Suboptimal Control of Small Dense Low‐Density Lipoprotein Cholesterol Is Associated With Coronary Plaque Progression: An Intravascular Ultrasound Study

Background Plaque progression (PP) is critical between subclinical atherosclerosis and plaque rupture. Small dense low‐density lipoprotein cholesterol (sdLDL‐C) is considered as the most atherogenic lipoprotein. This study aims to investigate the relationship between sdLDL‐C level and PP in patients with stable coronary artery disease. Methods We conducted a retrospective analysis of 146 lesions in 86 patients by repeat intravascular ultrasound examinations from January 2020 to May 2023. PP was determined by increases in percent atheroma volume, defined as the atheroma volume in proportion to the volume occupied by the entire vascular wall, ≥5% during follow‐up. Time‐averaged values were calculated for all cardiometabolic parameters including sdLDL‐C. Multivariate logistic regression analysis was performed to interrogate the association between time‐averaged sdLDL‐C and PP. Results During a median follow‐up of 12.6 months, PP was found in 65 lesions (44.5%), and mean changes in percent atheroma volume were 4.1%±10.2%. A positive correlation was observed between time‐averaged sdLDL‐C and changes in total atheroma volume (Pearson r =0.29, P =0.006), especially in diabetic patients (Pearson r =0.58, P <0.001). After multivariate adjustment, every 0.1‐mmol/L increase in time‐averaged sdLDL‐C conferred a 1.2‐fold increased risk of PP. Conclusions Our findings suggest that sdLDL‐C is an independent risk factor of PP in patients with coronary artery disease. Intensive control of sdLDL‐C along with other risk factors should be considered to mitigate PP and improve cardiovascular outcomes.