Author + information
- Received January 22, 2019
- Revision received April 11, 2019
- Accepted April 15, 2019
- Published online July 1, 2019.
- Martin Bødtker Mortensen, MD, PhDa,∗ (, )@AUHdk,
- Valentin Fuster, MD, PhDb,
- Pieter Muntendam, MDc,
- Roxana Mehran, MDb,
- Usman Baber, MD, MSb,
- Samantha Sartori, PhDb and
- Erling Falk, MD, DMSca
- aDepartment of Cardiology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Cardiology, Aarhus University Hospital, Aarhus, Denmark
- bCardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, New YorkCardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York
- cscPharmaceuticals, Lexington, MassachusettsscPharmaceuticals, Lexington, Massachusetts
- ↵∗Address for correspondence:
Dr. Martin Bødtker Mortensen, Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard, 8200 Aarhus N, Denmark.
Background Cardiovascular risk increases dramatically with age, leading to nearly universal risk-based statin eligibility in the elderly population. To limit overtreatment, elderly individuals at truly low risk need to be identified.
Objectives Discovering “negative” risk markers able to identify elderly individuals at low short-term risk for coronary heart disease and cardiovascular disease.
Methods In 5,805 BioImage participants (mean age 69 years; median follow-up 2.7 years), the authors evaluated 13 candidate markers: coronary artery calcium (CAC) = 0, CAC ≤10, no carotid plaque, no family history, normal ankle-brachial index, test result <25th percentile (carotid intima-media thickness, apolipoprotein B, galectin-3, high-sensitivity C-reactive protein, lipoprotein(a), N-terminal pro–B-type natriuretic peptide, and transferrin), and apolipoprotein A1 >75th percentile. Negative risk marker performance was compared using patient-specific diagnostic likelihood ratio (DLR) and binary net reclassification index (NRI).
Results CAC = 0 and CAC ≤10 were the strongest negative risk markers with mean DLRs of 0.20 and 0.20 for coronary heart disease (i.e., ≈80% lower risk than expected from traditional risk factor assessment) and 0.41 and 0.48 for cardiovascular disease, respectively, followed by galectin-3 <25th percentile (DLR 0.44 and 0.43, respectively) and absence of carotid plaque (DLR 0.39 and 0.65, respectively). Results obtained by other candidate markers were less impressive. Accurate downward risk reclassification across the Class I statin-eligibility threshold defined by the American College of Cardiology/American Heart Association was largest for CAC = 0 (NRI 0.23) and CAC ≤10 (NRI 0.28), followed by galectin-3 <25th percentile (NRI 0.14) and absence of carotid plaque (NRI 0.08).
Conclusions Elderly individuals with CAC = 0, CAC ≤10, low galectin-3, or no carotid plaque had remarkable low cardiovascular risk, calling into question the appropriateness of a treat-all approach in the elderly population.
The BioImage Study was designed by the High-Risk Plaque Initiative, a pre-competitive industry collaboration funded by Abbott, AstraZeneca, Merck, Philips, and Takeda. Dr. Muntendam is a shareholder in and employee of G3 Pharmaceuticals. Dr. Mehran has received research funding (institutional) from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, CSL Behring, Eli Lilly/DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich, and PLC/Renal Guard; has received consultant fees (institutional) from Abbott Laboratories and Spectranetics/Philips/Volcano has received consultant fees (personal) from Abbott Laboratories, Boston Scientific, Bracco Group, Medscape/WebMD, Siemens Medical Solutions, Roivant Sciences, Sanofi, Janssen Pharmaceuticals, Abiomed (spouse), and The Medicines Company (spouse), and (no fee) Regeneron Pharmaceuticals; has advisory board fees (personal) from PLx Opco/PLx Pharma and Medtelligence, and (institutional) from BMS; has received speaker fees from Medtelligence; and has received equity from Claret Medical and Elixir Medical. Dr. Baber has received speaker fees from AstraZeneca and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Ron Blankstein, MD, served as Guest Associate Editor for this paper. Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this paper.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received January 22, 2019.
- Revision received April 11, 2019.
- Accepted April 15, 2019.
- 2019 American College of Cardiology Foundation
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