-455G A POLYMORPHISM OF THE BETA-FIBRINOGEN GENE IS ASSOCIATED WITH THE PROGRESSION OF CORONARY ATHEROSCLEROSIS IN SYMPTOMATIC MEN - PROPOSED ROLE FOR AN ACUTE-PHASE REACTION PATTERN OF FIBRINOGEN/

Increased plasma fibrinogen levels have been identified as a risk indi cator for myocardial infarction, stroke, and thrombosis. Both environm ental and genetic factors make an important contribution to plasma fib rinogen levels in humans. In the present study we evaluated, in patien ts with serum cholesterol levels between 4 and 8 mmol/L, the relation of plasma levels and polymorphisms of fibrinogen with coronary artery disease (CAD), cross-sectionally at baseline and after a 2-year follow -up period in which they received either a placebo or pravastatin. Hig her plasma fibrinogen levels (3.9 g/L) were observed at baseline in pa tients with the -455AA genotype than in patients with the -455GA (3.2 g/L) and -455GG (3.1 g/L) genotypes of the -455G/A fibrinogen beta gen e polymorphism (P<.05). Plasma levels of fibrinogen were not related t o the baseline angiographic variables (mean segment diameter [MSD] and minimum obstruction diameter [MODI), nor to the quantitative changes in these angiographic variables. However, in the placebo group, patien ts with the -455AA genotype had more progression of CAD, expressed by a significantly greater decrease of the MSD and MOD, after the 2-year follow-up period than patients with the other genotypes, The -455G/A p olymorphism was related to the progression of CAD, and pravastatin the rapy seemed to offset this deleterious effect. We hypothesized that th e -455A allele may promote a stronger acute-phase response in fibrinog en and that the resulting higher fibrinogen levels may form the pathog enetic basis for the stronger progression of coronary atherosclerosis Experiments to verify this hypothesis are being proposed and advocated , in view of the possibility of identifying a genetic marker that can recognize a subgroup oi patients with an increased risk who may benefi t from early treatment with lipid-lowering or anticoagulant drugs.