title: The beneficial effects of raising high-density lipoprotein cholesterol depends upon achieved levels of low-density lipoprotein cholesterol during statin therapy: Implications for coronary atheroma progression and cardiovascular events.
abstract: OBJECTIVE
  Controversy exists regarding benefits of raising HDL-C in statin-treated coronary artery disease (CAD) patients. We assessed the anti-atherosclerotic efficacy of raising HDL-C in statin-treated individuals with CAD across a range of achieved LDL-C, including lower (<70 mg/dL) versus higher (≥70 mg/dL) levels.
  
  
  RESULTS
  In seven prospective randomized trials utilizing serial coronary intravascular ultrasound, 3469 statin-treated CAD patients were stratified according to achieved LDL-C (< vs ≥70 mg/dL) and changes in HDL-C (≥ vs < median), as well as across a broader spectrum of changes in HDL-C and achieved LDL-C levels. Changes in coronary percent atheroma volume and MACE (cardiovascular death, non-fatal MI, stroke, coronary revascularization, hospitalization for unstable angina) were evaluated across these groups.
  
  
  RESULTS
  Overall, median change in HDL-C was +6.03%, and mean achieved LDL-C in the lower and higher LDL-C groups were 55.1 ± 11 and 97.4 ± 22 mg/dL, respectively. Following multivariable adjustment, in patients with achieved LDL-C < 70 mg/dL, greater HDL-C-raising did not associate with disease progression/regression. In those with achieved LDL-C ≥ 70 mg/dL, greater HDL-C-raising associated with less disease progression (OR 0.80 (95% CI 0.67, 0.97)) and MACE (HR 0.78 (95% CI 0.64, 0.96)). Greater increases in HDL-C (up to 25% from baseline) across the continuous range of on-treatment LDL-C levels associated with less disease progression )OR 0.90 (95% CI 0.83, 0.98)) and lower MACE (HR 0.87 (95% CI 0.77, 0.998)).
  
  
  CONCLUSIONS
  Increasing HDL-C via a broad spectrum of mechanisms appears beneficial in statin-treated CAD patients, but is likely of greater benefit in patients with achieved LDL-C levels ≥70 mg/dL.
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland, Ohio, USA Department of Cardiovascular Medicine, Cleveland Clinic, Ohio, USA.
authors.forename: Rishi
authors.initials: R
authors.lastname: Puri
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland, Ohio, USA Department of Cardiovascular Medicine, Cleveland Clinic, Ohio, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland, Ohio, USA.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Shao
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, South Australia.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kataoka
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland, Ohio, USA.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Uno
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Ohio, USA.
authors.forename: Samir R
authors.initials: SR
authors.lastname: Kapadia
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Ohio, USA.
authors.forename: E Murat
authors.initials: EM
authors.lastname: Tuzcu
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, South Australia stephen.nicholls@sahmri.com.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D058226:Plaque, Atherosclerotic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: HDL-C; IVUS; LDL-C; coronary artery disease; statins