Collaborative meta-analysis of prospective studies of plasma fibrinogen and cardiovascular disease.
BACKGROUND: Many long-term studies have reported on associations of plasma fibrinogen concentration with cardiovascular disease, but few have been large enough to provide reliable estimates in different circumstances. Moreover, most published prospective studies have related disease risk only to baseline values of plasma fibrinogen (which can lead to substantial underestimation of any risk relationships) and have corrected only for baseline values of possible confounding factors (which can lead to residual biases). OBJECTIVES: By appropriate combination of data from individual participants from all relevant prospective studies in a systematic 'meta-analysis', with correction for regression dilution, the Fibrinogen Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age- and sex-specific associations of plasma fibrinogen with coronary heart disease (and, where data are sufficient, with other vascular diseases). It will also help to determine to what extent such associations are independent of possible confounding factors. METHODS: A central database has been established containing data on plasma fibrinogen, sex and other potential confounding factors, age at baseline fibrinogen measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of fibrinogen and potential confounding factors is being sought to allow study-specific correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available prospective studies of plasma fibrinogen will yield information on more than 10000 incident cardiovascular deaths and events among the approximately 200000 total participants who have been monitored, on average, for about 10 years.
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