Impact of residual cholesterol and inflammation risk on non-culprit plaque progression in patients with acute coronary syndrome: a serial optical coherence tomography study

Acute Coronary Syndrome (ACS) patients face recurrent cardiovascular events due to non-culprit plaque progression despite optimal secondary prevention, but the differential impacts of residual cholesterol risk (RCR, on-treatment LDL-C ≥ 1.8mmol/L) and residual inflammation risk (RIR, on-treatment hs-CRP ≥2 mg/L) on plaque microstructure dynamics remain undefined. This study aimed to clarify how residual cholesterol and inflammatory risk factors differentially modulate the progression of non-culprit plaques in patients with ACS using serial optical coherence tomography (OCT). A retrospective cohort of 243 ACS patients underwent baseline and 1-year (9–15 months) follow-up OCT. Patients were stratified into four groups (RCR, RIR, combined residual cholesterol-inflammation risk [RCIR], no residual risk). OCT assessed plaque morphology (e.g., thin-cap fibroatheroma [TCFA]) and quantitative parameters (lumen area, fibrous cap thickness [FCT], lipid arc). Multivariate logistic regression identified factors associated with plaque progression (defined as a decrease in minimal lumen area > 0.5 mm² from baseline to follow-up) and TCFA persistent. Of 583 evaluable non-culprit lesions, RIR was independently associated with patient-level plaque progression (odds ratio [OR]: 2.915, 95% confidence interval [CI]: 1.005–9.212, P = 0.046) and was linked to significant reductions in reference, mean, and minimal lumen area (all P < 0.05) vs. the no-risk group. RCR was associated with attenuated lipid plaque regression compared with the no residual risk group, as evidenced by smaller min-FCT increases (20.0 [-13.3, 73.3] µm vs. 50.0 [18.3, 86.7] µm, P = 0.014) and attenuated mean lipid arc reductions (-8.8 ± 27.1° vs. -17.7 ± 23.6°, P = 0.027). RCR (OR: 4.462, 95%CI: 1.723–12.521, P = 0.003) and RCIR (OR: 4.892, 95%CI: 1.623–15.467, P = 0.005) were independently associated with follow-up TCFA persistent. This study demonstrated distinct associations of RIR and RCR with non-culprit plaque progression: RIR was linked to luminal narrowing, while RCR attenuated lipid plaque stabilization. These findings provide imaging-based insights into plaque dynamics and may inform future risk stratification and residual risk management strategies in ACS patients. This study evaluated how residual cholesterol (RCR) and inflammation risk (RIR) affect non-culprit plaque progression in 243 acute coronary syndrome (ACS) patients (583 non-culprit plaques) via 1-year serial optical coherence tomography (OCT) follow-up. Patients were stratified into four groups: RIR (21 patients, LDL-C<1.8 mmol/L and hs-CRP≥2 mg/L), RCR (75 patients, LDL-C≥1.8 mmol/L and hs-CRP<2 mg/L), dual residual risk (RCIR, 45 patients), and no residual risk (102 patients).