Statins
Rising Lp(a) independently predicts coronary plaque progression on serial IVUS despite aggressive statin therapy, in 79 CAD patients (Sci Rep 2025)
Original title: Clinical significance of lipoprotein(a) as a residual risk factor for atherosclerotic coronary plaque progression in statin-treated patients with coronary artery disease
This observational cohort study pooled statin-treated coronary artery disease patients from two prospective trials, ENTERPRISE and Extended-ESTABLISH, who underwent serial grayscale intravascular ultrasound (IVUS) at baseline and 6-12 month follow-up; 79 patients (mean age 61 years, 89% men) completed the study. Lp(a) was not associated with LDL-C at baseline or on statin treatment, but correlated positively with an inflammatory marker. In multiple linear regression, the percentage change in Lp(a) independently predicted the absolute change in normalized total atheroma volume, regardless of the percentage change in LDL-C, though no association was found with percentage atheroma volume. Rising Lp(a) tracked with coronary plaque progression by IVUS even under strict LDL-C lowering, positioning it as a residual risk factor that persists despite statin therapy, in a modest but trial-derived, imaging-confirmed sample.
Original abstract
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 (TAVnormalized) 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 TAVnormalized 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.
epidemiologyplaque imagingstatins
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.