title: Carotid Plaque Lipid Content and Fibrous Cap Status Predict Systemic CV Outcomes: The MRI Substudy in AIM-HIGH.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Xue-Qiao
authors.initials: XQ
authors.lastname: Zhao
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Balu
authors.affiliation: The Mountain-Whisper-Light Statistics, Seattle, Washington.
authors.forename: Moni B
authors.initials: MB
authors.lastname: Neradilek
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Isquith
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Mechanical Engineering, University of Washington, Seattle, Washington.
authors.forename: Gádor
authors.initials: G
authors.lastname: Cantón
authors.affiliation: Department of Medicine, Wake Forest University, Winston-Salem, North Carolina.
authors.forename: John R
authors.initials: JR
authors.lastname: Crouse
authors.affiliation: Libin Cardiovascular Institute of Alberta and Cumming School of Medicine, Calgary, Alberta, Canada.
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Anderson
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: John
authors.initials: J
authors.lastname: Huston
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Kevin
authors.initials: K
authors.lastname: O'Brien
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Hippe
authors.affiliation: The Mountain-Whisper-Light Statistics, Seattle, Washington.
authors.forename: Nayak L
authors.initials: NL
authors.lastname: Polissar
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: Chun
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Surgery, University of Washington, Seattle, Washington. Electronic address: tomhat@u.washington.edu.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Hatsukami
mesh_terms: D054058:Acute Coronary Syndrome / Q000209:etiology; D000368:Aged; D002545:Brain Ischemia / Q000209:etiology; D002170:Canada; D002340:Carotid Artery Diseases / Q000150:complications / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D017536:Carotid Artery, Common / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005355:Fibrosis; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D008055:Lipids / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012422:Rupture, Spontaneous; D020521:Stroke / Q000209:etiology; D013997:Time Factors; D014481:United States
chemical_list: D008055:Lipids
keywords: atherosclerosis; cardiovascular events; carotid artery; magnetic resonance imaging; surrogate marker; vulnerable plaque