Aspirin resistance in cardiovascular disease: a review.

BACKGROUND: Aspirin is effective at reducing the cardiovascular event rate in defined patient groups. The introduction of antiplatelet therapies other than aspirin and the concept of aspirin resistance have led to critical reappraisal of current treatment. This review aims to clarify the evidence for aspirin resistance in patients with atherosclerosis. METHODS: Medline search was performed to identify publications concerned with antiplatelet effects of aspirin and failure of aspirin therapy. Manual cross referencing was also performed. RESULTS AND CONCLUSION: Wide variations in the rate of aspirin resistance (5.5-75%) have been reported. The lack of consensus on an appropriate definition and the number of different tests used to investigate aspirin resistance needs to be addressed. There are few studies where the primary aim was to document aspirin resistance or aspirin non-response. Further work should aim to investigate if aspirin resistance is clinically important and, if it is, what treatments may be beneficial to the at risk patient.

Combined endovascular and open surgery for four-vessel cerebrovascular occlusive disease.

PURPOSE: To report a case of bilateral simultaneous percutaneous transluminal angioplasty and stenting of the intracranial vertebral arteries prior to staged bilateral carotid endarterectomy. CASE REPORT: A 68-year-old man presented with a 3-month history of recurrent, intermittent left-sided weakness and diplopia. Imaging defined bilateral 80% to 99% internal carotid artery stenoses and >90% stenoses of both distal vertebral arteries at the level of the foramen magnum. Bilateral intracranial vertebral artery stenting was performed, followed by staged carotid endarterectomies. No complications occurred, and the patient recovered uneventfully from all 3 procedures. He remains symptom- and event-free 20 months later. CONCLUSIONS: Our initial success in this case indicates a role for percutaneous transluminal angioplasty and stenting as an alternative to open surgery for intracranial vertebral artery stenosis.

Prevalence and outcome of activated protein C resistance in patients after peripheral arterial bypass grafts.

The association of activated protein C resistance with peripheral arterial bypass graft patency was assessed. A retrospective cohort study of consecutive first-time femoro-popliteal or femoro-distal bypasses performed in patients living within the boundaries of the Area Health Service was performed. Of 242 patients eligible for inclusion, 73 had died, nine refused to participate and 40 were lost to follow-up. Activated protein C resistance was present in nine (7.5%) of the 120 patients tested. In the study group, smoking at the time of surgery, female gender and the use of prosthetic grafts were significantly associated with graft failure on univariate Cox regression analysis, but activated protein C resistance was not. After accounting for confounders, there was a trend (P = 0.098) for activated protein C resistance to be associated with graft failure (OR 2.90, 95% CL 0.82-10.3). Patients who died or who were lost to follow-up had significantly earlier operation dates than those who remained alive or tested for activated protein C resistance. However, there was also a highly significant (P = 0.006) trend for activated protein C resistance in patients who had undergone surgery closer to the end of the study period. Six of the nine patients with activated protein C resistance underwent surgery in the last 10 months of the review period and only three activated protein C resistance patients had a graft patent for more than 8 months. The prevalence of activated protein C resistance in patients undergoing peripheral arterial bypass grafting is greater than in the general population. There was a trend for activated protein C resistance to be associated with graft failure. A significantly higher proportion of patients with activated protein C resistance was found with more recently performed surgery. The observed results could be accounted for by excess mortality in patients with activated protein C resistance. This hypothesis requires testing prospectively.

Aortic reconstructive surgery for limb ischaemia: immediate and long-term follow-up to provide a standard for endovascular procedures.

PURPOSE: Aortobifemoral and aortobiliac bypass has been a preferred treatment of severe aortoiliac occlusive disease. Recently, endovascular procedures and unilateral bypass grafting have been introduced. We report the results of aortic reconstructive surgery over a 19-year period (1975-1994). METHODS: A total of 285 patients underwent surgery. Follow-up data from clinical notes, general practitioner questionnaire or phone interview was available in 93.3% (266/285). RESULTS: Of the total 68% were male (180/226) and the median age was 63 years (range 22-85 years). Indications for surgery were tissue loss/gangrene (n = 32), rest pain (n = 84), severe claudication (n = 40), moderate claudication (n = 110). Total of 177 bifurcated grafts, 51 iliofemoral, eight left/right aortofemoral, and 30 other procedures were performed. The median duration of follow-up was 49.8 months. Cumulative secondary graft patency for 2, 5 and 10 years was 97.7%, 95.9%, and 94.4%. The amputation rate was 4.5% (12/266). Early mortality occurred in eight of 266 patients (3%) and late mortality in 60 patients. The most common cause of late death was ischaemic heart disease (24/60 followed by cancer (14/60). Data was further analysed by type of graft, risk factors, complications and previous and subsequent surgery. In our experience, aortic reconstructive surgery is a successful option for the management of severe aortoiliac occlusive disease. The outcome of other methods of maintaining arterial patency should be measured against this standard.

Surgical thrombectomy and stent placement for iliac compression syndrome.

There have been several methods, both surgical and radiological, to attempt to treat ilio-femoral thrombosis secondary to the iliac compression syndrome. A case is reported here which was managed by a combination of surgical thrombectomy and radiological stenting of the left common iliac vein.

Limitations of intra-arterial thrombolysis.

The purpose of this study was to assess the efficacy, costs and complications of acutely ischaemic limbs initially treated with urokinase-induced thrombolysis, and to compare the subsequent patencies of occluded native arteries, vein grafts and prosthetic grafts. Data from 45 consecutive episodes of thrombolysis in 37 patients (37 limbs) were reviewed retrospectively. An initial bolus dose of urokinase was used in all limbs, with pulse-spray in nine 30 limbs received additional infusions of urokinase including six who received initial treatment with pulse-spray. Percutaneous transluminal angioplasty or surgical intervention was undertaken at any stage when considered appropriate. There were 14 occluded native arteries (31%), 12 vein grafts (27%), 16 prosthetic polytetrafluoroethylene grafts (35%), and three composite grafts (7%). Thrombolysis was initially successful in 33 episodes (73%). Of these, no additional procedure was required in three, percutaneous transluminal angioplasty in 23, other surgery in 11 and bypass surgery in seven with more than one additional procedure being undertaken in 10. Of the 12 episodes with initial failure, major surgery was performed in eight and no procedure in four. Lysis-related complications occurred in 19 treatment episodes (42%) with major bleeding in seven (16%), minor bleeding in 10 (22%), distal embolization in 11 (24%) and arterial dissection in two (4%). One amputation (2%) and one death (2%), both directly attributable to thrombolysis, occurred within 1 month of treatment. Complications occurred in 10 of 19 (53%) prosthetic or composite grafts, five of 12 (42%) vein grafts, and four of 14 (29%) native artery occlusions (P = 0.38). The median follow-up of patients remaining alive was 24 months. The overall mean (s.e.m.)patency rate at 6 months of lysed vessels or replacement bypass grafts was 44% (8%). Presentation with a native artery and or graft occlusion was associated with superior long-term patency (any subsequent conduit) compared with presentation with an occluded prosthetic graft (log rank chi2[1] = 7.00, P = 0.008) and reflects the inferior run-off of the latter patients. The average cost of thrombolysis in radiological procedures and disposables alone excluding intensive care and complications was AUD$2440.

Increased synthesis of matrix metalloproteinases by aortic smooth muscle cells is implicated in the etiopathogenesis of abdominal aortic aneurysms.

PURPOSE: The objective of this study was to identify the metalloproteinases elaborated by medial smooth muscle cells (SMCs) isolated from abdominal aortic aneurysm (AAA) and control arterial tissues and to ascertain if the levels produced by AAA SMCs were elevated. METHODS: SMC monolayers cultured from the outgrowth cells of tunica media explants were established, and their identity was determined by fluorescent microscopy by using a fluorescein isothiocyanate conjugated anti-SMC alpha-actin antibody. Matrix metalloproteinases (MMPs) produced by SMC monolayers in serum-free culture were examined by gelatin zymography and Western blotting with monoclonal antibodies to MMP-2, 3, and 9. RESULTS: Serum-free media from AAA SMCs contained metal-dependent elastolytic activity that cleaved the synthetic substrate succinyl trialanyl 4-nitroanilide (pH optima 7.2) and also 14C-insoluble elastin. The level of proteolytic activity found in these cultures was significantly greater than from control SMC media. Zymography established that AAA SMC media samples contained metal-dependent gelatinases of 50 to 64 and 92 kDa, which were identified respectively as MMP-2 and 9 by Western blotting by using monoclonal antibodies to these proteases. CONCLUSION: Medial SMCs isolated from AAA tissue produce significantly higher levels of MMP-9 and 2 than SMCs from control arterial tissues. These proteinases have the capacity to degrade elastin and a range of extracellular matrix proteins. From these data, we suggest SMCs may be involved in the abnormal degradation of the aortic wall in AAA through the excessive metalloproteinase activity produced by SMCs.

The incidence of deep venous thrombosis after laparoscopic cholecystectomy.

OBJECTIVE: To determine the incidence of deep venous thrombosis (DVT) after laparoscopic cholecystectomy. DESIGN: Prospective cross-sectional analysis, with a one-month follow-up, conducted in 1994. SETTING: University teaching hospital. SUBJECTS: 20 patients undergoing elective or urgent laparoscopic cholecystectomy, consecutively recruited. INTERVENTIONS: Patients received thromboprophylaxis according to the normal practice of the attending surgeon and underwent laparoscopic cholecystectomy. A venous duplex scan was performed before the operation and on Day 1, 7 and 30 after the operation. MAIN OUTCOME MEASURE: The presence of postoperative DVT. RESULTS: All patients were given graduated compression stockings to wear and 16 received electrical stimulation of the calf during the operation. Only 16 patients received pharmacological thromboprophylaxis before the operation, but all patients received this after the operation. The median duration of pneumoperitoneum was 80 minutes (40-160 minutes). Eleven of 19 patients completing all the required scans developed venous thrombosis (incidence, 55%); in three the thromboses involved major axial veins. In one patient the Day 7 and Day 30 scans were not performed, but the Day 1 scan was negative. Seven of the 11 thromboses were detected on the Day 1 scan. None of the DVTs were suspected clinically. CONCLUSIONS: This extremely high incidence of venous thrombosis correlates with the haemodynamic changes which occur in the venous system during pneumoperitoneum. Laparoscopic cholecystectomy should not be considered a procedure with a low risk of DVT, and further studies are needed to determine optimal DVT prophylaxis for laparoscopic surgery.

Smooth muscle cell migration and proliferation is enhanced in abdominal aortic aneurysms.

BACKGROUND: The aetiology of abdominal aortic aneurysms (AAA) is as yet undetermined. Smooth muscle cells (SMC) have been implicated in the pathogenesis of AAA as a result of their ability to produce elastin degrading proteases. The present study was undertaken to examine AAA SMC and aortic occlusive disease (AOD) SMC in terms of their respective migration and proliferation in vitro, in order to identify intrinsic differences between these cells. METHODS: Five AAA specimens, four AOD and five inferior mesenteric artery (IMA) specimens were established in culture. The cultures were examined for the extent and the rate of SMC outgrowth and proliferation. Cells were counted following trypsinization using a haemocytometer. RESULTS: For the AAA explants, the cellular outgrowths were first seen at 6.7 days, after culture initiation, while the corresponding outgrowth in the AOD group required 8.8 days (P < 0.05) and the IMA group 11.4 days (P < 0.05). AAA cells reached confluency at a mean of 22.4 days while AOD SMC required 28.6 days (P < 0.05) and IMA 31 days (P < 0.05). In the first passage, the time for AAA SMC doubling was 5.3 days compared to 6.2 days for AOD (P < 0.05) and 8.1 days for the IMA group (P < 0.05). Greater than 98% of the cells, in both groups, stained positive to SMC alpha-actin. CONCLUSION: From these data it is clear that there are intrinsic differences in cellular kinetics between SMC from the two disease states, supporting the hypothesis that AAA are not the result of atherosclerosis.

Ruptured abdominal aortic aneurysms: who should be offered surgery?

PURPOSE: Operation for ruptured abdominal aortic aneurysm is generally still associated with a high mortality rate. A review of our experience over a 9-year period was undertaken to identify factors present on admission associated with 30-day operative mortality. METHODS: A retrospective analysis of 154 patients with ruptured abdominal aortic aneurysm submitted for operation in a university teaching hospital between January 1985 and December 1993 was undertaken. RESULTS: The hospital mortality rate was 39%. Logistic regression identified a set of five independent preoperative factors associated with mortality: age (> 76 years), creatinine level (> 0.19 mmol/L), loss of consciousness after arrival, Hb (< 9 g%), and electrocardiographic ischemia. In the 52 patients with a single risk factor present, the mortality rate was 37%, with two factors (32 patients) it was 72%, with three or more factors (8 patients), it was 100%, and no patient had all five risk factors. A 16% mortality rate was found in the 62 patients with no risk factors. CONCLUSION: These risk factors can be easily determined on admission and may be used to help improve patient selection for surgical intervention. The current operative mortality rate for ruptured abdominal aortic aneurysm remains high, and in some cases health care resources are used in a nonproductive fashion. Restricted patient selection and allocation of scarce resources will bring advantages to both the patient and the community.

The economic cost of elective carotid endarterectomy.

Cost awareness and accountability for the use of health care resources have become major issues for clinicians. In order to identify the economic costs associated with carotid endarterectomy (CEA), a retrospective review of 50 elective CEA between May 1993 and April 1994 was undertaken. Despite our belief [based on the Australian National Diagnostic Related Groupings (ANDRG)], that our resource utilization had been refined to produce a median length of stay significantly below the New South Wales (NSW) State average, this study has identified several areas of non-productive expenditure. The mean cost of CEA per patient was $7053. This figure includes non-productive expenditure of $793 per patient in the pre-operative period and $395 per patient in the postoperative period. If these costs, which did not contribute to patient care, were removed the mean cost of CEA would be $5865. The major causes of non-productive resource utilization included prolonged pre-operative stay, duplicated or omitted investigations, as well as the use of the Intensive Care Unit for patient monitoring in the postoperative period.

Carotid endarterectomy for asymptomatic carotid artery stenosis: patients with severe bilateral disease a high risk subgroup.

Carotid endarterectomy if advised for asymptomatic disease must be associated with a low peri-operative morbidity and mortality and satisfactory long-term results. Over a 12 year period between 1978-1989 181 carotid endarterectomies were performed on 163 patients with asymptomatic carotid artery stenosis. There were 112 males and 51 females with a mean age of 64.9 years. All patients had a high-grade lesion (> 70% stenosis). The combined operative mortality and stroke rate was 2.8%. On long-term follow up six patients suffered a stroke. Only one patient however sustained a stroke in the same territory as the previously operated carotid artery. Four years following surgery 78% of patients were alive. Carotid restenosis or occlusion occurred in 8.3% of the remaining patients, all of whom were asymptomatic. All the immediate postoperative strokes occurred in patients with severe bilateral carotid artery disease. These patients with severe bilateral disease appear to constitute a high risk sub-group for peri-operative stroke. The role of 'normal pressure-hyperperfusion breakthrough' syndrome as the presumed aetiology of two of the postoperative cerebral haemorrhages is discussed.

Fibromuscular hyperplasia in an aberrant subclavian artery and neurogenic thoracic outlet syndrome: an unusual combination.

An aberrant right subclavian artery arising distal to the origin of the left subclavian artery is the most common anomaly of the aortic arch. Degenerative diseases of aberrant subclavian arteries including aneurysms and occlusive disease have been reported previously. We believe that this case is the first reported case of fibromuscular hyperplasia affecting an aberrant subclavian artery. A 25-year-old woman admitted with a history consistent with neurogenic thoracic outlet syndrome was found to have a reduced pulse and blood pressure on the ipsilateral side caused by fibromuscular hyperplasia of an aberrant subclavian artery. A carotid-subclavian bypass via a supraclavicular incision was performed at the same time as thoracic outlet decompression. Histologic examination confirmed the presence of fibromuscular hyperplasia in the aberrant subclavian artery. This case is discussed with reference to the available literature.

Reappraisal of duplex criteria to assess significant carotid stenosis with special reference to reports from the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial.

PURPOSE: Duplex examination is today the principal initial method of assessing extracranial carotid or vertebral artery disease. However, varying haemodynamic criteria have been described to categorize the degree of internal carotid artery stenosis, and similarly the degree of stenosis detected with angiography has been assessed with different methods as highlighted in studies performed by the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial. This study looks at the correlation between two commonly used methods of assessing carotid artery stenosis with duplex criteria and the two methods of angiographic interpretation used in these trials. Duplex parameters are also identified to determine the greater than 70% stenosis group identified as at risk in these studies. METHODS: A total of 120 carotid bifurcations were studied in patients who underwent both carotid duplex and angiography. Correlations of duplex with angiography were assessed with duplex criteria described by Zwiebel and by Strandness and the angiographic methods used in studies performed by the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial. Receiver operator curves were constructed from the duplex data for the detection of stenosis greater than 70% based on the angiographic assessment used in the study performed by the North American Symptomatic Carotid Endarterectomy Trial. RESULTS: The duplex criteria described by Zwiebel and Strandness differed in their accuracy depending on which of the two methods was used to report the angiograms. Zwiebel's criteria agreed more with the angiographic method used in the study performed by the European Carotid Surgery Trial (sensitivity 98%, specificity 81%, accuracy 88%), whereas Strandness' criteria agreed more with the angiographic method used in the study performed by the North American Symptomatic Carotid Endarterectomy Trial (sensitivity 96%, specificity 85%, accuracy 89%). For the detection of a stenosis greater than 70%, a peak systolic velocity greater than 270 cm/sec and end diastolic velocity greater than 110 cm/sec provided a sensitivity of 96%, specificity of 91%, and accuracy of 93%. CONCLUSIONS: The accuracy of duplex studies compared with angiography in the assessment of extracranial vascular disease depends on the method of angiographic determination of carotid stenosis. Vascular laboratories should validate the duplex criteria they use against a standard method of angiographic assessment of carotid artery stenosis, with special reference to the recently reported studies noting the significance of a stenosis greater than 70% in patients with symptoms.

The influence of graft type on patency of infrainguinal arterial bypass grafts.

Between 1985 and 1992, 328 patients underwent 392 infrainguinal reconstructions. Indications for operation were disabling claudication in 126 patients, critical limb ischemia in 246 and uncomplicated popliteal aneurysm in 20. Grafts were to the above knee popliteal artery in 134 patients, below knee popliteal artery in 176 and infrapopliteal ("distal") in 82 patients. Graft types included 160 reversed saphenous vein (RSV), 95 polytetrafluoroethylene (PTFE), 84 nonreversed saphenous vein (NRSV), 41 composite grafts (PTFE plus vein) and 12 others. Results show the five year patency rate for all grafts of 58 percent and limb salvage (for limb ischemia) of 74 percent. Above knee and below knee popliteal grafts (three year patency rates of 72 and 66 percent) performed significantly better than distal grafts (51 percent three year patency rate, p < 0.025). NRSV grafts comprised 63 ex situ ("translocated") and 21 in situ grafts. No significant difference was shown between these (two year patency rates of 62 and 65 percent). There was no significant difference between RSV and NRSV grafts in this series, although RSV tended to show higher patency rates. Composite grafts (below knee, three year patency rate of 45 percent) had significantly lower three year patency rates than below knee RSV (79 percent, p < 0.005). RSV remains the conduit of choice in this unit, with long term patency comparable with other published series. Use of NRSV (translocated and in situ) allows increased use of autogenous vein with the associated higher patency rates compared with prosthetic materials and is the graft of choice if the long saphenous vein is not suitable for use in the standard reversed method. The translocated technique allows more flexibility in the use of nonreversed vein with results comparable with the in situ technique. Composite grafts provide a useful alternative to PTFE alone for infrageniculate grafting when insufficient autogenenous vein is available.

Preliminary results from attenuation-slope mapping of plaque using intravascular ultrasound.

Excised femoral and iliac artery segments have been examined with 20 MHz intravascular ultrasound followed by histological assessment. During the ultrasound examinations, radio-frequency (RF) data were recorded digitally, and used for calculating local values of attenuation slope throughout the tissue, using a frequency-domain technique. The RF data were also reconstructed as conventional ultrasound images, and the attenuation-slope information presented as a threshold colour overlay. Areas identified as degenerative plaque in the histological assessments were usually found to correspond to areas of high attenuation slope, and were clearly identified from the pattern of colours on the combined image. Some examples are presented, illustrating the appearance of various pathologies imaged by this technique.