Carotid Surgery : A posse ad esse non valet consequentia

According to a large body of evidence, carotid endarterectomy (CEA) can prevent strokes, provided that appropriate inclusion criteria and high-quality perioperative treatment methods are utilised with low complication rates. From the patient s perspective, it is of paramount importance that the operation is as safe and effective as possible. From the community s point of view, it is important that CEA provision prevents as many strokes as possible. In order to define the stroke preventing potential of CEA in different communities, a comparison between eight European countries and Australia was performed including 53 077 carotid interventions. A more detailed evaluation was performed in Finland, the United Kingdom and Egypt. It could be estimated that many potentially preventable strokes occur due to insufficient diagnostics and CEA provision. The number of CEAs should be at least doubled in the Helsinki region. The theoretical power of CEA provision in stroke prevention varied significantly between the countries. Delay from symptom to surgery has been identified as one of the most important factors influencing the effectiveness of CEA. In 2008 only 11% of CEAs in Helsinki university central hospital (HUCH) were performed within the recommended14 days. Registered data of 673 CEAs in HUCH during 2000-2005 was analyzed. There was no systematic error that would have changed the outcome analysis. However it is important that registers are audited regularly and cross matching of different registries is possible. A previously unpublished method of combining medial mandibulotomy, neck incision and carotid artery interposition was carried out as a collaboration of maxillofacial, ear, nose and throat and vascular surgeons. Five patients were operated on with a technique that was feasible and possible to perform with little morbidity, but due to the significant risks involved, this technique should be reserved for carefully selected cases. In stroke prevention, organisational decisions seem far more important than details in interventional procedures when CEA is performed with low complication rates, as was the case in the present study. A TIA clinic approach with close co-operation between the on-call vascular surgeons, neurologists and radiologists should be available at all centres treating these patients. Patients should have a direct and fast admission to the hospital performing CEA.

Autophagic Marker MAP1LC3B Expression Levels Are Associated with Carotid Atherosclerosis Symptomatology

Objectives: The mechanism by which atheroma plaque becomes unstable is not completely understood to date but analysis of differentially expressed genes in stable versus unstable plaques may provide clues. This will be crucial toward disclosing the mechanistic basis of plaque instability, and may help to identify prognostic biomarkers for ischaemic events. The objective of our study was to identify differences in expression levels of 59 selected genes between symptomatic patients (unstable plaques) and asymptomatic patients (stable plaques). Methods: 80 carotid plaques obtained by carotid endarterectomy and classified as symptomatic (>70% stenosis) or asymptomatic (>80% stenosis) were used in this study. The expression levels of 59 genes were quantified by qPCR on RNA extracted from the carotid plaques obtained by endarterectomy and analyzed by means of various bioinformatic tools. Results: Several genes associated with autophagy pathways displayed differential expression levels between asymptomatic and symptomatic (i.e. MAP1LC3B, RAB24, EVA1A). In particular, mRNA levels of MAP1LC3B, an autophagic marker, showed a 5-fold decrease in symptomatic samples, which was confirmed in protein blots. Immune system-related factors and endoplasmic reticulum-associated markers (i.e. ERP27, ITPR1, ERO1LB, TIMP1, IL12B) emerged as differently expressed genes between asymptomatic and symptomatic patients. Conclusions: Carotid atherosclerotic plaques in which MAP1LC3B is underexpressed would not be able to benefit from MAP1LC3B-associated autophagy. This may lead to accumulation of dead cells at lesion site with subsequent plaque destabilization leading to cerebrovascular events. Identified biomarkers and network interactions may represent novel targets for development of treatments against plaque destabilization and thus for the prevention of cerebrovascular events.

Pulmonary hypertension in Switzerland: treatment and clinical course.

The prognosis of pulmonary hypertension (PH), especially idiopathic pulmonary arterial hypertension (IPAH), has improved during the recent years. The Swiss Registry for PH represents the collaboration of the various centres in Switzerland dealing with PH and serves as an important tool in quality control. The objective of the study was to describe the treatment and clinical course of this orphan disease in Switzerland. We analyzed data from 222 of 252 adult patients, who were included in the registry between January 1999 and December 2004 and suffered from either PAH, PH associated with lung diseases or chronic thromboembolic PH (CTEPH) with respect to the following data: NYHA class, six-minute walking distance (6-MWD), haemodynamics, treatments and survival. If compared with the calculated expected figures the one, two and three year mean survivals in IPAH increased from 67% to 89%, from 55% to 78% and from 46% to 73%, respectively. Most patients (90%) were on oral or inhaled therapy and only 10 patients necessitated lung transplantation. Even though pulmonary endarterectomy (PEA) was performed in only 7 patients during this time, the survival in our CTEPH cohort improved compared with literature data and seems to approach outcomes usually seen after PEA. The 6-MWD increased maximally by 52 m and 59 m in IPAH and CTEPH, respectively, but in the long term returned to or below baseline values, despite the increasing use of multiple specific drugs (overall in 51% of IPAH and 29% of CTEPH). Our national registry data indicate that the overall survival of IPAH and presumably CTEPH seems to have improved in Switzerland. Although the 6-MWD improved transiently, it decreased in the long term despite specific and increasingly combined drug treatment. Our findings herewith underscore the progressive nature of the diseases and the need for further intense research in the field.

A retrospective study of cholinesterase inhibitors for Alzheimer's disease : the effect of cerebrovascular disease on patient outcomes and the impact of biases on the results.

Introduction: La démence peut être causée par la maladie d’Alzheimer (MA), la maladie cérébrovasculaire (MCEREV), ou une combinaison des deux. Lorsque la maladie cérébrovasculaire est associée à la démence, les chances de survie sont considérées réduites. Il reste à démontrer si le traitement avec des inhibiteurs de la cholinestérase (ChEIs), qui améliore les symptômes cognitifs et la fonction globale chez les patients atteints de la MA, agit aussi sur les formes vasculaires de démence. Objectifs: La présente étude a été conçue pour déterminer si la coexistence d’une MCEREV était associée avec les chances de survie ou la durée de la période jusqu’au placement en hebergement chez les patients atteints de la MA et traités avec des ChEIs. Des études montrant de moins bons résultats chez les patients souffrant de MCEREV que chez ceux n’en souffrant pas pourrait militer contre l’utilisation des ChEIs chez les patients atteints à la fois de la MA et la MCEREV. L'objectif d'une seconde analyse était d'évaluer pour la première fois chez les patients atteints de la MA l'impact potentiel du biais de « temps-immortel » (et de suivi) sur ces résultats (mort ou placement en hebergement). Méthodes: Une étude de cohorte rétrospective a été conduite en utilisant les bases de données de la Régie de l’Assurance Maladie du Québec (RAMQ) pour examiner la durée de la période jusqu’au placement en hebergement ou jusqu’au v décès des patients atteints de la MA, âgés de 66 ans et plus, avec ou sans MCEREV, et traités avec des ChEIs entre le 1er Juillet 2000 et le 30 Juin 2003. Puisque les ChEIs sont uniquement indiquées pour la MA au Canada, chaque prescription de ChEIs a été considérée comme un diagnostic de la MA. La MCEREV concomitante a été identifié sur la base d'un diagnostic à vie d’un accident vasculaire cérébral (AVC) ou d’une endartériectomie, ou d’un diagnostic d'un accident ischémique transitoire au cours des six mois précédant la date d’entrée. Des analyses séparées ont été conduites pour les patients utilisant les ChEIs de façon persistante et pour ceux ayant interrompu la thérapie. Sept modèles de régression à risque proportionnel de Cox qui ont varié par rapport à la définition de la date d’entrée (début du suivi) et à la durée du suivi ont été utilisés pour évaluer l'impact du biais de temps-immortel. Résultats: 4,428 patients ont répondu aux critères d’inclusion pour la MA avec MCEREV; le groupe de patients souffrant seulement de la MA comptait 13,512 individus. Pour le critère d’évaluation composite considérant la durée de la période jusqu’au placement en hebergement ou jusqu’au décès, les taux de survie à 1,000 jours étaient plus faibles parmi les patients atteints de la MA avec MCEREV que parmi ceux atteints seulement de la MA (p<0.01), mais les différences absolues étaient très faibles (84% vs. 86% pour l’utilisation continue de ChEIs ; 77% vs. 78% pour la thérapie avec ChEIs interrompue). Pour les critères d’évaluation secondaires, la période jusqu’au décès était plus courte chez les patients avec la MCEREV que sans la MCEREV, mais la période jusqu’au vi placement en hebergement n’était pas différente entre les deux groupes. Dans l'analyse primaire (non-biaisée), aucune association a été trouvée entre le type de ChEI et la mort ou le placement en maison d'hébergement. Cependant, après l'introduction du biais de temps-immortel, on a observé un fort effet différentiel. Limitations: Les résultats peuvent avoir été affectés par le biais de sélection (classification impropre), par les différences entre les groupes en termes de consommation de tabac et d’indice de masse corporelle (ces informations n’étaient pas disponibles dans les bases de données de la RAMQ) et de durée de la thérapie avec les ChEIs. Conclusions: Les associations entre la coexistence d’une MCEREV et la durée de la période jusqu’au placement en hebergement ou au décès apparaissent peu pertinentes cliniquement parmi les patients atteints de la MA traités avec des ChEIs. L’absence de différence entre les patients atteints de la MA souffrant ou non de la MCEREV suggère que la coexistence d’une MCEREV ne devrait pas être une raison de refuser aux patients atteints de la MA l’accès au traitement avec des ChEIs. Le calcul des « personne-temps » non exposés dans l'analyse élimine les estimations biaisées de l'efficacité des médicaments.

Endarterectomía carotidea en octogenarios: comparasión de desenlaces con pacientes menores de 80 años. Experiencia en la fundación cardioinfantil

Introducion: Dado el incremento de los pacientes con edades por encima de los 80 años que son llevados a cirugía cada año en nuestra institución consideramos importante conocer el comportamiento en terminos de morbilidad y mortalidad temprana de los pacientes octogenarios sometidos a endarterectomia carotidea. Objetivo: Evaluar los resultados a 30 días en pacientes octogenarios con enfermedad carotidea severa sintomática y asintomática llevados a endarterectomía carotidea comparados con una cohorte historia de pacientes de menor edad operados desde 1995 en la fundación Cardioinfantil. Se registraron como variables dependientes mortalidad y evento cerebrovascular.

Omega-3 fatty acids, cardiovascular disease and stability of atherosclerotic plaques

Long-chain n-3 polyunsaturated fatty acids are found in oily fish and in fish oils and similar preparations. Substantial evidence from epidemiological and case-control studies indicates that consumption of fish, oily fish and long-chain n-3 fatty acids reduces risk of cardiovascular mortality. Secondary prevention studies using long-chain n-3 fatty acids in patients post-myocardial infarction have shown a reduction in total and cardiovascular mortality with an especially potent effect on sudden death. Long-chain n-3 fatty acids have been shown to beneficially modify a range of cardiovascular risk factors, which may result in primary cardiovascular prevention. However, reduced non-fatal and fatal events and a reduction in sudden death probably involve other mechanisms. Reduced thrombosis following long-chain n-3 fatty acids may play a role. A decrease in arrhythmias is a favoured mechanism of action of long-chain n-3 fatty acids and is supported by cell culture and animal studies. However human trials using implantable cardiac defibrillators have produced inconsistent findings and a recent meta-analysis does not support this mechanism of action. An alternative mechanism of action may be stabilisation of atherosclerotic plaques by long-chain n-3 fatty acids. This is suggested by one published human study which showed that incorporation of long-chain n-3 fatty acids into plaques collected at carotid endarterectomy resulted in fewer macrophages in the plaque and a morphology indicative of increased stability. These findings are supported from observations in an animal model and suggest that the primary effect of long-chain n-3 fatty acids might be on macrophages within the plaque.

Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial

Background N-3 polyunsaturated fatty acids (PUFAs) from oily fish protect against death from cardiovascular disease. We aimed to assess the hypothesis that incorporation of n-3 and n-6 PUFAs into advanced atherosclerotic plaques increases and decreases plaque stability, respectively. Methods We did a randomised controlled trial of patients awaiting carotid endarterectomy. We randomly allocated patients control, sunflower oil (n-6), or fish-oil (n-3) capsules until surgery. Primary outcome was plaque morphology indicative of stability or instability, and outcome measures were concentrations of EPA, DHA, and linoleic acid in carotid plaques; plaque morphology; and presence of macrophages in plaques. Analysis was per protocol. Findings 188 patients were enrolled and randomised; 18 withdrew and eight were excluded. Duration of oil treatment was 7-189 days (median 42) and did not differ between groups. The proportions of EPA and DHA were higher in carotid plaque fractions in patients receiving fish oil compared with those receiving control (absolute difference 0.5 [95% CI 0.3-0.7], 0.4 [0.1-0.6], and 0.2 [0.1-0.4] g/100 g total fatty acids for EPA; and 0.3 [0.0-0.8], 0.4 [0.1-0.7], and 0.3 [0.1-0.6] g/100 g total fatty acids for DHA; in plaque phospholipids, cholesteryl esters, and triacylglycerols, respectively). Sunflower oil had little effect on the fatty acid composition of lipid fractions. Fewer plaques from patients being treated with fish oil had thin fibrous caps and signs of inflammation and more plaques had thick fibrous caps and no signs of inflammation, compared with plaques in patients in the control and sunflower oil groups (odds ratio 0.52 [95% CI 0.24-0.89] and 1.19 [1.02-1.57] vs control; 0.49 [0.23-0.90] and 1.16 [1.01-1.53] vs sunflower oil). The number of macrophages in plaques from patients receiving fish oil was lower than in the other two groups. Carotid plaque morphology and infiltration by macrophages did not differ between control and sunflower oil groups. Interpretation Atherosclerotic plaques readily incorporate n-3 PUFAs from fish-oil supplementation, inducing changes that can enhance stability of atherosclerotic plaques. By contrast, increased consumption of n-6 PUFAs does not affect carotid plaque fatty-acid composition or stability over the time course studied here. Stability of plaques could explain reductions in non-fatal and fatal cardiovascular events associated with increased n-3 PUFA intake.

Transient heparin-induced platelet activation linked to generation of platelet 12-lipoxygenase: findings from a randomised controlled trial

Previously we demonstrated that heparin administration during carotid endarterectomy (CEA) caused a marked, but transient increase in platelet aggregation to arachidonic acid (AA) and adenosine diphosphate (ADP), despite effective platelet cyclo-oxygenase-1 (COX-1) inhibition with aspirin. Here we investigated the metabolism of AA via platelet 12-lipoxygenase (12-LOX) as a possible mediator of the observed transient aspirin resistance, and compared the effects of unfractionated (UFH) and low-molecular-weight (LMWH) heparin. A total of 43 aspirinated patients undergoing CEA were randomised in the trial to 5,000 IU UFH (n=22) or 2,500 IU LMWH (dalteparin, n=21). Platelet aggregation to AA (4x10⁻³) and ADP (3x10⁻⁶) was determined, and the products of the COX-1 and 12-LOX pathways; thromboxane B₂ (TXB₂) and 12-hydroxyeicosatretraenoic acid (12-HETE) were measured in plasma, and in material released from aggregating platelets.Aggregation to AA increased significantly (~10-fold) following heparinisation (p<0.0001), irrespective of heparin type (p=0.33). Significant, but smaller (~2-fold) increases in aggregation to ADP were also seen, which were significantly lower in the platelets of patients randomised to LMWH (p<0.0001). Plasma levels of TxB2 did not rise following heparinisation (p=0.93), but 12-HETE increased significantly in the patients' plasma, and released from platelets stimulated in vitro withADP, with both heparin types (p<0.0001). The magnitude of aggregation to ADP correlated with 12-HETE generation (p=0.03). Heparin administration during CEA generates AA that is metabolised to 12-HETE via the 12-LOX pathway, possibly explaining the phenomenon of transient heparin-induced platelet activation. LMWH has less effect on aggregation and 12-HETE generation than UFH when the platelets are stimulated with ADP.

The antithrombotic effect of dextran-40 in man is due to enhanced fibrinolysis in vivo

BACKGROUND: Dextran-40 is effective in reducing postoperative Doppler-detectable embolization in patients undergoing carotid endarterectomy (CEA). Dextrans are thought to have antithrombotic and antiplatelet effects. The mode of action is unclear. In rats, dextran blocks uptake of tissue plasminogen activator (tPA) by mannose-binding receptors. Because this would have the effect of enhancing endogenous fibrinolysis, we explored this effect of dextran-40 on fibrinolysis in man. METHODS: Twenty patients undergoing endovascular stenting for abdominal aortic aneurysm were randomized to receive 100 mL of 10% dextran-40 or saline, over 1 hour, during their operation in addition to heparin. Blood samples were taken preoperatively, intraoperatively (immediately after operative procedure), and 24 hours postoperatively. Thrombi were formed in a Chandler loop and used to assess endogenous fibrinolysis over 24 hours, measured as the fall in thrombus weight, and the release of fluorescently labelled fibrinogen from the thrombus. Plasma samples were analyzed for markers of fibrinolysis; plasmin-antiplasmin (PAP), PAI-1, and t-PA, and for functional von Willebrand factor (vWF). Platelet response to thrombin and other agonists was measured by flow cytometry. RESULTS: Thrombi formed ex vivo from the intraoperative blood samples from the dextran-treated patients exhibited significantly greater fibrinolysis vs preoperative samples, seen both as a significantly greater percentage reduction in thrombus weight (from 34.7% to 70.6% reduction) and as an 175% increase in the release of fluorescence (P < .05). Fibrinolysis returned to baseline levels the next day. No change was seen in the saline-treated group. Plasma levels of PAP and PAI-1 increased significantly postoperatively in the dextran-treated group vs the saline group (P < .05). The postoperative level of functional VWF was significantly lower in the dextran-treated group vs controls. A specific reduction occurred in the platelet response to thrombin, but not to other agonists, in the intraoperative samples from the dextran-treated group (11.1% vs 37.1%; P = .022), which was not seen in the controls. CONCLUSIONS: These data are consistent with a rise in plasmin due to dextran blockade of tPA uptake in vivo, leading to enhanced fibrinolysis, cleavage of vWF and of the platelet protease-activated receptor-1 (PAR-1) thrombin receptor. This suggests that dextran exerts a combined therapeutic effect, enhancing endogenous fibrinolysis, whilst also reducing platelet adhesion to vWF and platelet activation by thrombin. The proven antithrombotic efficacy of low-dose dextran in carotid surgery may be applicable to wider therapeutic use.

Therapeutic benefit of low-dose clopidogrel in patients undergoing carotid surgery is linked to variability in the platelet adenosine diphosphate response and patients' weight

BACKGROUND AND PURPOSE: We have previously shown that a single 75-mg tablet of clopidogrel, taken before carotid endarterectomy, significantly reduces postoperative embolization, a marker of thromboembolic stroke. This study explores the antiplatelet effect of this submaximal dose. METHODS: Fifty-six patients on long-term aspirin (150 mg) were randomized to 75 mg clopidogrel or placebo before carotid endarterectomy. Blood samples were taken pre- and postdrug administration and at the end of surgery to measure platelet activation and adenosine diphosphate (ADP) response by flow cytometry and aggregometry. RESULTS: Surgery produced a significant rise in platelet activation in vivo as evidenced by a rise in the percentage of monocyte-platelet aggregates in patients given placebo, but this was not seen in patients receiving clopidogrel. Before surgery, clopidogrel produced a significant reduction in the platelet response to ADP; for example, with 10(-6)M ADP, 77.32+/-2.3% bound fibrinogen in placebo group compared with 67.16+/-3.1% after clopidogrel (P=0.01). This was accentuated after surgery when the percentage of platelets binding fibrinogen in response to ADP was 76.53+/-2.2% in patients given placebo and 62.84+/-3.3% in the clopidogrel group (P=0.002). Similar differences were seen over a range of ADP concentrations and by aggregometry. Platelet responsiveness before treatment was highly variable and was positively correlated with the inhibitory effect of clopidogrel; patients with the highest baseline response to ADP showed the greatest response to clopidogrel. A negative correlation was seen between the effect of clopidogrel and patients' weight (r=0.57; P=0.002). CONCLUSIONS: These results explain how a single 75-mg dose of clopidogrel produces a significant clinical impact on embolization.

Quantitative detection of periodontopathic bacteria in atherosclerotic plaques from coronary arteries

Oral pathogens, including periodontopathic bacteria, are thought to be aetiological factors in the development of cardiovascular disease. In this study, the presence of Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum-periodonticum-simiae group, Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens and Tannerella forsythia in atheromatous plaques from coronary arteries was determined by real-time PCR. Forty-four patients displaying cardiovascular disease were submitted to periodontal examination and endarterectomy of coronary arteries. Approximately 60-100 mg atherosclerotic tissue was removed surgically and DNA was obtained. Quantitative detection of periodontopathic bacteria was performed using universal and species-specific TaqMan probe/primer sets. Total bacterial and periodontopathic bacterial DNA were found in 94.9 and 92.3 %, respectively, of the atheromatous plaques from periodontitis patients, and in 80.0 and 20.0%, respectively, of atherosclerotic tissues from periodontally healthy subjects. All periodontal bacteria except for the F. nucleatum-periodonticum-simiae group were detected, and their DNA represented 47.3 % of the total bacterial DNA obtained from periodontitis; patients. Porphyromonas gingivalis, A. actinomycetemcomitans and Prevotella intermedia were detected most often. The presence of two or more periodontal species could be observed in 64.1 % of the samples. In addition, even in samples in which a single periodontal species was detected, additional unidentified microbial DNA could be observed. The significant number of periodontopathic bacterial DNA species in atherosclerotic tissue samples from patients with periodontitis suggests that the presence of these micro-organisms in coronary lesions is not coincidental and that they may in fact contribute to the development of vascular diseases.

Detecção de bactérias periodontopatogênicas cultiváveis e não cultiváveis em placas ateromatosas

Periodontal infections consist of a group of inflammatory conditions caused by microorganisms that colonize the tooth surface through the formation of dental biofilm. Chronic infections such as periodontitis have been associated to the development and progression of atherosclerosis. AIM: Detect cultivatable and non-cultivatable periodontopathogenic bacteria in atheromatous plaques; search for factors associated to the presence of these bacteria in the atheromatous plaques and characterize the presence of cultivatable and non-cultivatable bacteria in these plaques. METHODOLOGY: A cross-sectional study was performed with a sample of 30 patients diagnosed with atherosclerosis in the carotid, coronary or femoral arteries and surgically treated with angioplasty and stent implant, bypass or endarterectomy. The plaques were collected during surgery and analyzed using the PCR molecular technique for the presence of the DNA of the cultivatable bacteria Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Treponema denticola and of the non-cultivatable Synergistes phylotypes. The patients were examined in the infirmary, after the surgery, where they also responded to a questionnaire aimed at determining factors associated to the presence of periodontopathogenic bacteria in the atheromatous plaques. RESULTS: All patients with tooth (66,7%) possessed disease periodontal, being 95% severe and 65% widespread. No periodontopathogenic bacteria were found in the atheromatous plaques. However, four samples (13.3%) were positive for the presence of bacteria. Of these, three participants were dentate, being two carriers of widespread severe chronic periodontite and one of located severe chronic periodontitis. None of them told the accomplishment of procedures associated to possible bacteremia episodes, as treatment endodontic, extraction the last six months or some procedure surgical dental. CONCLUSION: The periodontopathogenic bacteria studied were not found in the atheromatous plaques, making it impossible to establish the prevalence of these pathogens or the factors associated to their presence in plaques, the detection of positive samples for bacteria suggests that other periodontal and non-periodontal pathogens be studied in an attempt at discovering the association or not between periodontal disease and/or others infections and atherosclerosis, from the presence of these bacteria in atheromas

Correlation between carotid bifurcation calcium burden on non-enhanced CT and percentage stenosis, as confirmed by digital subtraction angiography

Objectives: Previous evidence supports a direct relationship between the calcium burden (volume) on post-contrast CT with the percent internal carotid artery (ICA) stenosis at the carotid bifurcation. We sought to further investigate this relationship by comparing non-enhanced CT (NECT) and digital subtraction angiography (DSA). Methods: 50 patients (aged 41-82 years) were retrospectively identified who had undergone cervical NECT and DSA. A 64-multidetector array CT (MDCT) scanner was utilised and the images reviewed using preset window widths/levels (30/300) optimised to calcium, with the volumes measured via three-dimensional reconstructive software. Stenosis measurements were performed on DSA and luminal diameter stenoses >40% were considered "significant". Volume thresholds of 0.01, 0.03, 0.06, 0.09 and 0.12 cm(3) were utilised and Pearson's correlation coefficient (r) was calculated to correlate the calcium volume with percent stenosis. Results: Of 100 carotid bifurcations, 88 were available and of these 7 were significantly stenotic. The NECT calcium volume moderately correlated with percent stenosis on DSA r=0.53 (p<0.01). A moderate-strong correlation was found between the square root of calcium volume on NECT with percent stenosis on DSA (r=0.60, p<0.01). Via a receiver operating characteristic curve, 0.06 cm(3) was determined to be the best threshold (sensitivity 100%, specificity 90.1%, negative predictive value 100% and positive predictive value 46.7%) for detecting significant stenoses. Conclusion: This preliminary investigation confirms a correlation between carotid bifurcation calcium volume and percent ICA stenosis and is promising for the optimal threshold for stenosis detection. Future studies could utilise calcium volumes to create a "score" that could predict high grade stenosis.

Ultrasonic tissue characterization of vulnerable carotid plaque: correlation between videodensitometric method and histological examination

Abstract Background To establish the correlation between quantitative analysis based on B-mode ultrasound images of vulnerable carotid plaque and histological examination of the surgically removed plaque, on the basis of a videodensitometric digital texture characterization. Methods Twenty-five patients (18 males, mean age 67 ± 6.9 years) admitted for carotid endarterectomy for extracranial high-grade internal carotid artery stenosis (≥ 70% luminal narrowing) underwent to quantitative ultrasonic tissue characterization of carotid plaque before surgery. A computer software (Carotid Plaque Analysis Software) was developed to perform the videodensitometric analysis. The patients were divided into 2 groups according to symptomatology (group I, 15 symptomatic patients; and group II, 10 patients asymptomatic). Tissue specimens were analysed for lipid, fibromuscular tissue and calcium. Results The first order statistic parameter mean gray level was able to distinguish the groups I and II (p = 0.04). The second order parameter energy also was able to distinguish the groups (p = 0,02). A histological correlation showed a tendency of mean gray level to have progressively greater values from specimens with < 50% to >75% of fibrosis. Conclusion Videodensitometric computer analysis of scan images may be used to identify vulnerable and potentially unstable lipid-rich carotid plaques, which are less echogenic in density than stable or asymptomatic, more densely fibrotic plaques.

Histological composition and progression of carotid plaque

Abstract Background To analyse histological composition and progression of carotid plaque. Methods Thirty-one patients (22 males, mean age 68.03 ± 7.3 years) admitted for carotid endarterectomy for extracranial high-grade internal carotid artery stenosis (≥ 70% luminal narrowing) were enrolled. The patients were divided into 2 groups according to symptomatology (group I, 17 symptomatic patients; and group II, 14 asymptomatic patients). A histological analysis and inflammatory cell quantification of each excised carotid plaque was made. Nine carotid arteries were removed from human cadavers that were not preselected for carotid artery disease. These specimens were used as a control tissue without any macroscopic signs of atherosclerotic plaques. Results Fifty eight percent of all carotid plaques were classified as complex plaque with possible surface defect, hemorrhage or thrombus. The inflammatory cells concentration did not differ between the two groups. All specimens from human cadavers were classified as preatheroma with extracellular lipid pools. Conclusion Asymptomatic and symptomatic patients could have the same histological components on their carotid plaques. Fibrotic and calcific plaques could become vulnerable as complex plaques with surface defect, hemorrhage and thrombus could remain silent. Asymptomatic carotid stenosis should be followed close with no invasive diagnostic methods and clinical evaluation.