Factor VIIc Research Articles

Greater Fish, Fruit, and Vegetable Intakes Are Related to Lower Incidence of Venous Thromboembolism

Little is known about the role of dietary intake in the development of deep vein thrombosis or pulmonary embolus (venous thromboembolism [VTE]). Homocysteine, factor VIII, and von Willebrand factor levels, risk factors for VTE, are influenced by dietary intake. We tested the hypothesis that foods rich in B vitamins and omega-3 fatty acids are negatively associated and meat intake is positively associated with incidence of VTE. In a prospective study over 12 years, 14,962 middle-aged adults participating in the Atherosclerosis Risk in Communities study were followed up for incident VTE. All hospitalizations were identified, and 196 VTEs were validated by chart review. A food frequency questionnaire assessed dietary intake at baseline and year 6. In separate proportional hazards regression analyses, risk of developing VTE was computed across quintiles of selected nutrients, major food groups, and the Western diet pattern, with adjustment for demographic and lifestyle factors, body mass index, and diabetes. Hazard ratios and 95% confidence intervals of VTE incidence across quintiles of fruit and vegetable intake were 1.0 (reference), 0.73 (0.48 to 1.11), 0.57 (0.37 to 0.90), 0.47 (0.29 to 0.77), and 0.59 (0.36 to 0.99) (P(trend)=0.03). Eating fish 1 or more times per week was associated with 30% to 45% lower incidence of VTE for quintiles 2 to 5 compared with quintile 1, suggestive of a threshold effect. Hazard ratios of VTE across quintiles of red and processed meat intake were 1.0, 1.24 (0.78 to 1.98), 1.21 (0.74 to 1.98), 1.09 (0.64 to 1.87), and 2.01 (1.15 to 3.53) (P(trend)=0.02). Hazard ratios were attenuated only slightly after adjustment for factors VIIc and VIIIc and von Willebrand factor. A diet including more plant food and fish and less red and processed meat is associated with a lower incidence of VTE.

Levels of intrinsic coagulation factors and the risk of myocardial infarction among men: opposite and synergistic effects of factors XI and XII

AbstractThe role of the intrinsic coagulation system on the risk of myocardial infarction is unclear. In the Study of Myocardial Infarctions Leiden (SMILE) that included 560 men younger than age 70 with a first myocardial infarction and 646 control subjects, we investigated the risk of myocardial infarction for levels of factor XI (factor XIc) and factor XII (factor XIIc). Furthermore, the risks for factor VIII activity (factor VIIIc) and factor IX activity (factor IXc) were assessed. Factor XIc was 113.0% in patients compared with 109.8% in control subjects (difference, 3.2%; 95% CI, 1.1%-5.4%). The risk of myocardial infarction adjusted for age for men in the highest quintile compared with those in the lowest quintile was 1.8-fold increased (ORadj, 1.8; 95% CI, 1.2-2.7). In contrast, factor XIIc among patients with myocardial infarction was lower than in control subjects, respectively, 93.0% and 98.6% (difference, 5.6%; 95% CI, 3.3%-7.9%). The odds ratio of myocardial infarction for men in the highest quintile versus those in the lowest quintile was 0.4 (ORadj, 0.4; 95% CI, 0.2-0.5). The highest risk was found among men with both high factor XIc and low factor XIIc (analyses in tertiles: ORadj, 6.4; 95% CI, 2.2-18.0). Factor VIIIc increased the risk of myocardial infarction although not dose dependently. Factor IXc increased the risk; odds ratio of myocardial infarction for men in the highest quintile versus those in the lowest quintile was 3.2 (ORadj, 3.2; 95% CI, 2.0-5.1). Thus, factors XIc and XIIc have opposite and synergistic effects on the risk of myocardial infarction in men; factor VIIIc and factor IXc increase the risk.

Relationship of Circulating Biomarkers of Inflammation and Hemostasis with Preclinical Atherosclerotic Burden in Nonsmoking Hypercholesterolemic Men

Relations of mediators of inflammation and hemostasis with preclinical atherosclerosis have been poorly analyzed. The aim of this study was to test potential associations of these blood markers with indicators of cardiovascular risk and atherosclerotic burden in asymptomatic, nonsmoking, hypercholesterolemic men. A total of 87 men underwent cardiovascular risk assessment by means of 10-year Framingham risk calculation (median 9%) and atherosclerotic burden evaluation by means of ultrasonographic measurement of common carotid intima-media thickness and assessment of atherosclerotic plaques at three arterial sites (three-site plaques). Of the markers C-reactive protein, tumor necrosis factor-alpha, interleukin-10, factor VIIc, fibrinogen, plasminogen activator inhibitor-activator, soluble intercellular adhesion molecule-1, soluble P-selectin (sP-selectin), and von Willebrand factor, only sP-selectin was positively and independently associated with high Framingham risk score (>9%) (71.7 +/- 3.6 ng/mL, n = 33 v 59.6 +/- 2.8, n = 54; mean +/- SEM; P < .05) and with three-site plaques (75.4 +/- 5.7 ng/mL, n = 14 v 62.0 +/- 2.5, n = 73; P < .05). After adjustment for all of the above markers and for cardiovascular risk factors, odd ratios of having high Framingham risk and three-site plaques were 3.38 (1.43 to 10.21) and 5.23 (1.74 to 23.52) respectively, per 1-standard deviation increase in sP-selectin. These results confirm that among several hemostasis and inflammation mediators, only sP-selectin blood level was associated with preclinical atherosclerosis. It might confer to sP-selectin measurement a clinical usefulness for detecting and managing high cardiovascular risk in primary prevention.

Análise de marcadores de estabilização da placa aterosclerótica após evento coronariano agudo

To evaluate the length of time required for atherosclerotic plaque stabilization in acute coronary syndromes (ACS), using inflammatory markers. In this prospective study, C-reactive protein (CRP), fibrinogen, factor VIIIc, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels were measured on admission, at discharge, and three and six months post-discharge in 40 patients with non-ST-segment elevation ACS (NSTE-ACS) and 40 healthy subjects. C-reactive protein levels were significantly higher on admission and at discharge, but not at three and six months post-discharge, compared with the control group. Fibrinogen levels remained unchanged, except at six months, when they were significantly lower than in the control group. Factor VIII-c did not differ from that of the control group on admission, but it was significantly higher at discharge, with no differences at three and six months. Interleukin-6 levels were significantly higher than in the control group in all time points. However, they declined significantly between discharge and three months. In no time point was TNF-alpha significantly different from that of the control group. Only IL-6 correlated significantly and independently with future cardiovascular events. With respect to CRP and factor VIIIc, plaque stabilization is suggested in up to three months; IL-6 analysis suggests stabilization as from the third month, although it remained higher than that of the control group for up to six months. Only IL-6 showed prognostic value for further events within a year.

Perinatal Stroke in Twins Without Co-twin Demise

Perinatal stroke in twins without co-twin demise has not been well-described. In this study, the International Classification of Diseases- 9th edition code searches and medical record review were used to identify all children with arterial ischemic stroke examined in a pediatric stroke clinic over a 2-year period. Four of the 35 children (11.4%) with perinatal arterial ischemic stroke were twins; none had co-twin demise. No co-twin had any clinical evidence of perinatal stroke. The most common findings on prothrombotic evaluation were elevated antiphospholipid antibodies (2), elevated lipoprotein a (2), and elevated Factor VIIIc (2). Twin gestation without co-twin demise may be a risk factor for perinatal stroke, and might help explain the higher incidence of cerebral palsy in twins.

Potentiation of angiogenic switch in capillary endothelial cells by cAMP: A cross-talk between up-regulated LLO biosynthesis and the HSP-70 expression

During tumor growth and invasion, the endothelial cells from a relatively quiescent endothelium start proliferating. The exact mechanism of switching to a new angiogenic phenotype is currently unknown. We have examined the role of intracellular cAMP in this process. When a non-transformed capillary endothelial cell line was treated with 2 mM 8Br-cAMP, cell proliferation was enhanced by approximately 70%. Cellular morphology indicated enhanced mitosis after 32-40 h with almost one-half of the cell population in the S phase. Bcl-2 expression and caspase-3, -8, and -9 activity remained unaffected. A significant increase in the Glc(3)Man(9)GlcNAc(2)-PP-Dol biosynthesis and turnover, Factor VIIIC N-glycosylation, and cell surface expression of N-glycans was observed in cells treated with 8Br-cAMP. Dol-P-Man synthase activity in the endoplasmic reticulum membranes also increased. A 1.4-1.6-fold increase in HSP-70 and HSP-90 expression was also observed in 8Br-cAMP treated cells. On the other hand, the expression of GRP-78/Bip was 2.3-fold higher compared to that of GRP-94 in control cells, but after 8Br-cAMP treatment for 32 h, it was reduced by 3-fold. GRP-78/Bip expression in untreated cells was 1.2-1.5-fold higher when compared with HSP-70 and HSP-90, whereas that of the GRP-94 was 1.5-1.8-fold lower. After 8Br-cAMP treatment, GRP-78/Bip expression was reduced 4.5-4.8-fold, but the GRP-94 was reduced by 1.5-1.6-fold only. Upon comparison, a 2.9-fold down-regulation of GRP-78/Bip was observed compared to GRP-94. We, therefore, conclude that a high level of Glc(3)Man(9)GlcNAc(2)-PP-Dol, resulting from 8Br-cAMP stimulation up-regulated HSP-70 expression and down-regulated that of the GRP-78/Bip, maintained adequate protein folding, and reduced endoplasmic reticulum stress. As a result capillary endothelial cell proliferation was induced.

Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study

Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study

The association of markers of inflammation with weight change in older adults: the Cardiovascular Health Study

Elevated levels of inflammation factors often precede weight loss and may be causally related to it. Newer studies suggest that elevated levels of inflammation factors also precede weight gain. In this study, we examined whether inflammation factors are elevated in individuals, age >or=65 years, who lost or gained >5% weight over a 3 year follow-up period compared to those with stable weight. In total, 3254 participants in the Cardiovascular Health Study whose weight was stable; 661 who gained >5% weight; and 842 who lost >5% weight. C-reactive protein (CRP), fibrinogen, factor VIIIc, white blood cell (WBC) and platelet counts, and interleukin-6 (IL-6) levels. As compared to participants whose weight was stable, those who lost >5% weight had higher baseline CRP concentration (1.05 (95% CI, 1.02, 1.08) per interquartile increase) and WBC count (1.10 (1.01, 1.19) per interquartile increase) on adjusted analyses. Those who gained >5% weight had higher baseline CRP (1.05 (1.01, 1.08)), fibrinogen (1.13 (1.01, 1.27)), and factor VIIIc (1.15 (1.03, 1.30)). Inflammation factors are associated with weight gain and weight loss in older individuals. These findings suggest that subclinical inflammation, or unknown factors associated with subclinical inflammation, contribute to weight change.

Relation of Cardiovascular Risk Factors in Women Approaching Menopause to Menstrual Cycle Characteristics and Reproductive Hormones in the Follicular and Luteal Phases

Menstrual cycle characteristics may be associated with cardiovascular disease (CVD) risk. The objective of this study was to describe the relationships between menstrual cycle characteristics and daily reproductive hormone measures with CVD risk factors in middle-aged women. Cross-sectional associations were examined between CVD risk factors and urinary LH, FSH, estrone conjugates, and pregnanediol glucuronide (Pdg) measured across one menstrual cycle or 50 d. Menstruating women (n = 500) who were free from diabetes or past stroke or heart attack enrolled in the Daily Hormone Study-Study of Women's Health across the Nation were studied. Body mass index (BMI), blood pressure, hemostatic, and metabolic factors were measured. Few differences existed in risk factors between women with evidence of luteal activity and those with no evidence of luteal activity. Associations between elevated CVD risk factors and long cycle length were reduced substantially by age and BMI adjustments. Those with lower estrone conjugate and PdG averaged across the follicular phase had higher waist circumference, triglycerides, insulin, plasminogen activator inhibitor type-1, tissue type plasminogen activator-antigen, and factor VIIc levels in age- and BMI-adjusted analyses (P < 0.05). In midlife menstruating women, a longer cycle length was related to CVD risk factors, in large part through their common association with BMI. More favorable levels of metabolic and hemostatic factors were associated with higher levels of follicular-phase estrogen, a pattern consistent with a more competent ovary, and higher levels of follicular-phase PdG, perhaps of adrenal origin. Metabolic and hemostatic factors may be sensitive to hormonal variation during the early perimenopausal transition.

Low-Fat Dietary Pattern and Risk of Cardiovascular Disease

Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed. To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk. Randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19,541 [40%]) or comparison group (29,294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years. Intensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials. Fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke). By year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits. Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk. ClinicalTrials.gov Identifier: NCT00000611.

Exchange transfusion activates coagulation and alters the coagulation profile in newborn infants

Exchange transfusion (ET) with adult blood is a standard procedure for neonates with severe hyperbilirubinemia. How ET affects newborn coagulation system remains, however, largely unknown. Thus, we prospectively evaluated the effect of ET on thrombin formation and coagulation profile in 18 newborns (22 ETs). Prothrombin fragment F1+2 and thrombin-antithrombin complexes increased considerably during ET while platelets were significantly reduced. Protein C increased less (p < 0.001) and factor VIIIc more (p < 0.001) than expected based on their levels in the infused blood. Further, in vitro thrombin generation initiated by 5 pM tissue factor was analysed. Before the first ET, newborn endogenous thrombin potential (ETP) and thrombin peak remained at approximately 60% of adult control plasma levels, but the lag time to thrombin burst in newborn plasma was approximately 45% shorter than the lag time in adult plasma. At the end of the first ET, the thrombin burst still started approximately 35% earlier in newborn than adult plasma, whereas ETP and thrombin peak were increased to > 90% of adult levels. ETP and peak remained elevated at adult levels until the beginning of the second ET. APC-induced reductions in newborn ETP remained unaltered throughout the first ET. The reductions of ETP by APC were less pronounced in newborn than adult plasma (p < 0.0001). We conclude that ET is associated with multiple procoagulant changes and increased in vivo thrombin formation. This ET-induced procoagulant challenge may be of clinical significance in sick newborns already prone to bleeding and thrombotic complications.

New Coagulation Assays Reference Ranges for Healthy Adults Using the Modern Sysmex CA-1500 Coagulometer.

Reference ranges (RRs) in coagulation are applicable only to specific analyser and reagent combinations and frequently need to be re-established if any of these are changed. In no other sphere of clinical laboratory practice are RRs more affected by such a wide range of multiple demographic and pre-analytical variables. For most routine clinical laboratories therefore, the collection of multiple, separate RRs is not feasible so a representative group of healthy adults such as laboratory staff frequently constitute the reference population from which these limits are calculated. Early morning venous samples were collected into glass B-D Vacutainers (Ref: 367691) from 221 healthy laboratory personnel (F= 159; M = 62) aged 20–63 yrs for both gender. Age groups were equally represented. Samples were processed on a Sysmex CA-1500 analyser within 1 hour of collection. Appropriate NCCLS guidelines were followed throughout. Reagents employed were - Actin FSL (APTT); Innovin (PT); Dade-Behring reference, calibration and deficient plasmas (factor assays); Dade-Behring kit ref: OWWR15 (ATIII); Chromogenix kit ref: 82209863 (Protein C). Outliers were excluded, data examined for normal distribution from histograms and significance levels calculated from the Anderson - Darling test of normality. RRs for normally distributed parameters were calculated using means ± 2SDs. RRs for non-normally distributed parameters were calculated using the log natural transformation and the antilog of 2.5- and 97.5- percentiles. Italicised parameters shown below are non-normally distributed.ParameterReference RangeAnderson Darling P-Value P-value for normal distributionMann Whitney U-test (M versus F) *=significant differencePT sec10.0 – 11.8<0.0050.003*APTT sec24.7 – 31.70.0060.232TCT sec13.8 – 17.40.0350.198Fib g/L Clauss1.6 – 4.20.190t-test not significantFib g/L Derived2.1 – 4.90.200t-test not significantII %82 – 133<0.0050.019*V%70 – 1500.0210.303VII %60 – 1640.0080.037*X%75 – 1470.539t-test not significantVIII %48 – 204<0.0050.520IX %65 – 142<0.0050.275XI %61 – 142<0.0050.394XII %59 – 1330.088t-test not significantProtein C %75 – 1600.0360.024*ATIII %86 – 1280.329t-test not significantKruskal Wallis tests on our data indicate that all coagulation factors are positively associated with age except factors IX and XII. Significant differences (p=0.014) in factor VIIIc was found between those of blood group O and non group O. Significant correlation was found between declining APTTs and associated increasing factor VIIIc when measured in individual volunteers.

Which Hemostatic Markers Add to the Predictive Value of Conventional Risk Factors for Coronary Heart Disease and Ischemic Stroke?

Few studies have examined whether hemostatic markers contribute to risk of coronary disease and ischemic stroke independently of conventional risk factors. This study examines 11 hemostatic markers that reflect different aspects of the coagulation process to determine which have prognostic value after accounting for conventional risk factors. A total of 2398 men aged 49 to 65 years were examined in 1984 to 1988, and the majority gave a fasting blood sample for assay of lipids and hemostatic markers. Men were followed up for a median of 13 years, and cardiovascular disease (CVD) events were recorded. There were 486 CVD events in total, 353 with prospective coronary disease and 133 with prospective ischemic stroke. On univariable analysis, fibrinogen, low activated protein C ratio, D-dimer, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) were associated significantly with risk of CVD. On multivariable analyses with conventional risk factors forced into the proportional hazards model, fibrinogen, D-dimer, and PAI-1 were significantly associated with risk of CVD, whereas factor VIIc showed an inverse association (P=0.001). In a model that contained the conventional risk factors, the hazard ratio for subsequent CVD in the top third of the distribution of predicted risk relative to the bottom third was 2.7 for subjects without preexisting CVD. This ratio increased to 3.7 for the model that also contained the 4 hemostatic factors. Fibrinogen, D-dimer, PAI-1 activity, and factor VIIc each has potential to increase the prediction of coronary disease/ischemic stroke in middle-aged men, in addition to conventional risk factors.

Hemostatic Factors and Estrogen during the Menopausal Transition

It has been speculated that gender differences in cardiovascular disease (CVD) mortality can be attributed to the effects of estrogens on inflammation and hemostatic marker profiles. Therefore, we evaluated endogenous hormone concentrations, menopause transition stages, and adoption of exogenous hormone use in relation to hemostatic and inflammation marker concentrations in women. Longitudinally, we studied 3302 participants from the Study of Women's Health Across the Nation, aged 42-52 yr at baseline and self-identified as African-American (28%), Caucasian (47%), Chinese (8%), Hispanic (8%), or Japanese (9%). Serum samples from baseline and years 2001, 2003, and 2005 were assayed for estradiol and FSH. Hormone concentrations were related to CVD markers, including fibrinogen, factor VII-c, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator, and human serum C-reactive protein (hsCRP). Lower estradiol levels were associated with higher levels of PAI-1 and tissue plasminogen activator, but there were no significant relationships with fibrinogen, factor VII-c, or hsCRP. Higher FSH concentrations were associated with higher PAI-1 and factor VII levels, but lower fibrinogen and hsCRP levels. Transitions from premenopause and early perimenopause to postmenopause were not associated with significant differences in levels of hemostatic factors. The hsCRP concentrations were approximately 25% higher, and the PAI-1 concentrations approximately 20% lower among women who initiated hormone therapy, compared with nonusers. Endogenous estrogens may reduce CVD risk via modulation of fibrinolytic factors, but not coagulation or inflammatory markers. Notably, conclusions derived from studies of exogenous hormones and CVD risk may not parallel or explain the effects of endogenous hormones or perimenopausal hormone changes on CVD risk.

Androgens Are Associated with Hemostatic and Inflammatory Factors among Women at the Mid-Life

The goal of this study was to relate annually measured endogenous androgens to hemostatic and inflammation markers in women longitudinally. A total of 3302 participants from the Study of Women's Health Across the Nation, aged 42-52 yr at baseline and self-identified as African-American (28%), Caucasian (47%), Chinese (8%), Hispanic (8%), or Japanese (9%) were evaluated for testosterone (T), dehydroepiandrosterone sulfate, and SHBG at four time points in 5 yr. Cardiovascular disease markers were fibrinogen, activated factor VII-c, C-reactive protein (hsC-RP), and the fibrolytic factors, plasminogen activator inhibitor type 1 (PAI-1), and tissue plasminogen activator [t(PA)]. T and free androgen index (FAI) were associated highly positively with PAI-1 and t(PA), and FAI was associated highly and positively with hsC-RP. Lower SHBG levels, associated with greater bioavailable T, were associated significantly with higher levels of PAI-1, t(PA), hsC-RP, and factor VII-c. SHBG was lower in Chinese and Japanese women markedly, resulting in FAI values that, on average, were higher among Chinese and Japanese women compared with African-American, Caucasian, and Hispanic women. There were strong, positive associations of androgens with fibrolytic and inflammation markers, even after considering age, body size, smoking, and race/ethnicity. It is important to study androgens, their precursors, and their carrier protein as part of the risk profile for heart disease in mid-aged women.

A Diet Rich in High-Oleic-Acid Sunflower Oil Favorably Alters Low-Density Lipoprotein Cholesterol, Triglycerides, and Factor VII Coagulant Activity

Objective To compare concentrations of factor VII coagulant activity (factor VIIc), fibrinogen, plasminogen activator inhibitor-1, and blood lipids on a saturated fat-rich diet with one rich in monounsaturated fat. Design Subjects were randomly allocated to two groups. The study design was an ABB/BAA extra-period crossover. One group consumed a diet rich in saturated fatty acid (SFA) with fat making up 20.8% of total energy, for 5 weeks and then one rich in monounsaturated fatty acid (MUFA), with fat making up 20.3% of total energy for 10 weeks. The other group consumed the MUFA diet for 5 weeks followed by the SFA diet for 10 weeks. Subjects/setting Men and women aged 35 to 69 years who were nonsmokers with no chronic illness and not on any medication were recruited to participate. Eighteen subjects were recruited and 15 (5 men, 10 women) completed the community-based study. Intervention Blood was sampled at the beginning and end point of each 5-week diet period for analysis of coagulation and fibrinolysis factors and blood lipids. Subjects kept 3-day food diaries twice during each of the three diet periods and were weighed on each visit for blood collection. Analysis of plasma fatty acids was used to indicate dietary compliance. Main outcome measures Differences in fasting factor VIIc, fibrinogen, plasminogen activator inhibitor-1, insulin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoproteins A-1 and B, and plasma oleic acid levels while receiving the SFA diet vs MUFA diet. Statistical analysis A general linear model allowing for the ABB/BAA extra-period crossover, was used for each of the outcome measures. Results Factor VIIc was lower on the MUFA diet ( P<.05) but fibrinogen and insulin concentrations and plasminogen activator inhibitor-1 activity did not differ between diets. Low-density lipoprotein cholesterol ( P<.001) and triglyceride ( P<.01) levels were lower on the MUFA diet compared with the SFA diet. A significant increase in both plasma phospholipid and neutral lipid oleic acid ( P<.0001) occurred on the MUFA diet. Conclusions Substitution of foods rich in saturated fat with foods rich in high-oleic-acid sunflower oil and margarine has favorable outcomes on blood lipids and factor VIIc. This oil presents another useful source of MUFA for diets aimed at prevention of heart disease.

Trombophilic screening for nonarteritic anterior ischemic optic neuropathy

Nonarteritic anterior ischemic optic neuropathy (NAION) is an ischemic infarction of the optic nerve head, frequently leading to sudden, mostly irreversible loss of vision. In this study blood thrombophilic factors, as well as cardiovascular risk factors were investigated for their relevance to this pathology. Trombophilic risk factors so far not evaluated were included in the study. 37 NAION patients (4 with sequential second eye involvement) and 81 matched control subjects were examined. From blood, protein C, protein S, antithrombin, von Willebrand antigen levels (vWFAg), and factor V (Leiden) mutation, factor VIIIC level, plasminogen activity, lipoprotein (a) and fibrinogen levels, and presence of anticardiolipin antibodies were investigated. Possibly relevant pathologies [e.g. diabetes mellitus (DM), hypertension, and ischemic heart disease] were also registered. Elevated Lp(a) and vWFAg levels, DM, F V (Leiden), hypercholesterolemia, and hyperfibinogenemia proved to be significant risk factors associated with NAION. Forward stepwise logistic regression analysis revealed that high Lp(a), DM, and FV (Leiden) were the main predictive components, with odds ratios 16.88 (p=0.012), 5.78 (p=0.022) and 4.44 (p=0.033), respectively. Based on our results it appears that thrombophilia is likely to contribute to the development of NAION besides vascular damage due to the presence of cardiovascular risk factors. Further data are needed, however, to justify the suggested use of secondary prophylaxis using anticoagulant/antiplatelet therapy.

Dyslipidemia and Thrombosis: Causal Relationship or Epiphenomenon of Sedentary Lifestyle?

To the Editor: Doggen et al report that low HDL cholesterol and high triglyceride levels are associated with an increased risk for venous thrombosis in a population-based case–control study. The authors explain their results with an interaction of triglycerides with different coagulant factors as activated protein C (APC), factor VIIc, factor VIII, factor IX, and fibrinogen.1 However, low HDL cholesterol and high triglycerides are found frequently in subjects with a predominantly sedentary lifestyle and are key features of the metabolic syndrome.2 Individuals with the metabolic syndrome are characterized by prothrombotic hemostatic abnormalities such as elevated plasma fibrinogen, elevated …

A protective contribution of the Q allele of the R353Q polymorphism of the Factor VII gene in individuals with chronic stable angina?

Background Factor VII polymorphisms have been suggested in some studies to show an association with some aspects of coronary disease, and there is a known association between FVII levels and polymorphic variants in the gene. The aim of the study was to assess whether Factor VII polymorphism R353Q is associated with the extent of coronary artery disease in patients with chronic stable angina. Methods and results There is evidence that Factor VII polymorphisms are markers of susceptibility to coronary artery disease (CAD), but two studies have suggested that there is no association between the degree of vessel disease and these polymorphisms. One of these studies did not exclude patients with unstable angina or MI. We therefore set up a prospective cohort study to determine Factor VIIa, VIIc and VIIAg levels, genotype for R353Q, lipid status, smoking history and the degree of vessel disease, in patients attending the hospital for routine day case angiography over a 20 month period. From 519 cases, 400 had no previous MI or revascularisation, including 153 with zero vessel disease, and were successfully genotyped: 9 (2%) QQ, 78 (20%) RQ and 313 (78%) RR. Compared with RR subjects, heterozygotes were 2.7 years older (95% CI: 0.3, 5.0; p=0.027), but were not significantly different regarding gender, cholesterol, extent of vessel disease or smoking history. If those with vessel disease were considered, then the heterozygotes were 3.5 years older than the RR homozygotes (95% CI: 0.6–6.4, p=0.016). There was a significant association between all measures of Factor VII and the R353Q polymorphism, with the Q allele associating with lower levels. There was no significant association between the degree of vessel disease and genotype. Conclusions The degree of vessel disease as seen at day case angiography is independent of polymorphism status, but there appears nonetheless to be a moderate protective effect of the Q allele against stable angina, in that angiographic investigation occurs a few years later for RQ heterozygotes than RR homozygotes. The effect may be mediated by reduced levels of Factor VII.

Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review

Combined oral contraceptives, oral hormone replacement therapy and thrombophilias are recognised risk factors for venous thromboembolism in women. The objective of this study was to assess the risk of thromboembolism among women with thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. Seven studies included pre-menopausal women on oral contraceptives and two studies included peri-menopausal women on hormone replacement therapy. For oral contraceptive use, significant associations of the risk of venous thromboembolism were found in women with factor V Leiden (OR 15.62; 95%CI 8.66 to 28.15); deficiencies of antithrombin (OR 12.60; 95%CI 1.37 to 115.79), protein C (OR 6.33; 95%CI 1.68 to 23.87), or protein S (OR 4.88; 95%CI 1.39 to 17.10), elevated levels of factor VIIIc (OR 8.80; 95%CI 4.13 to 18.75); and factor V Leiden and prothrombin G20210A (OR 7.85; 95%CI 1.65 to 37.41). For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47). Although limited by the small number of studies, the findings of this study support the presence of interaction between thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, thrombophilias with venous thromboembolism among hormone users.