Association between serum fibrinogen concentrations and HDL and LDL subfraction phenotypes in healthy men

Hyperfibrinogenemia and a dyslipoproteinemia characterized by reduced HDL₂ cholesterol and elevated levels of small, dense LDL particles are risk factors for coronary artery disease. However, the relationship between fibrinogen and lipoproteins, in particular LDL subfractions, is uncertain. We therefore measured serum fibrinogen levels and serum concentrations of cholesterol and apolipoproteins of VLDL, IDL, six LDL, and two HDL, subfractions by using the technique of density-gradient ultracentrifugation in 132 nonsmoking men without evidence of coronary artery disease or infection. Dividing the individuals into quartiles according to their fibrinogen values showed that men within the highest fibrinogen quartile (fibrinogen 2.90 to 4.34 g/L) had significantly higher concentrations of small, dense LDL (d>1.044 g/mL) apolipoprotein B and cholesterol and lower concentrations of HDL₂ cholesterol than men within the lower fibrinogen quartiles (fibrinogen < 2.55 g/L). Multivariate regression analysis revealed that the association between fibrinogen and small, dense LDL particles was independent of serum triglycerides, cholesterol, body mass index, and age. In contrast, the relationship between fibrinogen and HDL₂ cholesterol was primarily influenced by triglycerides and cholesterol and not independently influenced by fibrinogen. There were no significant differences between the quartiles in terms of insulin, glucose, insulin resistance, free fatty acids, lipoprotein(a), and blood pressure. This study show that fibrinogen is associated with the expression of a more atherogenic LDL subfraction phenotype independent of body mass index, age, other serum lipids, and insulin resistance in a healthy male nonsmoking population. The reason for this association is uncertain. These findings reinforce the evidence that fibrinogen should be determined when assessing coronary risk.