Fibrinogen: biochemistry, epidemiology and determinants

Abstract

Plasma fibrinogen is an important component of the coagulation cascade, as well as a major determinant of blood viscosity and blood flow. Increasing evidence from epidemiological studies suggests that elevated plasma fibrinogen levels are associated with an increased risk of cardiovascular disorders, including ischaemic heart disease (IHD), stroke and other thromboembolism.1,2 This increase in plasma fibrinogen levels may promote a prothrombotic or hypercoagulable state, and may in part explain the risk of stroke and thromboembolism in conditions such as atrial fibrillation (AF). Nevertheless, the relationship between hyperfibrinogenemia, atherosclerosis and thrombosis is complicated. As the process of thrombogenesis is very closely related to atheroma formation (atherogenesis), it follows that specific thrombogenic factors such as fibrinogen (with important effects on blood rheology) may play key roles in the process of atherosclerotic lesion formation, with subsequent effects on cardiovascular diseases (Figure 1). However, knowledge about the precise determinants of plasma fibrinogen levels in health and disease is as yet incomplete, and many paradoxes are still present. For example, it is known that plasma fibrinogen is higher in Black than in White patients,3 but (in the UK at least) coronary artery disease is less common in Blacks than in White patients, while hypertension and stroke are conversely more common.4,5 Plasma fibrinogen is also influenced by many factors: it increases with age, body mass index, smoking, diabetes and post menopause and is related to fasting serum insulin, low-density-lipoprotein (LDL) cholesterol lipoprotein(a) and leukocyte count. Conversely, it decreases with moderate alcohol intake, physical activity, increased high-density-lipoprotein (HDL) cholesterol, and with hormone replacement therapy (HRT).6–8