MODULATION OF PLASMA-FIBRINOGEN LEVELS BY CIPROFIBRATE AND GEMFIBROZIL IN PRIMARY HYPERLIPIDEMIA

An elevated plasma fibrinogen level is increasingly accepted as an ind ependent risk indicator of cardiovascular disease. This has enhanced t he interest in identifying agents that can normalize elevated plasma f ibrinogen levels. One group of agents with this capacity are the fibri c acid derivatives, e.g, ciprofibrate and gemfibrozil. We studied fibr inogen levels after 12 weeks of treatment with ciprofibrate (n = 48) a nd gemfibrozil (n = 51) in hypercholesterolemic patients. The correlat ion of the decrease in fibrinogen with lipid lowering and the contribu tion of the acute phase and genetic polymorphisms to this decrease wer e also evaluated.After 12 weeks of treatment; the fibrinogen levels we re significantly decreased (p<0.0005) with both drugs, although the de crease in the ciprofibrate group (mean 3.4 g/l pre-treatment to 2.4 g/ l after 12 weeks) was larger than in the gemfibrozil group (mean 3.4 g /l to 3.0 g/l). The lipid lowering effect was comparable for the two d rugs but there was no correlation for either ciprofibrate or gemfibroz il between the lipid lowering and the magnitude or the velocity of the fibrinogen lowering effect. An attenuation of the major regulatory me chanism of plasma fibrinogen levels, the acute phase reaction, was inv oked as the underlying mechanism. However, pre-treatment C-reactive pr otein levels were not increased and did not change after treatment. Mo reover, no effects of the polymorphisms of the fibrinogen beta-gene on the decrease of the plasma fibrinogen levels were observed. This sugg ests that a new, as yet unknown, mechanism is involved in fibrinogen l owering by fibrates.