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

Rishi Puri, Steven E. Nissen, Mingyuan Shao, Yu Kataoka, Kiyoko Uno, Samir R. Kapadia, E. Murat Tuzcu, Stephen J. Nicholls

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11 Citations (Scopus)


Aims 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. Methods and 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.

Original languageEnglish
Pages (from-to)474-485
Number of pages12
JournalEuropean Journal of Preventive Cardiology
Issue number5
Publication statusPublished - 1 Mar 2016
Externally publishedYes


  • coronary artery disease
  • HDL-C
  • IVUS
  • LDL-C
  • statins

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