Effects of Diet, Drugs, and Genes on Plasma Fibrinogen Levels

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Abstract
Plasma levels of fibrinogen have been identified as independent risk predictors of cardiovascular disease. This has greatly increased interest in the regulation of plasma fibrinogen levels. Many demographic and environmental factors are known to affect fibrinogen levels, such as diet, use of several drugs, age, smoking, body mass, gender, physical exercise, race, and season. Additionally, it is also known that genetic factors determine the fibrinogen levels, and also that they determine the response of fibrinogen levels to environmental factors. Estimates, based on twin studies, suggest that 30-50% of the plasma fibrinogen level is genetically determined. The effect of dietary components on plasma fibrinogen levels is modest. Several components have been identified as factors that influence fibrinogen levels. Among those are fish oil, other lipids, and fibers. Dietary components that were expected to have an effect on fibrinogen, but for which no association was observed are black and green tea. Several drugs are known to influence fibrinogen levels, the most studied of which are platelet aggregation inhibiting drugs, such as ticlopidine, and the lipid lowering fibric acid derivatives (fibrates). Both types of drugs decreased the plasma fibrinogen level by about 10%, and bezafibrate lowers fibrinogen even more in patients with diabetes. No clear effect was observed for the HMG-CoA reductase inhibitors (statins). In the Bezalip study, fibrinogen levels decreased in patients treated with bezafibrate, but this had no clear effect on the risk of cardiovascular disease. This suggests that several mechanisms influence the fibrinogen level and that these mechanisms may contribute differently to cardiovascular disease. Several variations in the fibrinogen genes have been described and especially variations in the promoter region of the fibrinogen beta-gene are interesting, because the synthesis of the fibrinogen B beta chain is considered to be the rate limiting step in the fibrinogen biosynthesis. In many studies the fibrinogen beta-gene polymorphisms (-455G/A, -148C/T, and BclI) are found to be associated with the plasma levels of fibrinogen. However, they are not associated with the risk of cardiovascular events, although in several studies an association with the severity and progression of atherosclerosis has been reported. It has also been observed frequently that the fibrinogen beta-gene promoter polymorphisms are associated with the response of fibrinogen levels to environmental factors, such as exercise and trauma. In conclusion, plasma fibrinogen levels are regulated by an interesting and complex interplay between environmental and genetic factors.