Plaque characteristics and arterial remodeling in coronary and peripheral arterial systems

doi:10.1016/j.atherosclerosis.2012.05.023

Atherosclerosis

Volume 223, Issue 2, August 2012, Pages 365-371

https://doi.org/10.1016/j.atherosclerosis.2012.05.023 Get rights and content

Abstract

Background

Few studies have examined plaque characteristics among multiple arterial beds in vivo. The purpose of this study was to compare the plaque morphology and arterial remodeling between coronary and peripheral arteries using gray-scale and radiofrequency intravascular ultrasound (IVUS) at clinical presentation.

Methods and results

IVUS imaging was performed in 68 patients with coronary and 93 with peripheral artery lesions (29 carotid, 50 renal, and 14 iliac arteries). Plaques were classified as fibroatheroma (VH-FA) (further subclassified as thin-capped [VH-TCFA] and thick-capped [VH-ThCFA]), fibrocalcific plaque (VH-FC) and pathological intimal thickening (VH-PIT). Plaque rupture (13% of coronary, 7% of carotid, 6% of renal, and 7% of iliac arteries; P = NS) and VH-TCFA (37% of coronary, 24% of carotid, 16% of renal, and 7% of iliac arteries; P = 0.02) were observed in all arteries. Compared with coronary arteries, VH-FA was less frequently observed in renal (P < 0.001) and iliac arteries (P < 0.006). Lesions with positive remodeling demonstrated more characteristics of VH-FA in coronary (84% vs. 25%, P < 0.001), carotid (72% vs. 20%, P = 0.001), and renal arteries (42% vs. 4%, P = 0.001) compared with those with intermediate/negative remodeling. There was positive relationship between remodeling index and percent necrotic area in all four arteries.

Conclusions

Atherosclerotic plaque phenotypes were heterogeneous among four different arteries; renal and iliac arteries had more stable phenotypes compared with coronary artery. In contrast, the associations of remodeling pattern with plaque phenotype and composition were similar among the various arterial beds.

Highlights

► Compared with coronary arteries, fibroatheroma was less frequently observed in renal and iliac arteries. ► Positive remodeled lesions demonstrated more fibroatheroma in coronary, carotid, and renal arteries. ► There was positive relationship between remodeling index and percent necrotic area in all four arteries.

Introduction

Atherosclerosis is a systemic process with manifestations in multiple arterial beds. Given the rising prevalence of peripheral artery disease (PAD) [1], understanding differences in plaque characteristics and clinical presentation may have implications for treatment and prevention of cardiovascular disease.

A previous postmortem study showed that foam cell lesions and lipid core plaques were highly prevalent in coronary and carotid arteries, while fibrous plaques dominated severe atherosclerosis in femoral arteries [2]. However, few studies have compared plaque characteristics in multiple arterial beds in vivo. We have recently reported a comparative analysis of atherosclerotic plaques between the coronary and the renal arterial beds [3]. The purpose of this study was to extend those previous observations and to test the hypothesis that there is a heterogeneous manifestation of atherosclerosis in different human arterial beds. In order to address our hypothesis we compared plaque morphology and arterial remodeling between coronary and peripheral arteries using gray-scale and radiofrequency intravascular ultrasound.

Section snippets

Patients

The Mayo Clinic Institutional Review Board approved this study protocol. Between May 2008 and June 2011, 256 interventional and diagnostic IVUS for left main coronary artery (LMCA) and peripheral arteries (carotid artery, renal artery, and iliac artery) were performed for clinical purposes. The decision to perform IVUS examination was based on the discretion of the operator. Seventy-eight patients with LMCA lesions, 34 with extracranial internal carotid artery (ICA) lesions, 66 with renal

Clinical characteristics

Table 1 shows clinical characteristics and laboratory data of our patients. Eleven (16%) patients with coronary artery disease presented with acute coronary syndrome and 57 (84%) presented with stable angina. Five patients (17%) with carotid artery disease had symptomatic stenosis and 24 (83%) had asymptomatic stenosis. All patients with carotid artery disease had been diagnosed with stenosis greater than or equal to 70% by carotid duplex (n = 16), magnetic resonance angiography (n = 11), or

Discussion

The present in vivo study demonstrates for the first time that there are artery-specific differences in atherosclerotic plaque phenotype and composition, as well as similarities in the association of plaque remodeling with plaque components in four different arterial beds. Such heterogeneity in plaque composition may explain the differential clinical presentation of atherosclerosis in different arterial beds.

VH-FAs were relatively infrequently observed in renal and iliac arteries where stable

Conclusion

Atherosclerotic plaque phenotypes and composition were heterogeneous in four different arterial beds at clinical presentation; compared with coronary artery, renal and iliac arteries had more stable phenotypes. In contrast, the associations of remodeling pattern with plaque phenotype and composition were similarly observed among the various arterial beds. There is likely an underlying shared pathogenic mechanism of plaque remodeling. The current study also points to a potential underlying

Disclosures

None.

References (30)

T. Kataoka et al.
Association of plaque composition and vessel remodeling in atherosclerotic renal artery stenosis: a comparison with coronary artery disease
JACC Cardiovasc Imag
(2009)
G.S. Mintz et al.
American college of cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (IVUS). A report of the American college of cardiology task force on clinical expert consensus documents
J Am Coll Cardiol
(2001)
T. Takumi et al.
The association between renal atherosclerotic plaque characteristics and renal function before and after renal artery intervention
Mayo Clin Proc
(2011)
P.A. Calvert et al.
Association between IVUS findings and adverse outcomes in patients with coronary artery disease: the VIVA (VH-IVUS in vulnerable atherosclerosis) study
JACC Cardiovasc Imag
(2011)
P.V. Stroev et al.
Distribution of wall shear rate throughout the arterial tree: a case study
Atherosclerosis
(2007)
H.A. Hildebrandt et al.
Differential distribution of vasa vasorum in different vascular beds in humans
Atherosclerosis
(2008)
G. Pasterkamp et al.
Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1, 2 and 9 in the human coronary artery
Atherosclerosis
(2000)
G. Pasterkamp et al.
Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox
J Am Coll Cardiol
(1998)
A.J. Lansky et al.
Gender and the extent of coronary atherosclerosis, plaque composition, and clinical outcomes in acute coronary syndromes
JACC Cardiovasc Imag
(2012)
T. Kawamoto et al.
The relationship between coronary plaque characteristics and small embolic particles during coronary stent implantation
J Am Coll Cardiol
(2007)

H. Okura et al.

Preintervention arterial remodeling affects clinical outcome following stenting: an intravascular ultrasound study

J Am Coll Cardiol

(2001)

R.C. Pasternak et al.

Atherosclerotic vascular disease conference: writing group I: epidemiology

Circulation

(2004)

S. Dalager et al.

Plaque in superficial femoral arteries indicates generalized atherosclerosis and vulnerability to coronary death: an autopsy study

Stroke

(2007)

H.M. García-García et al.

Tissue characterisation using intravascular radiofrequency data analysis: recommendations for acquisition, analysis, interpretation and reporting

EuroIntervention

(2009)

J. Kotani et al.

Intravascular ultrasound analysis of infarct-related and non-infarct-related arteries in patients who presented with an acute myocardial infarction

Circulation

(2003)

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Plaque characteristics and arterial remodeling in coronary and peripheral arterial systems

Abstract

Background

Methods and results

Conclusions

Highlights

Introduction

Section snippets

Patients

Clinical characteristics

Discussion

Conclusion

Disclosures

JACC Cardiovasc Imag

J Am Coll Cardiol

Mayo Clin Proc

JACC Cardiovasc Imag

Atherosclerosis

Atherosclerosis

Atherosclerosis

J Am Coll Cardiol

JACC Cardiovasc Imag

J Am Coll Cardiol

J Am Coll Cardiol

Atherosclerotic vascular disease conference: writing group I: epidemiology

Circulation

Plaque in superficial femoral arteries indicates generalized atherosclerosis and vulnerability to coronary death: an autopsy study

Stroke

Tissue characterisation using intravascular radiofrequency data analysis: recommendations for acquisition, analysis, interpretation and reporting

EuroIntervention

Intravascular ultrasound analysis of infarct-related and non-infarct-related arteries in patients who presented with an acute myocardial infarction

Circulation