Fibrinogen and the Severity of Coronary Atherosclerosis among Adults with and without Statin Treatment: Lipid as a mediator

BackgroundIt has been proposed that plasma fibrinogen is associated with lipid levels and increased cardiovascular risk. However, the interrelationship has not been well-elucidated. We hypothesise that lipids may be potential mediators.MethodsWe enrolled 4748 consecutive subjects scheduled for coronary angiography in this study. The severity of coronary atherosclerosis was assessed by Gensini score (GS). By principle component analysis, a multi-marker lipid index was extracted weighting the coefficients of six atherogenic lipid parameters: total cholesterol (TC), low-density lipoprotein-cholesterol, non-high-density lipoprotein-cholesterol (non-HDL-C), apolipoprotein (apo) B, apoB/apoA1, and TC/HDL-C ratio. Moreover, using mediation analysis, the relationship between fibrinogen and lipids with high GS was evaluated.ResultsFibrinogen was positively associated with GS after adjustment (β=0.100, p<0.001). We stratified our analyses by statin use status and found that subjects in the upper fibrinogen tertiles had higher levels of atherogenic lipid parameters irrespective of statin status (p<0.001, all). Significantly, we observed a synergistic effect of fibrinogen and concurrent elevated lipid index for high GS. The adjusted odds ratios were greater in participants who had high fibrinogen levels and also high lipid index compared to those with low lipid index [on statin: 1.725(1.258-2.364) vs. 1.261(0.962-1.652); not on statin: 2.197(1.450-3.328) vs. 1.166(0.417-3.258)]. Specifically, mediation analysis indicated that around 24% of the effect of fibrinogen on high GS was mediated by lipid index, which was attenuated to 13% by statin status.ConclusionsThe increased risk of fibrinogen on coronary atherosclerosis appeared to be enhanced by the high atherogenic lipid levels, which mediated around 24% of this effect.