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V Fuster

Publications and source records attributed to V Fuster.

At least 181 records · Page 10Linked to original sources
PubMed1997

Present concepts of coronary atherosclerosis-thrombosis, therapeutic implications and perspectives.

Our knowledge of the pathophysiology of coronary atherosclerosis has remarkably changed in the last few years. The types of atherosclerotic lesions, the mechanisms of progression of coronary atherosclerosis with plaque instability and disruption, and the subsequent thrombotic phenomenon leading to acute coronary syndromes are now better understood. Therapeutic strategies leading to atherosclerotic lesion stabilization and even regression, as well as new antithrombotic strategies to alleviate or prevent the thrombotic complications are being pursued. This review focuses on the coronary unstable atherosclerotic plaque and complicating thrombosis.

Acute Disease↗
PubMed1996

Macrophages, smooth muscle cells, and tissue factor in unstable angina. Implications for cell-mediated thrombogenicity in acute coronary syndromes.

BACKGROUND: Macrophage expression of tissue factor may be responsible for coronary thrombogenicity in patients with plaque rupture. In patients without plaque rupture, smooth muscle cells may be the thrombogenic substrate. This study was designed to identify the cellular correlations of tissue factor in patients with unstable angina. METHODS AND RESULTS: Tissue from 50 coronary specimens (1560 pieces) from patients with unstable angina and 15 specimens from patients with stable angina were analyzed. Total and segmental areas (in square millimeters) were identified with trichrome staining. Macrophages, smooth muscle cells, and tissue factor were identified by immunostaining. Tissue factor content was larger in unstable angina (42 +/- 3%) than in stable angina (18 +/- 4%) (P = .0001). Macrophage content was also larger in unstable angina (16 +/- 2%) than in stable angina (5 +/- 2%) (P = .002). The percentage of tissue factor located in cellular areas was larger in coronary samples from patients with unstable angina (67 +/- 8%) than in samples from patients with stable angina (40 +/- 5%) (P = .00007). Multiple linear stepwise regression analysis showed that coronary tissue factor content correlated significantly (r = .83, P < .0001) with macrophage and smooth muscle cell areas only in tissue from patients with unstable angina, with a strong relationship between tissue factor content and macrophages in the atheromatous gruel (r = .98, P < .0001). CONCLUSIONS: Tissue factor content is increased in unstable angina and correlates with areas of macrophages and smooth muscle cells, suggesting a cell-mediated thrombogenicity in patients with acute coronary syndromes.

Adult↗
PubMed1996

Macrophage infiltration predicts restenosis after coronary intervention in patients with unstable angina.

BACKGROUND: Restenosis remains the major limitation of percutaneous coronary revascularization. Macrophages release cytokines, metalloproteinases, and growth factors that may induce smooth muscle cell migration and proliferation. We tested the hypothesis that primary lesions that develop restenosis after coronary atherectomy have more macrophages and smooth muscle cells than primary lesions that do not develop restenosis. METHODS AND RESULTS: Fifty patients with unstable angina were identified. Total and segmental areas were quantified on trichrome-stained sections of coronary atherectomy tissue. Macrophages and smooth muscle cells were identified by immunohistochemical staining. Restenosis, defined as > 50% stenosis diameter by quantitative cineangiography, was present in 30 patients. The other 20 patients (< 50% stenosis) constitute the "no restenosis" group. The percentages of smooth muscle cell areas were similar in specimens from patients with and without restenosis (57 +/- 5% and 52 +/- 6%) (P = NS). However, macrophage-rich areas were larger in plaque tissue from patients with restenosis (20.4 +/- 2%) than in tissue from patients without restenosis (9.3 +/- 2%) (P = .0007). Multiple stepwise logistic regression analysis identified macrophages as the only independent predictor for restenosis (P = .006). CONCLUSIONS: Macrophages are increased in coronary atherectomy tissue from primary lesions that develop restenosis, suggesting a possible role for macrophages in the restenotic process after percutaneous coronary intervention.

Adult↗
PubMed1996

Distinct effects of recombinant desulfatohirudin (Revasc) and heparin on plasma levels of fibrinopeptide A and prothrombin fragment F1.2 in unstable angina. A multicenter trial.

BACKGROUND: Thrombin plays an important role in the pathogenesis of acute coronary thrombosis. We studied the effects of a direct thrombin inhibitor, recombinant desulfatohirudin, and heparin on plasma levels (at 0, 4, 12, and 24 hours) of fibrinopeptide A (FPA), which reflects thrombin action, and prothrombin fragment F1.2, which reflects thrombin generation, in patients with unstable angina. METHODS AND RESULTS: Patients were randomized to one of two doses of heparin (n = 50) (target activated partial thromboplastin time, 65 to 90 seconds or 90 to 110 seconds) or one of four doses of r-hirudin (n = 113) (0.05, 0.10, 0.20, or 0.30 mg.kg-1.h-1 by infusion). r-Hirudin induced a dose-dependent decline in plasma FPA. At 24 hours, FPA levels with 0.1- to 0.3-mg.kg-1.h-1 r-hirudin regimens were significantly lower than with 0.05 mg.kg-1.h-1 r-hirudin; levels with 0.1- to 0.2-mg.kg-1.h-1 r-hirudin regimens were lower than with both heparin regimens. Plasma F1.2 did not decline significantly during therapy with heparin or hirudin except at 0.3 mg.kg-1.h-1 hirudin. At 24 hours, they were higher with the 0.05-mg.kg-1.h-1 r-hirudin regimen than with other regimens. For comparable levels of thrombin generation (F1.2 levels), FPA levels were higher in heparin patients than in hirudin patients. For the same FPA values, the corresponding F1.2 values were higher in the hirudin group. CONCLUSIONS: Our findings provide evidence for distinct in vivo effects of the two agents and suggest that r-hirudin is a relatively more potent inhibitor of thrombin action but a less effective inhibitor of thrombin generation than heparin. The lower FPA levels in hirudin patients may reflect its ability to inactivate clot-bound thrombin. The relative clinical efficacies of the two agents need to be defined by clinical trials in progress.

Angina, Unstable↗
PubMed1996

Magnetic resonance images lipid, fibrous, calcified, hemorrhagic, and thrombotic components of human atherosclerosis in vivo.

BACKGROUND: Although MRI can discriminate the lipid core from the collagenous cap of atherosclerotic lesions in vitro with T2 contrast, it has not yet produced detailed in vivo images of these human plaque components. METHODS AND RESULTS: We imaged seven lesions from six patients who required surgical carotid endarterectomy and calculated T2 in vivo before surgery in various plaque regions. Using the same acquisition parameters, we repeated these measurements in vitro on the resected fragment and compared MR images with histology. T2 values calculated in vivo correlate with in vitro measurements for each plaque component; the in vitro discrimination we demonstrated previously with T2 contrast can therefore be performed similarly in vivo. CONCLUSIONS: MRI is the first noninvasive imaging technique that allows the discrimination of lipid cores, fibrous caps, calcifications, normal media, and adventitia in human atheromatous plaques in vivo. This technique also characterizes intraplaque hemorrhage and acute thrombosis. This result may support further investigations that include MRI of plaque progression, stabilization, and rupture in human atherosclerosis.

Aged↗
PubMed1996

Does antithrombotic therapy influence residual thrombus after thrombolysis of platelet-rich thrombus? Effects of recombinant hirudin, heparin, or aspirin.

BACKGROUND: Thrombolysis to normal flow in patients with acute myocardial infarction preserves left ventricular function and decreases mortality. Failure of early reperfusion, reocclusion, or residual thrombus may be due to concurrent activation of the platelet-coagulation system. Thus, we hypothesized that the best concomitant antithrombotic therapy (recombinant [r]-hirudin, heparin, or aspirin) will maximally accelerate thrombolysis by r-tissue-type plasminogen activator (rTPA) and reduce residual thrombus. METHODS AND RESULTS: Occlusive thrombi were formed in the carotid arteries of 29 pigs (by balloon dilatation followed by endarterectomy at the site of injury-induced vasospasm) and matured for 30 minutes before rTPA was started, with or without antithrombotic therapy. Thrombolysis was assessed with the use of angiography and measurement of residual thrombus. Pigs were allocated to one of five treatments: placebo, rTPA, rTPA plus r-hirudin, rTPA plus heparin, or rTPA plus intravenous aspirin. No placebo-treated pig reperfused. Two of six animals treated with rTPA alone reperfused compared with seven of seven animals treated with rTPA plus r-hirudin (reperfusion time, 33 +/- 10 minutes), six of seven animals treated with rTPA plus heparin (reperfusion time, 110 +/- 31 minutes), and two of six animals with rTPA plus aspirin. The activated partial thromboplastin time was prolonged in only the rTPA plus r-hirudin group (25 +/- 0.1 times baseline) and the rTPA plus heparin group (5.3 +/- 0.2 times baseline). Residual 111In-platelet and 125I-fibrin(ogen) depositions were lower in the heparin-treated group and lowest in the r-hirudin-treated group (heparin versus hirudin, respectively; incidence of residual macroscopic thrombus was six of six animals versus two of seven [P = .01]; 125I-fibrin(ogen), 170 +/- 76 versus 48 +/- 6 x 10(6) molecules/cm2 [P = .02]; 111In-platelets, 47 +/- 15 versus 13 +/- 2 x 10(6)/cm2, P = .10). No pigs developed spontaneous bleeding. CONCLUSIONS: Thrombin inhibition with heparin or r-hirudin significantly accelerated thrombolysis of occlusive platelet-rich thrombosis, but only the best antithrombotic therapy (r-hirudin) eliminated or nearly eliminated residual thrombus.

Animals↗
PubMed1996

Management of restenosis after coronary intervention.

Coronary restenosis has proven to be the "Achilles heel" of percutaneous coronary interventions, frequently leading to repeated procedures. The pathogenesis of restenosis can be divided into four phases: early elasic recoil (hours to days), mural thrombus formation (hours to days), neointimal proliferation and extracellular matrix formation (weeks), and chronic geometric arterial changes (months). Restenosis is device nonspecific except for intravascular stents, which can eliminate elastic recoil and prevent geometric vessel changes, leading to decreased restenosis. Of all antithrombotics tried so far, only an inhibitor of the platelet IIb/IIIa integrin, which may lead to early vessel wall passivation, has shown reduction of clinical restenosis. Trapidil (antiproliferative agent) and angiopeptin (somatostatin analog) have also resulted in improved restenosis rates. The field of local drug delivery is currently under investigation in association with radiation or molecular therapy. The current specific target of these approaches is the neointimal proliferation, especially because this is the most dominant mechanism of restenosis after stent placement. Evaluation of these novel methods is complex and interrelates the delivery system with the therapeutic agent administered. However, they provide the means for very specific and timely interruption of the pathogenic process that may lead to better understanding and, ultimately, elimination of restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1996

Transient thrombotic state after abrupt discontinuation of heparin in percutaneous coronary angioplasty.

Clinical and biochemical evidence of a rebound phenomenon after discontinuing thrombin inhibitors has been reported in patients with unstable angina. To investigate if a similar phenomenon occurs in patients undergoing coronary angioplasty, 14 patients were prospectively studied during and after discontinuation of heparin infusion. A transient thrombotic state identified by a significant increase in a polypeptide fragment and fibrinopeptide A was observed 3 hours after abruptly discontinuing heparin infusion. This observation may be clinically important in managing patients after coronary angioplasty.

Adult↗
PubMed1996

Plaque rupture, thrombosis, and therapeutic implications.

The basic mechanisms of atherosclerotic progression leading to the acute coronary syndromes (ACS) have been elucidated during the last few years. In this brief presentation, we outline 1) Definition of Atherosclerotic Lesions: eight morphologically different lesions are defined (Type I to VI) in various phases of disease. 2) Vulnerable Lipid-Rich Plaques and the ACS: The type IV and Va lesions tend to be relatively small in size, but soft or vulnerable to a "passive" phenomenon of plaque disruption; in addition, an "active" macrophage-dependent enzymatic (genesis of metalloproteinase) phenomenon of plaque disruption is evolving. 3) Thrombosis: we have shown that monocytes/macrophages in lipid-rich plaques may play a detrimental role after plaque disruption, promoting thrombin generation and thrombosis through the tissue factor pathway that can be prevented by tissue factor pathway inhibition; such pathway of thrombosis appears to be critical in the development of the ACS. 4) Effect of Lipid-Modifying Strategies and other Risk Factors on the Vulnerable Lipid-Rich Plaques: when high LDL-cholesterol is reduced therapeutically, efflux from the plaques of the liquid or sterified cholesterol, and also its hydrolysis into cholesterol crystals depositing in the vessel wall, predominate over the influx of LDL-cholesterol; consequently, there is a decrease in the softness of the plaque and so, presumably in the "passive" phenomenon of plaque disruption; modification of other risk factors presumably also favorably affect LDL-cholesterol influx and efflux. 5) Antithrombotic Strategies: the evolving antithrombotic approaches under investigation are briefly outlined.

Anticoagulants↗
PubMed1996

Pathophysiology of coronary artery disease.

Atherogenic risk factors provoke chronic injury to the endothelium in certain parts of the arterial tree leading to dysfunctional endothelium. Lipid accumulation, macrophage formation, and smooth muscle cell proliferation are key events in the initial slow progression of atherosclerotic lesions (phase 1). If extracellular lipid accumulation predominates, atherosclerotic process progresses into a more clinically relevant, advance lipid-rich lesion (phase 2)--the pathogenic basis for plaque rupture and thrombus formation. Small plaque fissures and mural thrombus formation may be responsible for the rapid, clinically silent progression of lesions (phase 3). Plaque rupture with large thrombus formation may be responsible for acute coronary syndromes (phase 4). Alternatively, if smooth muscle cell proliferation and collagen matrix synthesis predominate, atherosclerotic lesions may progress into advanced, stable sclerotic lesions (phase 5).

Aged↗
PubMed1996

Inbreeding patterns in the Gredos Mountain Range (Spain).

The relationships among the frequency of consanguineous marriages, inbreeding coefficient, period, village size, and altitude are analyzed for three rural valleys belonging to the Sierra de Gredos (central Spain). These valleys occupy an area of about 30 x 80 km2, and the average total number of inhabitants for the period 1877-1970 was 58,621. Information about a sample of 23,744 weddings celebrated between 1875 and 1974 was obtained from 48 village parish registers. The mean inbreeding level up to second cousins for the whole area was 0.0012. A high percentage of inbreeding variation (83%) can be explained by each village's census size, resulting in a different interslope consanguinity pattern consisting of higher inbreeding levels in most northern localities in the Gredos mountains. This north-south geographic trend is consistent with results on blood polymorphisms from the same area (Mesa et al. 1994).

Altitude↗