Author + information
- Received May 16, 2016
- Accepted June 9, 2016
- Published online March 6, 2017.
- Jie Sun, MDa,
- Xue-Qiao Zhao, MDb,
- Niranjan Balu, PhDa,
- Moni B. Neradilek, MSc,
- Daniel A. Isquith, BAb,
- Kiyofumi Yamada, MD, PhDa,
- Gádor Cantón, PhDd,
- John R. Crouse III, MDe,
- Todd J. Anderson, MDf,
- John Huston III, MDg,
- Kevin O’Brien, MDb,
- Daniel S. Hippe, MSa,
- Nayak L. Polissar, PhDc,
- Chun Yuan, PhDa and
- Thomas S. Hatsukami, MDh,∗ ()
- aDepartment of Radiology, University of Washington, Seattle, Washington
- bDepartment of Medicine, University of Washington, Seattle, Washington
- cThe Mountain-Whisper-Light Statistics, Seattle, Washington
- dDepartment of Mechanical Engineering, University of Washington, Seattle, Washington
- eDepartment of Medicine, Wake Forest University, Winston-Salem, North Carolina
- fLibin Cardiovascular Institute of Alberta and Cumming School of Medicine, Calgary, Alberta, Canada
- gDepartment of Radiology, Mayo Clinic, Rochester, Minnesota
- hDepartment of Surgery, University of Washington, Seattle, Washington
- ↵∗Address for correspondence:
Dr. Thomas S. Hatsukami, Department of Surgery, University of Washington, 850 Republican Street, Seattle, Washington 98109.
Objectives The aim of this study was to investigate whether and what carotid plaque characteristics predict systemic cardiovascular outcomes in patients with clinically established atherosclerotic disease.
Background Advancements in atherosclerosis imaging have allowed assessment of various plaque characteristics, some of which are more directly linked to the pathogenesis of acute cardiovascular events compared to plaque burden.
Methods As part of the event-driven clinical trial AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes), subjects with clinically established atherosclerotic disease underwent multicontrast carotid magnetic resonance imaging (MRI) to detect plaque tissue composition and high-risk features. Prospective associations between MRI measurements and the AIM-HIGH primary endpoint (fatal and nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, and symptom-driven revascularization) were analyzed using Cox proportional hazards survival models.
Results Of the 232 subjects recruited, 214 (92.2%) with diagnostic image quality constituted the study population (82% male, mean age 61 ± 9 years, 94% statin use). During median follow-up of 35.1 months, 18 subjects (8.4%) reached the AIM-HIGH endpoint. High lipid content (hazard ratio [HR] per 1 SD increase in percent lipid core volume: 1.57; p = 0.002) and thin/ruptured fibrous cap (HR: 4.31; p = 0.003) in carotid plaques were strongly associated with the AIM-HIGH endpoint. Intraplaque hemorrhage had a low prevalence (8%) and was marginally associated with the AIM-HIGH endpoint (HR: 3.00; p = 0.053). High calcification content (HR per 1 SD increase in percent calcification volume: 0.66; p = 0.20), plaque burden metrics, and clinical risk factors were not significantly associated with the AIM-HIGH endpoint. The associations between carotid plaque characteristics and the AIM-HIGH endpoint changed little after adjusting for clinical risk factors, plaque burden, or AIM-HIGH randomized treatment assignment.
Conclusions Among patients with clinically established atherosclerotic disease, carotid plaque lipid content and fibrous cap status were strongly associated with systemic cardiovascular outcomes. Markers of carotid plaque vulnerability may serve as novel surrogate markers for systemic atherothrombotic risk.
- cardiovascular events
- carotid artery
- magnetic resonance imaging
- surrogate marker
- vulnerable plaque
This study was supported by NIH R01 HL088214, R01 HL089504, and R01 HL103609. Carotid coils were provided by GE Healthcare and Philips Healthcare. Mr. Hippe has received research grants from Philips Healthcare and GE Healthcare. Dr. Balu has received a research grant from Philips Healthcare. Dr. Yuan has received research grants from Philips Healthcare; and is a member of Radiology Medical Advisory Network of Philips Healthcare. Dr. O’Brien has received grant support from Sanofi. Dr. Hatsukami has received a research grant from Philips Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Sun and Zhao contributed equally to this work.
- Received May 16, 2016.
- Accepted June 9, 2016.
- American College of Cardiology Foundation