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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Haemostatic and rheological factors may predict cardiovascular disease. We studied patients with intermittent claudication to see if the progression of peripheral arterial disease and the risks of coronary events could be predicted by baseline packed cell volume, plasma fibrinogen, blood and plasma viscosites, von Willebrand factor antigen, cross-linked fibrin degradation products (XLFDP), urinary fibrinopeptide A, and plasma leucocyte elastase. In 617 patients with claudication followed up for one year, baseline XLFDP was related most strongly to coronary events, relative risk 4.4 (95% CI 1.3-19.0) between top and bottom quintiles. Plasma fibrinogen was the strongest independent predictor of death from coronary disease. XLFDP was the only factor, in addition to age and cigarette smoking, that was independently associated (p = 0.008) with deterioration in peripheral arterial disease. We conclude that, in patients with peripheral arterial disease, plasma concentration of XLFDP, a measure of ongoing fibrin formation and degradation, is a strong predictor of both disease progression and future coronary risk. These results accord with the hypothesis that fibrin formation contributes to progression of coronary and peripheral atherosclerosis.
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PMID:Cross-linked fibrin degradation products, progression of peripheral arterial disease, and risk of coronary heart disease. 810 Sep 15

Methods and results from the quality assurance program of the Atherosclerosis Risk in Communities (ARIC) Study regarding hemostasis variables are presented, following up previous reports in this journal on standardized procedures for blood collection and processing (7) and an organized plan for the performance of those procedures (8). Efforts were made to control for and assess all sources of variability, from venipuncture to laboratory analysis, including also local field center processing and sample shipping. The quality control program included (a) a standardized protocol for blood collection and processing; (b) training, certification, and annual recertification of field center personnel for blood collection and processing; (c) monitoring of fasting times, phlebotomy times, processing times, and shipping problems; (d) hemostatic laboratory internal quality control; (e) a replicate blood sample program; (f) an intraindividual variability study; and (g) continual monitoring of quality control and study participants' data. This paper focused on items (c), (d), and (e). Measures of variation, generally standard deviations and coefficients of variation, are estimated for replicate blood sampling and internal quality control data, for activated partial thromboplastin time, fibrinogen, factor VII and VIII activity, von Willebrand factor, antithrombin-III, and protein C. The results demonstrate that it is possible to reliably measure these hemostatic variables in a large multicenter study.
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PMID:ARIC hemostasis study--III. Quality control. Atherosclerosis Risk in Communities. 811 84

von Willebrand factor (vWf), risk factors for atherosclerosis, body mass index (BMI) and waist-to-hip ratio (WHR) were measured in 108 non-diabetic patients attending lipid and vascular disease clinics and in 107 normal asymptomatic controls. High levels of vWf and increased BMI relative to controls were found in patients with hyperlipidaemia and vascular disease, but WHR was higher only in patients with vascular disease. Total serum cholesterol concentration (P < 0.001), systolic blood pressure (P < 0.001), smoking (P < 0.02) and BMI (P < 0.001), but not WHR, were associated with vWf. As raised levels of vWf are a probable indicator of endothelial damage in vascular disease, these data suggest that obesity has an adverse influence on the endothelium and may help explain its link with cardiovascular disease.
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PMID:von Willebrand factor, the endothelium and obesity. 811 78

Lipoprotein(a) [Lp(a)] plays an important role in atherosclerosis. The amino acid sequence of apolipoprotein(a) [apo(a)] reveals an arginyl-glycyl-aspartate (RGD) tripeptide that is the consensus sequence for binding of adhesive plasma proteins of the fibrinolytic system, such as fibrinogen and von Willebrand factor, to the platelet membrane glycoprotein IIb-IIIa (GPIIb-IIIa) complex. Therefore, we undertook the present study to further investigate the role of Lp(a) in hemostasis. Binding of 125I-Lp(a) to a single platelet membrane-associated protein (137 +/- 6 kD) comigrating with platelet GPIIb (140 kD) was found to be specific, saturable, and Ca2+ independent. Binding of 125I-Lp(a) to resting human blood platelets was saturable, insensitive to temperature, and independent of the apo(a) isoform (B, S1 through S3). Scatchard analysis revealed a Kd of 7.2 +/- 1.8 x 10(-9) mol/L, with 729 +/- 313 Lp(a) molecules bound per platelet. Monoclonal anti-GPIIb IgG diminished Lp(a) binding by approximately 80%, monoclonal anti-GPIIb-IIIa IgG by 60%, and anti-GPIIIa IgG by just 15%. 125I-Lp(a) binding was competitively inhibited to the same extent by either unlabeled Lp(a) or fibrinogen. Low- and high-density lipoproteins were much weaker competitors. A polyclonal antibody raised against the RGDGQSYRGT sequence of apo(a) was used to verify the presence of an RGD sequence in the different Lp(a) preparations investigated. However, two lines of evidence indicated that the RGD sequence is not the binding domain mediating Lp(a) binding to platelets. First, incubation of platelets with isolated RGD tripeptide did not influence Lp(a) binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of glycoprotein IIb as the lipoprotein(a)-binding protein on platelets. Lipoprotein(a) binding is independent of an arginyl-glycyl-aspartate tripeptide located in apolipoprotein(a). 812 37

The so-called classic risk factors of coronary heart disease (CHD) do not explain all its clinical and epidemiological features. Recent evidence suggests that certain infections, among them dental infections, are involved in the pathogenesis of CHD. Case-control studies have revealed an association between dental infections and acute myocardial infarction and chronic coronary heart disease. A large epidemiological survey revealed an association between missing teeth and CHD and a recent 14-year follow-up of 9760 individuals showed that periodontitis is associated with an increased risk of coronary heart disease. Preliminary results suggest that the severity of dental infections correlates with the extent of coronary atheromatosis. Individuals with severe dental infections also have higher level of von Willebrand factor antigen, leukocytes and fibrinogen. Streptococcus sanguis has been shown to aggregate human platelets in vitro. The mechanism behind the association between dental infections and CHD could be the effect of bacteria on the cells taking part in the pathogenesis of atherosclerosis and arterial thrombosis.
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PMID:Dental infections as a risk factor for acute myocardial infarction. 813 88

This hypothesis proposes that, in the absence of actively metastasising neoplasia, damage to the endothelium can be monitored by measuring circulating levels of von Willebrand factor. This specific product of the endothelial cell is important in thrombo-genesis as its functions include platelet aggregation and mediation of platelet adhesion to the subendothelium. High levels are found in all major risk factors of atherosclerosis, in frank atherosclerotic vascular disease and in most of the inflammatory vasculitides, and the highest levels are also associated with more severe disease and risk of mortality. It follows that high levels of von Willebrand factor may be a new risk factor for the development of thrombosis and atherosclerosis.
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PMID:Is raised von Willebrand factor a marker of endothelial cell damage? 814 53

von Willebrand factor (vWF), first described in a bleeding disorder, has numerous other roles, some of which can be viewed in terms of the pathogenesis of atherosclerosis and others in the formation of thrombus. As a marker of endothelial cell injury it provides a unique opportunity to observe the events involved in conditions where vasculitis may occur, e.g. inflammatory vascular disease and diabetes. Just as low levels predispose to disease, so excessively high levels may lead to adverse cardiovascular events such as myocardial infarction and femoral artery occlusion, which may both be precipitated by thrombus. It is possible that intervention (possibly with drugs, peptides or other agents) that reduces circulating vWF, perhaps by interfering with its activity in aggregating platelets and mediating their adhesion to the sub-endothelium, or reducing its release from the endothelium, may lead to a reduction in thrombotic disease.
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PMID:von Willebrand factor and the endothelium in vascular disease. 821 18

The relation of hemostatic factor levels to the occurrence of cardiovascular disease is incompletely established. The Atherosclerosis Risk in Communities Study measured fibrinogen, factor VII, factor VIII, von Willebrand factor, antithrombin III, protein C, activated partial thromboplastin time, and other cardiovascular risk factors in nearly 15,000 men and women aged 45 to 64. This analysis assessed the relations of these hemostatic factors with prevalent cardiovascular disease and asymptomatic carotid artery intimal-medial thickness measured by B-mode ultrasound. Compared with participants without cardiovascular disease, those with cardiovascular disease had higher levels of fibrinogen, factor VIII, and von Willebrand factor in both sexes. The other hemostatic factors were less consistently associated with prevalent cardiovascular disease. Only fibrinogen was associated with carotid intimal-medial thickness. Adjusted for age, race, and field center, the odds ratio for carotid wall thickness in the 90th percentile or greater, compared with < 50th percentile, for each SD higher fibrinogen concentration (65 mg/dL) was 1.42 (95% confidence interval, 1.25, 1.62) in men and 1.43 (1.25, 1.64) in women. This population-based study provides further evidence that fibrinogen and possibly factor VIII and von Willebrand factor are risk factors for cardiovascular disease.
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PMID:Association of hemostatic variables with prevalent cardiovascular disease and asymptomatic carotid artery atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. 824 Nov 4

Intimal thickening in human arteries is considered as a site of predilection for atherosclerosis. The placement of a flexible, physically nonconstrictive, silicone cuff around the rabbit carotid artery induced a neointima composed of smooth muscle cells (SMCs) within 14 days. To investigate possible alterations of the endothelial cells (ECs) during neointima formation, their morphology was examined with scanning electron microscopy (SEM), transmission electron microscopy (TEM), and confocal microscopy. In the early postoperative period (6 hours), both cuffed and sham-operated arteries demonstrated small foci (5 to 200 microns) of denudation, presumably as a consequence of the manipulation. Within 24 hours the luminal surface of the cuffed and sham-operated arteries was completely covered with endothelium, which remained continuous throughout the study. However, after 1 week the ECs of the cuffed arteries contained a pronounced rough endoplasmic reticulum. From 6 hours until 3 days, polymorphonuclear leukocytes infiltrated the cuffed but not the sham-operated arteries from the lumen. Subendothelial SMC accumulation in the cuffed arteries began after this time period. At day 14 a full-blown neointima composed of longitudinally oriented SMCs had formed in the cuffed arteries. The sham-operated arteries did not develop a neointima. During neointima formation immunoreactivity for von Willebrand factor (vWf) increased in the ECs, and vWf was deposited in the extracellular spaces of the neointima. At day 14 the area of vWf deposits correlated positively with the area of the neointima (r = .73, P < .001). In subsequent weeks, the intimal area did not increase, and vWf deposits vanished from the neointimal matrix. The endothelium of the sham-operated arteries showed no change in vWf immunoreactivity compared with untreated arteries throughout the study. The altered ultrastructural morphology of the ECs and the concurrent vWf deposition in cuffed but not in sham-operated arteries point to alterations in EC function during the development of the neointima. The vWf secretion could possibly lead to increased adhesiveness of the extracellular matrix for the ECs as well as modulate neointima formation.
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PMID:The endothelium during cuff-induced neointima formation in the rabbit carotid artery. 824 Nov 10

The aim of this study was to determine differences between cases of peripheral arterial disease and healthy controls in levels of haemostatic factors and lipid peroxides and the influence of cigarette smoking. The study groups were selected from the Edinburgh Artery Study which is a random sample survey of men and women aged 55-74 years. Mean levels of plasma fibrinogen, von Willebrand factor, beta-thromboglobulin, plasminogen activator inhibitor (type I), cross-linked fibrin degradation products and lipid peroxides were markedly elevated in 121 study cases compared with 126 age- and sex-matched controls. For example, cross-linked fibrin degradation products had a geometric mean of 106.8 ng/ml (95% confidence interval (CI) 95.3, 119.8) in study cases and 74.7 ng/ml (95% CI 67.0, 83.4) in controls (P < 0.001). Inclusion of smoking in logistic regressions of each factor on peripheral arterial disease significantly reduced the odds of disease for von Willebrand factor and for cross-linked fibrin degradation products, but had little effect on the increased odds associated with fibrinogen, beta-thromboglobulin, plasminogen activator inhibitor and lipid peroxides. We conclude that, in men and women in Edinburgh, peripheral atherosclerosis is associated with lipid peroxidation, endothelial disturbance, platelet activation, elevated fibrinogen, fibrin formation and increased inhibition of fibrinolysis. The most important effects of cigarette smoking in promoting atherosclerosis may be endothelial disturbance and fibrin formation.
Atherosclerosis 1993 Sep
PMID:Smoking, haemostatic factors and lipid peroxides in a population case control study of peripheral arterial disease. 825 Oct 1


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