No abstract

miological studies have reported positive associations between the risk of coronary heart disease (CHD) and plasma fibrinogen levels. Fibrinogen is the major coagulation protein in blood by mass, the precursor of fibrin, and an important determinant of blood viscosity and platelet aggregation. [38][39][40][41] Because fibrinogen levels can be reduced considerably by lifestyle interventions that also affect levels of established risk factors (such as regular exercise, smoking cessation, and moderate alcohol consumption), there is interest in the possibility that measurement (or modification) of fibrinogen may help in disease prediction or prevention. [38][39][40]42 A meta-analysis of published data from 18 such studies, involving about 4000 CHD cases, indicated a relative risk of 1.8 (95% confidence interval [CI], 1.6-2.0) per 1-g/L increase in plasma fibrinogen level. 43 However, such analyses are not able to provide detailed assessments of the nature of any independent association of fibrinogen level with CHD or with other vascular and nonvascular outcomes. [43][44][45] This meta-analysis differs from previous analyses in several ways that should increase its reliability and scientific value. First, it is large and comprehensive: the data comprise 6944 first nonfatal myocardial infarction (MI) or stroke events and 13 210 deaths (cause-*The Authors/Writing Committee, Authors/Members, and Other Members of the Fibrinogen Studies Collaboration are listed at the end of this article.

We have identified a genetic polymorphism of factor VII that is strongly associated with plasma factor VII coagulant activity (factor VIIc) in healthy individuals from the United Kingdom. This polymorphism was detected after Msp I digestion of polymerase chain reaction-amplified genomic DN A. In a sample of 284 men, the frequency of the M2 allele (loss of cutting site) is 0.1, and individuals with the M1M2 genotype have factor VIIc levels 22% below the sample mean (p<0.0001). F actor VII is a serine protease found in plasma and is one of the vitamin K-dependent coagulation factors, along with prothrombin (factor II), factors IX and X, and proteins C and S (for review, see Reference 1). Factor VII is synthesized principally in the liver and is secreted as a single-chain glycoprotein of apparent M, 48,000. 2Cleavage of human factor VII to factor Vila, a two-chain form held together by disulfide bonds, results in a 20-to 25-fold increase in enzyme activity.2 This cleavage can be effected by a number of activated coagulation factors, including factors Xlla, Xa, and IXa and thrombin.2 In the presence of tissue factor and calcium ions, factor Vila converts factor X to factor Xa in the initiating reaction of the extrinsic coagulation pathway.

Abstract'Objective-To determine whether reduced fetal and infant growth are associated with higher plasma fibrinogen and factor VII concentrations in adult life.Design-Follow up study of men born during 1920-30 whose weights at birth and at 1 year had been recorded by health visitors, and men born during 1935-43 whose size at birth had been measured in detail.Setting-Hertfordshire and Preston, England. Subjects-591 men born in east Hlertfordshire who still lived there and 148 men born in Preston who still lived-in or close to the city.Main outcome measures-Plasma fibrinogen and factor VII concentrations.Results-Among men in Hertfordshire mean plasma fibrinogen and factor VII concentrations fell with increasing weight at 1 year (from 3-21 g/l in men of -18 lb to 2-93 g/l in men of -27 lb and from 122% ofstandardto 103%;p<0 001, p<0 005 respectively).The trends were independent of cigarette smoking, alcohol consumption, body mass index, and social class. Neither plasma fibrinogen nor factor VII concentration was related to birth weight. In men in Preston, however, fibrinogen concentration fell progressively as the ratio of placental weight to birth weight decreased (p= 0.01).Conclusions-Reduced growth in fetal life and infancy is strongly related to high plasma concentrations of the haemostatic factors fibrinogen and -factor VII. This may be a persisting response to impaired liver development during a critical early period.