Higher Factor VII Levels Research Articles

Changes in procoagulants track longitudinally with insulin resistance: findings from the Coronary Artery Risk Development in Young Adults (CARDIA) study

To examine the association between changes in procoagulants (fibrinogen factors VII and VIII and von Willebrand factor) and the risk of insulin resistance. Using data from the Coronary Artery Risk Development in Young Adults study, we followed 2398 black and white adults without diabetes, aged 25-37years at year7, to year20. Levels of fibrinogen factors VII and VIII and von Willebrand factor were divided in tertiles (low/middle/high) at years7 and 20 and four groups reflecting changes were defined: 'low' (low at years7 and 20), 'stable' (low/middle at years7 and 20, but not both low at years7 and 20), 'high' (high at year7 and low/middle at year20; or low/middle at year7 and high at year20) and 'highest' (high at years7 and 20). Linear regression models were used to evaluate 13-year changes (year20-year7) in fibrinogen level and factors VII, VIII and von Willebrand change groups in relation to insulin resistance measures. Homeostasis model assessment of insulin resistance (year20) and changes in log homeostasis model assessment of insulin resistance (year20-year7) were significantly associated with the 13-year increase in fibrinogen (P<0.001). Compared with participants in the low group, those in the high group had significantly higher levels of homeostasis model assessment of insulin resistance (year20) and changes in homeostasis model assessment of insulin resistance (year20-year7) for fibrinogen factor VII and von Willebrand factor (P<0.017). No significant associations were observed between fibrinogen VIII and insulin resistance measures. An increase in fibrinogen level and persistently high levels of factor VII and von Willebrand factor are significantly associated with increased risk of insulin resistance. These findings provide new insight into the mechanisms to explain the heightened risk for thrombosis in adults with insulin resistance/diabetes.

Metabolic Syndrome Predicts Frailty

SAN FRANCISCO — Elderly individuals who have metabolic syndrome are about twice as likely to become frail as those who are healthy, Dr. Joshua I. Barzilay reported in a poster presentation at the Third World Congress on Insulin Resistance Syndrome. The study involved 2,376 individuals aged 69–74 who were followed prospectively for 7–9 years. At baseline none of the participants were frail, nor did they have other illnesses that increase inflammation markers or mimic frailty, reported Dr. Barzilay, of Emory University, Atlanta, and his colleagues. A participant was considered frail if he or she met at least three of the following five criteria: unintentional weight loss of 10 pounds or more in the previous year, low grip strength, self-reported exhaustion, slowness in walking, and low exercise tolerance. A participant was considered “prefrail” if he or she met one or two of the criteria. At the end of follow-up, 169 participants qualified as frail and another 1,082 qualified as prefrail. The three most commonly seen components of frailty were diminished walking speed, diminished strength, and diminished activity, all of which are consistent with sarcopenia. Participants who developed frailty or prefrailty had significantly higher fasting insulin levels, higher white blood cell counts, higher C-reactive protein levels, and higher factor VII levels than those who didn't develop frailty. These participants were 30%–100% more likely to have metabolic syndrome at baseline, compared with those who did not develop frailty or prefrailty. The most common components of the metabolic syndrome in this cohort were increased girth and increased homeostatic model assessment scores. They were also significantly more likely to have developed diabetes at follow-up. In view of the fact that frailty was defined mostly by sarcopenia, the investigators wrote, insulin resistance, inflammation, and frailty are all related to a primary disorder of muscle metabolism.

Association of depressive symptoms with coagulation factors in young healthy individuals

Background Depression has been reported to be an independent risk factor for coronary heart disease (CHD). We investigated the association of depressive symptoms with lipids and coagulation factors in young individuals free of CHD. Methods We recruited 1073 young healthy individuals candidates for military academies (mean age = 18.4 ± 0.8 years, males 762) in whom the presence of depressive symptoms was assessed by using the depression scale of Minnesota Multiphasic Personality Inventory test. Total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, lipoprotein (a), fibrinogen, factors VII, VIII and X were measured. Results The depression score ranged from 22 to 90. The participants were divided into quartiles according to the depression score. Three hundred twenty-two subjects were classified in the upper quartile (score > 48) and 269 in the lower quartile (score < 37) of the depression score. Factor VII (102.95 ± 24 versus 98.5 ± 20%) and X levels (92 ± 11 versus 89.7 ± 10%) were significantly higher in individuals in the upper quartile compared to the lower quartile of the depression score. In a logistic regression model with factor VII as dependent variable (upper versus lower quartile) and depression score, age, gender, body mass index, exercise and smoking as predictor variables, depression was an independent predictor of factor VII levels with an adjusted odds ratio for high levels of factor VII of 1.05 (95% confidence interval 1.008–1.09, p = 0.01). Factor VII levels were associated with triglycerides ( r = 0.21, p = 0.001) while factor X with triglycerides ( r = 0.22, p < 0.001) and cholesterol levels ( r = 0.12, p < 0.001). Conclusions Depressed mood is associated with a hypercoagulant profile as it is expressed by the higher levels of coagulation factors VII and X. This might partially explain the higher propensity for CHD of people with depressive symptoms.

A Genetic Propensity to High Factor VII Is not Associated with the Risk of Myocardial Infarction in Men

SummarySeveral studies have examined the relation between factor VII and coronary artery disease by measuring factor VII levels in plasma and some found an association between high levels and disease. This suffers problems of interpretation concerning the causality of high factor VII levels, because factor VII levels may be affected by atherogenic risk factors and may become elevated as a consequence of atherosclerosis. We investigated the association between a genetic variant (353Arg→Gln), shown to be related to factor VII levels, and myocardial infarction in a large case-control study, including 560 cases and 644 controls. Individuals carrying the 353Arg-Arg genotype seemed to have a lower risk of myocardial infarction (odds ratio 0.80 [95% confidence interval 0.60-1.06]). In this study, we confirmed higher factor VII antigen and activity level in 529 men homozygous for the 353Arg allele compared with 115 men carriers of the 353Gln allele (around 20% higher).Our results indicate that a genetic propensity to high factor VII levels is not associated with the risk of myocardial infarction. Since we confirmed the association of the 353Arg-Arg genotype with higher factor VII levels, we conclude that high levels of factor VII are not a causal determinant of myocardial infarction.

Plasma factor VII levels are influenced by a polymorphism in the promoter region of the FVII gene.

Genetic factors play a role in determining the variability of plasma factor VII (FVII) levels in healthy individuals. There is also evidence that high serum lipids are associated with high FVII levels in plasma. In the promoter region of the human FVII a DNA polymorphism has been described, originating from a decanucleotide insert present in the less frequent allele. This biallelic system, reflecting the absence (AA) or presence (Aa) of the decanucleotide, can be detected by a DNA enzyme immunoassay of PCR products. We evaluated the association between the polymorphic alleles and the levels of FVII:Ag and FVII:C in 100 healthy individuals and in 19 hypertriglyceridemic individuals. Among healthy individuals, mean FVII:Ag and FVII:C levels of those with the homozygous genotype (A/A; mean FVII:Ag 112%, mean FVII:C 109%) were significantly higher (P < 0.001) than the mean levels of those with the heterozygous genotype (A/a, mean FVII:Ag 80%, mean FVII:C 90%; P < 0.001). Similar genotype-associated differences for FVII:Ag and FVII:C were found in individuals with triglycerides above 250 mg/dl (P < 0.05). FVII:C and FVII:Ag levels were positively related to triglycerides only in individuals without the insert (P < 0.01); there was no significant relationship in those carrying the allele with the insert (A/a; P = 0.43 and 0.08). Our findings of genotype-associated differences in FVII levels and interactions with triglycerides are similar to those obtained with the amino acid dimorphism at position 353 of the factor VII protein.

Factor VII, antithrombin III, leukocyte and platelet counts in a sample of black and white Zimbabwean blood donors

Studies in Southern Africa have shown that whites have significantly greater morbidity and mortality from coronary heart disease than blacks. This study investigated the distribution of some haemostatic variables known or suspected to be correlated with greater risk for coronary heart disease in healthy black and white Zimbabwean men. Factor VII, antithrombin III, leukocyte and platelet counts were measured in 56 blacks and 29 whites aged between 20 and 50 years. We found significantly greater factor VII and leukocyte counts in the whites compared to the blacks. The other variables measured were similar in the two ethnic groups. These results suggest that the greater prevalence of coronary heart disease in whites is consistent with high levels of factor VII and white blood cell counts previously identified as risk factors for this condition.

Enzyme-linked immunosorbent assay of human factor VII based upon a monoclonal antibody that recognizes the native conformation of the protein

An enzyme-linked immunoassay (ELISA) was developed for measuring human factor VII antigen using two monoclonal antibodies, one of them reacting only with fully carboxylated factor VII. This assay permits to measure factor VII antigen in concentrations ranging from 0.78 to 100 ng/ml, with within- and between-assay coefficients of variation of less then 7%.In 53 normal subjects, 32 patients with liver cirrhosis, 21 pregnant women and 53 patients on oral anticoagulant therapy the plasma levels of FVII antigen were very similar to those of factor VII coagulant activity measured with a bioassay. The ELISA also gave very similar values of factor VII antigen in plasma and in serum, and in plasma before and after exposure to cold, indicating that the assay is not affected by factor VII activation. In five of 8 patients with severe congenital deficiency of factor VII values of factor VII antigen were higher than those of factor VII activity. The close concordance of factor VII values obtained by ELISA and bioassay in the majority of plasmas , including those from patients on oral anticoagulant therapy, indicates that the assay measures native factor VII and can perhaps replace the bioassay sistems in clinical conditions associated with normal or high levels of factor VII.

Coronary artery disease and factor VII hyperactivity in elderly Japanese

High levels of factor VII (FVII) coagulant activity (FVIIc) have been associated with an increased risk of coronary artery disease and cardiac death, and are thought to be of greater significance than cholesterol in the first 5 years after screening. 1 These studies have mainly been performed in Western countries and the subjects were generally adults aged <65 years. Japan is one of the countries where the incidence of coronary artery disease is low, 2 and we have recently reported on FVII hyperactivity in the elderly Japanese. 3 This time, to study the relation between coronary artery disease and FVII in elderly Japanese persons, we performed electrocardiography and measured FVIIc and FVII antigen (FVIIag) levels as well as blood lipid fractions.

高齢者の血清尿酸値と高凝固第ＶＩＩ因子血症

To study the relationship between serum uric acid, lipid fractions, and coagulation factor VII (FVII) in the elderly, we measured FVII coagulation activity (FVIIc). FVII antigen (FVIIag), in 138 normal subjects without alcohol intake ranging in age from 60 to 98 years. We also measured blood lipid fractions including apolipoprotein A-I, A-II, B, E, and serum cholinesterase activity (ChE). Serum uric acid levels significantly correlated with FVIIc (p less than 0.01) and FVIIag levels (p less than 0.05) as well as with tryglycerides, VLDL, LDL, total cholesterol, and ChE in elderly men, but not in women. However, multiple regression analysis showed these correlations in elderly men were not significant, after excluding the effect of triglycerides and VLDL. These results also suggest that elevation of uric acid may be a coronary risk factor in elderly men through high FVII levels.

Factor VII and ischaemic heart disease: epidemiological evidence.

High levels of factor VII are associated with an increased risk of death from cardiovascular disease, especially ischaemic heart disease (IHD). Theoretical considerations and experimental evidence, the latter including the results of clinical trials, suggest that the association may be one of cause and effect. The general epidemiology of factor VII also supports this view. Thus, characteristics such as increasing age, diabetes, obesity, the use of oral contraceptives and the occurrence of the menopause are each associated with raised factor VII levels as well as with an increased risk of IHD. Black ethnic group and vegetarianism, both apparently protective against IHD, are associated with low factor VII levels.

The effect of homo- and heterologous thromboplastins on plasmas of man, seven mammalian and two avian species: A comparative study

1. 1. The effect of 4 concentrations of 6 various thromboplastins (TRPL) on plasmas of man, 7 mammalian and 2 avian species was investigated. 2. 2. Every plasma was clotted in shortest time by the homologous TRPL. 3. 3. Plasmas of near related animals exhibited no difference when tested with TRPLs of these animals. 4. 4. Plasmas with high factor VII levels were clotted in a short time. 5. 5. In rodents the clotting time of plasmas seemed to be partially dependent on the factor VII levels. 6. 6. A given TRPL did not always clot the homologous plasma in the shortest time. 7. 7. The possible role of factor VII in homo- and heterologous test system is discussed.