or a relative change of ≥25%. Patients were categorized into low and high variability groups. Clinical characteristics and laboratory findings were compared, and multivariable logistic regression models (standard, stepwise, and LASSO) were used to identify predictors of high Lp(a) variability. Results: Among 5,305 patients, 55.2% exhibited high Lp(a) variability. Patients with high variability had a more adverse cardiovascular risk profile and increased use of lipid-lowering therapies. High variability was associated with elevated inflammatory markers (white blood cell count), metabolic disturbances (serum glucose levels), and comorbidities, including hypertension (78.9% vs. 74.1%, p < 0.01) and diabetes (49.7% vs. 44.4%, p < 0.01). High variability was most prevalent in high-risk Lp(a) categories (64.2%) and contributed to significant reclassification in the intermediate "grey zone" risk group, with 51.9% transitioning to other risk categories. Multivariable regression analysis identified baseline Lp(a) levels (OR = 0.78, 95% CI = 0.74–0.82), follow-up Lp(a) levels (OR = 1.36, 95% CI = 1.29–1.42), white blood cell count (OR = 1.04, 95% CI = 1.01–1.06), and serum glucose levels (OR = 1.00, 95% CI = 1.00–1.00) as significant predictors of high Lp(a) variability. Conclusions: Inflammatory and metabolic markers, particularly white blood cell count and serum glucose, are associated with high Lp(a) variability. Monitoring Lp(a) variability, especially in intermediate-risk patients, may enhance cardiovascular risk stratification.