Factor VIIc Research Articles

Insulin up-regulates a Glc3Man9GlcNAc2-PP-Dol pool in capillary endothelial cells not essential for angiogenesis.

Endothelial cells line blood vessels, and their proliferation during neovascularization ( i.e., angiogenesis) is essential for a normal growth and development as well as for tumor progression and metastasis. Mechanistic details indicated that down-regulation of Glc(3)Man(9)GlcNAc(2)-PP-Dol level reduced angiogenesis and induced apoptosis in capillary endothelial cells (Martínez JA, Torres-Negrón I, Amigó LA, Banerjee DK, Cellular and Molec Biochem 45, 137-152 (1999)). Unlike in any other insulin-responsive cells, insulin reduced capillary endothelial cell proliferation by increasing the cell doubling time. But, when analyzed, the rate of lipid-linked oligosaccharide-PP-Dol (LLO) synthesis as well as its turnover ( i.e., t(1/2)) were increased in insulin treated cells. No major differences in their molecular size were observed. This corroborated with an enhanced glycosylation of Factor VIIIC, an N-linked glycoprotein (essential cofactor of the blood coagulation cascade) and a marker for the capillary endothelial cell. Increased LLO synthesis was independent of elevating either Dol-P level or Man-P-Dol synthase gene (dpm) transcription. Insulin however, enhanced 2-deoxy-glucose transport across the endothelial cell plasma membrane and caused increased secretion of Factor VIIIC, thus, supporting the existence of additional LLO pool(s), and arguing favorably that growth retardation of capillary endothelial cells by insulin turned a highly proliferative cell into a highly secretory cell.

Haemostatic risk factors in healthy postmenopausal women taking hormone replacement therapy

Objective: To compare changes in haemostatic parameters in healthy postmenopausal women taking either tibolone or 17β-oestradiol/norethisterone acetate. Methods: Factor VIIc, antithrombin, fibrinogen, thrombin–antithrombin complex (TAT), FDP (D-Dimer), tissue plasminogen activator (tPA) and plasminogen activator inhibitor I (PAI-1) were measured in 80 healthy postmenopausal women after 3, 6 and 12 months therapy with either 17β-oestradiol/norethisterone acetate or tibolone. Results: Both treatments significantly reduced fibrinogen, factor VIIc, antithrombin, tPA and PAI-1 antigen. Significantly lower levels of factor VIIc activity were observed on treatment with tibolone compared with 17β-oestradiol/norethisterone acetate. TAT was unchanged with both treatments as was tPA activity. FDP (D-dimer) was increased on treatment with both preparations. Conclusions: The enhanced fibrin turnover and reduced antithrombin activity may play a role in the increased risk of venous thromboembolism in some susceptible women taking hormone replacement therapy (HRT) and could explain the lack of benefit of HRT in the secondary prevention of cardiovascular disease. The decreased levels of fibrinogen and factor VIIc found during treatment with 17β-oestradiol/norethisterone acetate or tibolone may offer some degree of cardioprotection in healthy woman without pre-existing disease.

Thromboembolism in children

Acquired and inherited prothrombotic risk factors increase the risk of thrombosis in children. This review is based on "milestone" pediatric reports and new literature data (January 2001-February 2002) on the presence of acquired and inherited prothrombotic risk factors, imaging methods, and treatment modalities in pediatric thromboembolism. After confirming clinically suspected thromboembolism with suitable imaging methods, pediatric patients should be screened for common gene mutations (factor V G1691A, prothrombin G20210A and MTHFR C677T genotypes), rare genetic deficiencies (protein C, protein S, antithrombin, and plasminogen), and new candidates for genetic thrombophilia causing elevated levels of lipoprotein(a), and homocysteine, and probable genetic risk factors (elevations in fibrinogen, factor IX, and factor VIIIC, and decreases in factor XII). Data interpretation is based on age-dependent reference ranges or the identification of causative gene mutations/polymorphisms with respect to individual ethnic backgrounds. Pediatric treatment protocols for acute thromboembolism, including thrombolytic and anticoagulant therapy, are mainly adapted from adult patient protocols.

A specific elevation in tissue plasminogen activator antigen in women with polycystic ovarian syndrome.

There is increasing evidence that elevated plasma levels of hemostatic factors [fibrinogen, factor VII, von Willebrand factor, fibrin D-dimer, and tissue plasminogen activator (t-PA) antigen] are independently linked to risk for coronary heart disease (CHD). Women with polycystic ovary syndrome (PCOS) are insulin-resistant and have increased risk for CHD and type 2 diabetes, but there are few data on hemostatic markers in women with PCOS. Seventeen women with PCOS (defined on the basis of elevated testosterone and oligomenorrhea) and 15 healthy women matched as a group for body mass index (BMI) were recruited. Insulin sensitivity was assessed using the hyperinsulinemic euglycemic clamp technique. Factor VIIc was determined by a clotting assay; fibrinogen was determined by nephelometry; and t-PA, D-dimer, and von Willebrand factor antigens were measured by ELISA techniques. Of these hemostatic markers, only t-PA concentration was significantly (P = 0.013) elevated in women with PCOS relative to controls. t-PA correlated with BMI in both PCOS and controls (r = 0.428, P < 0.1; and r = 0.686, P < 0.01) and inversely with the insulin sensitivity index (r = -0.590, P < 0.05; and r = -0.620, P < 0.05, respectively). After further adjustment for BMI and insulin sensitivity, there remained a significant difference in t-PA between cases and controls (P = 0.017). Together, age and insulin sensitivity explained 39% of the variance in t-PA in women with PCOS (P < 0.05). Total testosterone did not correlate significantly with t-PA in either group. We conclude that women with PCOS have significantly increased t-PA concentrations relative to women with normal menstrual rhythm and normal androgens. We suggest that elevated t-PA and dysfibrinolysis may be a factor in the increased cardiovascular morbidity seen in PCOS.

The role of thrombophilic risk factors in the severity of pulmonary thromboembolism.

High plasma factor-VIIIc concentration, presence of factor-V 1691 G-A (FVL) and prothrombin20210A (PT20210A) mutations were shown to be significant risk factors for venous thromboembolism (VTE) and recurrent VTE. The objective of this study was to investigate the role of these thrombotic risk factors in the severity of pulmonary thromboembolism (PTE). The plasma concentrations of factor VIIIc, presence of FVL and PT20210A mutations were studied in 32 patients with PTE. Eleven of the patients had documented recurrent VTE. Lung perfusion scans were scored according to the percentage of vascular obstruction. Patients who had a pulmonary vascular obstruction score (PVOs) >50% were compared to those with PVOs <50%. There was no significant difference between the patients with PVOs >50% and those with PVOs <50%, with regard to the presence of FVL and PT20210A mutation. However, patients with PVOs >50% had a significantly higher factor-VIIIc concentration than those with PVOs <50% (factor-VIIIc levels were 253.3 +/- 29.1 International Units (IU) x dL(-1) and 138.5 +/- 16.2 IU x dL(-1), respectively; p<0.005). Factor-VIIIc concentrations were significantly correlated with PVOs (r=0.52, p<0.005). Patients with recurrent VTE had significantly higher factor-VIIIc concentrations than those in which it occurred for the first time (factor-VIIIc concentrations were 232.6 +/- 30.9 IU x dL(-1) and 158.3 +/- 20.6 IU x dL(-1), respectively; p<0.05). The authors conclude that in addition to being a risk factor for venous thromboembolism, high factor-VIIIc concentration is an important factor in the severity of pulmonary thromboembolism.

Inflammation and coagulation factors in persons >65 years of age with symptoms of depression but without evidence of myocardial ischemia

Depression is associated with increased cardiovascular disease, but the underlying mechanisms are not well understood. This study examines associations of depressive symptoms with inflammation and coagulation factors in persons aged >65 years. Blood samples were obtained from 4,268 subjects free of cardiovascular disease (age 72.4 ± 5.5 years, 2,623 women). Inflammation markers were C-reactive protein (CRP), white blood cell (WBC) count, total platelet count, and albumin; coagulation factors included factors VIIc and VIIIc and fibrinogen. Depression was assessed with the Center for Epidemiologic Studies Depression scale, and states of energy depletion with a validated exhaustion index. Statistical adjustments were made for risk factors (age, sex, race, systolic blood pressure, smoking status, diabetes mellitus) and physical measures of frailty (isometric handgrip, timed 15-feet walk test, activity level). Depression was associated with elevated CRP (3.31 ± 0.10 vs 3.51 ± 0.21 mg/L), WBC (6.14 ± 0.03 vs 6.43 ± 0.11 10 6/L), fibrinogen (319 ± 1 vs 326 ± 3 mg/dl), and factor VIIc (124.6 ± 0.6% vs 127.2 ± 1.3%; all p <0.05). Exhaustion also was related to elevated inflammation and coagulation markers (p <0.05). Exhausted men had markedly elevated CRP levels (6.82 ± 2.10 mg/L) versus nonexhausted men (3.05 ± 0.16: p = 0.007). After adjustment for control variables, exhaustion remained associated with albumin (p = 0.033), fibrinogen (p = 0.017), CRP (p = 0.066), and WBC (p = 0.060), whereas associations of depressive symptoms with biochemistry measures lost statistical significance. Thus, depression and exhaustion are associated with low-grade inflammation and elevated coagulation factors in persons aged >65 years.

Detection and quantification of insertion/deletion variations by allele-specific real-time PCR: application for genotyping and chimerism analysis.

The DNA-based quantitative analysis of genetic chimerism is becoming increasingly more important for molecular biology in general and molecular medicine in particular. Useful genomic targets for these analyses are polymorphic sequences, but here the problem of a reliable quantification with high dynamic range is not yet satisfactorily solved. To this end we have combined the allele-specific amplification with a real-time PCR-based quantification for rapid allelotyping and chimerism analysis. The sequence variations are discriminated by the 3'-end of the allele-specific primer. Amplification is monitored by SYBR-Green I fluorescence. We demonstrate the efficiency of this method for two clinically relevant targets: (i) the 10 bp insertion/deletion polymorphism in the promoter of the factor VIIc (F-VIIc) gene and (ii) the 4G/5G single nucleotide polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene. Both polymorphisms are associated with clinical risk factors. Allelotyping results were in complete agreement with those obtained by reference methods. Mixed chimeric DNA samples could be quantified reliably with a dynamic range of 1:3000 for an easy target (F-VIIc) and of 1:64 for a difficult target (PAI-1). Our protocol is particularly useful for rapid, reliable and inexpensive genotyping and quantitative chimerism analysis without requiring expensive fluorophor dye labelled probes.

D-Dimer as a Risk Factor for Deep Vein Thrombosis: The Leiden Thrombophilia Study

We studied the association of D-dimer with the risk of deep vein thrombosis (DVT). D-dimer was measured in 474 patients more than 6 months after diagnosis of a first DVT and in 474 age- and sex-matched controls. For D-dimer above the 70th percentile (130.5 ng/ml), the odds ratio (OR) for DVT was 2.2 (95% CI, 1.6-2.9). The association was unchanged with adjustment for other risk factors. Excluding participants with Factor V Leiden, prothrombin 20210A, or factors VIIIc or IX above the 90th percentile, the OR was 1.6 (95% CI, 1.1-2.3). The risks of DVT with the joint presence of high D-dimer and either factor V Leiden or prothrombin 20210A were increased 12.4-fold (95% CI 5.6-27.7) and 7.2-fold (95% CI 2.1-25.1), respectively. Higher D-dimer concentration was associated with the risk of DVT, and was supra-additive to the risks associated with factor V Leiden and the prothrombin 20210A variant. Persistence of this association in the absence of other hemostatic risk factors for DVT suggests that high D-dimer may be related to other, as yet unknown, risk factors for venous thrombosis. Confirmation of these findings is desirable.

A Reliable von Willebrand Factor: Ristocetin Cofactor Enzyme-Linked Immunosorbent Assay to Differentiate between Type 1 and Type 2 von Willebrand Disease

von Willebrand disease (vWD) is the most common hereditary bleeding disorder due to either a qualitative or a quantitative defect in von Willebrand factor (vWF). vWF is a multimeric plasma protein that plays an important role in (1) primary hemostasis, by sustaining indirect platelet adhesion especially at high shear rates, and in (2) secondary hemostasis, by protecting factor VIIIc (FVIIIc) from degradation. A correct diagnosis of vWD is based on the accurate identification of one of the six different subtypes (type 1, 2A, 2B, 2M, 2N, 3). To do this, different laboratory tests are available. One aspect of the identification is the discrimination between type 1 and type 2 (2A, 2B, and 2M) vWD. In type 1 vWD, both vWF levels (vWF:Ag) and vWF activity (vWF:RCof) are decreased; in type 2, the vWF:Ag level is normal or decreased and vWF:RCof is decreased. Thus, ratios of vWF:Ag to vWF:RiCof above 1 allow identifation of type 2 vWD patients. The currently used vWF:RCof test is an agglutination test in which patients' plasma is added to washed fixed control platelets in the presence of ristocetin and the extent of agglutination is measured. This test suffers from high interlaboratory and intralaboratory variability. We have recently shown that the same vWF:RCof can also be measured in an enzyme-linked immunosorbent assay (ELISA) with a low interassay and intraassay variability and can be used to identify patients suffering from vWD. We here show that our test allows the discrimination between type 1 and type 2 vWD patients.

Laboratory diagnosis of congenital von Willebrand disease.

Von Willebrand disease (vWD) is caused by quantitative or qualitative defects, or both, of the von Willebrand factor (vWF), a multimeric high-molecular glycoprotein (GP). Typically, it affects the primary hemostatic system, which is reflected by a mucocutaneous bleeding tendency simulating a platelet function defect. The vWF promotes its function in two ways: (1) by supporting platelet adhesion to the injured vessel wall under conditions of high shear forces and (2) by its carrier function for factor VIIIc (FVIIIc) in plasma. Because of the complexity of the disease, diagnosis of vWD is one of the most challenging of any coagulation disorder. The stepwise diagnosis of vWD includes patients and family history, screening procedures (bleeding time [BT], filter tests, platelet counts, activated partial thromboplastin time [aPTT]), confirmatory tests (vWF antigen [vWF:Ag], vWF ristocetin cofactor activity [vWF:RCo], vWF collagen-binding [vWF:CB] assay, ristocetin-induced platelet aggregation [RIPA], FVIIIc) and tests for final classification (multimeric analysis, FVIII binding capacity of vWF [vWF:FVIIIB], platelet vWF). In 1999, we classified 303 patients with congenital vWD as type 1 (n = 122), type 2 (n = 171), and type 3 (n = 10). Type 2 was further subdivided into type 2A (n = 126), type 2B (n = 17), type 2M (n = 22), and type 2N (n = 6). Type 2A showed a remarkable heterogeneity, with only 27.8% (n = 36) of the "classic" IIA pattern. The other high-frequency patterns were type IB (25.4% n = 32) and type IIE/F/H-like structural abnormalities (28.6% n = 36). The spectrum was completed with samples from patients with types 2D, 2C, 2C Miami, smeary structures, and other rare subtypes (together 18.9% n = 23).

Lifestyle factors and coagulation activation markers: the Caerphilly Study.

Coagulation activation markers are being investigated as risk factors for cardiovascular disease; we examined the contribution of several lifestyle factors to variation in plasma levels of several activation markers measured in a population-based study of 1947 men. Smoking, alcohol, body mass index (BMI), leisure and work activity, social class, and use of prescribed medicines were each examined in turn. Specific assays of fibrin D-dimer and von Willebrand factor (vWF) activity showed similar relationships to lifestyle variables as we observed previously for less specific assays of D-dimer and vWF antigen. D-dimer levels increased with age, in smokers and in men taking prescribed medication, and were negatively associated with leisure time activity. vWF activity increased with age and showed a U-shaped distribution with BMI. Factors VIIc and VIIIc and thrombin-antithrombin complexes were associated with BMI, factor VIIIc and prothrombin fragments 1 + 2 (F1 + 2) were associated with age, activated partial thromboplastin time (aPTT) and F1 + 2 were associated with smoking, and aPTT showed a small negative association with alcohol consumption. We conclude that lifestyle modification has the possibility of favourably influencing several of these risk markers. In particular, cigarette smoking has a possibly reversible effect on coagulation activation (measured by F1 + 2 and D-dimer).

The relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study.

Several studies suggest that inflammation plays a role in the pathogenesis of some glucose disorders in adults. We tested this hypothesis in a longitudinal cohort study of older individuals who had normal fasting glucose (FG) values at baseline. We compared the baseline levels of six inflammatory markers in participants who had developed glucose disorders at follow-up with those of participants whose FG remained normal at follow-up. Participants were members of the Cardiovascular Health Study, a prospective study of risk factors for cardiovascular disease in adults > or =65 years. All 5,888 participants had baseline testing, including FG and markers of inflammation: white blood cell and platelet counts and albumin, fibrinogen, C-reactive protein (CRP), and factor VIIIc levels. At 3-4 years of follow-up, 4,481 (84.5%) of those who were alive had FG levels retested. Participants who developed diabetes (n = 45) had higher median levels of CRP at baseline than those who remained normoglycemic. On multivariate analysis, those with elevated CRP levels (75th percentile [2.86 mg/l] vs. 25th percentile [0.82 mg/l]) were 2.03 times (95% confidence intervals, 1.44-2.86) more likely to have diabetes on follow-up. Adjustment for confounders and other inflammatory markers did not appreciably change this finding. There was no relationship between the development of diabetes and other markers of inflammation. Inflammation, as measured by CRP levels, is associated with the development of diabetes in the elderly. Understanding the role of inflammation in the pathogenesis of glucose disorders in this age-group may lead to better classification and treatment of glucose disorders among them.

Increased Soluble P-Selectin Levels in Hepatitis C Virus-Related Chronic Hepatitis

BackgroundPlatelet functional abnormalities are commonly found in patients with chronic liver disease; however, their nature and clinical significance are still a matter of discussion.MethodsSoluble P-selectin (sP-selectin, a marker of in...

Prothrombotic disorders and abnormal neurodevelopmental outcome in infants with neonatal cerebral infarction.

The aim of this study was to evaluate the occurrence of prothrombotic disorders in a well-characterized cohort of infants with neonatal stroke and to document any association of prothrombotic disorders with the type of infarct seen on magnetic resonance imaging (MRI) and clinical outcome. Twenty-four infants with perinatal cerebral infarction confirmed by neonatal MRI were enrolled in the study. All the infants and, when possible, both parents were tested to identify inherited and acquired prothrombotic disorders. None of the infants had a significant bleeding diathesis, but 10 (42%) had at least 1 prothrombotic risk factor. Five children showed heterozygosity for factor V Leiden, and 6 had high factor VIIIc concentrations. There was a striking association between the occurrence of these abnormalities and both the presence of cerebral hemorrhage on MRI and poor neurologic outcome. Eight of the 11 patients (73%) with hemiplegia or global developmental delay had factor V Leiden and/or raised factor VIIIc, whereas only 1 of the 13 patients (8%) with normal outcome had any prothrombotic risk factors. In particular, all 5 infants with factor V Leiden had hemiplegia, compared with only 4 of the 19 infants without factor V Leiden (21%). These data suggest that the presence of prothrombotic risk factors and, in particular, of the factor V Leiden mutation, is significantly associated with poor outcome after perinatal cerebral infarction.

Obstetric and gynaecological aspects of von Willebrand disease

The impact of von Willebrand disease in females is pronounced in terms of menorrhagia and postpartum haemorrhage. There is a very high proportion of von Willebrand disease patients with menorrhagia and associated anaemia, impairment of quality of life, including loss of time from work or school, and a high rate of the use of hysterectomy for ultimate control of the bleeding. The ‘early’ detection of von Willebrand disease in females may avert these complications. Consequently, there have recently been ongoing international efforts to determine the prevalence of von Willebrand disease in females presenting with menorrhagia, providing a prevalence of 7–20% combined from three studies including a total of 300 patients. Issues remain regarding the optimal dose/schedule of intranasal or subcutaneous desmopressin use for menorrhagia and the relative efficacy of anti-fibrinolytic agents. The proper role of oral contraceptives deserves further study in von Willebrand disease patients with menorrhagia as recent studies have paradoxically demonstrated a lower response rate in type 1 than type 2 or 3 von Willebrand disease. Despite the well-known adage of the ‘gestational palliation’ of von Willebrand disease, there is also a high proportion of postpartum haemorrhage in type 1 patients, especially after the 24 hour post-delivery period. This may occur despite a normalization of the factor VIIIc level in the third trimester, particularly in type 2 and 3 patients. The care-giver must be aware that haemorrhage can occur up to 5 weeks postpartum. In sum, studies over the past decade have documented a substantial impact of menses and childbirth on von Willebrand disease patients. These results should serve as a basis for interventional studies to reduce the morbidity of menstruation and childbirth.

Acquired von Willebrand syndrome type 1 in hypothyroidism: reversal after treatment with thyroxine.

In 16 cases, acquired von Willebrand syndrome (AvWS) and hypothyroidism have been described that occur with each other: 15 women and one man, at a mean age of 32 years, range, 13 to 82 years of age. Activated partial thromboplastin time (APTT) was normal in six patients, and five patients had factor VIII concentration (factor VIIIc) levels in excess of 60%. The bleeding time was prolonged in nine of 13 evaluable patients. Activated partial thromboplastin time was prolonged in seven patients, and five of these had factor VIIIc levels between 18 and 45%, with two patients having levels in excess of 60%. A deficiency of other coagulation factors, including factor VII, V, IX, and X, caused by a generalized diminution in protein synthesis in hypothyroidism, may have contributed to the prolongation of the APTT. The AvWS was very likely type 1 in all cases because of a normal von Willebrand factor antigen/ristocetin cofactor (vWF Ag/RCF) ratio. Acquired von Willebrand syndrome was documented via cross immunoelectrophoresis in three patients and via multimeric analysis of vWF in six patients. A definite diagnosis of AvWS type I has to be confirmed by a normal response to 1-desamino-8-D-arginine vasopressin (DDAVP). Treatment of hypothyroidism with thyroxine was associated with the disappearance of the AvWS and the bleeding diathesis. Decreased factor VIIIc, vWF Ag and vWF RCF levels (50%, 33%, and 36% respectively) before thyroxine treatment increased to normal values (97%, 93%, and 107% respectively) after treatment. The absence of bleeding, or mild bleeding, symptoms, in relation to those more commonly recognized with hypothyroidism, has led to the complication of acquired vWF deficiency being underdiagnosed. Acquired von Willebrand syndrome type I should be considered whenever hypothyroidism is diagnosed and thyroid biopsy or surgery is contemplated. The complete relief of AvWS via treatment of hypothyroidism with thyroxine is the final proof of this association and causal relationship.

Changes in Hemostasis During Treatment of Hypertriglyceridemia With a Diet Rich in Monounsaturated and n−3 Polyunsaturated Fatty Acids in Comparison With a Low-Fat Diet

High levels of fibrinogen, factor (F) VIIc, plasminogen activator inhibitor-1 (PAI-1), and plasma viscosity are associated with an increased coronary risk. As positive correlations of these parameters with triglycerides have been shown, the increased coronary risk associated with high levels of triglycerides may be assumed to be due to alterations within the hemostatic system. To reduce the coronary risk to which hypertriglyceridemic patients are exposed, dietary treatment is recommended; the optimal composition of such a diet is, however, a matter of debate. With regard to the effects on hemostasis, we compared in a sequential approach two diets for treatment of 25 nonobese male patients (age, mean±S.D., 40.4±8.7 years) with fasting triglycerides >2.3 mmol/l. The first diet (high fat) was rich in monounsaturated fatty acids (MUFA) and marine n−3 polyunsaturated fatty acids (PUFA), whereas the second diet (low-fat) was rich in complex carbohydrates and dietary fiber. The high-fat diet induced a significant lowering of FIIc, FIXc, FXc, FVIIc, FVIIa, FXIIa, PAI-1, plasma viscosity, and platelet activity, but led to an increase in fibrinogen, whereas the low-fat diet lowered FXIIc values and induced a nonsignificant decrease in fibrinogen. Probands on this diet had a slightly higher FVIIa and platelet activity than those on the high-fat diet. However, as all changes appeared to be within the normal range of each hemostatic parameter, it remains to be clarified whether the likely beneficial effects of the high-fat diet on most hemostatic factors are outweighed by the small increase in fibrinogen levels.

Beneficial Effects of a Soy-Based Dietary Supplement on Lipid Levels and Cardiovascular Risk Markers in Type 2 Diabetic Subjects

Consumption of soy protein has recently been shown to improve the blood lipid levels in nondiabetic subjects. The purpose of this study was to evaluate if a dietary supplement of soy protein, isoflavones, and cotyledon fiber (Abalon) affects cardiovascular risk markers, blood glucose, and insulin levels in type 2 diabetic subjects. Twenty type 2 diabetic subjects participated in a crossover trial. They were randomized to double-blind supplementation for 6 weeks with Abalon (soy protein [50 g/day] with high levels of isoflavones [minimum 165 mg/day] and cotyledon fiber [20 g/day]) or placebo (casein [50 g/day] and cellulose [20 g/day]), separated by a 3-week wash-out period. The results are expressed as means +/- SD. The percentage mean treatment difference between Abalon and placebo demonstrated significantly lower mean values after Abalon for LDL cholesterol (10 +/- 15%, P < 0.05), LDL/UHDL ratio (12 +/- 18%, P < 0.05), apolipoprotein (apo) B100 (30 +/- 38%, P < 0.01), triglycerides (22 +/- 10%, P < 0.05), and homocysteine (14 +/- 21%, P < 0.01), whereas the total cholesterol value tended to be less significant but still lower (8 +/- 15%, P < 0.08). No change occurred in HDL cholesterol, apo B100/apo A1 ratio, plasminogen activator inhibitor 1, factor VIIc, von Willebrand factor, fibrinogen, lipoprotein(a), glucose, HbA1c, or 24-h blood pressure. These results indicate beneficial effects of dietary supplementation with Abalon on cardiovascular risk markers in type 2 diabetic subjects. This improvement is seen even in individuals with near-normal lipid values.

Relations between coagulation profiles, lipid profiles, and other risk factors with risk of first-ever ischemic stroke: a novel case-control study

P156 Background and objectives: Several hemostatic factors and lipid parameters are associated with risk of coronary heart disease. Few studies have investigated the relations between these factors and risk of ischemic stroke. The major aim of this study was to estimate the risks of hypercoagulability, hyperlipidemia, hypertension, and hyperglycemia in acquiring first-ever ischemic stroke. An ancillary aim was to observe changes including biochemical and coagulation profiles in first-ever ischemic stroke inpatients from admission to 3 months later. Methods: One hundred and forty-four first-ever ischemic stroke inpatients and two types of controls (including 142 stable ischemic stroke outpatients and 181 non-stroke outpatients) were recruited from 1996 to 1999. Uric acid and glucose levels, status of hypertension, diabetes, left ventricular hypertrophy (LVH), and atrial fibrillation (AF), and coagulation (clotting times, fibrinogen, factor VIIc, and factor VIIIc) and lipid (cholesterol, triglyceride, HDL-C and LDL-C) profiles were obtained. Results: The proportions of cases with elevated fibrinogen and factor VIIIc from admission to 3 months later were significantly higher than those of non-stroke controls, either with or without anticoagulants. The proportions of cases with decreased HDL-C and hyperglycemia were also significantly higher than those of non-stroke controls. After adjusting for multiple cardiovascular risk factors, elevated fibrinogen (OR=3.21; p=0.0071), hyperglycemia (OR=2.65; p=0.0076), hypertension (OR=1.97; p=0.0424), history of LVH (OR=3.15; p=0.0010), and carotid plaque states (OR=2.27; p=0.0185) were significantly associated with risk of first-ever ischemic stroke. Elevated factor VIIIc was at borderline significance level (OR=2.12; p=0.0722). Conclusion: Hypertension, hyperglycemia, LVH and positive carotid plaque were associated with risk of first-ever ischemic stroke. Elevated fibrinogen and factor VIIIc were also associated with first-ever ischemic stroke, indicating a role of coagulation profiles in the pathogenesis of ischemic stroke.

Relations between coagulation profiles, lipid profiles, and other risk factors with risk of first-ever ischemic stroke: a novel case-control study

P156 Background and objectives: Several hemostatic factors and lipid parameters are associated with risk of coronary heart disease. Few studies have investigated the relations between these factors and risk of ischemic stroke. The major aim of this study was to estimate the risks of hypercoagulability, hyperlipidemia, hypertension, and hyperglycemia in acquiring first-ever ischemic stroke. An ancillary aim was to observe changes including biochemical and coagulation profiles in first-ever ischemic stroke inpatients from admission to 3 months later. Methods: One hundred and forty-four first-ever ischemic stroke inpatients and two types of controls (including 142 stable ischemic stroke outpatients and 181 non-stroke outpatients) were recruited from 1996 to 1999. Uric acid and glucose levels, status of hypertension, diabetes, left ventricular hypertrophy (LVH), and atrial fibrillation (AF), and coagulation (clotting times, fibrinogen, factor VIIc, and factor VIIIc) and lipid (cholesterol, triglyceride, HDL-C and LDL-C) profiles were obtained. Results: The proportions of cases with elevated fibrinogen and factor VIIIc from admission to 3 months later were significantly higher than those of non-stroke controls, either with or without anticoagulants. The proportions of cases with decreased HDL-C and hyperglycemia were also significantly higher than those of non-stroke controls. After adjusting for multiple cardiovascular risk factors, elevated fibrinogen (OR=3.21; p=0.0071), hyperglycemia (OR=2.65; p=0.0076), hypertension (OR=1.97; p=0.0424), history of LVH (OR=3.15; p=0.0010), and carotid plaque states (OR=2.27; p=0.0185) were significantly associated with risk of first-ever ischemic stroke. Elevated factor VIIIc was at borderline significance level (OR=2.12; p=0.0722). Conclusion: Hypertension, hyperglycemia, LVH and positive carotid plaque were associated with risk of first-ever ischemic stroke. Elevated fibrinogen and factor VIIIc were also associated with first-ever ischemic stroke, indicating a role of coagulation profiles in the pathogenesis of ischemic stroke.