Carotid Plaque Lipid Content and Fibrous Cap Status Predict Systemic CV Outcomes: The MRI Substudy in AIM-HIGH

JACC Cardiovasc Imaging. 2017 Mar;10(3):241-249. doi: 10.1016/j.jcmg.2016.06.017.


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.

Keywords: atherosclerosis; cardiovascular events; carotid artery; magnetic resonance imaging; surrogate marker; vulnerable plaque.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Coronary Syndrome / etiology
  • Aged
  • Brain Ischemia / etiology
  • Canada
  • Carotid Artery Diseases / complications
  • Carotid Artery Diseases / diagnostic imaging*
  • Carotid Artery Diseases / mortality
  • Carotid Artery Diseases / pathology
  • Carotid Artery Diseases / therapy
  • Carotid Artery, Common / chemistry
  • Carotid Artery, Common / diagnostic imaging*
  • Carotid Artery, Common / pathology
  • Disease-Free Survival
  • Female
  • Fibrosis
  • Hospitalization
  • Humans
  • Kaplan-Meier Estimate
  • Lipids / analysis
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Plaque, Atherosclerotic*
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Rupture, Spontaneous
  • Stroke / etiology
  • Time Factors
  • United States


  • Lipids