Intra-Individual Lipoprotein(a) Variability and Effect of Lipid-Lowering Therapy on Lipoprotein(a): A Multi-Ethnic Asian Registry Study

Objectives: 

To characterise the extent and patterns of intra-individual lipoprotein(a) [Lp(a)] variability, and the independent effects of lipid-lowering therapies (LLT) on Lp(a), in a multi-ethnic Southeast Asian cohort with elevated Lp(a), where longitudinal data are sparse and guidance on repeat measurement is limited.

Materials and methods: 

In a prospective single-centre Lp(a) registry in Singapore, patients with baseline Lp(a) ≥70 nmol/L and ≥2 serial measurements were included (N=271; 1,036 measurements; median follow-up 16 months). Severity reclassification across categories was assessed, and Lp(a) changes between admissions for acute coronary syndrome (ACS) and subsequent outpatient visits were compared. Independent effects of LLT were estimated using a linear mixed-effects model with time-varying pharmacological covariates.

Results: 

Category reclassification from baseline to latest follow-up occurred in 27.7% of patients in the Very High (≥200 nmol/L), 47.4% in the High (120–199 nmol/L), and 56.2% in the Intermediate (70–119 nmol/L) Lp(a) categories. The median intra-individual coefficient of variation was 14.7% (11.7% in outpatient-only measurements). Among 65 patients with paired ACS and outpatient measurements, Lp(a) was 15.9% higher at the subsequent outpatient visit (p<0.001). In the mixed-effects model, PCSK9-directed therapy was associated with 21.8% lower geometric mean Lp(a) (95% CI, −26.1% to −17.3%; p<0.001), statin use with 12–14% higher subsequent Lp(a) (p≤0.001), and ezetimibe with 7.0% higher subsequent Lp(a) (p=0.005).

Conclusions: 

Intra-individual Lp(a) variability reclassified 27.7–56.2% of patients depending on baseline category. LLT and ACS events were independently associated with changes in Lp(a). Repeat measurement is informative when LLT is initiated or changed, particularly with PCSK9-directed therapy.