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Patterns of non-invasive imaging of carotid atherosclerosis
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Atherosclerosis is an inflammatory disease that can be generalized, affecting more than one arterial bed simultaneously, or localized, manifested in one system. Ultrasound based measurements of plaque textural features, such as low grey scale median (GSM), echolucent (hypoechoic) plaque types and juxtaluminal black (hypoechoic) area (JBA) are manifestation of potentially unstable lesions. Conventional carotid IMT (intima media thickness) and the recently introduced IM-GSM (echogenicity of the intima media complex) are important measures of subclinical atherosclerosis and are used to predict future ischemic events.

The aims of this thesis were to study, in detail, the systemic nature of atherosclerosis by evaluating the carotid disease burden contralateral to symptomatic arteries, determining the relationship between proximal (subclinical atherosclerosis) and distal segments (well established disease) of the same artery and comparing local plaque features with systemic burden of atherosclerosis disease. In addition, the effect of statins on carotid plaque echogenicity was evaluated in a systematic review and meta-analysis.

Methods:

We have measured ultrasound-based textural carotid plaque features (GSM, JBA, entropy, coarseness), surface morphology, as well as IMT and IM-GSM. An in-house custom developed research software package was used for plaque feature extraction. For the meta-analysis we used Comprehensive Meta-Analysis version 3 software.

Results:

Study 1. In 39 patients, the carotid plaques contralateral to symptomatic arteries had similar morphological and textural features to those in the symptomatic arteries and are more vulnerable than those in asymptomatic arteries; more often mildly or markedly irregular with more vulnerable textural plaque features (lower GSM and larger JBA).

Study 2. In 87 asymptomatic patients, an increased IMT in CCA correlated with plaque irregularities in the bifurcation and ICA while IM-GSM was closely related to plaque echogenicity (GSM), and other textural plaque features.

Study 3. In the same cohort in study 2, patients with previous disease in the coronary arteries had higher IMT and lower IM-GSM and those with prior stroke had lower IM-GSM. Neither IMT nor IM-GSM was different between patients with and without previous lower extremity disease. IM-GSM decreases significantly with increasing number of arterial territories p<0.001 (asymptomatic vs symptoms in one vs multiple arterial systems) but conventional IMT was not different between groups p=0.49.

Study 4. In a meta-analysis of 9/580 identified studies including 566 patients with 7.2 months follow-up, a consistent increase in the carotid plaques echogenicity after statin therapy, was reported. The perpetual (over 12 months) effects of which were shown in a meta-regression analysis to be related to changes in hsCRP.

Conclusion:

Symptomatic patients have similar plaque morphology and textural features of vulnerability in the contralateral carotid system, compared with asymptomatic ones. In the latter, measurements of proximal disease reflect distal pathology and the number of affected arteries. Finally, statin therapy and the drop of LDL cholesterol result in better plaque stability and optimum control of arterial inflammation, shown by arterial wall echogenicity and hsCRP changes, respectively.

Place, publisher, year, edition, pages
Umeå: Umeå University , 2015. , 87 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1759
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
URN: urn:nbn:se:umu:diva-110969ISBN: 978-91-7601-363-2 (print)OAI: oai:DiVA.org:umu-110969DiVA: diva2:866167
Public defence
2015-11-25, hörsal B, Unod T9, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2015-11-04 Created: 2015-11-01 Last updated: 2015-11-06Bibliographically approved
List of papers
1. Vulnerable plaques in the contralateral carotid arteries in symptomatic patients: a detailed ultrasound analysis
Open this publication in new window or tab >>Vulnerable plaques in the contralateral carotid arteries in symptomatic patients: a detailed ultrasound analysis
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2014 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, no 2, 526-531 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIM: Carotid plaques may represent a generalized atherosclerotic syndrome or a localized disease. The aim of this study was to assess the morphological and textural features of carotid plaques located contralateral to the symptomatic side and compare them with the symptomatic side and with plaques from asymptomatic patients. METHODS: We studied 66 arteries in 39 patients (mean age 70 ± 7 year, 33% females). Arterial plaques were classified as either symptomatic (n = 30), contralateral to symptomatic (n = 25) or asymptomatic (n = 11). We compared several plaque features between these groups including the mean values of the grey scale median (GSM), entropy, juxtaluminal black area (JBA) without visible echogenic cap, GSM of the JBA and surface irregularity. RESULTS: The plaques contralateral to symptomatic arteries had similar morphological and textural features to those in the symptomatic arteries. In contrast, they had more vulnerable morphological and textural features than those in asymptomatic arteries: less smooth plaques (12% vs. 55%) and instead more often mildly irregular (60% vs 36%) or markedly irregular (28% vs. 9%; p = 0.03), lower GSM (26.2 ± 8 vs. 49.4 ± 14, p < 0.001) and lower GSM of the JBA (5.0 ± 3.6 vs. 11.4 ± 2.1, p = 0.008). The frequency of entropy and plaque calcification was similar in all groups. CONCLUSION: Symptomatic patients with carotid artery disease seem to have similar morphological and textural features of vulnerability in the symptomatic and the contralateral carotid arteries, which are profound compared with asymptomatic carotid arteries. These findings support the concept of generalized carotid atherosclerotic pathology rather than incidental unilateral disease, and also emphasize a need for aggressive measures for plaque stabilization, particularly in symptomatic patients.

Place, publisher, year, edition, pages
Elsevier, 2014
Keyword
carotid artery disease, plaque vulnerability, gray scale median, juxtaluminal black area
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-93540 (URN)10.1016/j.atherosclerosis.2014.05.934 (DOI)000342411000941 ()24953493 (PubMedID)
Available from: 2014-09-24 Created: 2014-09-24 Last updated: 2017-12-05Bibliographically approved
2. Common carotid intima-media features determine distal disease phenotype and vulnerability in asymptomatic patients
Open this publication in new window or tab >>Common carotid intima-media features determine distal disease phenotype and vulnerability in asymptomatic patients
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2015 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 196, 22-28 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: There is a growing awareness of the importance of carotid plaque features evaluation in stroke prediction. Carotid intima-media thickness (IMT) and recently its echogenicity were used for stroke prediction, although their clinical relevance was not well determined. The aim of this study was to assess the relationship between common carotid artery (CCA) ultrasound markers of atherosclerosis and distal, bifurcation and internal carotid artery (ICA), plaque features. Methods: We analyzed 137 carotid arteries in 87 asymptomatic patients with known carotid disease (mean age 69 +/- 6 year, 34.5% females). Intima media thickness (IMT) and its gray scale median (IM-GSM) were measured at the CCA. Plaque textural features including gray scale median (GSM), juxtaluminal black area (JBA-mm(2)) without a visible cap, and plaque coarseness, at bifurcation and ICA were also determined. CCA measurements were correlated with those of the distal plaques. Results: An increased IMT in CCA correlated with plaque irregularities in the bifurcation and ICA (r = 0.53, p < 0.001), while IM-GSM was closely related to plaque echogenicity (GSM) (r = 0.76, p < 0.001), and other textural plaque features. Both, IMT and IM-GSM correlated weakly with stenosis severity (r = 0.27, p = 0.001 and r = -0.18, p = 0.026) respectively. Conclusion: In asymptomatic patients, measurements of CCA reflect distal, bifurcation and ICA disease, with IMT reflecting plaque irregularities and IM-GSM as markers of textural plaque abnormalities. Integrating measurements of both IMT and IM-GSM in a model could be used as a better marker of disease vulnerability over and above each measure individually. 

Keyword
Carotid atherosclerosis, Intima-media thickness, Intima-media-gray scale median, Plaque features, aque vulnerability
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-107150 (URN)10.1016/j.ijcard.2015.05.168 (DOI)000358314300005 ()26070179 (PubMedID)
Available from: 2015-09-02 Created: 2015-08-19 Last updated: 2017-12-04Bibliographically approved
3. Carotid IM-GSM is more accurate than conventional IMT for monitoring systemic burden of atherosclerosis
Open this publication in new window or tab >>Carotid IM-GSM is more accurate than conventional IMT for monitoring systemic burden of atherosclerosis
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(English)Manuscript (preprint) (Other academic)
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-111073 (URN)
Available from: 2015-11-03 Created: 2015-11-03 Last updated: 2015-12-04
4. Ultrasound assessment of carotid plaque echogenicity response to statin therapy: a systematic review and meta-analysis
Open this publication in new window or tab >>Ultrasound assessment of carotid plaque echogenicity response to statin therapy: a systematic review and meta-analysis
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2015 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 16, no 5, 10734-10747 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To evaluate in a systematic review and meta-analysis model the effect of statin therapy on carotid plaque echogenicity assessed by ultrasound.

METHODS: We have systematically searched electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to April, 2015, for studies evaluating the effect of statins on plaque echogenicity. Two researchers independently determined the eligibility of studies evaluating the effect of statin therapy on carotid plaque echogenicity that used ultrasound and grey scale median (GSM) or integrated back scatter (IBS).

RESULTS: Nine out of 580 identified studies including 566 patients' carotid artery data were meta-analyzed for a mean follow up of 7.2 months. A consistent increase in the echogenicity of carotid artery plaques, after statin therapy, was reported. Pooled weighted mean difference % (WMD) on plaque echogenicity after statin therapy was 29% (95% CI 22%-36%), p < 0.001, I2 = 92.1%. In a meta-regression analysis using % mean changes of LDL, HDL and hsCRP as moderators, it was shown that the effects of statins on plaque echogenicity were related to changes in hsCRP, but not to LDL and HDL changes from the baseline. The effect of statins on the plaque was progressive; it showed significance after the first month of treatment, and the echogenicity continued to increase in the following six and 12 months.

CONCLUSIONS: Statin therapy is associated with a favorable increase of carotid plaque echogenicity. This effect seems to be dependent on the period of treatment and hsCRP change from the baseline, independent of changes in LDL and HDL.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-105960 (URN)10.3390/ijms160510734 (DOI)000356241400097 ()25984600 (PubMedID)
Available from: 2015-07-02 Created: 2015-07-02 Last updated: 2017-12-04Bibliographically approved

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