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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.
Eur J Prev Cardiol. 2016 Mar; 23(5):474-85.EJ

Abstract

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.

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Authors+Show Affiliations

Puri R
Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland, Ohio, USA Department of Cardiovascular Medicine, Cleveland Clinic, Ohio, USA.
Nissen SE
Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland, Ohio, USA Department of Cardiovascular Medicine, Cleveland Clinic, Ohio, USA.
Shao M
Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland, Ohio, USA.
Kataoka Y
South Australian Health and Medical Research Institute, University of Adelaide, South Australia.
Uno K
Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland, Ohio, USA.
Kapadia SR
Department of Cardiovascular Medicine, Cleveland Clinic, Ohio, USA.
Tuzcu EM
Department of Cardiovascular Medicine, Cleveland Clinic, Ohio, USA.
Nicholls SJ
South Australian Health and Medical Research Institute, University of Adelaide, South Australia stephen.nicholls@sahmri.com.

MeSH

AgedBiomarkersChi-Square DistributionCholesterol, HDLCholesterol, LDLCoronary Artery DiseaseCoronary VesselsDisease ProgressionDrug Therapy, CombinationFemaleHumansHydroxymethylglutaryl-CoA Reductase InhibitorsKaplan-Meier EstimateLogistic ModelsMaleMiddle AgedMultivariate AnalysisOdds RatioPlaque, AtheroscleroticProportional Hazards ModelsProspective StudiesRandomized Controlled Trials as TopicRisk AssessmentRisk FactorsTime FactorsTreatment OutcomeUltrasonography, InterventionalUp-Regulation

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25691546

Citation

Puri, Rishi, et al. "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." European Journal of Preventive Cardiology, vol. 23, no. 5, 2016, pp. 474-85.
Puri R, Nissen SE, Shao M, et al. 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. Eur J Prev Cardiol. 2016;23(5):474-85.
Puri, R., Nissen, S. E., Shao, M., Kataoka, Y., Uno, K., Kapadia, S. R., Tuzcu, E. M., & Nicholls, S. J. (2016). 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. European Journal of Preventive Cardiology, 23(5), 474-85. https://doi.org/10.1177/2047487315572920
Puri R, et al. 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. Eur J Prev Cardiol. 2016;23(5):474-85. PubMed PMID: 25691546.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Puri,Rishi, AU - Nissen,Steven E, AU - Shao,Mingyuan, AU - Kataoka,Yu, AU - Uno,Kiyoko, AU - Kapadia,Samir R, AU - Tuzcu,E Murat, AU - Nicholls,Stephen J, Y1 - 2015/02/17/ PY - 2014/08/11/received PY - 2015/01/25/accepted PY - 2015/2/19/entrez PY - 2015/2/19/pubmed PY - 2016/12/15/medline KW - HDL-C KW - IVUS KW - LDL-C KW - coronary artery disease KW - statins SP - 474 EP - 85 JF - European journal of preventive cardiology JO - Eur J Prev Cardiol VL - 23 IS - 5 N2 - 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. SN - 2047-4881 UR - https://www.unboundmedicine.com/medline/citation/25691546/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_ L2 - https://journals.sagepub.com/doi/10.1177/2047487315572920?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -