LDL-C–stratified residual lipoprotein(a) and inflammatory risk after acute myocardial infarction among patients with prior statin use

Abstract

Patients can experience acute myocardial infarction (AMI) despite documented prior statin exposure, indicating persistent residual cardiovascular risk. The prognostic relevance of lipoprotein(a) [Lp(a)] and residual inflammation in this setting remains unclear. This retrospective multicentre cohort study included 6,498 adults hospitalized for AMI with prior statin use. Baseline low-density lipoprotein cholesterol (LDL-C) at admission was used to stratify patients into low (< 2.6 mmol/L) and high (≥ 2.6 mmol/L) LDL-C groups. Residual risk profiles were defined by elevated Lp(a) (> 30 mg/dL), elevated high-sensitivity C-reactive protein (hs-CRP > 3 mg/L), or both. The primary outcomes were major adverse cardiovascular events (MACE) and all-cause death. Baseline characteristics differed across residual LDL-C strata and risk profiles. During a median follow-up of 5.71 years (IQR 4.38–7.27), restricted cubic spline analyses showed a significant association between Lp(a) and outcomes only in the low LDL-C group, whereby high residual inflammatory risk (adjusted hazard ratio [aHR] 1.53, 95% CI 1.24–1.88), high residual Lp(a) risk (aHR 1.44, 95% CI 1.11–1.87), and combined residual risk (aHR 1.47, 95% CI 1.16–1.86) were each associated with higher MACE risk. In the high LDL-C group, no significant residual risk category was associated with MACE. Irrespective of LDL-C status, residual inflammatory risk alone and combined residual risk were associated with increased risks of all-cause mortality and cardiovascular death. Sensitivity analyses suggested that a 30 mg/dL Lp(a) cut-off may be more informative in this cohort. In patients with AMI despite documented prior statin exposure, the prognostic associations of residual inflammatory and Lp(a) risk appeared to differ across admission LDL-C strata, supporting the potential value of LDL-C–stratified residual risk assessment.