Clinical significance of lipoprotein(a) as a residual risk factor for atherosclerotic coronary plaque progression in statin-treated patients with coronary artery disease

Limited evidence exists on the role of lipoprotein(a) [Lp(a)] in the progression of atherosclerotic coronary plaques as assessed by intravascular imaging modality, particularly under low-density lipoprotein cholesterol (LDL-C) lowering therapy. In this study, we aimed to evaluate the clinical significance of Lp(a) as a residual risk factor for coronary plaque progression, using serial intravascular ultrasound (IVUS) in statin-treated patients with coronary artery disease (CAD). This observational cohort study included statin-treated patients from two clinical prospective trials (the ENTERPRISE trial and Extended-ESTABLISH trial) in which coronary plaques were assessed using serial grayscale IVUS at baseline and at 6-12 months follow-up. The primary endpoints were defined as absolute changes in normalized total atheroma volume (TAV_normalized) and percentage atheroma volume (PAV) from baseline to follow-up. A total of 79 patients (mean age: 61 years; 89% men) completed the study and were analyzed. There was no significant association between Lp(a) and LDL-C levels at baseline and on-statin treatment, whereas Lp(a) was positively correlated with inflammatory marker. Multiple linear regression analysis demonstrated that the percentage change in Lp(a) was an independent predictor of the absolute change in TAV_normalized under strict LDL-C lowering therapy, regardless of the percentage change in LDL-C. No significant association was found with absolute change in PAV. An increase in Lp(a) levels was associated with coronary plaque progression, as assessed by grayscale IVUS, despite aggressive LDL-C lowering. These findings highlight Lp(a) as a potential residual risk factor in statin-treated CAD patients.Trial registration: This study was registered with the University Hospital Medical Information Network (UMIN) (UMIN ID: UMIN000035587). https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000040552.