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Mounting data support a causal connection between high-normal fibrinogen levels and atherosclerotic cardiovascular disease. There is clearly a thrombogenic component to atherosclerosis and the onset of clinical manifestations. This offers the possibility to better identify high-risk candidates and also to protect them by reducing blood fibrinogen concentration or blocking its action. The relationship of antecedent fibrinogen to the subsequent development of cardiovascular disease is examined, based on 18 years of surveillance of a cohort of 1274 men and women aged 47 to 79 years who participated in the Framingham Study. The association with the development of peripheral arterial disease and cardiac failure is now examined in addition to previously studied relationships to coronary heart disease and stroke. In men and women, there is a significant age-adjusted relationship of fibrinogen level to coronary heart disease and to cardiovascular disease in general. In women, a significant relationship to cardiac failure and peripheral arterial disease, but not to stroke, was also found. These data on women are unique as they are not available elsewhere. Age-adjusted cardiovascular, all-cause, and coronary heart disease mortality were all related to fibrinogen in both sexes. In men, fibrinogen impact was the greatest for stroke and the least for peripheral arterial disease. For women, the impact on coronary heart disease was greatest. The absolute risk for an elevated fibrinogen level was greatest for coronary heart disease in both sexes. Average fibrinogen values are higher in women and in persons with other risk factors, including hypertension, cigarette smoking, diabetes, obesity, and elevated hematocrit. However, there is an independent contribution of fibrinogen to cardiovascular disease in general and coronary disease in particular, on adjustment for coexistent risk factors. Fibrinogen enhances the risk of cardiovascular disease in hypertensives, diabetics, and cigarette smokers. About half the cardiovascular risk of cigarette smoking appears due to the higher fibrinogen values. Now, five prospective studies document the excess incidence of cardiovascular events in persons with elevated fibrinogen levels within the "normal range." Each standard deviation increase in fibrinogen is associated with a 30% increment of coronary heart disease in men and a 40% increase in women. Fibrinogen should be added to the list of major cardiovascular risk factors. Trials of intervention to lower fibrinogen in high-risk coronary candidates are needed.
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PMID:Update on fibrinogen as a cardiovascular risk factor. 134 96

We studied 30 control women and 131 pill users to evaluate effects of birth control pills and clinical factors on hemostasis. When control patients were matched with an equal number of pill users, none of the direct markers of activated hemostasis (fibrinopeptide A, platelet factor 4, and beta thromboglobulin) were increased. Plasminogen, prekallikrein, and protein C (protective against clotting) were significantly higher in pill users. Fibrinogen, antithrombin, alpha-2 antiplasmin, and fibronectin were comparable. Among the 131 pill users, antithrombin levels decreased with a family history of thromboembolism. Fibrinogen and fibronectin were increased with obesity, but there was no evidence of activated hemostasis. Overall, pill use did not appear to result in hypercoagulability. Considering family history of thromboembolism might further improve the safety of oral contraceptive use.
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PMID:Oral contraceptives and the hemostatic system. 335 50

In over 30 years of surveillance of 2873 women, 574 developed initial clinical manifestations of CHD. A number of antecedent metabolic risk factors proved atherogenic, including blood lipids, glucose tolerance, uric acid, and menopause. Serum total cholesterol predicts as strongly in women as in men. The predictive power of cholesterol is strengthened when the total cholesterol is partitioned into its atherogenic LDL and protective HDL fractions. Contrary to the case in men, triglyceride may be a contributor to risk in older women. A total-to-HDL cholesterol ratio exceeding 7.5 equalizes the risk in men and women. Impaired glucose tolerance also eliminates the female CHD risk advantage over men, conferring a three-fold increased risk. Serum uric acid, although lower in women than in men, is equally predictive in the sexes. Central obesity confers an increased CHD risk in women and predisposes to diabetes, hyperuricemia, hypertension, and an unfavorable LDL/HDL cholesterol ratio. A combination of obesity, low HDL cholesterol, and impaired glucose tolerance predisposes especially. Age-adjusted risk of CHD is increased two- to threefold compared to pre menopausal women, even when induced surgically without removing the ovaries. It is not clear whether post menopausal estrogen replacement eliminates this excess risk. Fibrinogen is higher in women than in men, and is increased with hypertension, diabetes, hypercholesterolemia, high hematocrit, and cigarette smoking. At any level of multivariate risk, fibrinogen added to the CHD risk in women.
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PMID:Metabolic risk factors for coronary heart disease in women: perspective from the Framingham Study. 360

The ECAT Angina Pectoris Study is a European multicentre study investigating the pathogenetic and possibly predictive role of the haemostatic system in the progress of coronary heart disease. In this paper we report the cross-sectional analysis of haemostatic factors in 3043 patients, who underwent coronary angiography due to angina pectoris. Fibrinogen levels were higher in patients with one or more coronary stenoses of at least 50% than in patients without, by an average of 0.16 g.l-1 (P < 0.0001). Depressed fibrinolytic activity due to higher levels of PAI was also associated with the presence of coronary stenoses. There was no association with the extent of coronary arteriosclerosis, as assessed by the number of involved arteries, except that patients who had more vessels with total occlusions had higher fibrinogen levels. Depressed fibrinolytic activity was also clearly associated with diabetes, obesity, higher triglyceride levels, smoking and impaired cardiac pump function as assessed by ejection fraction. Cholesterol levels were particularly correlated with protein C and plasminogen.
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PMID:ECAT angina pectoris study: baseline associations of haemostatic factors with extent of coronary arteriosclerosis and other coronary risk factors in 3000 patients with angina pectoris undergoing coronary angiography. 843 97

The present study was carried out to explore the possible relation of plasma plasminogen activator inhibitor-1 (PAI-1), fibrinogen, and factor VII levels to other risk factors for coronary heart disease (CHD) and to serum sex hormone levels. The study group comprised 48 apparently healthy men. To avoid the confounding factor of obesity, correlations were determined in the 30 men in this group with a body mass index (BMI) < 26.4, after controlling for age. PAI-1 correlated with testosterone, estradiol/testosterone, and free testosterone/testosterone (FT/T), and fibrinogen correlated with FT/T. All three hemostatic factors correlated with glucose and with the ratio of cholesterol/high density lipoprotein cholesterol, while PAI-1 correlated with diastolic blood pressure. To test the effect of obesity, correlations were determined in the entire group of 48 men, which included 18 subjects with a BMI > 26.4. All three hemostatic factors correlated with BMI in this group after controlling for age; however, on controlling for testosterone, only PAI-1 correlated with BMI. Fibrinogen correlated with age in both groups after controlling for testosterone or BMI. These correlations support the hypothesis that PAI-1, fibrinogen, and factor VII are related to other risk factors for CHD and that an alteration in the sex hormone milieu may be the underlying factor linking them.
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PMID:Relation of hemostatic risk factors to other risk factors for coronary heart disease and to sex hormones in men. 846 82

Results from prevalence, case-control, angiographic and echocardiographic investigations incriminate elevated fibrinogen levels as a strong independent risk factor for the occurrence of initial and recurrent cardiovascular events. Average fibrinogen levels are higher in women and persons with other risk factors including hypertension, diabetes, cigarette smoking, obesity, elevated haematocrit value and dyslipidaemia. Fibrinogen tends to cluster with most of these major atherogenic cardiovascular risk factors and further enhances their risk. Prospective data indicate a relationship between fibrinogen and the subsequent development of all the major atherosclerotic cardiovascular events including coronary heart disease, stroke and peripheral artery disease. Fibrinogen adds to the multivariate risk of cardiovascular events, especially in the high risk subset of the population. In the Framingham Heart Study, a comparison of risk gradients, exemplified by their regression coefficients, was similar for all outcomes (coronary heart disease, stroke, peripheral artery disease and cardiovascular disease) in men, whereas, in women, the risk gradient for fibrinogen appeared weakest for stroke. Fibrinogen exerts an independent influence on the frequency of cardiovascular disease in general, and coronary heart disease in particular. For example, in both men and women, each standard deviation increase in fibrinogen level (about 0.56 g/L) within the range of usual values is associated with about a 20% age- and risk factor-adjusted increase in the incidence of an initial cardiovascular event. Fibrinogen should be added to the list of major atherogenic cardiovascular risk factors; in addition, there is a need for intervention trials designed to test the efficacy of lowering fibrinogen in individuals at high risk for cardiovascular disease.
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PMID:Influence of fibrinogen on cardiovascular disease. 936 Aug 50

Few studies have examined fibrinogen in Chinese populations in which the incidence of coronary heart disease (CHD) is lower than that in the West. This study aimed to examine the relationship between fibrinogen and other CHD risk factors in Hong Kong Chinese. Fibrinogen was measured by the Clauss method in 1359 men and 1405 women aged 25-74 years, randomly selected from the Hong Kong population. Mean fibrinogen level increased with age, from 2.22 g/l in those aged 25-34 years to 2.76 g/l in 65-74 years in men, and from 2.42 to 2.94 g/l respectively in women. The most important factors associated with fibrinogen were age, obesity and blood lipid levels in both genders. In men, smoking was associated with higher fibrinogen levels and cessation of smoking with lower levels. Prospective studies are needed to examine the role of fibrinogen in CHD in Chinese and other Asian populations.
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PMID:The relationship between fibrinogen and other coronary heart disease risk factors in a Chinese population. 1021 71

Factors operating in fetal life or during childhood may be important in determining fibrinogen and factor VII concentrations in adult life, and particularly in explaining social gradients in cardiovascular disease risk. In 1994, the authors measured fibrinogen and factor VIIc levels in 641 children aged 10-11 years (61% response rate) from schools in five towns in England and Wales. Birth weight was obtained by maternal recall, and other data on measures of fetal growth were obtained from birth records. Fibrinogen levels were higher in girls (258.8 mg/dl) than in boys (245.4 mg/dl) (95% confidence interval (CI) for difference: 5.5, 21.5). Fibrinogen and factor VIIc levels were linearly related to adiposity, rising by 37.1 mg/dl (95% CI: 24.7, 49.5) and 13.0% of standard (95% CI: 6.3, 19.7), respectively, between the bottom and top quintiles of ponderal index (weight (kg)/height (m)3). Fibrinogen was independently related to heart rate (p < 0.001) and was negatively but nonsignificantly related to measures of physical activity. Factor VIIc was positively correlated with total cholesterol (p < 0.001). No relations were found with measures of fetal growth or social class. These data do not support the concept that fibrinogen or factor VII levels are determined in utero or by social factors in childhood. Adiposity and physical training appear to be the important determinants of fibrinogen and factor VII levels in childhood.
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PMID:Fibrinogen and factor VII levels are related to adiposity but not to fetal growth or social class in children aged 10-11 years. 1051 26

The known metabolic cardiovascular disease risk factors associated with insulin resistance syndrome (IRS) do not adequately explain the excess cardiovascular disease risk attributed to this syndrome, and abnormalities in hemostatic variables may contribute to this excess risk. Using data from 322 nondiabetic elderly men and women (aged 65-100 years) participating in the Cardiovascular Health Study during 1989-1990, the authors performed factor analysis on 10 metabolic risk factors associated with IRS and 11 procoagulation, inflammation, and fibrinolysis variables to examine the clustering of the metabolic and hemostatic risk markers. Factor analysis of the metabolic variables confirmed four uncorrelated factors: body mass, insulin/glucose, lipids, and blood pressure. Adding the hemostatic variables yielded three new factors interpreted as inflammation, vitamin K-dependent proteins, and procoagulant activity. Plasminogen activator inhibitor-1 clustered with the body mass factor, supporting the hypothesis that obesity is related to impaired fibrinolysis. Fibrinogen clustered with the inflammation summary factor rather than procoagulant activity, supporting the position that fibrinogen principally reflects underlying inflammation rather than procoagulant potential. The authors conclude that should hemostatic variables be shown to contribute to IRS-related cardiovascular disease, apart from plasminogen activator inhibitor-1, they may do so independently of the established metabolic abnormalities.
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PMID:Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome. 1128

Adiposity in childhood is often associated with metabolic abnormalities and accompanied by a dysregulation of the coagulation and fibrinolytic systems. We studied the interrelationship of metabolic and hemostatic parameters and explored their relationship with measures of adiposity and fat distribution in obese children. In 34 obese boys (mean age, 11.7 years) and 57 obese girls (12.1 years), blood samples were determined for insulin, glucose, triglycerides, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and tissue-type plasminogen activator-antigen (tPA-Ag). Body composition was assessed by means of impedance. Waist (Wc) and hip circumference were measured. The thickness of subcutaneous adipose tissue-layers (SAT-layers) was measured at 15 different body sites (from 1-neck to 15-calf) by means of the optical device, Lipometer. Overall subcutaneous fatness (SAT) was calculated and SAT-distribution was estimated by means of factor analysis. Significant correlations were found between different measures of adiposity and Wc with metabolic parameters. Fibrinogen was mainly associated with upper body subcutaneous fatness (factor 1) in boys. In girls, hemostatic parameters were associated with nearly all measures of adiposity and also with factor 1 and SAT. Regression analysis showed that factor 1 together with PAI-1 (both P <.0001) contribute to fibrinogen (adjusted [adj], R(2) =.30). PAI-1 together with trigylcerides (both P <.0001) and age (P <.04) were main determinants for tPA-Ag (adj, R(2) =.41). tPA-Ag (P <.0001) together with glucose (P <.001, negative slope), fibrinogen (P <.001, negative slope), and percentage fat mass (%FM) (P <.01) contributed to PAI-1 (adj, R(2) =.54). These results favor the concept of an interrelationship between metabolic and hemostatic parameters resulting from increased adiposity, perhaps influenced by pubertal development of children. Although upper body subcutaneous fatness was found to be a main correlate of metabolic and hemostatic parameters, it remains to be investigated whether this type of subcutaneous fat distribution is involved in the expression of metabolic and hemostatic risk factors and participates in the dysregulation of the hemostatic system in the state of childhood obesity.
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PMID:Interrelationship between estimates of adiposity and body fat distribution with metabolic and hemostatic parameters in obese children. 1139 45


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