Author + information
- Received July 13, 2018
- Revision received October 7, 2018
- Accepted October 10, 2018
- Published online January 14, 2019.
- Wynn G. Hunter, MD, MHSca,
- Robert W. McGarrah III, MDb,c,
- Jacob P. Kelly, MD, MHSd,
- Michel G. Khouri, MDb,
- Damian M. Craig, MSc,
- Carol Haynes, ABc,
- G. Michael Felker, MD, MHSb,e,
- Adrian F. Hernandez, MD, MHSb,e,
- Eric J. Velazquez, MDb,e,
- William E. Kraus, MDb,c and
- Svati H. Shah, MD, MS, MHSb,c,e,∗ (, )@SvatiShah
- aDepartment of Medicine, Duke University School of Medicine, Durham, North Carolina
- bDivision of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina
- cDuke Molecular Physiology Institute, Durham, North Carolina
- dAlaska Heart and Vascular Institute, Anchorage, Alaska
- eDuke Clinical Research Institute, Durham, North Carolina
- ↵∗Address for correspondence:
Dr. Svati H. Shah, 300 North Duke Street, Duke University, Durham, North Carolina 27701.
Background Circulating high-density lipoprotein particle (HDL-P) subfractions impact atherogenesis, inflammation, and endothelial function, all of which are implicated in the pathobiology of heart failure (HF).
Objectives The authors sought to identify key differences in plasma HDL-P subfractions between patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) to determine their prognostic utility.
Methods Patients with HFrEF (n = 782), HFpEF (n = 1,004), and no HF (n = 4,742) were identified in the CATHGEN (Catheterization Genetics) biorepository of sequential patients undergoing cardiac catheterization. Nuclear magnetic resonance–based lipoprotein profiling was performed on frozen fasting plasma obtained at catheterization. The authors used multivariable analysis of covariance to compare high-density lipoprotein particle (HDL-P) subfractions across groups, and Cox proportional hazards modeling to determine associations between HDL-P subfractions and time to death or major adverse cardiac events.
Results Mean HDL-P size was greater in HFrEF than HFpEF, both of which were greater than in no HF (all 2-way p < 0.0001). By contrast, concentrations of small HDL-P and total HDL-P were lesser in HFrEF than HFpEF, which were both lesser than no HF (all 2-way p ≤ 0.0002). In both HFrEF and HFpEF, total HDL-P and small HDL-P were inversely associated with time to adverse events. These findings persisted after adjustment for 14 clinical covariates (including high-density lipoprotein cholesterol content, coronary artery disease, and the inflammatory biomarker GlycA), and in sensitivity analyses featuring alternate left ventricular ejection fraction definitions, or stricter inclusion criteria with diastolic dysfunction or left ventricular end-diastolic pressure thresholds.
Conclusions In the largest analysis of HDL-P subfractions in HF to date, derangements in HDL-P subfractions were identified that were more severe in HFrEF than HFpEF and were independently associated with adverse outcomes. These data may help refine risk assessment and provide new insights into the complex interaction of HDL and HF pathophysiology.
- heart failure
- heart failure with preserved ejection fraction
- high-density lipoprotein
- high-density lipoprotein particles
Dr. McGarrah is supported by American Heart Association grant 16SFRN31800000 and National Institutes of Health Grant K08HL135275. Dr. Felker has received funding support from Amgen, Ostuka, and Roche Diagnostics; and consultant fees/honoraria from Amgen, Novartis, Trevena, Singulex, and Medtronic. Dr. Hernandez has received funding support from Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Novartis, and Portola; and consultant fees/honoraria from Bristol-Myers Squibb, Boston Scientific, Gilead, GlaxoSmithKline, Janssen, Merck, and Novartis. Dr. Velazquez has received funding support from Amgen, Alnylam, National Heart, Lung, and Blood Institute, Ikaria Pharmaceuticals, Novartis, and Pfizer; and consultant fees/honoraria from Amgen, Novartis, and Philips. Dr. Kraus has received funding support from LipoScience, Pfizer, Gilead, and the Health Effects Institute. Dr. Shah has received funding support from National Institutes of Health grants 5R01-HL095987-05 and R01-HL127009-02, and American Heart Association grant 16SFRN31800000; and consultant fees/honoraria from Biosense Webster, Boston Scientific, CardioNet, and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received July 13, 2018.
- Revision received October 7, 2018.
- Accepted October 10, 2018.
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