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Biomedical subjects

K C Kent

Publications and source records attributed to K C Kent.

At least 19 recordsLinked to original sources

Enhancement of migration by protein kinase Calpha and inhibition of proliferation and cell cycle progression by protein kinase Cdelta in capillary endothelial cells.

Activation of protein kinase C (PKC) induces angiogenesis, migration, and proliferation of endothelial cells (EC), but can also prevent growth factor-induced EC proliferation. To determine whether these disparate effects are mediated by substrates of individual PKC isoenzymes, PKCalpha and PKCdelta were overexpressed in rat microvascular EC. Basal and stimulated migration were enhanced in PKCalpha EC compared with either PKCdelta or control EC. Serum-induced growth of PKCdelta EC was decreased, while that of PKCalpha cells was similar to control EC. Phorbol ester markedly inhibited PKCdelta EC growth but enhanced growth of PKCalpha and control EC. To determine possible causes for this altered proliferation, the effect of PKCdelta on adhesion, mitogen-activated protein kinase activity, and cell cycle progression was measured. Adherence of PKCdelta EC to vitronectin was significantly enhanced. Serum-induced extracellular signal-regulated kinase-2 activity was increased equally in both PKCalpha and PKCdelta EC above that of control, while extracellular signal-regulated kinase-1 activity was similar in all EC. Cell cycle analysis suggested that PKCdelta EC entered S phase inappropriately and were delayed in passage through S phase. Thus, PKCalpha may mediate some proangiogenic effects of PKC activation; conversely, PKCdelta may direct antiangiogenic aspects of overall PKC activation, including slowing of the cell cycle progression.

Animals

The role of integrins in saphenous vein vascular smooth muscle cell migration.

PURPOSE: Smooth muscle cell (SMC) migration is an essential feature of the intimal hyperplastic process that so frequently limits the patency of vascular reconstructions. The purpose of this investigation was to evaluate the effect of a series of integrins, or cell surface receptors that mediate cellular attachment, on platelet-derived growth factor (PDGF) and extracellular matrix (ECM) protein-induced migration of human SMCs. METHODS: Immunofluorescence staining was used to search for various integrins and subunits on the surface of SMCs derived from human saphenous vein. Chemotaxis and haptotaxis of SMCs to various matrix proteins and PDGF were assayed using a 48-well microchemotaxis chamber in the presence or absence of antibodies that blocked the function of these integrins. RESULTS: Several subunits (beta 1, alpha 2, alpha 5) and one integrin (alpha v beta 3) were identified in saphenous vein SMCs. The beta 1 integrin antibody inhibited chemotaxis to collagen I and IV, laminin, and PDGF. The alpha 2 integrin antibody inhibited collagen I and IV, and laminin-induced chemotaxis. The alpha 5 integrin antibody had no effect on SMC migration. The alpha v beta 3 integrin antibody inhibited chemotaxis to PDGF but not to the ECM proteins. CONCLUSIONS: Integrins are necessary for SMC migration induced by PDGF and ECM proteins. The integrin or subunits responsible for facilitating migration varies with the stimulant. Agonists designed to inhibit integrin function might be used to suppress SMC migration and suppress the formation of intimal hyperplasia.

Cell Movement

Duplex ultrasound criteria for the identification of carotid stenosis should be laboratory specific.

BACKGROUND AND PURPOSE: Published criteria for the determination of carotid stenosis have been widely applied by vascular laboratories. We compared two vascular laboratories and their duplex ultrasound (DU) machines in terms of their overall diagnostic performance and the optimal criteria to identify patients who have a 70% to 99% stenosis of the internal carotid artery. METHODS: Measurements of stenosis by DU and angiography were compared for 123 carotid arteries (60 arteries, laboratory A; 63 arteries, laboratory B). Receiver operating characteristic (ROC) curves were created, and the areas under the ROC curves and the optimal criteria for determining a 70% to 99% stenosis were compared. Multiple regression analysis was used to measure the effect of laboratory on the relationship between angiographic stenosis and DU velocity parameters. RESULTS: Areas under the ROC curves were similar for both laboratories (0.89 to 0.90, laboratory A; 0.90 to 0.92, laboratory B). However, the optimal criterion for the identification of a 70% to 99% carotid stenosis was different for each laboratory. For most velocity parameters, based on regression analyses, the predicted percent angiographic stenosis for laboratory A was significantly greater than that for laboratory B. In addition, performance differed between the laboratories when established criteria from the literature were applied. CONCLUSIONS: Two vascular laboratories with similar diagnostic accuracy by ROC analysis have markedly different "optimal" DU criteria. For a given angiographic stenosis, velocities in one laboratory were consistently greater than those in the other laboratory. Laboratory-specific criteria rather than published criteria should be used to identify patients with internal carotid artery stenoses.

Aged

Is carotid endarterectomy cost-effective? An analysis of symptomatic and asymptomatic patients.

BACKGROUND: The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the Asymptomatic Carotid Atherosclerosis Study (ACAS) showed significant risk reductions for carotid endarterectomy (CE) but did not consider the cost-effectiveness of CE. METHODS AND RESULTS: We developed Markov models based on NASCET and ACAS to simulate hypothetical cohorts of patients with carotid stenosis and calculated quality-adjusted life expectancies and direct medical costs for those receiving either CE or medical therapy. For symptomatic patients, we used a surgical stroke risk of 5.8%, a 2-year stroke risk of 27.6% for medical patients, and a post-30-day surgical risk reduction of 87% for ipsilateral strokes. For symptom-free patients, we used a surgical stroke risk of 1.7%, a 5-year stroke risk of 17.5% for medical patients, and a post-30-day surgical risk reduction of 74% for ipsilateral strokes. Cost and quality-of-life estimates were estimated from the literature. The incremental cost-effectiveness ratio of CE versus medical therapy was $4100 and $52700 per quality-adjusted life year (QALY) gained for symptomatic and symptom-free patients, respectively. Incremental cost effectiveness ratios were < $50000/QALY gained for symptomatic patients for wide variations in baseline assumptions. For asymptomatic patients, the incremental cost-effectiveness ratio was $100900/QALY gained if the perioperative risk was 4%, $36400/QALY gained if the risk of untreated patients was doubled, and $13500/QALY gained if the cost of CE was halved. CONCLUSIONS: Performance of CE is associated with favorable incremental cost-effectiveness ratios compared with other accepted medical interventions; however, the analysis for symptom-free patients was sensitive to a number of parameters.

Aged

Role of protein kinase C in attachment, spreading, and migration of human endothelial cells.

Attachment, spreading, and migration of vascular endothelial cells (EC) are necessary for angiogenesis, reendothelialization of an injured artery, or seeding of a prosthetic graft. However, little is known about the signaling pathways that mediate these effects. Protein kinase C (PKC) is a ubiquitous intracellular messenger which we have previously shown to be necessary for EC proliferation (Kent et al., 1995, Circ. Res. 77, 231-238). In this study, we investigate whether activation of PKC is necessary for EC attachment, spreading, and migration. Using human umbilical vein EC, we found that direct activation of PKC with the phorbol ester phorbol 12-myristate-13-acetate enhanced all three processes. Inhibition of PKC by the selective agent, chelerythrine, markedly diminished the ability of EC to attach, spread, and migrate. Depletion of intracellular PKC by downregulation (prolonged exposure of EC to phorbol ester) reduced EC attachment and migration; however, downregulation had no effect on endothelial spreading. PKC is a family of isotypes, each of which may control specific cellular functions. By Western blotting, we identified PKC alpha, beta, delta, epsilon, eta, theta, and zeta isotypes in human EC. Downregulation led to a significant reduction in the quantity of PKC alpha and epsilon. These data demonstrate that activation of PKC is both necessary and sufficient for attachment, spreading, and migration of human EC. An isotype of PKC that is susceptible to downregulation (either alpha and/or epsilon) is at least partially responsible for attachment and migration. Pharmacological activation of PKC may be used as a method to enhance reendothelialization.

Alkaloids

Prospective study of wound complications in continuous infrainguinal incisions after lower limb arterial reconstruction: incidence, risk factors, and cost.

BACKGROUND: Wound complications after lower extremity arterial reconstruction can range from a minor lymphatic leak that causes minimal disability to a severe infection that jeopardizes the limb and life of the affected patient. This study was designed to define more clearly the incidence, severity, and the cost of these complications. METHODS: During a 1-year period the infrainguinal incisions of all patients undergoing lower limb arterial reconstruction were evaluated prospectively. One hundred fifty-six infrainguinal incisions were monitored serially for the presence of infection, hematoma, seroma, serous leak, necrosis, or wound dehiscence. The need for additional treatment or services related to these complications and the cost of these services were determined. RESULTS: Complications occurred in 10% of 77 infrainguinal incisions that were isolated to the groin (groin incisions) e.g., after aortobifemoral bypass, femoral endarterectomy). In only one of these patients was significant cost related to treatment of a complication. Complications occurred in 44% of 79 incisions used for femoral popliteal/tibial and pedal bypasses (distal incisions). In this latter group independent predictors of any complication were age (p=0.02) and obesity (p=0.05); predictors of in-hospital infection were preoperative evidence of venous stasis (p=0.01) and preoperative infection in the same extremity (p=0.08). Fifteen distal wound complications provided additional expense related to reoperation, extended hospitalization or rehospitalization, and rehabilitation or visiting nurse services, with a mean cost per patient undergoing reconstruction of $688. CONCLUSIONS: After lower limb arterial reconstruction, infrainguinal wound complications in isolated groin incisions produce minimal morbidity and cost, whereas complications in incisions after distal bypass are both frequent and associated with significant additional expense.

Arteries

Differential effects of platelet-derived growth factor isotypes on human smooth muscle cell proliferation and migration are mediated by distinct signaling pathways.

BACKGROUND: Platelet-derived growth factor (PDGF) is a potent mitogen and chemoattractant for vascular smooth muscle cells (SMCs). Three isotypes of PDGF (BB, AB, and AA) have been identified; each of these isotypes may have differing effects on the behaviour of vascular SMCs. In this study we evaluated the influence of PDGF isotypes on proliferation and migration of human venous SMCs and explored the signaling pathways through which these effects are mediated. METHODS: Proliferation was measured by a 72-hour assay of cell number, and migration was evaluated by a 4-hour microchemotaxis assay. The effects of PDGF isotypes on the activities of the signaling proteins mitogen-activated protein kinase (MAP-K), p 125 focal adhesion kinase (p125FAK), and tensin were measured by immunoprecipitation of these proteins and subsequent phosphorylation on myelin basic protein (in MAP-K) and Western blotting with antiphosphotyrosine (in tensin and p125FAK). RESULTS: All three isotypes stimulated SMC proliferation (PDGF-BB > AB > AA). PDGF-BB and -AB, but not -AA, stimulated chemotaxis. All three isotypes activated MAP-K with an intensity that corresponded to their proliferative effects. PDGF-BB and -AB tyrosine phosphorylated tensin and p125FAK, whereas PDGF-AA had no effect on either of these proteins. CONCLUSIONS: For human vascular SMCs the physiologic effects and the signaling pathways that mediate these effects are specific for each of the three PDGF isotypes. These data also suggest an association between MAP-K and SMC proliferation and between the proteins, p125FAK and tensin, and migration.

Calcium-Calmodulin-Dependent Protein Kinases

Extracellular matrix proteins are potent agonists of human smooth muscle cell migration.

PURPOSE: Extracellular matrix proteins can stimulate smooth muscle cell (SMC) migration by three distinct mechanisms: chemokinesis (nondirected migration in the presence of soluble protein), chemotaxis (directed migration toward soluble protein), and haptotaxis (directed migration toward insoluble, substrate-bound protein). This study investigates the effects of four prevalent extracellular matrix proteins (collagen types I and IV, fibronectin, and laminin), and platelet-derived growth factor (PDGF) on haptotaxis, chemotaxis, and chemokinesis of human SMCs. The role of large guanosine triphosphate-binding proteins (G-proteins) in the signaling mediating these effects is also evaluated. METHODS: Human saphenous vein SMCs were used in all migration studies. Chemokinesis, chemotaxis, and haptotaxis to each of the matrix proteins were measured and compared with PDGF through the use of a 48-well microchemotaxis chamber. The role of G-proteins in matrix-induced SMC migration was studied with the modulators of G-protein function, cholera and pertussis toxins. RESULTS: For all matrix proteins the relative strength of the various stimuli for migration was haptotaxis > chemotaxis > chemokinesis (p < 0.05). For all three stimuli collagen I and IV produced the most significant migration followed by fibronectin > PDGF-AB > laminin (p < 0.05). Pertussis toxin completely inhibited chemotaxis and partially inhibited haptotaxis by laminin but did not affect migration by other matrix proteins, whereas cholera toxin abolished migration in response to all four matrix proteins. CONCLUSION: Matrix proteins, with the exception of laminin, provide a more significant stimulus for SMC locomotion than does the prototypical agonist, PDGF-AB. Of the three mechanisms by which migration can be stimulated, haptotaxis elicits the most profound effect. The importance of G-proteins as second messengers for migration varies with each matrix protein and with the mechanism of stimulation.

Cell Movement

Mid-term and long-term results with directional atherectomy of vein graft stenoses.

PURPOSE: The purpose of this study was to evaluate the outcomes of our 6-year experience with directional atherectomy used for treatment of stenoses in infrainguinal vein grafts. METHODS: From March 1988 to April 1994, 52 directional atherectomy procedures were undertaken in 42 patients to treat 67 stenoses in 44 vein grafts. Follow-up consisted of periodic physical examinations and graft surveillance; ankle/brachial indexes, pulse volume recordings, and color-flow duplex ultrasonography. Follow-up angiography (n = 18) was performed for recurrent symptoms, reproducible drop in ankle/brachial index of greater than 0.15, a twofold to threefold focal increase in peak systolic velocity, or incidentally during evaluation of the opposite leg. RESULTS: Forty-nine of 52 (94%) procedures were technically successful. In two the residual diameter stenosis was greater than 30%, and in one atherectomy could not be performed. Complications were minor in six (11%) and major in three (6%): two acute graft occlusions and one delayed pseudoaneurysm at the atherectomy site. There were no deaths at 30 days. With a mean follow-up of 21 +/- 18 months, 36 of 44 grafts (82%) remained patent without restenosis; 6 others were patent but considered "failed"--5 (11%) with restenosis, 1 with a pseudoaneurysm; and 2 grafts (5%) occluded. Clinically 33 of 44 extremities (75%) were asymptomatic during follow-up. Claudication improved in five, recurred in three, and was unchanged in one. There was one below-knee amputation. Life-table analysis including all 52 procedures reveals cumulative primary atherectomy patency rates for the 44 grafts of 82%, 78%, and 78%, respectively, at 1, 2, and 3 years after atherectomy, and 86%, 83%, and 83% for the 67 individual stenoses treated. CONCLUSIONS: Directional atherectomy of vein graft stenoses has high technical and clinical success rates, acceptably low morbidity rates, and offers better sustained patency rates than balloon angioplasty. Its long-term patency rate seems to approach that of surgical vein patch angioplasty.

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Mitogen-activated protein kinase and proliferation of human vascular smooth muscle cells.

The intracellular messenger mitogen-activated protein kinase (MAPK) is activated in vascular smooth muscle cells (SMC) by various growth factors as well as by agonists that have no proliferative effect. We explored the hypotheses that SMC proliferation is associated with a specific pattern of MAPK activation by evaluating the kinetics of MAPK activation and tyrosine phosphorylation and the intracellular location of MAPK in SMC following addition of agonists of varying mitogenic potential. A peak in MAPK activation and tyrosine phosphorylation occurred 3-10 min after the addition of agonists to SMC derived from human saphenous vein (early phase), followed by a plateau of activity, which was variable in duration (late phase). A correlation was not found between mitogenicity and the degree to which MAPK became activated or tyrosine phosphorylated in the early phase. However, the duration of MAPK activation and tyrosine phosphorylation correlated strongly with the ability of agonists to stimulate SMC proliferation. Nuclear translocation of MAPK was associated with SMC proliferation, although the degree to which each agonist induced nuclear translocation did not parallel its mitogenic potential. The relative dependency of all three events on protein kinase C differed for each agonist and was greater in the late versus the early phase. Thus, in human SMC, nuclear translocation of MAPK and prolonged activation and tyrosine phosphorylation of MAPK are associated with growth factor-induced mitogenesis.

Calcium-Calmodulin-Dependent Protein Kinases

Sequential helical CT angiography of aortoiliac disease.

OBJECTIVE: The purpose of this work was to study aortoiliac disease with sequential helical CT angiography. SUBJECTS AND METHODS: Sequential helical CT angiography combines two successive helical sets for data acquisition obtained during two successive bolus injections of IV contrast material and two breath-holds. Twenty-eight patients with aneurysm and 11 with occlusive disease had CT angiography. Of those 39 patients, 18 also had conventional catheter angiography. For each of the 39 patients, a CT angiogram of three segments of the aorta and 13 arteries was assessed, including the suprarenal, juxtarenal, and infrarenal aorta; celiac axis; superior and inferior mesenteric arteries; and pairs of renal, common iliac, hypogastric, external iliac, and common femoral arteries. In 18 patients undergoing both CT and conventional angiography, the appearance of these vessels was graded as occlusive (grade 0), severely stenotic (grade 1), moderately stenotic (grade 2), mildly stenotic (grade 3), normal (grade 4), ectatic (grade 5), and aneurysmal (grade 6). RESULTS: Of the 624 arteries expected to be opacified in 39 patients, 585 (94%) were actually imaged with CT angiography. In the 18 patients who had both CT angiography and catheter angiography, the two studies were in complete agreement in 243 (90%) of 269 arteries. In 13 vessels (5%), CT angiography produced an image that was one grade higher-and in 11 vessels (4%), one grade lower-than conventional angiography. In two vessels, a two-grade difference was noted. The independent readings matched on the 0-6 scale in 95% of the evaluations. An additional 5% of the readings differed by one unit. Compared with conventional angiography, CT angiography of clinically significant (> or = 85%) narrowing (grades 0 and 1) and aneurysm (grade 6) yielded sensitivity of 93%, specificity of 96%, and accuracy of 95%. CONCLUSION: Sequential helical CT angiography of the abdomen can provide sufficient vascular detail to allow evaluation of expanded vascular territories. The technique can allow accurate assessment of both stenotic and aneurysmal disease of the aorta and the iliac arteries.

Adult

Perioperative imaging strategies for carotid endarterectomy. An analysis of morbidity and cost-effectiveness in symptomatic patients.

OBJECTIVE: To assess the cost-effectiveness of four diagnostic strategies for the preoperative evaluation of symptomatic patients who are potential candidates for carotid endarterectomy (ie, 70% to 99% stenosis): (1) duplex sonography (DS), (2) magnetic resonance angiography (MRA), (3) contrast angiography (CA), and (4) the combination of DS and MRA supplemented by CA for disparate results. METHODS: Cost-effectiveness analysis based largely on published clinical trial data. Sensitivities and specificities of noninvasive tests were estimated from 81 patients undergoing prospective evaluation with DS, MRA, and CA. OUTCOME MEASURE: Incremental cost per quality-adjusted year of life gained. RESULTS: For a hypothetical cohort of symptomatic patients undergoing evaluation for carotid endarterectomy, the combination of tests resulted in the greatest quality-adjusted life expectancy of the four options considered. After incorporating the costs of testing, surgery, and stroke, we found that neither the MRA nor the CA strategy was cost-effective. The combination of tests was more effective but more costly than DS, resulting in an additional cost of $22,400 per quality-adjusted year of life gained. For centers that do not have adequate MRA, CA resulted in an additional cost of $99,200 per quality-adjusted year of life saved compared with DS. CONCLUSIONS: Our results suggest that for the preoperative detection of a 70% to 99% carotid stenosis, the combination of DS and MRA, supplemented by CA for disparate results, is associated with the lowest long-term morbidity and mortality and has a favorable cost-effectiveness ratio. The combination of tests, or DS alone when MRA is not available, could potentially replace the current practice of using CA alone in the preoperative evaluation of patients with symptomatic carotid stenosis.

Aged

Severe Clostridium difficile colitis.

PURPOSE: Reports of fatality related to Clostridium difficile colitis and a sharp increase in prevalence of this infection prompted a study of patients who develop a more aggressive form of this disease. METHODS: Over 38 months, 710 patients at our institution developed C. difficile colitis. Twenty-one (3 percent) of these patients either required intensive care unit admission or died as a result of their infection. A retrospective, case-controlled study was undertaken to compare these patients, who were considered to have severe C. difficile colitis, with the remaining patients with milder disease. RESULTS: Factors that predisposed to the development of severe C. difficile colitis included intercurrent malignancy, chronic obstructive pulmonary disease, immunosuppressive and antiperistaltic medications, renal failure, and administration of clindamycin (P < 0.05 for all). Patients with severe C. difficile colitis were more likely to have abdominal pain, tenderness and distention, peritonitis, hemoconcentration (> 5 points), hypoalbuminemia (< 3 mg/dl), and elevated or suppressed white blood cell count (> 25,000; < 1,500; P < 0.05 for all). These factors were used to create a scoring system that could distinguish between patients with severe C. difficile colitis and those with mild disease. Thirteen patients in the late stages of terminal illness with metastatic malignancy or age > 90 were considered poor or inappropriate surgical candidates. Only the remaining eight patients could have potentially recovered from operation with hope for long-term survival. Of these, seven were treated without colonic resection, and six of the seven survived, whereas one patient underwent colectomy and did not survive. CONCLUSIONS: Patients with severe C. difficile colitis can be readily identified. Often they have coexisting illness that precludes operation. In this series, only 1 of 21 patients with severe C. difficile might have benefited from an aggressive surgical approach.

Age Factors

Preliminary evaluation of a technique for inhibiting intimal hyperplasia: implantation of a resorbable luminal collagen membrane.

Pharmacologic control of intimal hyperplasia has been attempted through oral and intravenous administration of smooth muscle cell inhibitors. We report a more direct method of altering arterial healing using a novel bioresorbable membrane that can be applied to the lumen of an artery or anastomosis following endarterectomy or vascular reconstruction. Following a standard balloon injury, the infrarenal aortas of 3 kg female New Zealand white rabbits were opened and a thin membrane composed of collagen/chondroitin 6-sulfate copolymer was sutured to the posterior wall of each artery. Animals were killed at intervals of up to 3 months. All arteries remained patent. By 24 hours the membrane had become infiltrated with fibrin and red blood cells. An inflammatory response ensued and by 8 days the membrane was filled with mononuclear cells. At 3 months only a small remnant of the membrane remained. Intimal hyperplasia developed throughout the injured aorta. However, the hyperplastic response beneath the membrane was no greater than that observed in the adjacent injured aorta. A bioresorbable membrane can be sutured into the lumen of a small-diameter vessel without inducing thrombosis and without locally increasing intimal hyperplasia. A prosthesis of this type might be used to deliver inhibitors of smooth muscle cell proliferation and migration to the injured arterial wall.

Absorption

Platelet attachment stimulates endothelial cell regeneration after arterial injury.

BACKGROUND: Arterial injury is associated with endothelial disruption and attachment of platelets to an exposed subintimal layer. A variety of factors released by platelets may affect the ability of endothelial cells bordering an injury to regenerate. In this study an organ culture model of arterial injury was used to investigate the relationship between attachment of platelets to a superficial arterial injury and endothelial regeneration. METHODS: A defined superficial endothelial injury was made in whole vessel wall explants of rabbit thoracic aorta. Injured explants were treated with either fresh whole platelets, the supernatant of platelets aggregated by collagen, or basic fibroblast growth factor. Four days after injury and treatment, the average distance of endothelial regeneration was determined. RESULTS: A dramatic increase in the rate of endothelial cell regeneration was observed when injured vessels were exposed to fresh whole platelets (p = 0.003). This increase in regeneration was comparable to that observed with fibroblast growth factor. No increase in the regenerative rate was found after exposure of explants to the supernatant of aggregated platelets (p = 0.69). CONCLUSIONS: Platelets stimulate endothelial regeneration at a rate equal to that observed with the potent endothelial mitogen basic fibroblast growth factor. Because this effect was not demonstrated with the supernatant of aggregated platelets, endothelial regeneration may be dependent on attachment of the platelets to the area of injury.

Animals

Carotid endarterectomy in asymptomatic patients--is contrast angiography necessary? A morbidity analysis.

PURPOSE: Findings from the Asymptomatic Carotid Atherosclerosis Study (ACAS) indicate that carotid endarterectomy can be beneficial in symptom-free patients with 60% to 99% carotid artery stenosis. However, patients in ACAS who underwent contrast angiography (CA) before carotid endarterectomy were exposed to an additional 1.2% risk of stroke. METHODS: We used the methods of decision analysis to assess whether the overall 5-year stroke risk in symptom-free patients with suspected carotid artery disease can be reduced by preoperative imaging with magnetic resonance angiography (MRA) or duplex ultrasonography (DU). We compared four strategies for the preoperative evaluation of carotid artery stenosis in symptom-free patients: 1) CA alone, 2) MRA alone, 3) DU alone, and 4) MRA and DU with CA when the results of these tests disagree. Accuracies of MRA and DU were estimated from 81 patients exposed to all three procedures; stroke risks for patients with 60% to 99% carotid artery stenosis were obtained from ACAS. RESULTS: For predicting 60% to 99% carotid stenoses, sensitivity and specificity for noninvasive tests, optimized to reduce morbidity, were as follows: DU (0.96, 0.66), MRA (1.00, 0.76), DU/MRA (1.00, 0.86; 26% would require CA). The 5-year stroke risk of these four strategies in order of decreasing benefit was MRA, 6.17%; MRA/DU, 6.34%; DU, 6.35%; and CA, 7.12%. In sensitivity analyses, noninvasive tests were advantageous even if the stroke rate with CA diminished to 0.4%, or if the sensitivity and specificity of noninvasive tests fell to 70%. CONCLUSION: The preoperative use of noninvasive tests resulted in a lower 5-year stroke risk compared with CA in symptom-free patients with suspected carotid artery stenosis.

Aged