The utility of ultrasonic tissue characterization of carotid plaque in the prediction of cardiovascular events in diabetic patients
Introduction
Since cardiovascular disease (CVD) remains the main cause of death and impairment of quality of life in diabetic patients, early identification of individuals at high risk for CVD events and subsequent rapid interventions are important. Recently, ultrasound examination of the carotid artery has been in use to non-invasively identify individuals at high risk for CVD. Some studies have shown that the presence/absence of carotid plaque assessed by ultrasound could improve the prediction ability for CVD over and above conventional coronary risk factors [1], [2], [3], [4], [5].
It is well known that disruption of an atherosclerotic plaque plays a crucial role in the pathogenesis of CVD event and that plaque disruption is dependent on the content of lipid, neovascular vessel, and inflammatory cells in the atheroma, and the thickness of the fibrous cap [6], [7], [8], [9]. Therefore, tissue characterization of a plaque lesion is considered to be useful for identifying patients at high risk for CVD and death. Presently, various modalities such as Computed Tomography (CT), Magnetic Resonance Imaging (MRI), or Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) are being used to detect vulnerable plaque in coronary and carotid arteries [10], [11], [12]. However, it is unrealistic to screen all the asymptomatic patients for individuals at high risk for CVD with these tools, since these tests are limited by the potential of significant adverse effects, technical difficulty, availability, and cost.
Carotid arteries as well as the aorta develop foam cell lesions and lipid core plaque at an early age [13]. Interestingly, a recent study reported that the prevalence of lipid-rich plaques in carotid arteries was higher in coronary death than in non-coronary death [14]. Another study using carotid endarterectomy specimens also reported that a soft carotid plaque with a large necrotic core and a marked inflammatory component may be predictive of an increased risk of cerebrovascular events [15]. These findings indicate that the individuals who have vulnerable plaques in their carotid arteries are prone to also have vulnerable plaques in their coronary and/or cerebral arteries, which will lead to CVD events, and thus, the assessment of tissue characteristics of carotid plaques will help to identify the patients with a high risk for CVD event. Indeed, based on a prospective study in 85 asymptomatic type 2 diabetic patients, we have already shown that a quantitative ultrasonic tissue characterization of carotid plaque using integrated backscatter (IBS) analysis can be a predictor of future CVD event [16]. However, the measurement of IBS values requires a specific software package, “Acoustic Densitometry,” installed in a SONOS echocardiograph system (Philips Medical Systems), which would limit the widespread use of this approach. In a qualitative evaluation using conventional B-mode ultrasound imaging performed by experienced sonographers, vulnerable plaques, which consist mainly of neovascular vessel, high lipid content, and inflammatory infiltration [8], [9], are believed to appear “hypoechoic.” On the other hand, stable plaques, which consist mainly of fibrous tissue and calcific components, appear “hyperechoic” [17]. Recently, echogenicity of carotid plaques has become semi-quantitatively evaluable with high-resolution B-mode ultrasound and computer-assisted image processing: the gray-scale median (GSM) of the frequency distribution of gray values of the pixels within the plaque serves as a measure of echogenicity. Since the evaluation of GSM values in carotid plaques requires neither specific software nor a specific ultrasonograph, it can be a more universal and practical approach as compared with IBS analysis.
Based on the background described above, the current study prospectively evaluated whether non-invasive and inexpensive ultrasonic tissue characterization of carotid plaque using GSM can improve the risk prediction of CVD event in asymptomatic type 2 diabetic patients with carotid plaque.
Section snippets
Subjects
Middle-aged and older Japanese type 2 diabetic patients with carotid plaque but without apparent CVD participated in this study. Patients who fulfilled the following criteria were considered eligible: (1) age ≥ 40 years at the time of enrollment, and (2) diagnosed with type 2 diabetes based on the criteria of the Japan Diabetes Society. Exclusion criteria were (1) history of ischemic stroke, coronary heart disease, or peripheral artery disease; (2) elevated liver enzymes (GOT or GPT ≥ 2.5 times
Patient characteristics
The baseline characteristics of the study population are shown in Table 1. Among a total of 287 patients (males, 72%; age, 65 ± 7 years (mean ± SD); diabetes duration, 13 ± 9 years; HbA1c, 7.5 ± 1.1%.), 236 (82%) patients had hypertension and 215 (75%) had dyslipidemia.
During a median follow-up of 55 months, 34 of the 287 patients (12%) had new CVD events: 11 had ischemic stroke, 21 had coronary heart disease, and 2 had peripheral artery disease (Supplementary Table 1). During the observation
Discussion
Atherosclerotic changes such as intima-media thickness (IMT) and plaque formation in carotid artery, markers of early atherosclerosis and vascular remodeling that can be assessed quickly, non-invasively, and economically with high-resolution ultrasound, are correlated with conventional coronary risk factors and regarded as surrogates of CVD. Indeed, previous studies showed that carotid IMT was an independent predictor of CVD in asymptomatic patients [1], [24], [25], [26]. However, previous
Author contributions
Y.I., N.K., M.T. and H.K. researched data and wrote the manuscript. M.N., R.K., K.S., Y.Um., and S.S. researched the data. Y.Ue., K.K, and I.S. contributed to the interpretation of the results and the discussion. All authors reviewed and approved the report. N.K. is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis.
Funding sources
The Diabetes Masters Conference supported by the Japan Diabetes Foundation and Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Science, Sports, Culture and Technology [KAKENHI 25461349].
Conflict of interest disclosures
None.
References (36)
- et al.
Carotid intima-media thickness and presence or absence of plaque improves prediction of coronary heart disease risk: the ARIC (Atherosclerosis Risk in Communities) study
J Am Coll Cardiol
(2010) Pathogenesis of atherosclerosis
J Am Coll Cardiol
(2006)- et al.
Lipid-rich carotid artery plaques appear echolucent on ultrasound B-mode images and may be associated with intraplaque haemorrhage
Eur J Vasc Endovasc Surg
(1997) - et al.
Pixel distribution analysis of B-mode ultrasound scan images predicts histologic features of atherosclerotic carotid plaques
J Vasc Surg
(2002) - et al.
Echolucent carotid plaques predict future coronary events in patients with coronary artery disease
J Am Coll Cardiol
(2004) - et al.
Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group
N Engl J Med
(1999) - et al.
Carotid-wall intima-media thickness and cardiovascular events
N Engl J Med
(2011) - et al.
Carotid plaque area and intima-media thickness in prediction of first-ever ischemic stroke: a 10-year follow-up of 6584 men and women: the Tromsø study
Stroke
(2011) - et al.
Carotid atherosclerosis is a stronger predictor of myocardial infarction in women than in men: a 6-year follow-up study of 6226 persons: the Tromsø study
Stroke
(2007) - et al.
The pathogenesis of coronary artery disease and the acute coronary syndromes
N Engl J Med
(1992)
Structure-dependent dynamic mechanical behavior of fibrous caps from human atherosclerotic plaques
Circulation
Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content
Br Heart J
Detection of disrupted plaques by coronary CT: comparison with angioscopy
Heart
The prevalence of inflammation in carotid atherosclerosis: analysis with fluorodeoxyglucose-positron emission tomography
Eur Heart J
Visualization of fibrous cap thickness and rupture in human atherosclerotic carotid plaque in vivo with high-resolution magnetic resonance imaging
Circulation
General findings of the international atherosclerosis project
Lab Invest
Artery-related differences in atherosclerosis expression: implications for atherogenesis and dynamics in intima-media thickness
Stroke
Can carotid plaque histology selectively predict the risk of an acute coronary syndrome?
Int Heart J
Cited by (42)
Deep-stratification of the cardiovascular risk by ultrasound carotid artery images
2024, Biomedical Signal Processing and ControlAssociation between carotid ultrasonographic parameters and microvascular and macrovascular complications in diabetes: A systematic review and meta-analysis
2023, Journal of Diabetes and its Complications2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD
2020, Revista Espanola de CardiologiaMolecular imaging of diabetes and diabetic complications: Beyond pancreatic β-cell targeting
2019, Advanced Drug Delivery ReviewsPrognostic tools for cardiovascular disease in patients with type 2 diabetes: A systematic review and meta-analysis of C-statistics
2019, Journal of Diabetes and its ComplicationsEcholucency-based phenotype in carotid atherosclerosis disease for risk stratification of diabetes patients
2018, Diabetes Research and Clinical PracticeCitation Excerpt :Various studies showed the relationship between echolucent plaque and an increase in the risk of cardiovascular (CV) and stroke events [17–19]. The use of GSMconv in diabetes patients has been reported by some studies to enhance the CVD or stroke risk assessment [12,20,21]. Two main findings can be drawn from these studies: (1) echolucent plaques (low GSMconv value) are associated with elevated risk of stroke and CV events, and (2) patients with diabetes have a high prevalence of echolucent plaque.