Serial lipoprotein(a) measurements reclassify cardiovascular risk and identify additional candidates for lipoprotein(a)-lowering therapy

Background

Lipoprotein(a) (Lp(a)) has emerged as an important cardiovascular risk factor and is expected to become modifiable through several Lp(a)-lowering therapies in the near future. Current guidelines recommend measuring Lp(a) at least once in a lifetime, as levels are considered largely genetically determined. However, recent studies using a single repeat measurement have demonstrated substantial intraindividual variability in Lp(a), while the clinical implications of more extensive serial testing remain insufficiently defined.

Purpose

To assess the impact of serial Lp(a) measurements on cardiovascular risk categorization and potential eligibility for Lp(a)-lowering therapies in a real-world cohort.

Methods

Lp(a) measurements were retrospectively extracted from the data management system of a tertiary cardiology centre in Germany and analysed using R. Lp(a) was measured in mg/dL using a standardized immunoassay with established internal quality controls. Patients with ≥4 Lp(a) measurements spaced ≥30 days apart were included; repeat measurements occurred as part of routine laboratory panels rather than Lp(a)-specific clinical indication. Risk categories were defined as low (<30 mg/dL), intermediate (30–49 mg/dL), and high (≥50 mg/dL). Drug eligibility thresholds were based on inclusion criteria of major ongoing phase 3 trials (70, 80, and 90 mg/dL).

Results

Among 14,024 available datasets, 919 patients (median age 70 years, 75% male) had ≥4 Lp(a) measurements between June 2015 and October 2025 and were included in the analysis. Median time between measurements was 233 days. Median Lp(a) concentration was 12.0 mg/dL, consistent with 13.0 mg/dL in the overall population. Median intraindividual coefficient of variation was 15%, and 61% of patients exhibited at least one ≥25% change from baseline.

Risk categorization remained stable in most patients in the low-risk (92.8%) and high-risk (85.6%) groups. In contrast, only 32.9% of intermediate-risk patients remained in the same category across all measurements. Each additional test resulted in further reclassification events, predominantly transitions from intermediate to high risk.

Serial testing identified additional patients meeting drug eligibility thresholds. Although only 4.5–5.9% of patients initially below cutoff crossed eligibility thresholds, these individuals accounted for 23.8–28.5% of all patients who ever met eligibility criteria. Each subsequent measurement identified additional candidates.

Conclusion

In a real-world setting, a four-test Lp(a) strategy led to substantial reclassification among intermediate-risk patients and identified a clinically relevant proportion of potential candidates for Lp(a)-lowering therapies who would have been missed using a single-test approach. Repeated Lp(a) measurements should be considered in intermediate-risk patients and when Lp(a) levels are close to therapeutic decision thresholds.