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

Jie Sun, Xue Qiao Zhao, Niranjan Balu, Moni B. Neradilek, Daniel A. Isquith, Kiyofumi Yamada, Gádor Cantón, John R. Crouse, Todd J. Anderson, John III Huston, Kevin O'Brien, Daniel S. Hippe, Nayak L. Polissar, Chun Yuan, Thomas S. Hatsukami

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)241-249
Number of pages9
JournalJACC: Cardiovascular Imaging
Volume10
Issue number3
DOIs
StatePublished - Mar 1 2017

Fingerprint

Magnetic Resonance Imaging
Lipids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Carotid Artery Diseases
Acute Coronary Syndrome
Proportional Hazards Models
Atherosclerosis
Triglycerides
Hospitalization
Biomarkers
Stroke
Myocardial Infarction
Clinical Trials
Hemorrhage
Survival
Population
Therapeutics
Global Health

Keywords

  • atherosclerosis
  • cardiovascular events
  • carotid artery
  • magnetic resonance imaging
  • surrogate marker
  • vulnerable plaque

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Sun, J., Zhao, X. Q., Balu, N., Neradilek, M. B., Isquith, D. A., Yamada, K., ... Hatsukami, T. S. (2017). Carotid Plaque Lipid Content and Fibrous Cap Status Predict Systemic CV Outcomes: The MRI Substudy in AIM-HIGH. JACC: Cardiovascular Imaging, 10(3), 241-249. https://doi.org/10.1016/j.jcmg.2016.06.017

Carotid Plaque Lipid Content and Fibrous Cap Status Predict Systemic CV Outcomes : The MRI Substudy in AIM-HIGH. / Sun, Jie; Zhao, Xue Qiao; Balu, Niranjan; Neradilek, Moni B.; Isquith, Daniel A.; Yamada, Kiyofumi; Cantón, Gádor; Crouse, John R.; Anderson, Todd J.; Huston, John III; O'Brien, Kevin; Hippe, Daniel S.; Polissar, Nayak L.; Yuan, Chun; Hatsukami, Thomas S.

In: JACC: Cardiovascular Imaging, Vol. 10, No. 3, 01.03.2017, p. 241-249.

Research output: Contribution to journalArticle

Sun, J, Zhao, XQ, Balu, N, Neradilek, MB, Isquith, DA, Yamada, K, Cantón, G, Crouse, JR, Anderson, TJ, Huston, JIII, O'Brien, K, Hippe, DS, Polissar, NL, Yuan, C & Hatsukami, TS 2017, 'Carotid Plaque Lipid Content and Fibrous Cap Status Predict Systemic CV Outcomes: The MRI Substudy in AIM-HIGH', JACC: Cardiovascular Imaging, vol. 10, no. 3, pp. 241-249. https://doi.org/10.1016/j.jcmg.2016.06.017
Sun, Jie ; Zhao, Xue Qiao ; Balu, Niranjan ; Neradilek, Moni B. ; Isquith, Daniel A. ; Yamada, Kiyofumi ; Cantón, Gádor ; Crouse, John R. ; Anderson, Todd J. ; Huston, John III ; O'Brien, Kevin ; Hippe, Daniel S. ; Polissar, Nayak L. ; Yuan, Chun ; Hatsukami, Thomas S. / Carotid Plaque Lipid Content and Fibrous Cap Status Predict Systemic CV Outcomes : The MRI Substudy in AIM-HIGH. In: JACC: Cardiovascular Imaging. 2017 ; Vol. 10, No. 3. pp. 241-249.
@article{332999f96582496098058a2d02f14c12,
title = "Carotid Plaque Lipid Content and Fibrous Cap Status Predict Systemic CV Outcomes: The MRI Substudy in AIM-HIGH",
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",
author = "Jie Sun and Zhao, {Xue Qiao} and Niranjan Balu and Neradilek, {Moni B.} and Isquith, {Daniel A.} and Kiyofumi Yamada and G{\'a}dor Cant{\'o}n and Crouse, {John R.} and Anderson, {Todd J.} and Huston, {John III} and Kevin O'Brien and Hippe, {Daniel S.} and Polissar, {Nayak L.} and Chun Yuan and Hatsukami, {Thomas S.}",
year = "2017",
month = "3",
day = "1",
doi = "10.1016/j.jcmg.2016.06.017",
language = "English (US)",
volume = "10",
pages = "241--249",
journal = "JACC: Cardiovascular Imaging",
issn = "1936-878X",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Carotid Plaque Lipid Content and Fibrous Cap Status Predict Systemic CV Outcomes

T2 - The MRI Substudy in AIM-HIGH

AU - Sun, Jie

AU - Zhao, Xue Qiao

AU - Balu, Niranjan

AU - Neradilek, Moni B.

AU - Isquith, Daniel A.

AU - Yamada, Kiyofumi

AU - Cantón, Gádor

AU - Crouse, John R.

AU - Anderson, Todd J.

AU - Huston, John III

AU - O'Brien, Kevin

AU - Hippe, Daniel S.

AU - Polissar, Nayak L.

AU - Yuan, Chun

AU - Hatsukami, Thomas S.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

AB - 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.

KW - atherosclerosis

KW - cardiovascular events

KW - carotid artery

KW - magnetic resonance imaging

KW - surrogate marker

KW - vulnerable plaque

UR - http://www.scopus.com/inward/record.url?scp=85014423944&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014423944&partnerID=8YFLogxK

U2 - 10.1016/j.jcmg.2016.06.017

DO - 10.1016/j.jcmg.2016.06.017

M3 - Article

C2 - 28279371

AN - SCOPUS:85014423944

VL - 10

SP - 241

EP - 249

JO - JACC: Cardiovascular Imaging

JF - JACC: Cardiovascular Imaging

SN - 1936-878X

IS - 3

ER -