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

Randomized Controlled Trial

. 2017 Mar;10(3):241-249.

doi: 10.1016/j.jcmg.2016.06.017.

Xue-Qiao Zhao 2, Niranjan Balu 1, Moni B Neradilek 3, Daniel A Isquith 2, Kiyofumi Yamada 1, Gádor Cantón 4, John R Crouse 3rd 5, Todd J Anderson 6, John Huston 3rd 7, Kevin O'Brien 2, Daniel S Hippe 1, Nayak L Polissar 3, Chun Yuan 1, Thomas S Hatsukami 8

Affiliations

Randomized Controlled Trial

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

Jie Sun et al. JACC Cardiovasc Imaging. 2017 Mar.

Abstract

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.

Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1. Identification of carotid plaque characteristics on multi-contrast MRI

Upper panel: multicontrast images of a representative carotid plaque with all the common plaque characteristics. Lower panel: markers for specific plaque characteristics are added. Areas that are hypointense on all contrast weightings indicate calcification (asterisks); non-calcified areas that have no- or little-enhancement on post-contrast images indicate LRNC (yellow arrows); hyperintense signals on MPRAGE indicate IPH (red arrows). The absence of fibrous cap signals (LRNC is immediately adjacent to lumen) on TOF and CE-T1W indicates the presence of thin/ruptured fibrous cap (white arrows). CE-T1W = contrast enhanced T1-weighted; LRNC = lipid-rich necrotic core; T1W = T1-weighted; T2W = T2-weighted; TOF = time-of-flight.

Figure 2

Figure 2. Kaplan-Meier estimates of event-free survival

Kaplan-Meier curves show event-free survival in the group with (red line) and without (green line) thin/ruptured fibrous cap. The corresponding hazard ratio is 4.31 (95% CI: 1.67 to 11.12, p=0.003) for the AIM-HIGH primary endpoint (fatal or non-fatal myocardial infarction or ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebrovascular revascularization). The estimated 3-year primary event-free survival rate was 74.6% for subjects with thin/ruptured fibrous cap versus 94.0% for those without.

Comment in

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