The main finding this study is that elevated levels of fibrinogen predict CAC progression in type 1 diabetes subjects. Recently, higher fibrinogen levels have been associated with subsequent atherosclerosis assessed by CAC and carotid thickness in young adults (5
); however, Green et al did not measure CAC at baseline, they only suggested that calcification would likely not have been detected if the exam had been done, because their population was young. We found an association between fibrinogen levels and CAC progression in our cohort of T1D subjects. In non-DM controls we did not observe this association, however CAC progression was more frequent in T1D subjects than in controls (67% from progressors were T1D versus while only 33% were non-DM controls, p<0.0001); this could justify the lack of effect of fibrinogen in CAC progression in controls.
The presences of fibrinogen, fibrin, and LDL cholesterol have been detected in atherosclerotic plaques, suggesting that a common mechanism may exist for fibrinogen and lipoprotein entry into the vessel wall (11
). The potential involvement of fibrinogen in the pathogenesis of atherosclerosis is supported by the demonstration that fibrinogen induces endothelial cell disorganization and migration, stimulates smooth muscle proliferation, and enhances the release of endothelial cell–derived growth factors (13
Previously, Soedamah-Muthu et al (1
) demonstrated that fibrinogen levels predicted coronary heart disease; however this effect was reported only in men with type 1 diabetes. The results of previous studies have shown inconsistent gender effect (1
), our results suggest similar association between fibrinogen and vascular complications in men and women. Fibrinogen levels may be associated with nephropathy in type 1 diabetes subjects (2
); importantly our analyses were adjusted for AER.
Highest fibrinogen levels in comparison to lowest levels have recently been associated with presence of subclinical atherosclerosis in a large population-based study, independent of the adjustment for know cardiovascular risk factors. However this association was only modest and then disappeared when the association with CAC burden was considered (15
). Previous studies have shown a weak association between the presence of CAC and fibrinogen levels (14
). These results, in addition to our finding, support the idea that inflammatory biomarkers and CAC could offer integrative information about CAD. Additionally we reported, for the first time, that higher fibrinogen levels predict CAC progression in type 1 diabetes subjects, independently of standard cardiovascular risk factors.