Author + information
- Received March 25, 2013
- Revision received July 8, 2013
- Accepted July 23, 2013
- Published online November 12, 2013.
- Subroto Acharjee, MD∗,
- William E. Boden, MD†∗ (, )
- Pamela M. Hartigan, PhD‡,
- Koon K. Teo, MB, BCh, PhD§,
- David J. Maron, MD‖,
- Steven P. Sedlis, MD¶,
- William Kostuk, MD#,
- John A. Spertus, MD, MPH∗∗,
- Marcin Dada, MD††,
- Bernard R. Chaitman, MD‡‡,
- G.B. John Mancini, MD§§ and
- William S. Weintraub, MD‖‖
- ∗Einstein Medical Center Philadelphia, Philadelphia, Pennsylvania
- †Samuel S. Stratton VA Medical Center and Albany Medical College, Albany, New York
- ‡Cooperative Studies Program Coordinating Center and VA Connecticut Health Care System, West Haven, Connecticut
- §McMaster University Medical Center, Hamilton, Ontario, Canada
- ‖Vanderbilt University Medical Center, Nashville, Tennessee
- ¶Veterans Affairs (VA) New York Harbor Health Care System and New York University School of Medicine, New York, New York
- #London Health Sciences Centre, London, Ontario, Canada
- ∗∗Mid America Heart Institute and University of Missouri–Kansas City, Kansas City, Missouri
- ††Hartford Hospital, Hartford, Connecticut
- ‡‡St. Louis University, St. Louis, Missouri
- §§University of British Columbia, Vancouver, British Columbia, Canada
- ‖‖Christiana Care Health System, Newark, Delaware
- ↵∗Reprint requests and correspondence:
Dr. William E. Boden, Department of Medicine, Samuel Stratton VA Medical Center, 113 Holland Avenue, Albany, New York 12208.
Objectives This study sought to assess the independent effect of high-density lipoprotein-cholesterol (HDL-C) level on cardiovascular risk in patients with stable ischemic heart disease (SIHD) who were receiving optimal medical therapy (OMT).
Background Although low HDL-C level is a powerful and independent predictor of cardiovascular risk, recent data suggest that this may not apply when low-density lipoprotein-cholesterol (LDL-C) is reduced to optimal levels using intensive statin therapy.
Methods We performed a post-hoc analysis in 2,193 men and women with SIHD from the COURAGE trial. The primary outcome measure was the composite of death from any cause or nonfatal myocardial infarction (MI). The independent association between HDL-C levels measured after 6 months on OMT and the rate of cardiovascular events after 4 years was assessed. Similar analyses were performed separately in subjects with LDL-C levels below 70 mg/dl (1.8 mmol/l).
Results In the overall population, the rate of death/MI was 33% lower in the highest HDL-C quartile as compared with the lowest quartile, with quartile of HDL-C being a significant, independent predictor of death/MI (p = 0.05), but with no interaction for LDL-C category (p = 0.40). Among subjects with LDL-C levels <70 mg/dl, those in the highest quintile of HDL-C had a 65% relative risk reduction in death or MI as compared with the lowest quintile, with HDL-C quintile demonstrating a significant, inverse predictive effect (p = 0.02).
Conclusions In this post-hoc analysis, patients with SIHD continued to experience incremental cardiovascular risk associated with low HDL-C levels despite OMT during long-term follow-up. This relationship persisted and appeared more prominent even when LDL-C was reduced to optimal levels with intensive dyslipidemic therapy. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657)
The COURAGE study was supported by the Cooperative Studies Program of the U.S. Department of Veterans Affairs Office of Research and Development, in collaboration with the Canadian Institutes of Health Research; and by unrestricted research grants from the following companies: Merck, Pfizer, Bristol-Myers Squibb, Fujisawa, Kos Pharmaceuticals, Datascope, AstraZeneca, Key Pharmaceutical, sanofi-aventis, First Horizon, and GE Healthcare, including in-kind support with Food and Drug Administration-approved drugs used by study participants. All industrial funding in support of the trial was directed through the U.S. Department of Veterans Affairs. Dr. Mancini has received grants, honoraria, and is on the speakers' bureau of Amgen Merck CanaSanofi, and AstraZeneca; and has received honoraria from Merck, Amgen, Roche, Miraculins, Pfizer, sanofi-aventis, Servier, GlaxoSmithKline, and Valeant. Dr. Spertus owns the copyright to the Seattle Angina Questionnaire; is a consultant for United Healthcare, St. Jude Medical, Abbott Vascular, and Genentech; has received research grant support from Gilead, Genentech, Amgen, and Eli Lilly & Company; has received support from the American Heart Association, American College of Cardiology Foundation, United Healthcare, Health Outcomes Science; and owns the copyright to Seattle Angina Questionnaire; Kansas City Cardiomyopathy Questionnaire; and Position Analysis Questionnaire. Dr. Chaitman is a consultant to Pfizer, Forest, Merck, Roche, Sanofi, and Takeda; and is a member of the speakers' bureau for Gilead. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received March 25, 2013.
- Revision received July 8, 2013.
- Accepted July 23, 2013.
- American College of Cardiology Foundation