Plaque microstructures in patients with coronary artery disease who achieved very low low-density lipoprotein cholesterol levels

Objective: Lowering low-density lipoprotein cholesterol (LDL-C) with statins reduces cardiovascular events and slows plaque progression. While this therapeutic approach has been reported to favorably modify plaque composition, this is not well characterized in humans. Also, the benefit of achieving LDL-C levels below current recommended targets remains unknown. Frequency-domain optical coherence tomography (FD-OCT) enables visualization of plaque microstructures associated with plaque instability. We investigated plaque morphologies in patients with low LDL-C levels by using FD-OCT. Methods: 293 and 122 non-obstructive lipid and fibrous plaques in 280 stable statin-treated CAD patients were evaluated by FD-OCT imaging in vessels requiring percutaneous coronary intervention. Study subjects were stratified according to achieved LDL-C levels (<50, 50-70, 70-100, <100 mg/dL). FD-OCT derived plaque microstructures were compared. Results: LDL-C levels <50 mg/dL and <70 mg/dL were observed in 13.9% (39/280) and 29.2% (82/280) of patients, respectively. Patients with LDL-C <50 mg/dL were more likely to be older (p < 0.001) and receive a high-dose statin (p = 0.01). On FD-OCT imaging, patients with LDL-C <50 mg/dL were more likely to have fibrous plaque (51.7, 43.2, 22.2 and 12.3%, p = 0.01) and less likely to have lipid plaques (48.2, 56.7, 77.7 and 87.6%, p = 0.01). In addition, LDL-C level was significantly associated with lipid arc (173 ± 76, 175 ± 88, 196 ± 102 and 234 ± 85°, p = 0.01) and fibrous cap thickness (139.9 ± 93.9, 103.1 ± 66.4, 92.5 ± 48.5 and 92.1 ± 47.8 um, p = 0.001). In particular, the smallest lipid arc and thickest fibrous cap were observed in patients who achieved LDL-C <50 mg/dL. Multivariable analysis revealed LDL-C levels (beta coefficient -0.254, p = 0.009) and high-dose statin use (beta coefficient 1.814, p = 0.003) to independently associate with fibrous cap thickness. Conclusions: More stable plaque features were observed within non-obstructive atheromas in patients with very low LDL-C levels. These findings underscore LDL-C level to stabilize plaques in patients with CAD and high residual atherosclerotic risk.