We appreciate Dr. Egom’s interest in our study. We agree that high-density lipoprotein (HDL) particles have multiple functions, including cholesterol efflux, anti-inflammatory, anti-thrombotic, antioxidative, and endothelial protective properties, among others.1 Given the extreme heterogeneity of HDL function and structure, measuring only the cholesterol content of HDL (HDL-C) will at best only partially reflect the potential role of HDL in cardiovascular risk assessment and therapeutic drug development.2 In this regard, our study found that the number of HDL particles (HDL-P) may be a better marker of residual vascular risk after potent statin therapy in the JUPITER trial than chemically measured HDL-C or apolipoprotein A-I.3 These results support the growing body of literature suggesting that HDL-P may be a promising metric of HDL that is more independent of other metabolic and lipoprotein risk factors than HDL-C or HDL size.4 We agree with Dr. Egom that bioactive lipids such as sphingosine-1-phosphate (S1P) may play a key role in the antiatherogenic function of HDL particles and may be modulated by statin therapy,5 and look forward to future work in this area.
Acknowledgments
Funding Sources: Research reported in this publication was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R01HL117861 to Dr Mora. LipoScience Inc (Raleigh, NC) absorbed the cost of performing the HDL-P measurements, but otherwise had no role in the management, analysis and interpretation of the data, and preparation, review, or approval of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. JUPITER was financially supported by AstraZeneca, who collected trial data and monitored sites but had no role in the design or conduct of the current study, including data analysis or interpretation, drafting or editing this report, or in preparation, review or the decision to submit the manuscript for publication.
Footnotes
Disclosures
Dr. Mora has received research support from AstraZeneca, Merck, and NHLBI, served as a consultant to Pfizer, Quest Diagnostics, and Cerenis Therapeutics, received speaker honoraria from AstraZeneca, Abbott, and the National Lipid Association for educational (non-promotional) activities, and received travel expense reimbursement from Pfizer. Dr. Glynn has received research support from AstraZeneca and NIH. Dr. Ridker has received research grant support from AstraZeneca, Novartis, Amgen, and NHLBI, and has served as a consultant to Genzyme, Jannsen, Aegerion, ISIS, Vascular Biogenics, BostonHeart, Pfizer, and Merck. Dr. Ridker is listed as a co-inventor on patents held by the Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease that have been licensed to AstraZeneca and Siemens.
References
- 1.Rosenson RS, Brewer HB, Jr, Ansell B, Barter P, Chapman MJ, Heinecke JW, Kontush A, Tall AR, Webb NR. Translation of high-density lipoprotein function into clinical practice: Current prospects and future challenges. Circulation. 2013;128:1256–1267. doi: 10.1161/CIRCULATIONAHA.113.000962. [DOI] [PubMed] [Google Scholar]
- 2.Ridker PM, Genest J, Boekholdt SM, Libby P, Gotto AM, Nordestgaard BG, Mora S, MacFadyen JG, Glynn RJ, Kastelein JJ. HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: An analysis from the JUPITER trial. Lancet. 2010;376:333–339. doi: 10.1016/S0140-6736(10)60713-1. [DOI] [PubMed] [Google Scholar]
- 3.Mora S, Glynn RJ, Ridker PM. High-density lipoprotein cholesterol, size, particle number, and residual vascular risk after potent statin therapy. Circulation. 2013;128:1189–1197. doi: 10.1161/CIRCULATIONAHA.113.002671. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Mackey RH, Greenland P, Goff DC, Jr, Lloyd-Jones D, Sibley CT, Mora S. High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events: MESA (Multi-Ethnic Study of Atherosclerosis) J Am Coll Cardiol. 2012;60:508–516. doi: 10.1016/j.jacc.2012.03.060. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Kontush A, Lhomme M, Chapman MJ. Unraveling the complexities of the HDL lipidome. J Lipid Res. 2013;54:2950–2963. doi: 10.1194/jlr.R036095. [DOI] [PMC free article] [PubMed] [Google Scholar]