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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postmenopausal hormone replacement therapy is associated with a reduction in the incidence of coronary heart disease. However, inconclusive results have been reported with respect to the risk of stroke, and recent studies consistently showed an increased risk of venous thromboembolism in postmenopausal women using oral estrogen. There are surprisingly few interventional studies to assess the true effects of estrogen-progestin regimens on blood coagulation and fibrinolysis, and the impact of the route of estrogen administration on hemostasis has not been well documented. Therefore, we investigated the effects of oral and transdermal estradiol/progesterone replacement therapy on hemostatic variables. Forty-five healthy postmenopausal women, aged 45 to 64 years, were assigned randomly to one of the three following groups: cyclic oral or transdermal estradiol, both combined with progesterone, or no hormonal treatment. Hemostatic variables were assayed at baseline and after a 6-month period. Pairwise differences in the mean change between the three groups were compared using nonparametric tests. Oral but not transdermal estradiol regimen significantly increased the mean value of prothrombin activation peptide (F1 + 2) and decreased mean antithrombin activity compared with no treatment. Differences in fragment F1 + 2 levels between active treatments were significant. The oral estrogen group was associated with a significant decrease in both mean tissue-type plasminogen (t-PA) concentration and plasminogen activator inhibitor (PAI-1) activity and a significant rise in global fibrinolytic capacity (GFC) compared with the two other groups. A transdermal estrogen regimen had no significant effect on PAI-1, t-PA, and GFC levels. There were no significant changes in mean values of fibrinogen, factor VII, von Willebrand factor, protein C, fibrin D-dimer, and plasminogen between and within the three groups. We conclude that oral estrogen/progesterone replacement therapy may result in coagulation activation and increased fibrinolytic potential, whereas opposed transdermal estrogen appears without any substantial effects on hemostasis. Whereas these results may account for an increased risk of venous thromboembolism in users of oral postmenopausal estrogen, they emphasize the potential importance of the route of estrogen administration in prescribing hormone replacement therapy to postmenopausal women, especially to those at high risk of thrombotic disease.
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PMID:Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. 940 95

Plasma fibrinogen is a consistent predictor of ischemic heart disease (IHD) in prospective studies, but there are fewer data relating other hemostatic variables to IHD and also to stroke. We therefore studied the relationships of plasma fibrinogen, von Willebrand factor antigen, tissue plasminogen activator (TPA) antigen, factor VII, and fibrin D-dimer to incidence of IHD and stroke and determined whether any associations could be explained by conventional risk factors and baseline heart disease. In the Edinburgh Artery study, 1592 men and women aged 55 to 74 years, randomly sampled from the general population, were followed prospectively over 5 years to detect fatal and nonfatal IHD and stroke events. During the 5 years, 268 new vascular events were identified. Baseline plasma fibrinogen was independently related to risk of stroke in multivariate analysis that adjusted for cigarette smoking, LDL-cholesterol, systolic blood pressure, and preexisting IHD (relative risk [RR] 1.52, 95% confidence interval [CI] 1.17, 1.98). TPA antigen, and fibrin D-dimer were also independently associated with risk of stroke (RR 1.69,95% CI 1.22,2.35 and RR 1.96, 95% CI 1.12,3.41, respectively). Significant relationships were found between TPA antigen and myocardial infarction (P < or = .05). In older men and women, increased coagulation activity and disturbed fibrinolysis are predictors of future vascular events (both IHD and stroke).
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PMID:Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study. 940 28

We carried out a case-control study to determine whether von Willebrand factor (vWF) antigen (and factor VII and tissue plasminogen activator [tPA] antigens) are associated with ischemic stroke. Ninety-five patients with transient ischemic attack or minor ischemic stroke recruited from the Oxfordshire Community Stroke Project and one neurology clinic were compared with 236 controls, group-matched for age and sex, from the same general practitioners as the incident cases. In crude analyses, concentrations of vWF antigen were significantly higher in cases than in controls (p = 0.004). The age- and sex-adjusted odds ratios from lowest (referent) to highest quartile of vWF antigen were 1.00, 1.15, 2.34, and 2.36 (trend test, p = 0.006). Factor VII antigen and tPA antigen were not significantly different between cases and controls. Although adjustment for other potential risk factors abolished the statistical significance of the association between vWF and disease, this was largely due to the influence of history of ischemic heart disease. We conclude that vWF is a potent and independent risk factor for transient ischemic attack, minor ischemic stroke, and, by extrapolation, ischemic stroke in general. The data also suggest that vWF may be a risk factor for both ischemic stroke and ischemic heart disease. We found no evidence to implicate factor VII and tPA as risk factors for ischemic stroke.
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PMID:Von Willebrand factor and risk of ischemic stroke. 940 45

Although the arterial tree is exposed to increased pressure in hypertensive patients, paradoxically, the complications of hypertension (heart attacks, stroke) are mainly thrombotic rather than hemorrhagic. Patients with left ventricular (LV) hypertrophy are at high risk of the complications of hypertension. We performed a cross-sectional study of 178 patients attending a hypertension clinic in a city center teaching hospital, and measured plasma levels of the soluble adhesion molecule P-selectin (associated with platelet activity/function and atherosclerosis), the von Willebrand factor (vWf; a marker of endothelial dysfunction), fibrin D-dimer (an index of thrombogenesis), plasminogen activator inhibitor (PAI, an index of fibrinolysis), lipoprotein(a) (Lp(a), associated with thrombogenesis and atherogenesis) and hemorheological indexes (fibrinogen, hematocrit, plasma viscosity, hemoglobin) in patients with essential hypertension, in whom the LV mass and LV mass index were determined using echocardiography. The 178 patients (86 men, mean age 54 +/- 15 years) were compared with 47 normotensive healthy controls (aged 56 +/- 20 years). Hypertensive patients had higher P-selectin, PAI, vWf, fibrin D-dimer, Lp(a), plasma fibrinogen, and plasma viscosity when compared with controls. Black hypertensive patients had higher Lp(a) levels and LV septal and posterior wall thickness on echocardiography, but lower plasma PAI levels. Patients with LV hypertrophy (defined as a LV mass index > 134 g/m2 in men or > 110 g/m2 in women) had higher plasma fibrinogen compared with those without LV hypertrophy. Systolic blood pressures were significantly correlated to age, plasma viscosity, plasma fibrinogen, and vWf. Diastolic blood pressures were significantly correlated with age and plasma fibrinogen. Fibrinogen levels were correlated with LV mass, LV mass index, left atrial size, plasma viscosity, and vWf. Fibrin D-dimer levels were significantly correlated with vWf and fibrinogen levels. Thus, hypertensive patients have high plasma fibrinogen levels, thrombogenesis, and impaired fibrinolysis (as indicated by high D-dimer and PAI levels, respectively), platelet activation (raised soluble P-selectin), and endothelial dysfunction (high vWF). The high plasma fibrinogen levels were related to blood pressures, LV mass index (and LV hypertrophy), and left atrial size. These abnormalities in hemorheologic factors and markers of thrombogenesis and endothelial function may act synergistically to increase the risk of thrombogenesis and atherosclerosis in hypertensive patients.
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PMID:Relation of endothelium, thrombogenesis, and hemorheology in systemic hypertension to ethnicity and left ventricular hypertrophy. 941 37

In vivo microvascular studies and postmortem studies of large and small blood vessels in a variety of species and vascular beds show that platelet adhesion and aggregation can occur over endothelium that is not denuded; the basal lamina and collagen need not be exposed. Moreover, evidence suggests that, at least in arterioles, locally adherent degranulating platelets can actually produce disruption and denudation of endothelial cells. Therefore, one should not assume, at least in small vessels, that observed sites of denudation were the cause rather than the result of adhesion/aggregation. All of this evidence should encourage a greatly increased emphasis on causes of adhesion/aggregation that do not depend upon collagen and/or collagen-bound von Willebrand factor (vWF). This emphasis does not deny the importance of collagen or collagen-bound vWF as the trigger for adhesion/aggregation when such exposure occurs. However, the emphasis on a structurally intact endothelial surface does lead to the corollary caution: even when endothelium is interrupted and potential triggers of adhesion/aggregation are exposed, this does not mean that these substances were, in fact, the cause of the locally observed adhesion/aggregation. Local exposure of key endothelial cell adhesion molecules such as PECAM may contribute to the adhesion/aggregation of platelets over structurally intact but injured endothelium. Adhesion/aggregation over injured but intact endothelium can also be modified by maneuvers that alter the local production of antiplatelet paracrine substances like endothelium-derived relaxing factor/nitric oxide. This supports the hypothesis that local decrements in the release of antiplatelet paracrine substances from perturbed but structurally intact endothelium leads to local adhesion/aggregation especially of platelets activated by a preexisting pathology. Coronary artery disease, ischemic stroke and diabetes are examples of diseases associated with both hyperaggregable platelets and with impaired endothelial synthesis/release of antiplatelet paracrine mediators. In addition, repetitive stereotypic symptoms in transient ischemic attacks may be related to repetitive and increasing damage to endothelium produced by successive episodes of platelet adhesion/aggregation/degranulation at the same sites.
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PMID:Platelet adhesion and aggregation without endothelial denudation or exposure of basal lamina and/or collagen. 942 93

We performed a case-control study to investigate the role of recent infection as stroke risk factor and to identify pathogenetic pathways linking infection and stroke. We examined 166 consecutive patients with acute cerebrovascular ischemia and 166 patients hospitalized for nonvascular and noninflammatory neurologic diseases. Control subjects were individually matched to patients for sex, age, and season of admission. We assessed special biochemical parameters in subgroups of stroke patients with and without recent infection (n = 21) who were similar with respect to demographic and clinical parameters. Infection within the preceding week was a risk factor for cerebrovascular ischemia in univariate (odds ratio [OR] 3.1; 95% confidence interval (CI), 1.57 to 6.1) and age-adjusted multiple logistic regression analysis (OR 2.9; 95% CI, 1.31 to 6.4). The OR of recent infection and age were inversely related. Both bacterial and viral infection contributed to increased risk. Infection elevated the risk for cardioembolism and tended to increase the risk for arterioarterial embolism. Stroke patients with and without preceding infection were not different with respect to factor VII and factor VIII activity, fibrin monomer, fibrin D-dimer, von Willebrand factor, C4b-binding protein, protein S, anticardiolipin antibodies, interleukin-1 receptor antagonist, soluble tumor necrosis factor-alpha receptor, interleukin-6, interleukin-8, and neopterin. In conclusion, recent infection is an independent risk factor for acute cerebrovascular ischemia. Its role appears to be more important in younger age groups. The pathogenetic linkage between infection and stroke is still insufficiently understood.
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PMID:Recent bacterial and viral infection is a risk factor for cerebrovascular ischemia: clinical and biochemical studies. 944 80

In order to clarify the coagulation profile accompanying ischemic stroke, which may have implications on therapeutic strategies, we performed a prospective study to evaluate the hemostatic parameters in the first 24 h after the onset of cortical atherothrombotic infarct and lacunar infarction. Twenty-seven patients with cortical atherothrombotic infarction and 27 patients with lacunar infarction, diagnosed on clinical and CT-scan criteria, had blood samples taken within the first 24 h after onset of the stroke, and before anticoagulant treatment had been started. Levels of fibrinogen, von Willebrand factor, D-dimers, prothrombin factors 1 + 2, anti-thrombin III, and C-protein and S-proteins, were measured. Laboratory tests detected the following abnormalities: a protein C deficiency was observed in 1 case of cortical infarction and in 1 case of lacunar infarction; a decrease in S-protein was observed in 1 case of cortical infarction, and the presence of lupus anticoagulant in 4 cases (2 in cortical and 2 in lacunar infarction). Various degrees of coagulation activation were observed. Statistically significant activation of the coagulation was observed in the patients with cortical infarction, compared to normal patients adjusted for age: the levels of DDI were significantly raised (2298 +/- 2221 ng ml-1 vs. 750 +/- 400 ng ml-1) (p < 0.03) as were F1 + 2 levels (3.9 +/- 2.8 nmol l-1 vs. 1.5 +/- 0.9 nmol l-1). (p < 0.01). In the lacunar infarction group, there was a significant rise in F1 + 2 compared with normal patients adjusted for age (2.2 +/- 1.7 nmol l-1 vs. 1.5 +/- 0.9 nmol l-1) (p < 0.01), while the DDI level was in the normal range, when age was taken into account. In the cortical infarction group, we observed a significantly raised fibrinogen level (4.8 +/- 1.7 g l-1 vs. 3.7 +/- 1.0 g l-1) (p < 0.05) and von Willebrand factor level (271 +/- 104% vs. 178 +/- 103%) (p < 0.01) compared to the lacunar infarction group. In addition, we observed a significantly low level of S-protein in the cortical infarction group (105 +/- 29%) compared to the lacunar infarction group (127 +/- 28%) (p < 0.01). Confirmation of the role of enhanced thrombin activity in the pathogenesis of acute stroke may be an important determinant in its therapeutic management.
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PMID:Coagulation abnormalities in lacunar and cortical ischemic stroke are quite different. 947 Oct 97

The expression and localization of P- and E-selectins in rat brain (n=126) were examined using immunohistochemical techniques at various time points after induction of middle cerebral artery (MCA) occlusion in the suture, thrombotic and embolic models of stroke. Expression of P- or E-selectin was not observed in brain tissue of sham operated control rats (n=9). P-selectin immunoreactivity was detected as early as 15 min and decreased to control level at 1 h after the onset of the MCA occlusion in all three models. P-selectin then slightly increased at 2 h and peaked at 6 h after MCA occlusion. E-selectin immunoreactivity was first observed at 2 h and peaked at 6 h and 12 h of after MCA occlusion in all three models. P- and E-selectin immunoreactivity was colocalized with von Willebrand factor immunoreactive microvessels. 90.4+/-2.0% of all vessels expressing P-selectin immunoreactivity were 7.5 to 30.0 micron in diameter; 3.6+/-1.4% were contained in vessels smaller than 7.5 micron, and 6.0+/-1.8% were localized in vessels greater than 30.0 micron in diameter. The percent distribution of E-selectin immunoreactive vessels were 75.9+/-2.1% in vessels 7.5 to 30.0 micron in diameter; 23.6+/-2.2% were in vessels smaller than 7.5 micron, and 0.6+/-0.4% were localized in vessels greater than 30.0 micron in diameter. These findings indicate that the temporal profiles of P- and E-selectin expression are independent of these models of MCA occlusion and are consistent with the time course of selectin mediated leukocyte infiltration after focal cerebral ischemia in the rat.
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PMID:The expression of P- and E-selectins in three models of middle cerebral artery occlusion. 951 15

Thrombotic risk factors may be important in determining cardiovascular outcome in patients with symptomatic peripheral arterial disease. A cohort study with a 6-year follow-up period was established to determine the relationships between haemostatic and rheological factors and incident ischaemic heart disease (IHD) and stroke events in patients with peripheral arterial disease. A consecutive series of 607 patients with intermittent claudication was examined between 1989 and 1990 at the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. Main outcome measures were combined fatal and non-fatal stroke, non-fatal myocardial infarction (MI), coronary death and total coronary events. A total of 210 patients died during follow-up. 203 patients did not experience a vascular event or deterioration of limb ischaemia. Median levels of fibrinogen, von Willebrand factor (VWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer and whole blood viscosity were significantly higher in those who experienced an event compared with those who did not. After adjusting for age and sex, fibrin D-dimer was significantly associated with risk of non-fatal myocardial infarction (RR 1.50, 95% CI 1.09-2.06, P < or = 0.01). Both fibrinogen and fibrin D-dimer were associated with risk of total coronary events (P < or = 0.05). The risk of stroke was related to baseline levels of t-PA antigen (RR 1.87, 95% CI 1.04-3.34, P < or = 0.05) and whole blood viscosity (RR 1.33, 95% CI 1.07-1.65, P < or = 0.01). All the relationships became weaker and statistically non-significant after further adjustment for cigarette smoking, systolic blood pressure, glucose and baseline IHD. The associations of these factors to IHD and stroke may therefore be partly related to cardiovascular risk factors, but are likely to be important in the pathogenesis of future atherothrombotic events in subjects with peripheral arterial disease.
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PMID:Haemostatic factors and prediction of ischaemic heart disease and stroke in claudicants. 953 45

Strong evidence from large observational epidemiological studies links haemostatic variables to the future risk of myocardial infarction and stroke. Recent data provide further evidence for an early involvement of haemostatic parameters in atherosclerosis. So far, a variety of markers of a procoagulatory tendency e.g. elevated fibrinogen, coagulation factor VII, factor VIII and von Willebrand factor, platelet hyperaggregation, increased plasma levels of D-dimer, and decreased fibrinolytic capacity, e.g. characterized by increased levels of PAI-1 activity and decreased t-PA concentrations have been identified prospectively. Thus, a complex disturbed haemostatic system plays an important role in the development of atherothrombotic events in several vascular beds. This review discusses the epidemiologic evidence of the association between the haemostatic system and cardiovascular disease.
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PMID:Haemostatic risk factors for cardiovascular diseases. 959 24


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