ObjectiveIt is widely accepted that elevated low-density lipoprotein cholesterol (LDL-C) levels are a major risk factor for coronary heart disease (CHD). However, even patients who have achieved LDL-C levels below the currently recommended targets may still have residual risk. Recently, Lipoprotein(a) [Lp(a)] has attracted significant attention as independent causal risk factor for CHD. Nonetheless, the role of Lp(a) in acute coronary syndrome (ACS) patients with type 2 diabetes mellitus (T2DM) who have undergone percutaneous coronary intervention (PCI) and achieved the LDL-C target (≤1.4 mmol/L) remains unclear.MethodsThis retrospective study enrolled 462 ACS patients with comorbid T2DM who underwent PCI, with a median follow-up duration of 27 months post-procedure. The primary endpoint was major adverse cardiovascular events (MACE), defined as all-cause death, recurrent acute myocardial infarction (AMI), ischemic stroke, or hospitalization due to recurrent angina. Based on MACE occurrences, patients were divided into MACE group and non-MACE group. Furthermore, patients were further divided into three groups according to their Lp(a) levels. Kaplan-Meier and Cox regression analyses were performed.ResultsPatients with MACE had more coronary artery lesions, and the plasma Lp(a) concentrations in the MACE group were significantly higher than in the non-MACE group. The incidence of MACE and recurrent AMI was higher in the Lp(a) ≥ 180 mg/dL group compared to the other two groups. Even after multivariate adjustment, Lp(a) ≥ 180 mg/dL remained closely associated with an increased risk of MACE (HR 2.82, 95% CI: 1.47-5.41,  = .002) and recurrent AMI (HR 3.71, 95% CI: 1.17-11.81,  = .026).ConclusionElevated Lp(a) levels were strongly associated with poor prognosis in ACS patients with T2DM who underwent PCI.