Author + information
- Received October 29, 2018
- Revision received January 13, 2019
- Accepted January 22, 2019
- Published online April 29, 2019.
- Pradeep Natarajan, MD, MMSca,b,c,d,∗ (, )@pnatarajanmd,
- Tim S. Collier, PhDe,
- Zhicheng Jin, PhDe,
- Asya Lyass, PhDf,g,
- Yiwei Li, MSf,
- Nasrien E. Ibrahim, MDa,b,
- Renata Mukai, BAa,
- Cian P. McCarthy, MDa,b,
- Joseph M. Massaro, PhDf,h,
- Ralph B. D’Agostino Sr., PhDf,g,
- Hanna K. Gaggin, MD, MPHa,b,
- Cory Bystrom, PhDe,
- Marc S. Penn, MD, PhDe,i and
- James L. Januzzi Jr., MDa,b,f
- aDivision of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
- bDepartment of Medicine, Harvard Medical School, Boston, Massachusetts
- cCardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts
- dProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts
- eCleveland Heart Lab, Cleveland, Ohio
- fBaim Institute for Clinical Research, Boston, Massachusetts
- gDepartment of Mathematics & Statistics, Boston University, Boston, Massachusetts
- hDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
- iSumma Health Heart and Vascular Institute, Summa Health, Akron, Ohio
- ↵∗Address for correspondence:
Dr. Pradeep Natarajan, Massachusetts General Hospital, 185 Cambridge Street, CPZN 3.184, Boston, Massachusetts 02114.
Background Concentrations of circulating apolipoproteins are strongly linked to risk for coronary artery disease (CAD). The relative importance of the additional knowledge of apolipoprotein concentrations within specific lipoprotein species for CAD risk prediction is limited.
Objectives This study sought to evaluate the performance of a high-density lipoprotein (HDL) apolipoproteomic score, based on targeted mass spectrometry of HDL-associated apolipoproteins, for the detection of angiographic CAD and outcomes.
Methods HDL-associated apolipoprotein (apo) A-1, apoC-1, apoC-2, apoC-3, and apoC-4 were measured in 943 participants without prevalent myocardial infarction (MI) referred for coronary angiography in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study. A composite HDL apolipoproteomic score (pCAD) was associated with likelihood of obstructive CAD (≥70% lesion in ≥1 vessel) and with incident cardiovascular outcomes over 4-year follow-up.
Results There were 587 (62.2%) patients with coronary stenosis. The pCAD score was associated with the presence of obstructive CAD (odds ratio: 1.39; 95% confidence interval [CI]: 1.14 to 1.69; p < 0.001), independently of conventional cardiovascular risk factors including circulating plasma apoA-1 and apoB. The C-index for pCAD was 0.63 (95% CI: 0.59 to 0.67) for the presence of obstructive CAD. Although pCAD was not associated with cardiovascular mortality among all individuals (hazard ratio: 1.24; 95% CI: 0.93 to 1.66; p = 0.15), there was evidence of association for individuals with obstructive CAD (hazard ratio: 1.48; 95% CI: 1.07 to 2.05; p = 0.019).
Conclusions An HDL apolipoproteomic score is associated with the presence of CAD, independent of circulating apoA-1 and apoB concentrations and other conventional cardiovascular risk factors. Among individuals with CAD, this score may be independently associated cardiovascular death. (The CASABLANCA Study: Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA]; NCT00842868)
This investigator-initiated study was sponsored by Cleveland Heart Labs. The sponsor measured high-density lipoprotein (HDL) proteins and calculated the pCAD score for each participant in a blinded fashion. The sponsor was not involved in the study design or data interpretation; the sponsor participated in drafting methods related to HDL proteomic assessment. Dr. Natarajan is supported by an award from the National Heart, Lung, and Blood Institute (K08HL140203); is the coinventor of helical synthetic peptides that stimulate cellular cholesterol efflux (US7691965B2, WO2005058938A3); has received research grants from Amgen, Apple, and Boston Scientific; and has received consulting income from and served on a Scientific Advisory Board for Apple. Drs. Collier, Jin, Bystrom, and Penn are employees of Cleveland Heart Labs. Drs. Collier and Bystrom have stock ownership in Quest Diagnostics. Dr. Ibrahim has received a speaking honorarium from Novartis. Dr. Gaggin has received research grant support from Roche Diagnostics, Jana Care, Ortho Clinical, and Novartis; has received consulting income from Merck and Roche Diagnostics; and has received research payments for clinical endpoint committees from Radiometer. Dr. Penn serves as a paid consultant to Cleveland Heart Lab/Quest Diagnostics; and is named on relevant patents for which he is not eligible for royalties or equity. Dr. Januzzi has received grant support from Roche Diagnostics, Abbott Diagnostics, Singulex, Prevencio, and Cleveland Heart Labs; has received consulting income from Roche Diagnostics and Critical Diagnostics; and participates in Clinical Endpoint Committees/Data Safety Monitoring Boards for Siemens Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Philip Barter, MBBS, PhD, served as Guest Associate Editor for this paper.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received October 29, 2018.
- Revision received January 13, 2019.
- Accepted January 22, 2019.
- 2019 American College of Cardiology Foundation
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