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

We investigated the relationship between fasting insulin level and various hemostatic factors, including fibrinolytic factors (active plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (tPA)-PAI-1 complex, plasmin-alpha 2-plasmin inhibitor (PIC), and D-dimer), coagulation factors (activated factor VII, factor VII coagulant activity and antigen, factor VIII, factor X, and fibrinogen), coagulation inhibitors (antithrombin III, heparin cofactor II, and protein C), and an acute phase marker (sialic acid) in 102 healthy individuals aged > or = 75 years (46 men and 56 women). Active PAI-1 levels had a significant negative correlation with PIC levels (r = -0.342, P = 0.0006), indicating that PAI-1 influences in vivo fibrinolytic activity in the very elderly. Gender differences were found in the relationship between insulin and hemostatic abnormalities, with the insulin level being positively correlated with coagulation factors in men (factor VIII activity: r = 0.422, P < 0.01; factor VII activity: r = 0.386, P < 0.01) and with hypofibrinolysis in women (active PAI-1: r = 0.549, P < 0.0001). Insulin levels were positively correlated with the levels of factor VII antigen and factor VII activity in men (P < 0.01), but there was no correlation with activated factor VII levels. The fasting insulin level was also correlated with the levels of heparin cofactor II and sialic acid in men (P < 0.05). However, other hemostatic factors were not related to the insulin level in either sex.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1995 Aug
PMID:Gender differences of disturbed hemostasis related to fasting insulin level in healthy very elderly Japanese aged > or = 75 years. 757 76

Hypercoagulability of blood, monocytic infiltration, and changes in pericellular and extracellular matrix glycosaminoglycans (GAGs) are observed in atherosclerosis, inflammation, and neoplasia. In the present studies, monocyte procoagulants and different GAGs including chondroitin sulfate (CS) A, CSB, CSC, CSD, CSE, and heparan sulfate, were tested either in clotting assays with whole plasma or in chromogenic assays with purified coagulation proteases. Procoagulant activity in plasma was inhibited by three of the seven GAGs, including heparan sulfate, CSE, and CSB. In contrast, activity of purified coagulation protease was inhibited only by CSE, and the inhibition was observed with intrinsic (factor VIIIa/IXa) but not extrinsic (tissue factor/factor VII) components. Reciprocal titration experiments with enzyme and substrate and Scatchard type analyses were consistent with concentration-dependent inhibitory interactions between CSE and sites on both factor VIIIa and IXa. On purified phospholipids, CSE concentration resulting in half-maximal inhibition (Ki) was 5 ng/ml for interaction with factor IXa and > 500 ng/ml for interaction with factor VIIIa. The Ki values were lower for reactions on purified lipid than for reactions on monocyte surfaces and for reactions on resting than on endotoxin-stimulated monocytes. Experiments with CSE oligosaccharides of defined size indicated that the smallest CSE fragment capable of inhibitory activity was composed of 12-18 monosaccharide units. Collectively, these results indicate that factor X-activating reactions are inhibited by GAGs expressed on monocyte membranes. Inhibition is specific with respect to the structure of both the GAG and the activating protease. Lack of inhibition by added CSA, CSB, and CSC in contrast to CSE strongly suggests a direct role of 4,6-di-O-sulfated N-acetylgalactosamine GAG structures in the inhibition of intrinsic pathway protease. These findings also suggest potential pharmacologic use of CSE as specific anticoagulant in the management of prothrombotic states mediated by intrinsic pathway coagulation reactions.
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PMID:Specific regulation of procoagulant activity on monocytes. Intrinsic pathway inhibition by chondroitin 4,6-disulfate. 759 13

The levels of different lipid, lipoprotein and haemostatic variables were assessed in 615 control subjects of the ECTIM Study, defined by five groups of alcohol consumption: non-drinkers, 0 < or = 15 g/day, 15 < . < or = 36 g/day, 36 < . < or = 66 g/day and > 66 g/day. After adjustment for age, body mass index, cigarette consumption and country, alcohol consumption was associated with an increase in HDL-cholesterol (0.47 +/- 0.02 to 0.59 +/- 0.01 g/l in non-drinkers and > 66 g/day consumers, mean +/- S.E.M., P < 0.0001), apolipoproteins A-I and A-II (1.37 +/- 0.03 to 1.60 +/- 0.03 g/l and 0.32 +/- 0.01 to 0.41 +/- 0.01 g/l, respectively, P < 0.0001), LpA-I, LpA-I:A-II (0.46 +/- 0.01 to 0.50 +/- 0.01 g/l and 0.75 +/- 0.02 to 0.91 +/- 0.02 g/l, respectively, P < 0.001) and PAi-1 activity (134 +/- 11 to 177 +/- 11 U/ml, P < 0.001). Conversely, no increases were found for total and LDL-cholesterol, triglycerides, apolipoproteins B and C-III, LpE:B, LpC-III:B, fibrinogen and factor VII. Hence, among the lipid and haemostatic variables studied, only HDL parameters and PAi-1 activity were increased by alcohol consumption.
Atherosclerosis 1995 Jun
PMID:Cardiovascular risk factors and alcohol consumption in France and Northern Ireland. 766 81

Plasma phospholipid fatty acid composition reflects, to a moderate degree, the fatty acid composition of the diet. To determine whether plasma phospholipid fatty acid composition might influence factor VII coagulant activity (factor VIIc), we examined 2207 middle-aged adults free of diabetes and cardiovascular disease. Factor VIIc was associated positively with the percentage of fatty acids that was saturated, and it was associated negatively with the linoleic acid percentage and the phospholipid polyunsaturated/saturated fatty acid ratio. For example, a 1.9% greater saturated fatty acid level was associated with approximately a 5% higher factor VIIc. These results suggest a role for dietary fat composition, or related dietary patterns, in determining levels of factor VIIc.
Atherosclerosis 1994 Dec
PMID:Plasma phospholipid fatty acid composition and factor VII coagulant activity. 771 22

Plasma clotting factor VII and plasma fibrinogen have been claimed as independent risk factors for occlusive cardiovascular disease. The aim of this study was to investigate whether these coagulation parameters affect early atherosclerosis, additional to their possible effect on arterial thrombosis. We used high-resolution quantitative ultrasonography to measure carotid intima-media thickness in 121 healthy volunteers, aged 18 to 56 years. It has previously been demonstrated that an increased artery wall thickness is seen in advanced atherosclerosis. To validate our methodology for relatively young individuals, we assessed the association of intima-media thickness with the risk-factor status of our subjects, by including classical cardiovascular risk factors, e.g. age, sex, serum cholesterol, smoking habits and blood pressure. Thereafter, we studied the effect of factor VII and fibrinogen plasma levels on carotid intima-media thickness, as well as that of polymorphisms of the factor VII and fibrinogen genes. All classical risk factors except smoking and family history were associated with intima-media thickness. When adjusted for by multivariate linear regression analysis, age, blood pressure and cholesterol appeared to be independent determinants of intima-media thickness. Factor VII and fibrinogen levels showed no association in multivariate analysis with intima-media thickness. We conclude that artery wall thickness measurement by ultrasound is a useful tool to investigate the role of clotting factors in early atherosclerosis. Factor VII and fibrinogen levels in young and middle-aged volunteers have no association with early artherosclerotic vessel wall changes.
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PMID:Relation of plasma coagulation factor VII and fibrinogen to carotid artery intima-media thickness. 783 61

The early belief that the haemostatic system has no active role in the formation of the atheromatous plaque is no longer tenable. Rather, the association between hypercholesterolaemia and atherosclerosis appears to arise in part because of various effects of high concentrations of LDL and VLDL particles on the cellular and humoral components of the system, thereby promoting plaque growth and thrombosis. These may be summarized as follows: 1. High concentrations of native LDL have been reported to promote the adhesion of monocytes to the endothelial cell, suggesting that the latter undergoes a form of activation upon such exposure. Oxidized LDL is more potent in this respect, and persistent exposure of endothelium to such particles can eventually lead to cell injury. 2. Activated endothelial cells acquire characteristics on their luminal surface conducive to thrombin generation and fibrin production. Thrombin has several actions on the endothelial cell, monocyte, smooth muscle cell and platelet which in the presence of hypercholesterolaemia will promote the formation of atheroma. 3. Oxidatively modified LDL can activate circulating monocytes, when they also acquire procoagulant properties which favour thrombin production. 4. Platelets show an increased tendency to aggregate when exposed to hypercholesterolaemic plasma. This effect may arise in part because the platelet of the hypercholesterolaemic patient expresses an increased number of fibrinogen binding sites on its surface following activation by agonists such as ADP. These hyperaggregable platelets adhere to activated endothelial cells which express von Willebrand factor on their surface, and to subendothelial proteins exposed in the gaps that open between injured endothelial cells. Platelets exposed to raised LDL levels also show a reduced sensitivity to prostacyclin, an antiaggregatory agent. Oxidatively modified LDL has been reported to stimulate aggregation of platelets in the absence of other agonists such as ADP or thrombin (spontaneous aggregation). 5. Platelet aggregation and fibrin deposition at sites of endothelial injury will create microthrombi which become incorporated into the lesion by organization, thereby increasing the fibrous and cellular content of the atheromatous plaque. 6. Lipolysis of triglyceride-rich lipoproteins at the endothelial cell surface leads to transient activation of the coagulation mechanism with activation of factor VII. Activated factor VII is a potent procoagulant when it forms a complex with tissue factor in the atheromatous lesion. Persistent hypertriglyceridaemia is accompanied by raised concentrations of factor X, factor IX, factor VII and prothrombin. 7. Hypertriglyceridaemia is associated with an increased plasma concentration of PAI-1 and a reduction in plasma fibrinolytic activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lipoproteins and the haemostatic system in atherothrombotic disorders. 784 7

The relationship between thrombosis and atherosclerosis has been already suggested in the middle of the last century. More recently, in 1976 a hypothesis has been put forward which emphasize the leading role of chronic injury to endothelial cells followed by platelet attachment and the release of platelet derived growth factors in pathogenesis of atherosclerosis. There is also a growing body of evidence that cytokines, thrombin and the fibrinolytic system are involved in the initiation and progression of atherosclerotic lesions. Lipoprotein (a) is emerging as a link between atherogenic role of lipids and the haemostatic system. At the same time epidemiological data are pointing at the possible role of fibrinogen, factor VII and plasminogen activator inhibitor-1 as risk factors for ischemic heart disease. Thrombus formation is also responsible for the majority of acute coronary syndromes. On the other hand aspirin and other antiplatelet drugs seem to protect from vascular complications of atherosclerosis. Than the question which rather arises is: what is the best antithrombotic strategy in patients with cardiovascular diseases?
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PMID:[Should hemostatic factors be considered in the prevention of cardiovascular disease?]. 797 94

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

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

In the first Whitehall study, plasma cholesterol was a strong predictor of coronary heart disease (CHD) but it showed a positive association with grade of employment: the higher the grade the higher the level. Because it could not explain the higher rate of CHD in lower employment grades, further investigation of biochemical CHD risk factors has been conducted with data from the baseline examination of the Whitehall II cohort in 1985-88. These data also allow investigation of gender differences and the effect of menopause. Serum cholesterol (6860 men and 3374 women) and apolipoproteins A-I and B (apo AI and apo B) were measured in those aged 35-55 working in the London offices of twenty Civil Service departments. Plasma fibrinogen and factor VII were determined in 45-55 year olds. The apo B/apo AI ratio (95% confidence interval) after age adjustment is lowest in premenopausal women: 0.557 (0.549-0.565), intermediate in postmenopausal women: 0.601 (0.589-0.613) and highest in men: 0.703 (0.698-0.709). After age adjustment fibrinogen is higher in postmenopausal (2.90 (2.85-2.95) g/l) than in premenopausal women (2.78 (2.71-2.84) g/l), who have higher levels than men (2.64 (2.62-2.67) g/l). A positive association with employment grade is seen for apo AI and a negative association is seen for fibrinogen, apo B (women only) and the apo B/apo AI ratio, after age adjustment. These patterns are consistent with the higher rates of CHD in lower grades. Cholesterol and factor VII show no gradient with our sensitive measure of social position. After adjusting for the effects of smoking rates, alcohol consumption, exercise and dietary pattern, as well as age, ethnicity, body mass index and report of symptoms, the regression coefficient for apo AI on employment grade is reduced by 43% in men and 70% in women. Corresponding reductions for fibrinogen are 53% and 65%. These attenuations suggest that a considerable part of the social gradients in apo AI and fibrinogen are explained by variations in health related behaviours. The remaining gradients may represent effects independent of these behaviours.
Atherosclerosis 1993 Sep
PMID:Gender and employment grade differences in blood cholesterol, apolipoproteins and haemostatic factors in the Whitehall II study. 825 Oct 6


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