George Geroulakos

Venous thrombosis from air travel: the LONFLIT3 study--prevention with aspirin vs low-molecular-weight heparin (LMWH) in high-risk subjects: a randomized trial.

The LONFLIT1 and 2 studies established that in high-risk subjects after long (> 10 hours) flights, the incidence of deep venous thrombosis (DVT) may be between 4% and 6%. The LONFLIT3 study aimed to evaluate methods of prevention in high-risk subjects. Of 467 subjects contacted for the study, 300 were included. These 300 subjects at high risk for DVT were randomized, after informed consent, into three groups: 1) a control group that had no prophylaxis; 2) an aspirin treatment group, in which patients were treated with 400 mg , (tablets of oral, soluble aspirin; one dose daily for 3 days, starting 12 hours before the beginning of the flight); and 3) a low-molecular-weight heparin (LMWH) group, in which one dose of enoxaparine was injected between 2 and 4 hours before the flight. The dose was weight-adjusted (1000 IU [equivalent to 0.1 mL] per 10 kg of body weight). Subjects with potential problems due to prophylaxis with aspirin or LMWH or at risk of drug interactions were excluded. Of the 100 included subjects in each group, a total of 249 subjects completed the study (dropouts due to low compliance or traveling/connections problems were 17%). Age and sex distribution were comparable in the three groups as well as risk distributions. Mean age was 47 (range, 28-75; SD, 11; 65% males). Of the 82 subjects in the control group, there were 4.82% of subjects with DVT with two superficial thromboses. In total 4.8% of limbs suffered a thrombotic event. Of 84 subjects in the aspirin treatment group, there were 3.6% of patients with DVT and three superficial thrombosis. In total 3.6% of limbs had a throm botic event. In the LMWH group (82 subjects), there were no cases of DVT. One superficial thrombosis was documented. In total only 0.6% of limbs had a thrombotic event (p < 0.002 in comparison with the other two groups). DVT was asymptomatic in 60% of subjects; 85% of DVTs were observed in passengers in non-aisle seats. Mild gastrointestinal symptoms were reported in 13% of patients taking aspirin. One dose of LMWH is an important option to consider in high-risk subjects during long-haul flights.

Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification

BACKGROUND The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis. METHODS This was a prospective, multicenter, cohort study of patients undergoing medical intervention for vascular disease. Hazard ratios for ICA stenosis, clinical features, and plaque texture features associated with ipsilateral cerebrovascular or retinal ischemic (CORI) events were calculated using proportional hazards models. RESULTS A total of 1121 patients with 50% to 99% asymptomatic ICA stenosis in relation to the bulb (European Carotid Surgery Trial [ECST] method) were followed-up for 6 to 96 months (mean, 48). A total of 130 ipsilateral CORI events occurred. Severity of stenosis, age, systolic blood pressure, increased serum creatinine, smoking history of more than 10 pack-years, history of contralateral transient ischemic attacks (TIAs) or stroke, low grayscale median (GSM), increased plaque area, plaque types 1, 2, and 3, and the presence of discrete white areas (DWAs) without acoustic shadowing were associated with increased risk. Receiver operating characteristic (ROC) curves were constructed for predicted risk versus observed CORI events as a measure of model validity. The areas under the ROC curves for a model of stenosis alone, a model of stenosis combined with clinical features and a model of stenosis combined with clinical, and plaque features were 0.59 (95% confidence interval [CI] 0.54-0.64), 0.66 (0.62-0.72), and 0.82 (0.78-0.86), respectively. In the last model, stenosis, history of contralateral TIAs or stroke, GSM, plaque area, and DWAs were independent predictors of ipsilateral CORI events. Combinations of these could stratify patients into different levels of risk for ipsilateral CORI and stroke, with predicted risk close to observed risk. Of the 923 patients with ≥ 70% stenosis, the predicted cumulative 5-year stroke rate was <5% in 495, 5% to 9.9% in 202, 10% to 19.9% in 142, and ≥ 20% in 84 patients. CONCLUSION Cerebrovascular risk stratification is possible using a combination of clinical and ultrasonic plaque features. These findings need to be validated in additional prospective studies of patients receiving optimal medical intervention alone.

Measurement of the ultrasonic intima-media complex thickness in normal subjects

PURPOSE The evolution of atherosclerosis can be studied before development of symptomatic plaque by evaluating morphologic changes of the intima-media (I-M) complex, seen on high-resolution ultrasonography of the arterial wall. These qualitative changes require large alterations in vessel wall appearance to recognize progression of atherosclerosis. It has been suggested that measurement of the thickness of the I-M complex may be a quantitative and more sensitive method of assessing these early atherosclerotic changes. METHODS High-resolution ultrasonography has been used to measure the thickness of the I-M complex in 140 symptom-free subjects. RESULTS The mean thickness of the I-M complex of the common carotid arteries was linearly related to the age (r = 0.77; p < 0.001), pack-years of smoking (r = 0.39; p < 0.05), the systolic blood pressure (r = 0.51, p < 0.01), and to the arterial ultrasound score (r = 0.85). The arterial ultrasound score has previously been shown to correlate with the presence of asymptomatic myocardial ischemia and with the development of cardiovascular symptoms. The mean thickness of the I-M complex in subjects without plaque (in the common carotid or common femoral artery bifurcations) was significantly thinner than in subjects with plaque (p < 0.001). CONCLUSION The thickness of the I-M complex of the common carotid arteries is a measure of the risk for the development of cardiovascular symptoms in symptom-free individuals.

Computer-assisted carotid plaque characterisation

OBJECTIVE To determine the relationship between plaque echogenicity as measured by computer and the incidence of cerebral brain infarction. PATIENTS AND METHODS Eighty-seven patients with 148 plaques producing more than 50% internal carotid artery stenosis were studied. Sixty-nine plaques were in asymptomatic patients, 35 were associated with amaurosis fugax, 19 with transient ischaemic attacks and 25 with stroke. All patients had a CT brain scan and the presence of ipsilateral cerebral infarction was noted. Images of the plaques obtained with an ATL Ultramark-4 Duplex scanner (7.5 MHz high resolution probe) were transferred to a computer. Using an image analysis program a histogram for each plaque was obtained with the number of pixels plotted against the grey scale (0-225). The median of the grey scale was used as a measure of echogenicity. RESULTS Fifty-three (36%) of the 148 plaques were associated with ipsilateral CT brain infarction. Plaques with a grey scale median more than 32 (echogenic) were associated with an incidence of 11% (7/64) CT infarction. In contrast, plaques with grey scale median below or equal to 32 (echolucent) were associated with 55% (46/84) incidence of CT infarction (chi 2 = 30.35, p < 0.001, relative risk = 22, 95% confidence interval from 4.7 to 108). CONCLUSION This study indicates that computer analysis of carotid plaque can identify high-risk carotid plaques. The potential of such analysis in the identification of asymptomatic high-risk patients should be explored in further studies.

Venous Thromboembolism from Air Travel The LONFLIT Study

The LONFLIT study was planned to evaluate the incidence of deep venous thrombosis (DVT) occurring as a consequence of long flights. In the Lonflit 1 study 355 subjects at low-risk for DVT and 389 at high-risk were studied. Low-risk subjects had no cardiovascular disease and used no drugs. All flights were in economy class. The average flight duration was 12.4 hours (range, 10-15 hr). The mean age of the studied subjects was 46 years (range 20-80 yr, SD 11; 56% males). DVT diagnosis was made by ultrasound scans after the flights (within 24 hours). In low-risk subjects no events were recorded while in high-risk subjects 11 had DVT (2.8%) with 13 thromboses in 11 subjects and 6 superficial thromboses (total of 19 thrombotic events in 389 patients [4.9%]). In the Lonflit2 study the authors studied 833 subjects (randomized into 422 control subjects and 411 using below-knee stockings). Mean age was 44.8 years (range, 20-80 yr, SD 12; 57% males). The average flight duration was 12.4 hours. Scans were made before and after the flights. In the control group there were 4.5% of subjects with DVT while only 0.24% of subjects had DVT in the stockings group. The difference was significant. The incidence of DVT observed when subjects were wearing stockings was 18.75 times lower than in controls. Long-haul flights are associated to DVT in some 4-5% of high-risk subjects. Below-knee stockings are beneficial in reducing the incidence of DVT.

Venous hemodynamic abnormalities in patients with leg ulceration

PURPOSE Venous ulceration in the leg has been predominantly associated with deep venous insufficiency, although a few reports have implicated the superficial veins. The aim of this study was to identify the distribution of valvular incompetence in patients with active leg ulceration. PATIENTS AND METHODS Color flow duplex imaging (CFDI) ultrasonography was used to evaluate the entire venous system--superficial, perforator and deep--from groin to ankle in 112 limbs of 94 patients with venous leg ulcers. RESULTS Seventy two limbs (64%) had multisystem incompetence and 36 (32%) had one system involved only, whereas in 4 limbs (4%) there was no venous incompetence. Deep venous reflux exclusively was present in 7 limbs (6%) and the perforator system alone was involved only in 3 limbs (3%). However, isolated superficial incompetence was seen in 26 extremities (23%) and combination of superficial with perforator system alone in 23 (21%). In addition, reflux overall in the superficial system (alone and in combination with perforator and deep systems) was seen in 94 limbs (84%). The most common pattern (28%) of abnormality was reflux in all systems, superficial, perforator, and deep. CONCLUSIONS The results of this study show that variable combined patterns account for over two thirds of patients with ulceration. No comprehensive surgical policy for alleviating ulceration can be justified; we suggest that a complete evaluation of all venous systems from groin to ankle with CFDI ultrasonography in patients with venous ulceration is practical on a routine basis and will be particularly valuable before surgery in order to target intervention at specific incompetent sites.

Validation of the new venous severity scoring system in varicose vein surgery

OBJECTIVES We performed this observational study to validate the three components of a new venous severity scoring (VSS) system, ie, venous clinical severity score (VCSS), venous segmental disease score (VSDS), and venous disability score (VDS), and to evaluate VCSS, VDS, and CEAP clinical class and score in quantifying outcome of varicose vein surgery. Patients and methods The study included 45 patients who underwent superficial venous surgery in 48 legs with primary varicose veins. Venous color duplex scanning, clinical examination, and a questionnaire were used preoperatively and at 6 weeks and 6 months postoperatively to assign VSS and CEAP clinical class and score. RESULTS CEAP clinical score, VCSS, and VDS demonstrated a linear association with CEAP clinical class (P <.001, P <.001, P =.002, respectively). Good correlation among all severity scores was found, particularly between CEAP clinical score and VCSS (r = 0.94; P <.001). CEAP clinical score was also highly correlated with CEAP clinical class (r = 0.84; P <.001) and VDS (r = 0.70; P <.001). Similarly, VCSS correlated with CEAP clinical class (r = 0.83; P <.001) and also VDS (r = 0.72; P <.001). The anatomic severity marker VSDS demonstrated a weak correlation with clinical severity indicators VCSS (r = 0.29; P =.048) and VDS (r = 0.31; P =.03) but not with age, gender, or CEAP clinical class and score. Six months after surgery the median (interquartile range) percent change in VCSS (73%; range, 50%-100%) and CEAP clinical score (70%; range, 50%-100%) were both significantly greater (P <.001) than the corresponding change in CEAP clinical class (17%; range, 0%-50%). In legs with high VDS at baseline, median (interquartile range) percent change in VDS was 100% (range, 50%-100%), significantly greater (P <.001) than the corresponding change in CEAP clinical class (0%; range, 0%-17%). CONCLUSIONS Venous severity scores are significantly higher in advanced venous disease, demonstrating correlation with anatomic extent. Both venous clinical severity scores, VCSS and CEAP clinical score, are equally sensitive and significantly better for measuring changes in response to superficial venous surgery than is the already in use CEAP clinical class. VDS demonstrated comparable and even better performance. Although the assignment of CEAP clinical class might be adequate for daily clinical purposes, venous severity scoring systems should be used in clinical studies to quantify venous outcome.

The Identification of the High Risk Carotid Plaque

OBJECTIVE To determine the influence of carotid plaque morphology and severity of stenosis on symptoms of cerebrovascular disease and cerebral infarction. PATIENTS AND METHODS One hundred and ninety patients with 329 carotid plaques producing 50-99% stenosis were studied. Carotid plaque echogenicity on ultrasonography was evaluated using computerised measurement of the median of the overall grey scale content (GSM). Heterogeneity was evaluated as the difference between the GSMs of the most echogenic and the most echolucent areas within each plaque and expressed as the heterogeneity index (HI). All patients had a CT brain scan and the presence of ipsilateral cerebral infarction noted. RESULTS Cerebral infarction was more common in symptomatic than asymptomatic plaques (42% vs. 29%, p<0.02) and in echolucent than echogenic plaques (mean GSM of 37.8 vs. 29.7, p<0.01). Plaques with GSM below or equal to 32 were associated with a higher incidence of cerebral infarction as compared to those above this level, this was significant in both symptomatic and asymptomatic plaques. Symptomatic carotid plaque were less heterogenous than asymptomatic plaques. Plaques associated with cerebral infarction were less heterogenous than those not associated with infarction. CONCLUSION This study has shown that the identification of the high risk carotid plaques, i.e. those associated with a high incidence of cerebral infarction is possible both in symptomatic and asymptomatic patients. The potential of such analysis in the identification of patients with asymptomatic carotid stenosis with high and low risk of stroke should be explored in a natural history study.

Hemispheric symptoms and carotid plaque echomorphology.

PURPOSE In patients with carotid bifurcation disease, the risk of stroke mainly depends on the severity of the stenosis, the presenting hemispheric symptom, and, as recently suggested, on plaque echodensity. We tested the hypothesis that asymptomatic carotid plaques and plaques of patients who present with different hemispheric symptoms are related to different plaque structure in terms of echodensity and the degree of stenosis. METHODS Two hundred sixty-four patients with 295 carotid bifurcation plaques (146 symptomatic, 149 asymptomatic) causing more than 50% stenosis were examined with duplex scanning. Thirty-six plaques were associated with amaurosis fugax (AF), 68 plaques were associated with transient ischemic attacks (TIAs), and 42 plaques were associated with stroke. B-mode images were digitized and normalized using linear scaling and two reference points, blood and adventitia. The gray scale median (GSM) of blood was set to 0, and the GSM of the adventitia was set to 190 (gray scale range, black = 0; white = 255). The GSM of the plaque in the normalized image was used as the objective measurement of echodensity. RESULTS The mean GSM and the mean degree of stenosis, with 95% confidence intervals, for plaques associated with hemispheric symptoms were 13.3 (10.6 to 16) and 80.5 (78.3 to 82.7), respectively; and for asymptomatic plaques, the mean GSM and the mean degree of stenosis were 30.5 (26.2 to 34.7) and 72. 2 (69.8 to 74.5), respectively. Furthermore, in plaques related to AF, the mean GSM and the mean degree of stenosis were 7.4 (1.9 to 12. 9) and 85.6 (82 to 89.2), respectively; in those related to TIA, the mean GSM and the mean degree of stenosis were 14.9 (11.2 to 18.6) and 79.3 (76.1 to 82.4), respectively; and in those related to stroke, the mean GSM and the mean degree of stenosis were 15.8 (10.2 to 21.3) and 78.1 (73.4 to 82.8), respectively. CONCLUSION Plaques associated with hemispheric symptoms are more hypoechoic and more stenotic than those associated with no symptoms. Plaques associated with AF are more hypoechoic and more stenotic than those associated with TIA or stroke or those without symptoms. Plaques causing TIA and stroke have the same echodensity and the same degree of stenosis. These findings confirm previous suggestions that hypoechoic plaques are more likely to be symptomatic than hyperechoic ones. They support the hypothesis that the pathophysiologic mechanism for AF is different from that for TIA and stroke.

Ultrasonic carotid artery plaque structure and the risk of cerebral infarction on computed tomography

PURPOSE The North American and the European Symptomatic Carotid Endarterectomy Trial investigators reported a conclusive benefit of carotid endarterectomy for patients with symptomatic 70% to 99% internal carotid artery (ICA) stenosis. However, it has been suggested that plaque structure may be an even more important factor in producing stroke than the degree of stenosis. The aim of this study was to test the hypothesis that the ultrasonic characteristics of carotid artery plaques were closely related to symptoms and to the prevalence of cerebral infarcts on computed tomography (CT). METHODS One hundred five carotid artery plaques causing greater than 70% stenosis in the ICA in 83 consecutive patients who underwent brain CT were characterized into four ultrasonic types: echolucent plaques, predominantly echolucent plaques, predominantly echogenic plaques, and echogenic plaques. Patients with permanent neurologic deficit were excluded. RESULTS There was a significant ipsilateral association between type 1 plaques and symptomatic hemispheres (p < 0.002). Twenty-six of the 105 cerebral hemispheres assessed by CT had infarcts. There was an increased incidence of brain infarcts in type I plaques (37%) compared with 18% in types II, III, and IV combined (p < 0.02). CONCLUSION Our results support the hypothesis that echolucent plaques are more frequently associated with symptoms and cerebral infarctions and provide further evidence that these plaques are unstable and tend to embolize. Studies on the natural history of asymptomatic carotid artery stenosis should investigate whether plaque characterization could identify a high-risk group.