title: Plaque microstructures in patients with coronary artery disease who achieved very low low-density lipoprotein cholesterol levels.
abstract: 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.
authors: South Australian Health & Medical Research Institute, University of Adelaide, Adelaide, Australia. Electronic address: jimmyk67@yahoo.co.jp.
authors: Yu
authors: Y
authors: Kataoka
authors: Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA.
authors: Muhammad
authors: M
authors: Hammadah
authors: Cleveland Clinic Coordinating Center for Clinical Research (C5), Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
authors: Rishi
authors: R
authors: Puri
authors: Cleveland Clinic Coordinating Center for Clinical Research (C5), Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
authors: Bhanu
authors: B
authors: Duggal
authors: Cleveland Clinic Coordinating Center for Clinical Research (C5), Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
authors: Kiyoko
authors: K
authors: Uno
authors: Cleveland Clinic Coordinating Center for Clinical Research (C5), Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
authors: Samir R
authors: SR
authors: Kapadia
authors: Cleveland Clinic Coordinating Center for Clinical Research (C5), Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
authors: E
authors: E
authors: Murat Tuzcu
authors: Cleveland Clinic Coordinating Center for Clinical Research (C5), Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
authors: Steven E
authors: SE
authors: Nissen
authors: South Australian Health & Medical Research Institute, University of Adelaide, Adelaide, Australia.
authors: Stephen J
authors: SJ
authors: Nicholls
mesh_terms: D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000503:physiopathology*; D003331:Coronary Vessels / Q000473:pathology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D062645:Percutaneous Coronary Intervention; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000503:physiopathology*; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D041623:Tomography, Optical Coherence
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Frequency-domain optical coherence tomography; LDL-C; Plaque vulnerability; Statin