Search tips
Search criteria 


Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Stroke. Author manuscript; available in PMC 2009 March 11.
Published in final edited form as:
PMCID: PMC2654324

Carotid Plaque Surface Irregularity Predicts Ischemic Stroke The Northern Manhattan Study


Background and Purpose

There is scant population-based evidence regarding extracranial carotid plaque surface irregularity and ischemic stroke. Using a prospective cohort design, we evaluated the association of carotid plaque surface irregularity and the risk of ischemic stroke in a multiethnic population.


High-resolution B-mode ultrasound of the carotid arteries was performed in 1939 stroke-free subjects (mean age 69±10.0 years; 59% women; 53% Hispanic, 25% black, 22% white). Plaque was defined as a focal protrusion 50% greater than the surrounding area and localized along the extracranial carotid tree (internal carotid artery/bifurcation vs common carotid artery). Plaque surface was categorized as regular or irregular. Cox proportional hazard models were used to assess the association of surface characteristics and the risk of ischemic stroke.


Among 1939 total subjects, carotid plaque was visualized in 56.3% (1 plaque: 21.6%, >1 plaque: 34.7%, irregular plaque: 5.5%). During a mean follow up of 6.2 years after ultrasound examination, 69 ischemic strokes occurred. Unadjusted cumulative 5-year risks of ischemic stroke were: 1.3%, 3.0%, and 8.5% for no plaque, regular plaque, and irregular plaque, respectively. After adjusting for demographics, traditional vascular risk factors, degree of stenosis, and plaque thickness, presence of irregular plaque (vs no plaque) was independently associated with ischemic stroke (Hazard ratio, 3.1; 95% CI, 1.1 to 8.5).


The presence of irregular carotid plaque independently predicted ischemic stroke in a multiethnic cohort. Plaque surface irregularities assessed by B-mode ultrasonography may help identify intermediate- to high-risk individuals beyond their vascular risk assessed by the presence of traditional risk factors.

Keywords: carotid artery, irregular plaque, stroke, ultrasound

Large artery atherothrombosis accounts for approximately 16% of all ischemic stroke (IS) with the extracranial carotid artery being the most common site of involvement.1 Presence of stenotic atherosclerotic carotid plaque is a well-established risk factor for IS.2,3 Furthermore, randomized trials have demonstrated that carotid endarterectomy significantly reduces the risk of ipsilateral stroke in both asymptomatic and symptomatic patients with carotid stenosis.47

Besides degree of carotid stenosis, other measurements of carotid artery plaque such as plaque surface features and morphology may be powerful determinants of stroke risk. B-mode ultrasonography has been a useful noninvasive technique for identifying many of these high-risk plaque features such as echolucent plaque.8 Irregular or ulcerated plaque surface morphology has also been correlated with advancing stenosis and independently with ischemic stroke in angiographic studies.9,10 There is less evidence, however, regarding plaque surface morphology in prospective cohorts using noninvasive methods such as ultrasonography.11,12

We therefore studied carotid plaque surface characteristics among stroke-free subjects in the Northern Manhattan Study (NOMAS), an ongoing multiethnic prospective cohort study of stroke risk factors and outcomes. We assessed the risk of IS as a primary outcome and the risks of myocardial infarction (MI) and vascular death (VD) as secondary outcomes in a cohort of 1939 subjects from NOMAS who underwent carotid ultrasonography. We hypothesized that irregular carotid plaque surface, as assessed by ultrasonography, increases the risk of IS.


Patient Selection

The methods of subject recruitment and enrollment have been previously described.13,14 Briefly, 3298 subjects were enrolled between 1993 and 1997 by random digit dialing of approximately 29 000 households. Subjects were eligible if they (1) had never been diagnosed with stroke, (2) were >40 years of age, and (3) resided in northern Manhattan for ≥3 months in a household with a telephone. The Institutional Review Board at Columbia University Medical Center approved the study.

Carotid ultrasound imaging in NOMAS was initiated after standardization of the procedure and limited to a sample of those who were not enrolled at home (89.1%). We obtained high-quality carotid ultrasonography images among 1939 subjects within 1 year of enrollment. Sensitivity analyses using imputed data for the entire cohort (n=3298) to assess for possible selection bias did not show a significant bias.

Baseline Evaluation

Data were collected through interviews, in-person measurements, and blood sample collection by trained research assistants, and physical and neurologic examinations were done by the study physicians, as described elsewhere.13 Race–ethnicity was based on self-identification and conformed to standard definitions.15 Standardized questions were adapted from the Behavioral Risk Factor Surveillance System16 regarding the following conditions: hypertension, diabetes, hypercholesterolemia, transient ischemic attack, cigarette smoking, and cardiac disease such as coronary artery disease, congestive heart failure, atrial fibrillation, and valvular heart disease.

Carotid Ultrasound Measurements

Carotid artery plaque was assessed by high-resolution B-mode ultrasound using a GE LOGIQ 700 system with a multifrequency 9 to 13 MHz linear-array transducer. All measurements were performed by technologists trained in ultrasound research according to a standard scanning and reading protocol as previously described.17 Plaque was defined as a focal protrusion 50% greater than the surrounding area. Data were collected on presence of plaque (yes or no), locations of plaques (internal carotid artery including bifurcation or any common carotid artery involvement), number of plaques (0 to 4 plaques at 4 locations trichotomized as 0, 1, or >1), surface characteristics (regular or irregular), degree of stenosis (<40%, 40% to 60%, or >60%), and maximal carotid plaque thickness (MCPT). Figure 1 illustrates examples of regular and irregular plaque surfaces. In a sample of 88 stroke-free community subjects, the intraclass correlation coefficients for plaque thickness ranged from 0.87 to 0.94.18 Intra- and interrater correlations of plaque surface characteristics were also greater than 0.90 in our laboratory.

Figure 1
Left panel, Regular carotid plaque surface; Right panel, irregular carotid plaque surface.

Annual Prospective Follow Up

As previously described,14 all subjects were followed annually by telephone. Subjects were interviewed to detect vascular symptoms and events and to review interval hospitalizations with in-person visit for those who screened positive. Hospital surveillance provided data on mortality and morbidity not otherwise captured.

Outcome Classifications (stroke, myocardial infarction, and death)

Stroke was defined as the first symptomatic occurrence of any type of stroke, including intracerebral hemorrhage, subarachnoid hemorrhage, and cerebral infarction, and based on the World Health Organization criteria.19 Medical records of all hospitalizations were reviewed. Two neurologists classified all strokes independently after review of the data and the principal investigator adjudicated disagreements.

MI was defined by previously published criteria.20,21 Deaths were classified as vascular or nonvascular. Causes of vascular death included stroke, MI, heart failure, pulmonary embolus, cardiac arrhythmia, and other vascular causes. Time to combined vascular outcome was defined as time to first ischemic stroke, MI, or vascular death.

Statistical Analysis

The prevalence (or mean) of sociodemographic factors, conventional risk factors, potential confounders, and plaque characteristics were calculated. Demographics (age, sex, race, and education), hypertension, diabetes, any cardiac disease, hypercholesterolemia, and current cigarette smoking were included in univariate and multivariate analyses.

We estimated 5-year cumulative risks for outcomes stratified by plaque characteristic. Cox proportional hazard regression models were used to examine the association between plaque characteristics and the incidence of each outcome during follow up adjusting for other covariates. The models were adjusted for age, sex, race–ethnicity, education, current smoking, hypertension, diabetes, any cardiac disease, and hypercholesterolemia. For plaque surface irregularity, we also adjusted carotid stenosis (<40%, 40% to 60%, or >60%) and MCPT (<75th percentile or ≥75th percentile). All statistical analyses were performed using SAS software (SAS Institute).


A group of 1939 NOMAS subjects underwent carotid ultrasonography within 1 year of enrollment. The mean age was 68.6±10.0 years with 41.0% male and 51.4% Hispanic. Carotid plaque was visualized in 1091 subjects (56.4%); 418 (21.6%) had one plaque, and 673 (34.7%) had more than one plaque. Median MCPT was 1.0 mm (75th percentile 1.8 mm). By plaque location, 1009 (52.0%) subjects had plaque in the internal carotid arteries or bifurcations only, whereas 82 (4.3%) had involvement of the common carotid segment; only 4 subjects had isolated common carotid artery plaque. Irregular plaque surface was recorded in 107 (5.5%) subjects, whereas 984 (51.8%) had regular plaques only. Of those with irregular surface, 36 (33.6%) were bilateral. Stenosis greater than 40% was present in only 68 subjects (3.6%). Other baseline demographic, vascular, and plaque characteristics of the cohort are presented in Table 1. During a mean follow-up time of 6.2 years, 89 subjects were diagnosed with strokes (4.6%), of which there were 69 ischemic strokes (3.6%), 102 myocardial infarctions (5.3%), 134 vascular deaths (6.9%), and 246 combined outcomes of IS, MI, or VD (12.7%).

Baseline Characteristics of the Cohort (n=1939)

Table 2 shows the 5-year cumulative risks of IS, MI, VD, and combined outcomes stratified by plaque characteristic. The 5-year IS risk among those with irregular plaque surface was 8.5% versus 3.0% among those with regular surface (Figure 2). Plaque surface irregularity (vs regular surface) was also associated with approximately 2 times greater 5-year cumulative risks of MI and VD, respectively. Subjects with carotid stenosis >60% had 13.4% 5-year risk of ischemic stroke, 23.6% for MI, and 17.8% for vascular death.

Figure 2
Cumulative risk of ischemic stroke by plaque surface type. Log-rank test: P<0.01 for homogeneity across strata.
Unadjusted Cumulative 5-Year Risks of Vascular Events by Carotid Plaque Characteristic

After adjusting for age, sex, race–ethnicity, level of education, current smoking, diabetes, hypertension, hypercholesterolemia, and cardiac disease, plaque surface irregularity (adjusted hazard ratio [HR], 4.0; 95% CI, 1.7 to 9.4) and carotid stenosis >60% (adjusted HR, 6.4; 95% CI, 2.2 to 18.7) significantly increased the risk for IS compared with no plaque (Table 3). Plaque number and location were not significantly predictive of ischemic stroke. However, carotid stenosis (40% to 60%: adjusted HR, 3.0; 95% CI, 1.2 to 7.4; >60%: adjusted HR, 5.0; 95% CI, 2.2 to 11.4), presence of >1 carotid plaque (adjusted HR, 1.7; 95% CI, 1.1 to 3.0), and common carotid artery plaque (adjusted HR, 2.6; 95% CI, 1.2 to 5.6) independently predicted MI. In addition, presence of common carotid artery plaque significantly elevated risk of VD (adjusted HR, 1.9; 95% CI, 1.0 to 3.6). Irregular plaque, stenosis of 40% to 60% and >60%, >1 plaque, and common carotid artery plaque were all predictive of the combined vascular outcome.

Adjusted HR (95% CI) for Vascular Outcomes Stratified by Carotid Plaque Characteristic (reference: no plaque)*

Compared with those with regular plaque surface, irregular plaque surface increased IS risk nearly 3-fold (adjusted HR, 2.7; 95% CI, 1.3 to 5.5). Having bilateral plaque surface irregularity (adjusted HR, 3.9; 95% CI, 1.4 to 11.0) increased the risk more than unilateral irregular surface with contralateral regular surface (adjusted HR, 2.6; 95% CI, 1.1 to 6.2). Of 10 IS among 107 subjects with irregular plaque surface, 7 were ipsilateral to the lesion.

We further adjusted for plaque thickness and degree of stenosis to remove their potential confounding effects on the relationship between plaque surface morphology and IS risk. In a final model adjusting for demographics, vascular risk factors, MCPT (< or ≥75th percentile), and categorical degree of stenosis (<40%, 40% to 60%, >60%), irregular plaque surface remained an independent predictor of IS risk (adjusted HR, 3.1; 95% CI, 1.1 to 8.8). Compared with regular plaque, the IS risk for irregular plaque surface was attenuated (adjusted HR, 2.3; 95% CI, 1.0 to 5.4).


In a population-based cohort, we found that carotid plaque with irregular surface increased the risk of ischemic stroke 3-fold. The cumulative 5-year IS risk among individuals with an irregular plaque surface was over 8%, whereas those with regular plaque had <3% 5-year risk. These data suggest that plaque surface irregularity, even after adjusting for degree of stenosis and plaque thickness, is an independent predictor of IS. Moreover, the 5-year coronary risk (9.5%) for those with irregular plaque surface approaches the 2% annual risk commonly used to define the highest risk category.22

In addition to irregular plaque surface, we found that presence of >1 plaque, common carotid artery plaque, and carotid stenosis were predictive of the combined vascular outcome but with differences across specific vascular events. Individuals with asymptomatic stenosis >60% carried a 13.4% 5-year IS risk and an even greater 5-year MI risk (23.6%), similar to the prior large studies.5,7 Also consistent with other studies,23,24 we found that presence of regular plaque surface or plaque alone increased the risks of vascular outcomes, although these associations did not reach statistical significance (perhaps because of insufficient power). Although the Rotterdam Study reported an increased IS risk among those with 5 to 6 plaques,25 presence of >1 carotid plaque in our study was not significantly associated with IS but increased the risk of MI. This discrepancy may be attributable in part to the different methods of plaque number categorization (0 to 4 in our study vs 0 to 6 in Rotterdam). Lastly, presence of common carotid artery plaque predicted MI and VD in our study.

Advancing degree of carotid stenosis is a potent risk factor for ischemic stroke.2,26 Among those with asymptomatic carotid stenosis, the annual stroke risk is estimated to be 1.3% to 3.3%.27 Because only a small minority with asymptomatic carotid stenosis develops stroke or transient ischemic attack, predicting who will develop ischemic symptoms remains a challenge. Furthermore, the relative mechanistic contributions of perfusion failure and artery-to-artery embolism in large artery strokes are largely unknown.9,28 Analogous to MI, “rupture-prone” or “unstable” plaques may be important in the pathophysiology of large artery ischemic stroke.29 Although degree of carotid stenosis may be the most powerful predictor of ischemic stroke among those with severe stenosis, there is prospective evidence that other plaque characteristics8,30,31 aid in the identification of “unstable” plaques and stroke risk stratification.

Although many studies have suggested a strong correlation between carotid plaque surface irregularity and neurologic symptoms,9,3234 there have been few prospective studies.1012 In the only other large community-based prospective study using ultrasonography, markedly irregular plaque was independently predictive of IS among elderly Japanese men.12 Other smaller prospective studies have suggested that large or compound ulcerations, in particular, lead to transient ischemic attack or stroke in one third of patients35 with an annual stroke risk as high as 4.5% to 7.5%.36 Our data corroborate this elevated risk associated with irregular plaque in a multiethnic population-based cohort.

The exact mechanisms linking irregular plaque surface and ischemic stroke are unclear. Angiographic studies have observed a strong correlation between carotid plaque surface irregularity and microscopic plaque rupture and hemorrhage.37 Others have observed that proinflammatory markers are elevated in patients with complex or unstable carotid plaques17,3739 implying an inflammatory mechanism in plaque vulnerability and ipsilateral stroke risk. However, we were unable to show a direct ipsilateral relationship in this study. Our data support an alternate hypothesis that plaque surface irregularity may be a marker of generalized atherosclerosis rather than a potential embolic source. Such plaques may indicate an “unstable” systemic atherosclerotic state.

A major strength of this study is its population-based, multiethnic prospective cohort design with excellent follow up. There are also limitations. First, ultrasound data were not collected regarding plaque echomorphology, a known predictor of stroke.8,30 Second, we included all (not just ipsilateral) ischemic strokes because we lacked sufficient power to test for laterality. Although we cannot make definitive conclusions regarding stroke mechanisms, carotid plaque with irregular surface may still serve as a useful marker of the “high-risk” patient.

Sources of Funding

The study was supported by the following grants: R01 NS 29993, T32 NS 07153.





1. Petty GW, Brown RD, Jr, Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO. Ischemic stroke subtypes: a population-based study of functional outcome, survival, and recurrence. Stroke. 2000;31:1062–1068. [PubMed]
2. Bock RW, Gray-Weale AC, Mock PA, App Stats M, Robinson DA, Irwig L, Lusby RJ. The natural history of asymptomatic carotid artery disease. J Vasc Surg. 1993;17:160–169. discussion 170 –161. [PubMed]
3. Satiani B, Porter RM, Jr, Biggers KM, Das BM. Natural history of nonoperated, significant carotid stenosis. Ann Vasc Surg. 1988;2:271–278. [PubMed]
4. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis North American Symptomatic Carotid Endarterectomy Trial collaborators. N Engl J Med. 1991;325:445–453. [PubMed]
5. Endarterectomy for asymptomatic carotid artery stenosis Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. 1995;273:1421–1428. [PubMed]
6. Randomised trial of endarterectomy for recently symptomatic carotid stenosis final results of the MRC European Carotid Surgery Trial (ECST). Lancet. 1998;351:1379–1387. [PubMed]
7. Halliday A, Mansfield A, Marro J, Peto C, Peto R, Potter J, Thomas D. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet. 2004;363:1491–1502. [PubMed]
8. Polak JF, Shemanski L, O'Leary DH, Lefkowitz D, Price TR, Savage PJ, Brant WE, Reid C. Hypoechoic plaque at us of the carotid artery: an independent risk factor for incident stroke in adults aged 65 years or older. Cardiovascular Health Study. Radiology. 1998;208:649–654. [PubMed]
9. Eliasziw M, Streifler JY, Fox AJ, Hachinski VC, Ferguson GG, Barnett HJ. Significance of plaque ulceration in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial. Stroke. 1994;25:304–308. [PubMed]
10. Rothwell PM, Gibson R, Warlow CP. Interrelation between plaque surface morphology and degree of stenosis on carotid angiograms and the risk of ischemic stroke in patients with symptomatic carotid stenosis. On behalf of the European Carotid Surgery Trialists’ Collaborative Group. Stroke. 2000;31:615–621. [PubMed]
11. Handa N, Matsumoto M, Maeda H, Hougaku H, Kamada T. Ischemic stroke events and carotid atherosclerosis. Results of the Osaka follow-up Study for ultrasonographic Assessment of Carotid Atherosclerosis (the OSACA study). Stroke. 1995;26:1781–1786. [PubMed]
12. Kitamura A, Iso H, Imano H, Ohira T, Okada T, Sato S, Kiyama M, Tanigawa T, Yamagishi K, Shimamoto T. Carotid intima-media thickness and plaque characteristics as a risk factor for stroke in Japanese elderly men. Stroke. 2004;35:2788–2794. [PubMed]
13. Sacco RL, Roberts JK, Boden-Albala B, Gu Q, Lin IF, Kargman DE, Berglund L, Hauser WA, Shea S, Paik MC. Race–ethnicity and determinants of carotid atherosclerosis in a multiethnic population. The Northern Manhattan Stroke Study. Stroke. 1997;28:929–935. [PubMed]
14. Sacco RL, Anand K, Lee HS, Boden-Albala B, Stabler S, Allen R, Paik MC. Homocysteine and the risk of ischemic stroke in a triethnic cohort: the Northern Manhattan Study. Stroke. 2004;35:2263–2269. [PubMed]
15. Office of Management and Budget Race and ethnic standards for federal statistics and administrative reporting (directive no. 15). Federal Register. 1978;43:19629.
16. Gentry EM, Kalsbeek WD, Hogelin GC, Jones JT, Gaines KL, Forman MR, Marks JS, Trowbridge FL. The Behavioral Risk Factor Surveys: II. Design, methods, and estimates from combined state data. Am J Prev Med. 1985;1:9–14. [PubMed]
17. Elkind MS, Cheng J, Boden-Albala B, Paik MC, Sacco RL. Elevated white blood cell count and carotid plaque thickness: the Northern Manhattan Stroke Study. Stroke. 2001;32:842–849. [PubMed]
18. Rundek T, Elkind MS, Pittman J, Boden-Albala B, Martin S, Humphries SE, Juo SH, Sacco RL. Carotid intima–media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes: the Northern Manhattan Prospective Cohort Study. Stroke. 2002;33:1420–1423. [PMC free article] [PubMed]
19. WHO Task Force on Stroke and Other Cerebrovascular Disorders: stroke Recommendations on stroke prevention, diagnosis and therapy. Stroke. 1989;20:1407–1431. [PubMed]
20. Greene HL, Richardson DW, Barker AH, Roden DM, Capone RJ, Echt DS, Friedman LM, Gillespie MJ, Hallstrom AP, Verter J. Classification of deaths after myocardial infarction as arrhythmic or nonarrhythmic (the Cardiac Arrhythmia pilot study). Am J Cardiol. 1989;63:1–6. [PubMed]
21. Morris DL, Kritchevsky SB, Davis CE. Serum carotenoids and coronary heart disease. The Lipid Research Clinics Coronary Primary Prevention Trial and follow-up study. JAMA. 1994;272:1439–1441. [PubMed]
22. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285:2486–2497. [PubMed]
23. Held C, Hjemdahl P, Eriksson SV, Bjorkander I, Forslund L, Rehnqvist N. Prognostic implications of intima-media thickness and plaques in the carotid and femoral arteries in patients with stable angina pectoris. Eur Heart J. 2001;22:62–72. [PubMed]
24. Hunt KJ, Evans GW, Folsom AR, Sharrett AR, Chambless LE, Tegeler CH, Heiss G. Acoustic shadowing on b-mode ultrasound of the carotid artery predicts ischemic stroke: the Atherosclerosis Risk In Communities (ARIC) study. Stroke. 2001;32:1120–1126. [PubMed]
25. Hollander M, Bots ML, Del Sol AI, Koudstaal PJ, Witteman JC, Grobbee DE, Hofman A, Breteler MM. Carotid plaques increase the risk of stroke and subtypes of cerebral infarction in asymptomatic elderly: the Rotterdam study. Circulation. 2002;105:2872–2877. [PubMed]
26. Bogousslavsky J, Despland PA, Regli F. Prognosis of high-risk patients with nonoperated symptomatic extracranial carotid tight stenosis. Stroke. 1988;19:108–111. [PubMed]
27. Norris JW, Zhu CZ, Bornstein NM, Chambers BR. Vascular risks of asymptomatic carotid stenosis. Stroke. 1991;22:1485–1490. [PubMed]
28. Powers WJ. Cerebral hemodynamics in ischemic cerebrovascular disease. Ann Neurol. 1991;29:231–240. [PubMed]
29. Fuster V, Moreno PR, Fayad ZA, Corti R, Badimon JJ. Atherothrombosis and high-risk plaque: Part I: evolving concepts. J Am Coll Cardiol. 2005;46:937–954. [PubMed]
30. Gronholdt ML, Nordestgaard BG, Schroeder TV, Vorstrup S, Sillesen H. Ultrasonic echolucent carotid plaques predict future strokes. Circulation. 2001;104:68–73. [PubMed]
31. Mathiesen EB, Bonaa KH, Joakimsen O. Echolucent plaques are associated with high risk of ischemic cerebrovascular events in carotid stenosis: the Tromso study. Circulation. 2001;103:2171–2175. [PubMed]
32. AbuRahma AF, Covelli MA, Robinson PA, Holt SM. The role of carotid duplex ultrasound in evaluating plaque morphology: potential use in selecting patients for carotid stenting. J Endovasc Surg. 1999;6:59–65. [PubMed]
33. Kessler C, von Maravic M, Bruckmann H, Kompf D. Ultrasound for the assessment of the embolic risk of carotid plaques. Acta Neurol Scand. 1995;92:231–234. [PubMed]
34. Steinke W, Hennerici M, Rautenberg W, Mohr JP. Symptomatic and asymptomatic high-grade carotid stenoses in Doppler color-flow imaging. Neurology. 1992;42:131–138. [PubMed]
35. Johnson JM, Ansel AL, Morgan S, DeCesare D. Ultrasonographic screening for evaluation and follow-up of carotid artery ulceration. A new basis for assessing risk. Am J Surg. 1982;144:614–618. [PubMed]
36. Dixon S, Pais SO, Raviola C, Gomes A, Machleder HI, Baker JD, Busuttil RW, Barker WF, Moore WS. Natural history of nonstenotic, asymptomatic ulcerative lesions of the carotid artery. A further analysis. Arch Surg. 1982;117:1493–1498. [PubMed]
37. Lovett JK, Gallagher PJ, Hands LJ, Walton J, Rothwell PM. Histological correlates of carotid plaque surface morphology on lumen contrast imaging. Circulation. 2004;110:2190–2197. [PubMed]
38. Businaro R, Digregorio M, Rigano R, Profumo E, Buttari B, Leone S, Salvati B, Capoano R. D’Amati G, Fumagalli L. Morphological analysis of cell subpopulations within carotid atherosclerotic plaques. Ital J Anat Embryol. 2005;110:109–115. [PubMed]
39. Lombardo A, Biasucci LM, Lanza GA, Coli S, Silvestri P, Cianflone D, Liuzzo G, Burzotta F, Crea F, Maseri A. Inflammation as a possible link between coronary and carotid plaque instability. Circulation. 2004;109:3158–3163. [PubMed]