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Biomedical subjects

V Fuster

Publications and source records attributed to V Fuster.

At least 127 records · Page 7Linked to original sources
PubMed1998

Hirudin reduces tissue factor expression in neointima after balloon injury in rabbit femoral and porcine coronary arteries.

BACKGROUND: Tissue factor (TF) is a transmembrane glycoprotein that, after binding to factor VII/VIIa, initiates the extrinsic coagulation pathway, resulting in thrombin generation and its sequelae. Thrombin has been shown to induce TF mRNA in endothelium, monocytes, and smooth muscle cells, further perpetuating the thrombogenic cycle. This study was designed to determine the effect of specific inhibition of thrombin by recombinant hirudin (r-hirudin) on TF distribution after balloon angioplasty in the cholesterol-fed rabbit femoral artery and porcine coronary artery models. METHODS AND RESULTS: Thirty-five femoral arteries from 32 cholesterol-fed New Zealand White rabbits and 84 coronary arteries from 55 Yorkshire-Albino swine were studied by use of a recently developed in situ method of TF localization based on digoxigenin labeling of recombinant factor VIIa (Dig-VIIa), with correlative studies of TF immunoreactivity by use of anti-rabbit (AP-1) or anti-human (sTF) antibodies. At sites of balloon angioplasty in rabbit femoral or pig coronary arteries (double or single injury), TF-antibody and Dig-VIIa staining were noted in association with endothelial cells, smooth muscle cells, and foam cells and within the fibrous tissue matrix primarily of the adventitia and neointima. Staining was significantly greater after balloon angioplasty than in vessels that had not undergone angioplasty but was similar after single and double balloon injury. Animals treated with r-hirudin (rabbits, 1 mg/kg bolus plus 2-hour infusion; pigs, 1 mg/kg bolus plus 0.7 mg x kg(-1) x d(-1) infusion for 14 days with implantable pump) had diminished TF-antibody and Dig-VIIa staining 28 days after balloon angioplasty compared with controls (bolus heparin only). This effect was more prominent on the neointima and was more striking in the porcine than the rabbit model. CONCLUSIONS: TF expression, persistent 1 month after balloon angioplasty in rabbit femoral arteries and porcine coronary arteries, is attenuated by specific thrombin inhibition with hirudin. These results suggest that thrombin inhibition, in addition to its effect on acute thrombus formation and its effect on luminal narrowing by plaque in experimental animals, may result in a prolonged reduction in thrombogenicity of the restenotic plaque through this effect on TF expression.

Angioplasty, Balloon↗
PubMed1998

Effects of practice setting on quality of lipid-lowering management in patients with coronary artery disease.

We undertook a study to determine whether there were differences in the quality of lipid management in patients with coronary artery disease (CAD) in 2 different practice settings (which represent different socioeconomic classes), and to determine the level of compliance with the National Cholesterol Education Program guidelines by academic physicians in managing patients with CAD. A retrospective cross-sectional study was performed using a systematic chart review of 270 medical records (131 from the cardiology clinic, 139 from the cardiology private practice) of patients with known CAD at an academic tertiary care center in New York City. The total proportion of patients with CAD having a lipid profile ordered in the clinic and private suite was 43%. Of these people, 22% had a low-density lipoprotein cholesterol (LDL) < or = 100 mg/dl and 54% had an LDL < or = 130 mg/dl (10% and 23% of the total population, respectively). The total proportion of patients taking lipid-lowering medications was 29%. When comparing the quality of treatment between the 2 settings, there were no statistically significant differences in the percentages of patients who had lipid profiles measured (40% clinic vs 47% private suite, p >0.10), in the percentage of patients with LDL < or = 130 mg/dl (50% clinic vs 57% private suite, p >0.10) or in the weighted percentage of patients taking lipid-lowering medications (29% clinic vs 48% private suite, p = 0.099). The performances of individual physicians, however, varied widely. The percentages of patients with lipid profiles measured by individual physicians ranged from 0% to 83%, while the percentages of patients on drug treatment by a physician ranged between 10% and 88%. These findings indicate that socioeconomic differences, represented by different practice settings, do not account for differences in the screening for, control of, or use of medications in managing hyperlipidemia. Rather, individual physicians are accountable for differences in lipid management.

Age Factors↗
PubMed1998

Elderly patients receive less aggressive medical and invasive management of unstable angina: potential impact of practice guidelines.

BACKGROUND: The Agency for Health Care Policy and Research (AHCPR) released a practice guideline on the diagnosis and management of unstable angina in 1994. OBJECTIVE: To examine practice variation across the age spectrum in the management of patients hospitalized with unstable angina 2 years before release of the AHCPR guideline. DESIGN: Retrospective cohort. SETTING: Urban academic hospital. PATIENTS: All nonreferral patients diagnosed as having unstable angina who were hospitalized directly from the emergency department to the intensive care or telemetry unit between October 1, 1991, and September 30, 1992. MEASUREMENTS: Percentage of eligible patients receiving medical treatment concordant with 8 important AHCPR guideline recommendations. RESULTS: Half of the 280 patients were older than 66 years; women were older than men on average (70 vs 64 years; P<.001). After excluding those with contraindications to therapy, patients in the oldest quartile (age, 75.20-93.37 years) were less likely than younger patients to receive aspirin (P<.009), beta-blockers (P<.04), and referral for cardiac catheterization (P<.001). Overall guideline concordance weighted for the number of eligible patients declined with increasing age (87.4%, 87.4%, 84.0%, and 74.9% for age quartiles 1 to 4, respectively; chi2, P<.001). Increasing age, the presence of congestive heart failure at presentation, a history of congestive heart failure, previous myocardial infarction, increasing comorbidity, and elevated creatinine concentration were associated with care that was less concordant with AHCPR guideline recommendations; only age and congestive heart failure at presentation remained significant in the multivariate analysis (odds ratios, 1.28 per decade [95% confidence interval, 1.02-1.61] and 3.16 [95% confidence interval, 1.57-6.36], respectively). CONCLUSIONS: Older patients were less likely to receive standard therapies for unstable angina before release of the 1994 AHCPR guideline. Patients presenting with congestive heart failure also received care that was more discordant with guideline recommendations. The AHCPR guideline allows identification of patients who receive nonstandard care and, if applied to those patients with the greatest likelihood to benefit, could lead to improved health care delivery.

Age Factors↗
PubMed1998

Dissolution of mural thrombus by specific thrombin inhibition with r-hirudin: comparison with heparin and aspirin.

BACKGROUND: The presence of residual mural thrombus may predispose to recurrent thrombotic events in acute coronary syndromes. The purpose of this study was to evaluate the effects of antithrombotic and antiplatelet agents on a preformed, fresh mural thrombus during growth of thrombus. METHODS AND RESULTS: A fresh mural thrombus was formed by perfusing severely injured arterial wall with porcine blood for 5 minutes at a shear rate of 1690 s(-1). Thrombus formation was measured by morphometric analysis (mm2/mm). The average size of a mural thrombus formed in 5 minutes was 0.14+/-0.03 mm2/mm. Progression of thrombus growth within 10 minutes triggered by the preformed thrombus was evaluated in pigs treated with r-hirudin (1 mg/kg per hour i.v.) as a probe for thrombin, high-dose heparin (250 IU/kg per hour i.v.), moderate-dose heparin (100 IU/kg per hour), moderate-dose heparin (100 IU/kg per hour) plus aspirin, aspirin alone (5 mg/kg i.v.), and placebo. Hirudin was associated with a significant decrease (48%) of mural thrombus area and significantly reduced growth of thrombus (0.07+/-0.01), even compared with the highest dose of heparin (0.15+/-0.03), although at lower levels of anticoagulation. Inhibition of growth of thrombus with heparin was dose dependent, showing an inverse correlation of thrombus area with mean plasma heparin concentrations (r=.77, P=.0001). Thrombus size was unchanged by aspirin (0.29+/-0.07) compared with controls (0.28+/-0.07). CONCLUSIONS: Direct inhibition of thrombin activity with r-hirudin completely inhibits growth of thrombus, causes dissolution of a preexisting mural thrombus, and is more effective at lower levels of anticoagulation than the highest dose of heparin at shear rates typical of a moderate coronary stenosis.

Animals↗
PubMed1998

Prolonged thrombin inhibition reduces restenosis after balloon angioplasty in porcine coronary arteries.

BACKGROUND: Arterial injury after percutaneous transluminal coronary angioplasty (PTCA) triggers acute thrombus formation and thrombin generation. Hirudin, a potent and direct thrombin inhibitor, prevents thrombus formation after arterial injury. Two large clinical trials showed marked reduction in acute clinical events but no long-term benefits in reducing restenosis during short-term administration of thrombin inhibitors. Our hypothesis is that adequate, maintained thrombin inhibition, by inhibiting all the thrombin-dependent mechanisms, will reduce neointima formation after PTCA. METHODS AND RESULTS: Thirty-six pigs received three different regimens of hirudin: bolus (1 mg/kg), short-term (bolus + 0.7 mg/kg per day for 2 days), and long-term (bolus + 0.7 mg/kg per day for 14 days). The results on neointima formation at 4 weeks after coronary angioplasty were compared with the control group (100 IU heparin/kg bolus). Hirudin was continuously administered for 2 weeks through an infusion pump. In vivo thrombin generation was persistently increased up to 2 weeks after angioplasty. Inhibition of thrombin activity for 14 days reduced luminal narrowing by 40% (58+/-3% versus 35+/-3%; P<.001). No differences were observed among the bolus and short-term hirudin groups and the control group. CONCLUSIONS: Our results indicate that there is a continued, marked thrombin generation that lasts for at least 2 weeks after PTCA. Administration of r-hirudin for 2 weeks significantly reduces neointima formation after PTCA. This observation, if extrapolated to humans, could explain the lack of effect on restenosis observed in the clinical trials with antithrombin agents despite the clear benefits on reducing acute thrombotic complications after PTCA. Therefore an adequate and prolonged administration of thrombin inhibitors is needed to "passivate" the thrombogenic substrate (disrupted arterial wall) and achieve full benefit of this therapeutic approach.

Angioplasty, Balloon, Coronary↗
PubMed1998

Pathophysiologic bases for adjunctive therapies in the treatment and secondary prevention of acute myocardial infarction.

Postmyocardial infarction (MI) survival has been steadily improving. This improvement has been due, in part, to the actions of the adjunctive medical therapies for the treatment of MI. Aspirin, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, and lipid-lowering agents have been shown to improve survival in the treatment and secondary prevention of MI. Nitrates have beneficial effects as well. These medications complement the reperfusion strategies through different mechanisms. Other adjunctive medical therapies, namely magnesium, antiarrhythmic agents, and calcium-channel blockers, have not been shown to improve mortality with routine post-MI use despite their theoretical benefits.

Adrenergic beta-Antagonists↗
PubMed1998

Acute coronary syndromes in the United States and United Kingdom: a comparison of approaches. The Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

BACKGROUND: Patients with coronary artery disease are managed differently in different countries. HYPOTHESIS: These variations in patient management may affect clinical outcome, a possibility that should be taken into consideration in multicenter studies. METHODS: In a binational, 3 months study of antithrombotic treatment of patients with unstable angina and non-Q-wave infarction (ATACS), we compared the experience in the four enrollment centers in the United States (US) with the three centers in the United Kingdom (UK). The 59 US patients and the 299 UK patients were similar with regard to age, rates of prior revascularization, prior positive exercise tests, medication use, and aspirin use. RESULTS: US patients were more commonly women (45 vs. 28%), diabetic (30 vs. 4%), or hypertensive (52 vs. 31%), and had a prior coronary angiogram (30 vs. 18%). After enrollment, coronary angiography was performed more frequently in the US than in the UK (61 vs. 22%). Although the distribution of coronary disease was similar, revascularization without recurrent angina (19 vs. 4%, p < 0.001), or following recurrent angina (8 vs. 3%), was significantly more frequent in the US. Combined primary end points (recurrent angina, myocardial infarction, or death) did not differ between US (29%) and UK (25%) patients. CONCLUSION: Therefore, international studies of acute coronary disease need to account for different treatments in different countries. These differences, in the small ATACS study, did not have a major impact on the composite primary outcome variables.

Adult↗
PubMed1998

Histopathology of coronary lesions with early loss of minimal luminal diameter after successful percutaneous transluminal coronary angioplasty: is thrombus a significant contributor?

BACKGROUND: Early loss of minimal luminal diameter of >0.3 mm after successful percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher incidence of restenosis. The underlying mechanism of this early loss is unknown and thrombus may be a contributing factor. METHODS: We performed a prospective study using quantitative computerized planimetry on coronary tissue specimens obtained by directional coronary atherectomy of 24 lesions in which early loss occurred 22+/-9 minutes after successful PTCA. RESULTS: Thrombus was present in 9 (37%) of 24 coronary specimens. Segmental areas (mm2) and percentage of total area were distributed as follows: sclerotic tissue, 4.07+/-0.7 mm2 (63%+/-6%); fibrocellular tissue, 0.97+/-0.27 mm2 (16%+/-4%); hypercellular tissue, 0.99+/-0.29 mm2 (12%+/-3%); atheromatous gruel, 0.18+/-0.07 mm2 (3%+/-0.1%); and thrombus, 0.24+/-0.15 mm2 (6%+/-0.4%). There was no difference in the relative early loss index between lesions with or without thrombus (35%+/-7% vs 26%+/-2%, respectively; P= .87). Multiple stepwise regression analysis did not identify any histologic predictors of relative early loss index. CONCLUSION: Histopathologic analysis of coronary lesions with early loss after successful PTCA suggests that thrombus may not play a significant role in this angiographic phenomenon.

Adult↗
PubMed1998

Different response to balloon angioplasty of carotid and coronary arteries: effects on acute platelet deposition and intimal thickening.

PTCA is a well-established intervention to reduce the severity of atherosclerotic coronary stenosis. Its primary success rate is seriously handicapped by the high incidence of late restenosis. Given the clinical and social importance of this proliferative process, new strategies are needed to prevent or reduce restenosis. Several animal models as well as different arteries have been used to study neointimal proliferation after arterial injury. A number of agents have shown to reduce neointimal proliferation after arterial injury in the carotids and iliac arteries of rodent models. Unfortunately, these results have not been replicated in humans. We have compared the acute and late response to vascular injury of the carotid and coronary arteries in the pig. Arterial injury was induced by performing balloon angioplasty of the carotid (elastic) and coronary (muscular) arteries in swine. Acute platelet-thrombus formation was evaluated by quantitation of Indium-labeled platelets deposited on the injured segments 1 h after procedure. Measurement of intimal area was performed by morphometry of the most stenotic cross-section at 28 days after balloon angioplasty. Platelet deposition after mild and severe injury in carotids (4 +/- 1 and 56 +/- 13 x 10(6) platelets/cm2, respectively) and coronaries (15 +/- 5 and 141 +/- 20 x 10(6) platelets/cm2, respectively) are significantly greater in deep, than in mild injury (P < 0.005), and significantly greater in coronary than in carotid arteries after deep injury (P < 0.05). Likewise, late neointima formation was significantly greater (P < 0.05) after mild and severe injury in coronary (17 +/- 0.5 and 56 +/- 2%, respectively) than in carotid arteries (5 +/- 0.5 and 12 +/- 1%, respectively). Acute platelet-thrombus formation and late neointimal thickening are modulated by the degree of injury induced during the interventions; and after disruption of the internal elastic lamina, coronary arteries always had significantly more acute thrombus and neointimal thickening. This study emphasizes the importance of the animal species, the type of injury and the artery chosen for studies on restenosis post interventions.

Acute Disease↗
PubMed1998

Behavior of atherosclerotic plaque components after in vitro angioplasty and atherectomy studied by high field MR imaging.

AIMS: Using magnetic resonance imaging (MRI), we developed in vitro models to image the response of fatty, fibrous, and calcified plaques to in vitro models of angioplasty and atherectomy, and tested the resistance of collagenous cap and lipid core to radial compression. METHODS AND RESULTS: We studied the effects of balloon compression on 10 fibrous plaques with a complete collagenous cap (group A), 6 fatty plaques without cap (group B), and 5 calcified plaques (group C). Atherectomy was performed on nine other fibrous lesions (group D). In group A, fibrous cap, lipid core, and plaque did not change after radial compression despite a decrease in luminal obstruction due to medial stretching. In group B, a reduction of plaque (-30%) and lipid core (-35%) were observed. Compression dissected calcified plaques at the shoulder level. In group D, atherectomy reduced collagenous cap by 54%, and plaque by 35%. CONCLUSIONS: In these models, MRI shows 1) the high resistance of collagenous caps to radial compression, 2) a stretching effect of compression on disease-free walls, enlarging lumen in case of fibrous plaque, but a reduction and redistribution of lipid cores in case of fatty plaques, 3) the rupture of calcified arteries at the plaque shoulder, and 4) the reduction of fibrous components by atherectomy but not by angioplasty. By characterizing plaque composition, MRI may allow a predictable response of atherosclerotic arteries to interventional procedures.

Angioplasty, Balloon↗
PubMed1998

Randomized comparison of direct thrombin inhibition versus heparin in conjunction with fibrinolytic therapy for acute myocardial infarction: results from the GUSTO-IIb Trial. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO-IIb) Investigators.

OBJECTIVES: We sought to show that hirudin might interact differently with streptokinase (SK) and tissue-type plasminogen activator (t-PA), which could reduce the incidence of death or reinfarction at 30 days. BACKGROUND: In a large-scale trial of patients with acute coronary syndromes, hirudin provided modest benefit compared with heparin. However, the interaction with thrombolytic agents was not specifically assessed. METHODS: Patients with symptoms of acute myocardial infarction and electrocardiographic ST segment elevation were treated with thrombolytic therapy and randomly assigned to receive hirudin or heparin. RESULTS: A total of 2,274 patients received t-PA, and 1,015 received SK. Baseline characteristics were balanced by antithrombin assignment. Among SK-treated patients, death or reinfarction at 30 days occurred more often in those treated with adjunctive heparin (14.4%) rather than hirudin (8.6%, odds ratio [OR] 1.78, 95% confidence interval [CI] 1.20 to 2.66, p = 0.004). Among t-PA-treated patients, the rates were 10.9% with heparin and 10.3% with hirudin (OR 1.06, 95% CI 0.81 to 1.38, p = 0.68; for treatment heterogeneity: chi-square 4.20, degrees of freedom [df] 1, p = 0.04). After adjustment for baseline differences between thrombolytic groups, the rates were 9.1% for SK with hirudin, 10.3% for t-PA with hirudin, 10.5% for t-PA with heparin and 14.9% for SK with heparin (for treatment heterogeneity: chi-square 4.5, df 1, p = 0.03), suggesting that the beneficial treatment effect of hirudin was limited to the SK-treated patients. CONCLUSIONS: Hirudin interacts favorably with SK but not t-PA, highlighting the importance of thrombin activity after SK therapy and the potential for simulating the effects of a more potent fibrinolytic agent through direct antithrombin therapy.

Aged↗
PubMed1998

Mechanisms of arterial thrombosis: foundation for therapy.

Intravascular thrombus often occurs when the rupture or fissure of an atherosclerotic plaque exposes procoagulant elements lying below the plaque surface. This process of plaque rupture is the result both of passive mechanical forces and an active cell-mediated mechanism. Recently a number of investigators have developed imaging technologies based on magnetic resonance to characterize atherosclerotic lesions or the use of radioactively labeled platelets to dynamically visualize clot formation and lysis in vivo. These methods may permit early detection of developing thrombus, improve selection of treatment, and allow direct monitoring of the progression of antithrombotic therapy.

Anticoagulants↗
PubMed1998

Antithrombotic therapy and venous graft disease.

Venous graft disease is a thromboproliferative process and places a serious limitation on the symptom-free survival of patients after coronary artery bypass grafting. The efficacy of antithrombotics, especially during the first year after surgery, is suggested by an understanding of the four described phases of disease development. Studies examining the usefulness of hemostatic factors, such as lipoprotein (a) and fibrinogen, in identifying patients at added risk for graft occlusion are reviewed. Aspirin begun within the first day after surgery remains the mainstay of current preventive therapy, but the potential for other antiplatelet agents alone or in combination is explored. In a two-by-two trial, the efficacy of low-dose oral anticoagulation with warfarin (Coumadin) was equivocal. Aggressive cholesterol reduction decreased progression and need for revascularization by 30%. Future examinations are needed to define the optimal intensity and timing of therapy and to explore the role of newer, more potent antithrombotic agents.

Anticoagulants↗