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V Fuster

Publications and source records attributed to V Fuster.

At least 181 records · Page 10Linked to original sources
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↗
PubMed1995

Elucidation of the role of plaque instability and rupture in acute coronary events.

The basic mechanisms of atherosclerotic progression have been well elucidated during the last few years. In this brief presentation on the acute coronary syndromes, the fate of plaque rupture and our understanding of "passive" versus "active" rupture are defined. In addition to the phenomenon of plaque rupture, the thrombogenicity of atherosclerotic plaques in the genesis of coronary syndromes is defined. The combination of plaque disruption and high thrombogenic risk profile--including local and systemic factors--is vital to understanding the genesis of the acute coronary syndromes.

Acute Disease↗
PubMed1995

Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture.

BACKGROUND: Rupture of the fibrous cap of the atherosclerotic plaque is a key event that predisposes to coronary thrombosis, leading to acute coronary syndromes. Recent studies have shown that the fibrous caps of vulnerable and ruptured atherosclerotic plaques have reduced collagen and glycosaminoglycan content in association with an increased macrophage density and a reduced smooth muscle cell density. Since collagen breakdown in the fibrous caps may contribute to a thinning and weakening of the cap, increasing its vulnerability to rupture, we tested the hypothesis that monocyte-derived macrophages, by producing matrix-degrading metalloproteinases (MMPs), could induce collagen breakdown in human atherosclerotic fibrous caps. METHODS AND RESULTS: Monocytes were isolated from human blood by Ficoll-Paque density gradient and allowed to grow in cell culture until phenotypic and staining characteristics indicated transformation into macrophages (4 to 7 days). Fibrous caps were dissected from human aortic or carotid plaques and incubated for 48 hours with macrophages in serum-free medium without (n = 21) and with (n = 10) an MMP inhibitor or with cell- and serum-free medium only (n = 9). Hydroxyproline released in the culture medium was measured by a spectrophotometric method and used as evidence of collagen breakdown in the fibrous caps. Immunocytochemistry with specific monoclonal antibodies was used to identify expression of MMP-1 (interstitial collagenase) and MMP-2 (72-kD gelatinase) in cell culture, and zymography was used to detect MMP activity in the culture supernatant. The amount of hydroxyproline released was significantly greater when fibrous caps were incubated with macrophages than when incubated with cell-free medium (0.4 +/- 0.16 micrograms.mL-1.mg-1 versus 0.02 +/- 0.03 micrograms.mL-1.mg-1 of tissue; P < .04 by Mann-Whitney test). There was no hydroxyproline release when fibrous caps were incubated with macrophages in the presence of an MMP inhibitor. Immunocytochemistry demonstrated MMP-1 and MMP-2 expression by macrophages between days 4 and 7, and zymography confirmed the presence of MMP-2 activity in the supernatant. CONCLUSIONS: In this study, human monocyte-derived macrophages were shown to induce collagen breakdown in fibrous caps of human atherosclerotic plaques associated with cellular expression and zymographic evidence of MMP activity; no evidence of collagen breakdown was found in the presence of an MMP inhibitor. These findings support the hypothesis that increased macrophage density and/or activation in the atherosclerotic plaque may induce collagen breakdown in the fibrous cap by secreting MMPs and possibly other proteases, thus contributing to vulnerability to plaque rupture.

Arteriosclerosis↗
PubMed1995

A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.

This report is the continuation of two earlier reports that defined human arterial intima and precursors of advanced atherosclerotic lesions in humans. This report describes the characteristic components and pathogenic mechanisms of the various advanced atherosclerotic lesions. These, with the earlier definitions of precursor lesions, led to the histological classification of human atherosclerotic lesions found in the second part of this report. The Committee on Vascular Lesions also attempted to correlate the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes. In the histological classification, lesions are designated by Roman numerals, which indicate the usual sequence of lesions progression. The initial (type I) lesion contains enough atherogenic lipoprotein to elicit an increase in macrophages and formation of scattered macrophage foam cells. As in subsequent lesion types, the changes are more marked in locations of arteries with adaptive intimal thickening. (Adaptive thickenings, which are present at constant locations in everyone from birth, do not obstruct the lumen and represent adaptations to local mechanical forces). Type II lesions consist primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells and include lesions grossly designated as fatty streaks. Type III is the intermediate stage between type II and type IV (atheroma, a lesion that is potentially symptom-producing). In addition to the lipid-laden cells of type II, type III lesions contain scattered collections of extracellular lipid droplets and particles that disrupt the coherence of some intimal smooth muscle cells. This extracellular lipid is the immediate precursor of the larger, confluent, and more disruptive core of extracellular lipid that characterizes type IV lesions. Beginning around the fourth decade of life, lesions that usually have a lipid core may also contain thick layers of fibrous connective tissue (type V lesion) and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are largely calcified (type Vb), and some consist mainly of fibrous connective tissue and little or no accumulated lipid or calcium (type Vc).

Aneurysm↗
PubMed1995

Acute Myocardial Infarction and the Role of Aspirin, Heparin, and Warfarin.

Acute myocardial infarction is initiated by plaque disruption of a fatty plaque with a thin fibrous cap which has been infiltrated by macrophages. The macrophages are attracted and stimulated by oxidized lipids to secrete metalloproteinases which dissolve collagen and arterial wall matrix and to synthesize tissue factor which accumulates in the fatty gruel, and initiates the thrombotic process when exposed to flowing blood after plaque disruption. This initiates thrombin generation which is greatly amplified by the coagulation cascade.Minute amounts of thrombin initiate platelet aggregation, deposition and secretion with growth of platelet-rich thrombus and an accompanying network of fibrin which is at the base of platelet deposition, and increased over regions of deep injury where there appears to be enhanced thrombin generation. Thrombin is necessary for upregulation of platelet membrane receptors, growth of thrombus, maintenance of platelet cohesion, conversion of fibrinogen to fibrin, cross-linking of fibrin and, in part, for activation of the fibrinolytic system.Thrombosis is directly related to local rheology (shear force, turbulence), thrombogenicity of the exposed arterial wall substrates, and modified by systemic factors. Acute vasoconstriction is directly related to platelet deposition, enhanced by endothelial dysfunction or absence, and increased by hypercholesterolemia which induces production of the potent vasoconstrictor endothelin.Direct thrombin inhibition with a high affinity inhibitor, such as hirudin, totally blocks growth of thrombus, inhibits fibrin formation at lower doses and platelet deposition at somewhat higher doses, and enhances dissolution of residual thrombus. Dissolution of residual thrombus reduces luminal obstruction, and may reduce the need for revascularization procedures since plaque disruption most often occurs in arteries with minor obstruction (<50% stenosis).Current recommendations include intravenous heparin 5000 U bolus + 1,000 U/hr to maintain the aPTT at 60-85 sec, and aspirin (160-325 mg loading followed by 80 mg/day). Maximal inhibition of thrombus at the culprit lesion includes maintenance of heparin infusion plus daily aspirin and conversion of heparin to warfarin to maintain the INR at 2.0-3.0 for 3-6 months along with aspirin 80 mg/day as suggested by the ATACS trial. The value of fixed-dose warfarin plus low-dose aspirin in the acute and chronic phase after myocardial infarction is currently being evaluated in the Coumadin Aspirin Reinfarction Study.

Journal Article↗
PubMed1995

Coumadin Aspirin Reinfarction Study: Rationale and Design of the CARS Study.

Acute myocardial infarction remains the leading cause of death in the United States. Following increased recognition of the role of thrombosis in the pathogenesis of myocardial infarction, both antiplatelet and anticoagulant therapy have been proven effective in preventing recurrent infarction. However, the optimal antithrombotic regimen remains undetermined. In particular, the role of combination antithrombotic therapy has not been studied. The Coumadin Aspirin Reinfarction Study (CARS) will compare the safety and efficacy of fixed-dose combination Coumadin plus aspirin versus aspirin alone among 8000 survivors of acute myocardial infarction. Patients will be followed for up to 4 years. CARS will provide important information regarding the optimal antithrombotic regimen for myocardial infarct survivors.

Journal Article↗
PubMed1995

Early identification of patients with native valve infectious endocarditis at risk for major complications by initial clinical presentation and baseline echocardiography.

Early identification of a high risk patient subgroup with infective endocarditis which develops a major complication (emboli, congestive heart failure, surgery for valve replacement, or death) during hospitalization would reduce morbidity, mortality and cost. Thus, for 74 patients with native valve infective endocarditis with documented vegetation by transthoracic two-dimensional echocardiogram, we reviewed 67 variables: history (15), physical examination (9), hematology/miscellaneous (7), chest X-ray (2), electrocardiogram (4), transthoracic two-dimensional echocardiograms (15) and hospital course (15). There were 48 men and 26 women, ages 45 +/- 19 years: 35 intravenous drug abusers and 39 non-users. There were 32 mitral, 21 tricuspid, 20 aortic, and 1 pulmonic valve vegetations; mean vegetation size was 1.4 +/- 0.9 cm2. Over the course of their hospitalization, 14 patients died (19%), 27 developed congestive heart failure (36%), 27 had systemic emboli (36%), and 22 required surgery (30%). The incidence of complications (death, heart failure or embolic events) did not differ between the drug abusers and non-users. Initial complaint of dyspnea on admission predicted the subsequent development of heart failure (P < 0.001), and a pre-admission embolus predicted a second in-hospital embolus (P < 0.001). Left atrial size, ventricular systolic or diastolic dimension did not effect prognosis. Importantly, a vegetation > 1.8 cm2 was 100% specific but only 30% sensitive for predicting the development of a complication. Vegetation mobility, shape, and number of cusps involved were not predictive. However, aortic valve vegetations had significantly more complications than those on the mitral valve (P < 0.03). By discriminant function analysis, 87% of major complications were predicted with the patient profile of having aortic valve vegetation, dyspnea on admission, prolonged preadmission fever, and no history of drug abuse; 75% of patients who developed heart failure were predicted by their having aortic valve vegetation, dyspnea, hypotension (systolic < 90 mm Hg), and no history of drug abuse; and 77% of patients requiring surgery were predicted by their having larger vegetation size, rales, and leftward shift of white blood cells. Thus, in native valve bacterial endocarditis with transthoracic echocardiographic documented vegetations, non-drug abusers with aortic vegetations, preadmission prolonged fevers, dyspnea, emboli and larger sized vegetations are at high risk for developing a major complication during their hospitalization.

Echocardiography↗
PubMed1995

High risk of thromboemboli early after bioprosthetic cardiac valve replacement.

OBJECTIVES: We studied the rate of thromboembolism in patients undergoing bioprosthetic replacement of the aortic or mitral valve, or both, at serial intervals after operation and the effects of anticoagulant or antiplatelet treatment and risk factors. BACKGROUND: Thromboembolism appears to occur early after operation, but the incidence, timing and risk factors for thromboembolism and the role, timing, adequacy, effectiveness, duration and risk of anticoagulation and antiplatelet agents are uncertain. METHODS: The rate of thromboembolism was studied at three time intervals after operation (1 to 10, 11 to 90 and > 90 days) in 816 patients who underwent bioprosthetic replacement of the aortic or mitral valve, or both, at the Mayo Clinic from January 1975 to December 1982. The effect of antithrombotic therapy (warfarin, aspirin or dipyridamole, alone or in combination) was evaluated. RESULTS: Median follow-up of surviving patients was 8.6 years. The rate of thromboembolism (%/year) decreased significantly (p < 0.01) at each time interval after operation (1 to 10, 11 to 90 and > 90 days) for mitral valve replacement (55%, 10% and 2.4%/year, respectively) and over the first time interval for aortic valve replacement (41%, 3.6% and 1.9%/year, respectively). During the first 10 days, 52% to 70% of prothrombin time ratios were low (< 1.5 x control). Patients with mitral valve replacement who received anticoagulation had a lower rate of thromboembolism for the entire follow-up period (2.5%/year with vs. 3.9%/year without anticoagulation, p = 0.05). Of 112 patients with a first thromboembolic episode, permanent disability occurred in 38% and death in 4%. Risk factors for emboli were lack of anticoagulation, mitral valve location, history of thromboembolism and increasing age. Only 10% of aortic, 44% of mitral and 17% of double valve recipients had anticoagulation at the time of an event. Patients with bleeding episodes (2.3%/year) were older and usually underwent anticoagulation. Blood transfusions were required in 60 of 111 patients (1.2%/year), and 13 patients (0.3%/year) died. CONCLUSIONS: Thromboembolic risk was especially high for aortic and mitral valve replacement for 90 days after operation, and overall was increased with lack of anticoagulation, mitral valve location, previous thromboembolism and increasing age. Anticoagulation reduced thromboemboli and appears to be indicated in all patients as early as possible for 3 months and thereafter in those with risk factors, but needs prospective testing.

Adult↗
PubMed1995

Birth intervals regarding infant mortality and extramarital reproduction in a Spanish rural community.

Record linking provided information on the complete reproductive schedules of a sample of 1102 couples with at least two children born alive from a rural Spanish community characterised by very high extramarital reproduction. Birth spacing was analysed considering final family size as well as the legitimate-illegitimate status and sex of the newborn, and survival of the preceding sibling.

Birth Intervals↗