Temporal changes in lipoprotein(a) after acute coronary syndrome

Background

Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease and is typically considered stable over time. However, the acute-phase dynamics of Lp(a) following an acute coronary syndrome (ACS) are not well understood.

Purpose

To define the longitudinal trajectory of Lp(a) levels following ACS.

Methods

In this observational longitudinal study, patients presenting with an ACS were enrolled and underwent serial measurements of Lp(a) at baseline (within 24 hours of MI), Day 1, Day 3, Days 4-7, Day 30, and late follow-up (≥6 months). Longitudinal changes in Lp(a) were analyzed using linear mixed-effects models, with time modeled as a categorical fixed effect and participant-level random intercepts to account for repeated measurements. Lp(a) values were natural log-transformed prior to analysis to address right-skewness and allow interpretation of effects as relative changes. Model-based contrasts were used to compare each timepoint with baseline and Wilcoxon signed-rank test to compare the baseline and ≥6 months values.

Results

A total of 78 patients were enrolled; mean age was 61.4 ± 12.1 years, 39% were women, 31% were Black individuals, 63% presented with a non-ST-segment elevation myocardial infarction (NSTEMI), 37% with an ST-segment elevation myocardial infarction (STEMI), and 64% underwent percutaneous coronary intervention (PCI) during admission (Table). Median baseline Lp(a) was 61.5 (29.0; 184.0) nmol/L.

Lp(a) demonstrated a significant overall time effect in linear mixed-effects modeling (p < 0.001). Compared with baseline, Lp(a) did not change significantly at Day 1 (+1.5%, 95% CI -8.8% to +13.0 %; p = 1.00), but increased significantly by Day 3 (+18.5%, 95% CI +4.3% to +34.8%; p = 0.0007) and peaked during the early subacute phase (Days 4-7), increasing by 30.0 % relative to baseline (95% CI +8.7% to +54.8%; p = 0.0001).

By Day 30, Lp(a) remained modestly but significantly elevated compared with baseline (+15.0%, 95% CI +2.2% to +29.3%; p = 0.0042). At late follow-up (≥6 months), Lp(a) was no longer significantly different from baseline (+6.5%, 95% CI -6.0% to +20.7%; p = 0.90). (Figure)

A paired analysis of the 44 patients with both baseline and ≥6-month follow-up Lp(a) measurements demonstrated no statistically significant change in Lp(a) concentrations, with median values of 61.5 (31.75–187.8) at baseline and 86.0 (26.25–194.5) at ≥6 months (Wilcoxon signed-rank test, p = 0.52).

Conclusion(s)

Lp(a) exhibits a dynamic but transient increase following an ACS, with a significant rise during the early subacute phase and returning near baseline at late follow-up. These findings highlight the importance of measurement timing when interpreting Lp(a) levels after ACS. The pronounced elevation during the early post-ACS phase suggests a potential window for therapeutic targeting of Lp(a), supporting further investigation of early Lp(a)-lowering strategies.