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.