Clinical Predictors of Plaque Progression Despite Very Low Levels of Low-Density Lipoprotein Cholesterol

Objectives: The purpose of this study was to characterize the determinants of plaque progression despite achieving very low levels of low-density lipoprotein cholesterol (LDL-C). Background: Despite achieving very low levels of LDL-C, many patients continue to demonstrate disease progression and have clinical events. Methods: A total of 3,437 patients with coronary artery disease underwent serial intravascular ultrasound examination in 7 clinical trials. Patients who achieved an on-treatment LDL-C level of ≤70 mg/dl (n = 951) were stratified as progressors (n = 200) and nonprogressors (n = 751) and compared. Results: Despite achieving LDL-C ≤70 mg/dl, >20% of patients continued to progress. There were no demographic differences between groups. Progressors demonstrated higher baseline levels of glucose (117.1 ± 42.5 mg/dl vs. 112.1 ± 40.0 mg/dl, p = 0.02), triglycerides (157.5 mg/dl vs. 133.0 mg/dl, p = 0.004), and a smaller decrease of apolipoprotein B (-25.1 ± 3.4 mg/dl vs. -27.4 ± 3.35 mg/dl, p = 0.01) at follow-up. Multivariable analysis revealed that independently associated risk factors of progression in patients with LDL-C ≤70 mg/dl included baseline percent atheroma volume (p = 0.001), presence of diabetes mellitus (p = 0.02), increase in systolic blood pressure (p = 0.001), less increase in high-density lipoprotein cholesterol (p = 0.01), and a smaller decrease in apolipoprotein B levels (p = 0.001), but not changes in C-reactive protein (p = 0.78) or LDL-C (p = 0.84). Conclusions: Residual risk factors are associated with the likelihood of disease progression in patients who achieve very low LDL-C levels. In addition, the association between apolipoprotein B and atheroma progression highlights the potential importance of LDL particle concentration in patients with optimal LDL-C control. This finding highlights the need for intensive modification of global risk in patients with coronary artery disease.