Risk factors associated with increased prevalence of abdominal aortic aneurysm in women.

BACKGROUND: Four randomized trials of men aged 65-80 years showed that aneurysm-related mortality was reduced by 40 per cent by ultrasound screening. Screening is considered economically viable when the prevalence of abdominal aortic aneurysm (AAA) is 1·0 per cent or higher. This is not the case for women, in whom the prevalence of AAA is less than 1 per cent. The aim of the present investigation was to determine the prevalence of AAA 3·0 cm or larger in women screened with ultrasound imaging, the risk factors associated with AAA in this population, and whether high-risk groups can be identified with an AAA prevalence of 1 per cent or greater. METHODS: Demographic data and risk factors were collected from the first 50 000 women who attended for private cardiovascular screening in the UK. Tests included ultrasound screening for AAA, ankle : brachial pressure index (ABPI), carotid duplex imaging for carotid atherosclerosis, and electrocardiography for atrial fibrillation. RESULTS: AAA was detected in 82 of 50 000 women screened; these aneurysms were rare below the age of 66 years (7 of 24 499). In the 66-85-years age group there were 72 AAAs in 25 170 women (0·29 per cent). Univariable analysis demonstrated that a history of stroke/transient ischaemic attack (TIA), hypertension, smoking, atrial fibrillation, ABPI of less than 0·9 and internal carotid artery stenosis of at least 50 per cent were associated with an increased prevalence of AAA (P < 0·001). In multivariable linear logistic regression of risk factors, age 76 years or more, history of stroke/TIA, hypertension and smoking were independent predictors of AAA. This model had an area under the receiver operating characteristic (ROC) curve (AUC) of 0·711 (95 per cent c.i. 0·649 to 0·772) and could identify 2235 women who had 22 AAAs (prevalence 0·98 per cent). By adding ABPI, atrial fibrillation and carotid stenosis, the prediction improved to an AUC of 0·775 (0·724 to 0·826). This model could identify 3701 women who had 58 AAAs (prevalence 1·57 per cent). CONCLUSION: This report should stimulate consideration of a targeted AAA screening programme for women aged over 65 years.

Long-term Mortality in Patients with Asymptomatic Carotid Stenosis: Implications for Statin Therapy.

OBJECTIVE: Recent studies with asymptomatic carotid patients on best medical management have shown that the annual risk of stroke has decreased to approximately 1%. There is no evidence that a similar decrease in mortality has occurred. In addition, the intensity of statin therapy for these patients has not yet been determined. The aims of this review were to determine (a) the reported long-term all-cause and cardiac-related mortality in patients with asymptomatic carotid stenosis (ACS) > 50%, (b) whether there has been a decrease in mortality in recent years, (c) the available methods of mortality risk stratification, and (d) whether the latest ACC/AHA guidelines on the treatment of serum lipids can be applied to this group of patients. METHODS: Systematic review of PubMed, EuroPubMed, and Cochrane Library and meta-analysis using random effects for pooled proportions were performed regarding long-term all-cause and cardiac-related mortality and the associated risk factors in ACS patients. The last day for literature search was October 30, 2014. RESULTS: Seventeen studies were retrieved reporting 5-year all-cause mortality in 11,391 patients with ACS >50%. The 5-year cumulative all-cause mortality across all 17 studies was 23.6% (95% CI 20.50-26.80). Twelve additional studies, reporting both all-cause and cardiac mortality with a minimum of 2 year follow-up and involving 4,072 patients were identified. Of the 930 deaths reported, 589 (62.9%; 95% CI 58.81-66.89) were cardiac-related. This translates into an average cardiac-related mortality of 2.9% per year. CONCLUSIONS: All-cause and cardiac mortality in ACS patients are very high. Although risk stratification is possible, most patients are classified as high risk. In view of this high risk, aggressive statin therapy is indicated if the new ACC/AHA guidelines on serum lipids are to be adhered to.

Identification of patients with a histologically unstable carotid plaque using ultrasonic plaque image analysis.

OBJECTIVES: In patients with carotid stenosis the risk of stroke is highest in the first few days after onset of symptoms and it is low in asymptomatic patients. The ability to identify patients with a high (or low) probability of having a histologically unstable plaque might become a complimentary method that can refine the indications for surgical intervention. METHODS: Two histopathologists, using validated American Heart Association criteria, independently graded plaques harvested during carotid endarterectomy. Preoperative Duplex images were independently assessed for juxtaluminal black area, plaque type, plaque area, and grey-scale median (GSM) following image normalization. Logistic regression analysis was then performed to create a model for predicting predominantly histologically unstable or stable plaques. RESULTS: A total of 126 patients were included in the study. Based on the presence and extent of histological features including haemorrhage, thrombus, fibrous tissue, lipid core, inflammation, neovascularity, foam cells, and cap rupture, 39 plaques were graded as predominantly stable, while 87 were predominantly unstable. Unstable plaques were associated with a plaque area >95 mm(2) (OR 4.15; 95% CI 1.34-12.8 p = .009), a juxtaluminal black area >6 mm(2) (OR 2.77; 95% CI 1.24 to 6.17 p = .01) and a GSM <25 (OR 3.76; 95% CI 1.14-12.39). Logistic regression indicated that patients with the first two features had a 90% probability of having a histologically unstable plaque. The model was used to calculate the probability of having an unstable plaque in each patient. The receiver operating characteristic curve using the p value was 0.68 (95% CI 0.59-0.78). CONCLUSIONS: Computerized plaque analysis has the potential to identify patients with histologically unstable carotid plaques. This model requires validation, but offers the potential to influence patient selection for emergency interventions and the monitoring of medical therapy.

Association of ultrasonic texture and echodensity features between sides in patients with bilateral carotid atherosclerosis.

OBJECTIVES: Our objective was to estimate the correlation of echodensity and textural features, using ultrasound and digital image analysis, between plaques in patients with bilateral carotid stenosis. DESIGN: Cross-sectional observational study. METHODS: Patients undergoing carotid endarterectomy were recruited from Vascular Surgery at the Royal Victoria and Jewish General hospitals in Montreal, Canada. Bilateral pre-operative carotid ultrasound and digital image analysis was performed to extract echodensity and textural features using a commercially available Plaque Texture Analysis software (LifeQMedical Ltd). Principal component analysis (PCA) was performed. Partial correlation coefficients for PCA and individual imaging variables between surgical and contralateral plaques were calculated with adjustment for age, sex, contralateral stenosis, and statin use. RESULTS: In the whole group (n = 104), the six identified PCA variables and 42/50 individual imaging variables were moderately correlated (r = .211-.641). Correlations between sides were increased in patients with ≥50% contralateral stenosis and symptomatic patients. CONCLUSION: Textural and echodensity features of carotid plaques were similar between two sides in patients with bilateral stenosis, supporting the notion that plaque instability is determined by systemic factors. Patients with unstable features of one plaque should perhaps be monitored more closely or treated more aggressively for their contralateral stenosis, particularly if this is hemodynamically significant.

Patients with recurrent ischaemic events from carotid artery disease have a large lipid core and low GSM.

OBJECTIVES: The aim of the current study was to determine whether computerised ultrasound plaque analysis could identify features predictive of an increased risk of early recurrent events after symptom onset. METHODS: Between August 2008 and December 2010, 158 consecutive symptomatic patients undergoing carotid endarterectomy (CEA) had their plaques harvested at CEA and then independently scored for markers of histological plaque instability. Duplex ultrasound images recorded prior to CEA were independently assessed using the Iconsoft software. RESULTS: One hundred and fifty eight recently symptomatic patients underwent CEA with 118 (75%) undergoing their operation within 14 days of their most recent clinical event. Twenty (12.7%) suffered a recurrent cerebral ischaemic event following admission to the vascular unit and before undergoing CEA. Using multivariate stepwise analysis; lipid core (OR 4.00, 95% CI 1.07 to 14.83, P = 0.042) and a low GSM (OR 6.21, 95% CI 1.86 to 20.4, P = 0.003) were independently associated with recurrent cerebrovascular events. CONCLUSION: Within a cohort of patients presenting with recent onset cerebral ischaemic events undergoing CEA, the plaques of patients with recurrent events following admission to hospital had evidence a large lipid core and a low GSM.

Screening for chronic cerebrospinal venous insufficiency (CCSVI) using ultrasound: recommendations for a protocol.

Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome characterized by stenoses or obstructions of the internal jugular and/or azygos veins with disturbed flow and formation of collateral venous channels. Ultrasound and venographic studies of the internal jugular and azygos venous systems in patients with multiple sclerosis (MS) have demonstrated a high prevalence of CCSVI (mean 71%, range 0-100%; n=1336) associated with activation of collaterals. By contrast, ultrasound and venographic examinations of normal controls and patients without MS have demonstrated a much lower prevalence (mean 7.1%, range 0-22%; n=505). Ultrasound in the form of duplex scanning uses a combination of physiological measurements as well as anatomical imaging and has been used for the detection of CCSVI by different centers with variable results. A high prevalence of obstructive lesions, ranging from 62% to 100%, has been found by some teams in patients with MS compared with a low prevalence (0-25%) in controls. However, others have reported absence of these lesions or a lower prevalence (16-52%). This variability could be the result of differences in technique, training, experience or criteria used. In order to ensure a high reproducibility of duplex scanning with comparable accuracy between centers a detailed protocol with standard methodology and criteria is needed. Also, standardization of the method of reporting of duplex measurements and other findings will facilitate validation of the proposed criteria by different centers. The aim of this document is to produce recommendations for such a protocol and indicate what future research is needed in order to address areas of uncertainty.

The efficacy of a new stimulation technology to increase venous flow and prevent venous stasis.

OBJECTIVES: Electrical stimulation of calf muscles has been shown to be effective in prevention of DVT. The aim was to determine: (a) dependence of venous blood velocity and ejected volume on the rates of stimulated calf contractions: (b) clinical factors affecting efficacy in healthy individuals. METHODS: The maximum intensity stimulus tolerated was applied to calves of 24 volunteers. In popliteal veins, peak systolic velocities (PSV), ejected volume per individual stimulus (stroke volume SV) and ejected total volume flow per minute (TVF) of expelled blood were determined using ultrasound. Stimulation rates from 2 to 120 beats per minute (bpm) were applied. RESULTS: Mean baseline popliteal PSV was 10 cm/s. For stimulation rates between 2 and 8 bpm, the PSV was 10 times higher and reached 96-105 cm/s. Stroke volume (SV) per individual stimulus decreased in a similar fashion. With increasing rates of stimulation the TVF increased by a factor of 12 times (from 20 ml/min to 240 ml/min). CONCLUSION: Electrical stimulation is an effective method of activating the calf muscle pump. Enhancements of popliteal blood velocity and volume flow are key factors in the prevention of venous stasis and DVT. Further studies are justified to determine the stimulation rates in those with a compromised venous system.

Association of plaque echostructure and cardiovascular risk factors with symptomatic carotid artery disease.

AIM: Severity of stenosis remains the main factor for assessing risk of stroke in patients with internal carotid artery (ICA) disease. This study was conducted to investigate the association of plaque echostructure and other established and emerging cardiovascular risk factors with symptomatic ICA disease. METHODS: Cross-sectional study of consecutive patients with significant (>50%) ICA stenosis. Carotid plaque echostructure, smoking, hypertension, diabetes mellitus, serum lipoprotein (a), homocysteine, vitamin B12, folate, cholesterol to high-density lipoprotein ratio, triglycerides, C-reactive protein, and the Framingham risk score were assessed in 124 consecutive patients (70 asymptomatic; 54 symptomatic) with significant (>50%) ICA stenosis. RESULTS: The asymptomatic and symptomatic groups did not differ in terms of gender distribution (P=0.76) and severity of stenosis (P=0.62). Echolucent plaques (type 1 and 2) were more predominant in patients with symptomatic disease (P=0.004, OR=2.13, 95% CI=1.26-3.6). Patients with plaques type 1 were relatively younger than those with type 4 (P=0.02). None of the other factors assessed had any significant association with symptomatic disease and any type of carotid plaque. CONCLUSION: Besides the severity of carotid stenosis, the presence of an echolucent plaque appears as an important factor associated with symptomatic ICA disease. Also young patients are more likely to have an echolucent plaque suggesting an age-related association with plaque maturation.

Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thrombo-embolism in high-risk patients.

BACKGROUND: It has been suggested that combined modalities (methods of treatment) are more effective than single modalities in preventing venous thrombo-embolism (defined as deep vein thrombosis and pulmonary embolism, or both) in high-risk patients. OBJECTIVES: To assess the efficacy of intermittent pneumatic leg compression combined with pharmacological prophylaxis versus single modalities in preventing venous thrombo-embolism in high-risk patients. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases (PVD) Group searched the reference lists of their Specialised Register (last searched 17 July 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched The Cochrane Library 2008, issue 3) for relevant articles to identify additional trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) of combined intermittent pneumatic leg compression and pharmacological interventions used to prevent venous thrombo-embolism in high-risk patients. DATA COLLECTION AND ANALYSIS: Data extraction was undertaken independently by two review authors using data extraction sheets.

ESVS guidelines. Invasive treatment for carotid stenosis: indications, techniques.

The European Society for Vascular Surgery brought together a group of experts in the field of carotid artery disease to produce updated guidelines for the invasive treatment of carotid disease. The recommendations were rated according to the level of evidence. Carotid endarterectomy (CEA) is recommended in symptomatic patients with >50% stenosis if the perioperative stroke/death rate is <6% [A], preferably within 2 weeks of the patient's last symptoms [A]. CEA is also recommended in asymptomatic men <75 years old with 70-99% stenosis if the perioperative stroke/death risk is <3% [A]. The benefit from CEA in asymptomatic women is significantly less than in men [A]. CEA should therefore be considered only in younger, fit women [A]. Carotid patch angioplasty is preferable to primary closure [A]. Aspirin at a dose of 75-325 mg daily and statins should be given before, during and following CEA. [A] Carotid artery stenting (CAS) should be performed only in high-risk for CEA patients, in high-volume centres with documented low peri-operative stroke and death rates or inside a randomized controlled trial [C]. CAS should be performed under dual antiplatelet treatment with aspirin and clopidogrel [A]. Carotid protection devices are probably of benefit [C].

Association of plaque echostructure and cardiovascular risk factors with symptomatic carotid artery disease.

BACKGROUND: Severity of stenosis remains the main factor for assessing risk of stroke in patients with internal carotid artery (ICA) disease. This study was conducted to investigate the association of plaque echostructure and other established and emerging cardiovascular risk factors with symptomatic ICA disease. DESIGN: Cross-sectional study of consecutive patients with significant (> 50%) ICA stenosis. PATIENTS AND METHODS: Carotid plaque echostructure, smoking, hypertension, diabetes mellitus, serum lipoprotein (a), homocysteine, vitamin B12, folate, cholesterol to high-density lipoprotein ratio, triglycerides, C-reactive protein, and the Framingham risk score were assessed in 124 consecutive patients (70 asymptomatic; 54 symptomatic) with significant (> 50%) ICA stenosis. RESULTS: The asymptomatic and symptomatic groups did not differ in terms of gender distribution (p = 0.76) and severity of stenosis (p = 0.62). Echolucent plaques (type 1 and 2) were more predominant in patients with symptomatic disease (p = 0.004, OR = 2.13, 95% CI = 1.26-3.6). Patients with plaques type 1 were relatively younger than those with type 4 (p = 0.02). None of the other factors assessed had any significant association with symptomatic disease and any type of carotid plaque. CONCLUSIONS: Besides the severity of carotid stenosis, the presence of an echolucent plaque appears as an important factor associated with symptomatic ICA disease. Also, young patients are more likely to have an echolucent plaque suggesting an age-related association with plaque maturation.

Common femoral artery intima-media thickness as marker for cardiovascular disease in asymptomatic adults.

BACKGROUND: The common carotid intima-media thickness (IMT) is considered as a marker of cardiovascular disease, while the value of the common femoral IMT is not well defined. The aim of the present study was to investigate the value of common femoral IMT alone or in combination with the common carotid IMT as a marker of cardiovascular disease in asymptomatic adults. PATIENTS AND METHODS: Eighty-three individuals with no history of cardiovascular disease were subjected to IMT measurement of both common carotid and common femoral arteries with high-resolution ultrasonography. The Framingham Heart Study (FHS) risk score was calculated for each subject (according to gender) and was correlated with the carotid IMT, femoral IMT, and the combined IMT measured at both arterial sites. RESULTS: The carotid and femoral IMT separately and in combination were found to be correlated with the FHS risk score, calculated based on either the total cholesterol or low density lipoprotein plasma levels (carotid IMT: r = 0.28, p = 0.035, and r = 0.35, p = 0.007, respectively, femoral IMT: r = 0.38, p = 0.003, and r = 0.43, p = 0.001, respectively, carotid-femoral IMT: r = 0.37, p = 0.005, and r = 0.46, p = 0.0001, respectively). In addition, femoral IMT was found to be correlated with the carotid IMT (r = 0.41, p = 0.001). CONCLUSIONS: Common carotid and common femoral IMT showed similar correlation with the FHS risk score. Additionally, the combination of IMT from both arterial sites was found to have similar correlation with the FHS risk score to carotid IMT alone.

ApoB/ApoA1 ratio and subclinical atherosclerosis.

AIM: It has been demonstrated that an increased apolipoprotein B (ApoB)/apolipoprotein A-I (ApoA1) ratio is associated with atherogenic low density lipoprotein (LDL) particles and the development of clinical cardiovascular disease. The aim of this study was to test the hypothesis that ApoB/ApoA1 ratio is associated with early subclinical atherosclerosis as demonstrated by ultrasonic measurements. METHODS: Both common carotid and common femoral bifurcations have been scanned with high-resolution ultrasound in 767 volunteers over the age of 40. The latter consisted of 95% of the population of two randomly selected areas. IMTcc, IMTmax (including plaques), total plaque thickness (TPT) (the sum of the thickest plaques present at each bifurcation in cm) and black plaque burden (BPB) (TPT means plaque type) using the Widder classification with type 1 being the most hyperechoic and calcified and type 5 the most hypoechoic plaque were recorded. A medical history was taken with emphasis on risk factors present and a fasting lipid profile including ApoB and ApoA1 was determined. RESULTS: In the total population (N.=767) the mean (+/-SD) ApoB/ApoA1 ratio was 0.85 (+/-0.22). In linear regression analysis, the Apob/ApoA1 ratio was significantly associated with all the ultrasonic measurements of early atherosclerosis (intima media thickness, IMTcc, IMTmax, TPT and BPB). These findings remained significant after correcting for age, gender, smoking, hypertension and diabetes (P<0.001 for all). CONCLUSION: The results indicate that a high ApoB/ApoA1 ratio is associated not only with early atherosclerosis but also with hypoechoic (BPB) and by inference unstable plaques.

Cost benefit of intermittent pneumatic compression for venous thromboembolism prophylaxis in general surgery.

AIM: In moderate to high-risk general surgical patients, the cost effectiveness of mechanical prophylaxis for venous thromboembolism (VTE) is uncertain. Therefore, we determined the costs and savings of intermittent pneumatic compression (IPC) plus graduated compression stockings (GCS). METHODS: Postoperative VTE events in the absence of prophylaxis, efficacy of prophylaxis and costs of prophylaxis have been obtained from the English literature and Medicare 2004 reimbursement schedule. RESULTS: In 1000 moderate to high risk general surgical patients, in the absence of prophylaxis, the cost of investigating and treating 72 patients with clinical suspicion of DVT and 32 with PE is calculated to be $263,779. This corresponds to a cost of $263 per surgical patient. The cost of IPC combined with TED stockings in 1000 similar patients would be $66 760, and the cost of diagnosis and treatment of the reduced numbers (69% reduction) of clinical VTE is $ 83,574 making a total of $150 344. This means a saving of $133,435 ($263,779 - $150,344) per 1000 patients. This corresponds to a saving of $113 per surgical patient. Sensitivity analysis demonstrates that despite variation in costs or efficacy for IPC plus GCS, marked savings persist. CONCLUSIONS: Prophylaxis with IPC not only prevents VTE but also saves money.

Transoral laser surgery for laryngeal carcinoma: has Steiner achieved a genuine paradigm shift in oncological surgery?

Transoral laser microsurgery applies to the piecemeal removal of malignant tumours of the upper aerodigestive tract using the CO2 laser under the operating microscope. This method of surgery is being increasingly popularised as a single modality treatment of choice in early laryngeal cancers (T1 and T2) and occasionally in the more advanced forms of the disease (T3 and T4), predominantly within the supraglottis. Thomas Kuhn, the American physicist turned philosopher and historian of science, coined the phrase 'paradigm shift' in his groundbreaking book The Structure of Scientific Revolutions. He argued that the arrival of the new and often incompatible idea forms the core of a new paradigm, the birth of an entirely new way of thinking. This article discusses whether Steiner and colleagues truly brought about a paradigm shift in oncological surgery. By rejecting the principle of en block resection and by replacing it with the belief that not only is it oncologically safe to cut through the substance of the tumour but in doing so one can actually achieve better results, Steiner was able to truly revolutionise the management of laryngeal cancer. Even though within this article the repercussions of his insight are limited to the upper aerodigestive tract oncological surgery, his willingness to question other peoples' dogma makes his contribution truly a genuine paradigm shift.

Expression of int-2 oncogene in Kaposi's sarcoma lesions.

Fibroblast growth factors (FGFs), such as basic FGF, have been implicated in the growth of Kaposi's sarcoma (KS) cells in vitro. In the evaluation of the expression of the various genes of the different members of the FGF family and their receptors in fresh KS tissue specimens, int-2 was found to be expressed in more than half of the KS tumors examined. Using reverse transcription PCR, the expression of int-2 was detected in 21 of 38 (55.2%) fresh KS biopsy specimens. In contrast, int-2 mRNA transcripts were not found in normal appearing skin from the same patients except in one sample which was obtained from an AIDS patient with disseminated KS lesions. Sequence data confirmed that the amplified sequences were derived from int-2 mRNA with proper splicing. In addition, 12 nucleic acid alterations were identified in eight out of nine KS tumor samples sequenced. Using immunohistochemical methods, int-2 protein was detected in some of the spindle-shaped tumor cells surrounding the abnormal endothelial-lined vascular slits histologically characteristic of KS. Int-2 specific immunostaining was shown to be present in both the nuclei and cytoplasm of these spindle cells but was more pronounced in the nuclei. Neither amplification nor gross rearrangement of the int-2 gene was detected in KS lesions by Southern blot analysis. These results suggest that the expression of int-2 may play a role in the pathogenesis KS by stimulating local angiogenesis and cell proliferation.

Normalisation of ultrasonic images of atherosclerotic plaques and reproducibility of grey scale median using dedicated software.

AIM: Image normalization using ''Adobe Photoshop'' a commercially available software package designed for photography has provided the means of making reproducible measurements of grey scale in ultrasonic images of carotid bifurcation plaques. A dedicated software package ''Plaque Texture Analysis'' has been developed by the authors that is simple to use, provides facilities for measurement of other texture features in addition to grey scale median (GSM) and allows the operator to save the normalised images, plaques and GSM measurements in a database for subsequent analysis. The aim of the study was to determine (a) the intraobserver variability of GSM when the same plaque images were analysed using both Adobe Photoshop and the dedicated software and (b) the interobserver variability when the same plaque images were analysed using the dedicated software by different observers. METHODS: A sample of 33 images of carotid bifurcation plaques (16 symptomatic and 17 asymptomatic) producing greater than 50% stenosis of the internal carotid artery were analysed by two observers. RESULTS: The intraclass correlation coefficient and correlation coefficient (r) for GSM were 0.992 (95% CI 0.984 to 0.996) and 0.992 respectively for the first observer (MG); they were 0.986 (95% CI 0.972 to 0.993) and 0.987 respectively for the second observer (AN). The interobserver intraclass correlation coefficient and correlation coefficient (r) were 0.932 (95% CI 0.863 to 0.967) and 0.933 respectively. CONCLUSION: These findings and the automatic saving of the normalised images and measurements in a database for subsequent statistical analysis make the ''Plaque Texture Analysis'' software a powerful research tool.