Transient surge, persistent risk: longitudinal changes in lipoprotein(a) following acute coronary syndrome

Background Lipoprotein(a) [Lp(a)] is a causal, largely genetically determined risk factor for atherosclerotic cardiovascular disease and residual risk after LDL-cholesterol lowering. Contrary to the traditional assumption of lifelong stability, several recent studies suggest that Lp(a) may rise after acute myocardial infarction, and that peri-infarct values may not reflect subsequent steady-state levels. However, the temporal profile and persistence of these changes beyond 6 months after acute coronary syndrome (ACS) remain poorly characterized. Purpose To characterise individual and categorical trajectories of Lp(a) from index ACS admission to 1 month and 12 months, and to determine whether post-ACS Lp(a) elevations persist over time. Methods We retrospectively included consecutive ACS patients undergoing percutaneous coronary intervention at a tertiary cardiac centre (2022–2025) with Lp(a) measured at index admission, 1 month, and 12 months. Lp(a) was quantified in mg/dL and categorised as <30, 30–50, 50–70, and >70 mg/dL. Individual longitudinal trajectories were visualised with alluvial plots, and changes in median Lp(a) and risk-category distribution were assessed using paired non-parametric tests. Results Among 338 patients (mean age 61.3 ± 10.6 years, 81.3% male), median Lp(a) increased from 31.9 mg/dL at baseline to 64.3 mg/dL at 1 month, followed by partial decline to 53.2 mg/dL at 12 months (p<0.001 for trend). The proportion with Lp(a) >70 mg/dL almost doubled from 22.5% at baseline to 46.2% at 1 month and remained markedly elevated at 38.8% at 12 months. Conversely, patients with Lp(a) <30 mg/dL fell from 47.9% at baseline to 22.2% at 1 month, with only partial recovery to 29.6% after 12 months. Alluvial plots revealed substantial interindividual heterogeneity but showed that a large subset transitioned from low to persistently high Lp(a) categories. Conclusions Lp(a) rises sharply after ACS, peaks around 1 month, and shows only incomplete normalisation at 12 months, indicating that peri-infarct measurements substantially underestimate the proportion of patients with sustained high Lp(a). These data support a paradigm in which ACS unmasks genetically mediated Lp(a) risk through an acute-phase response that only partially wanes over time, with potential implications for timing of Lp(a) testing, risk stratification, and selection for emerging Lp(a)-lowering therapies.