SEVERITY OF PERIPHERAL ATHEROSCLEROSIS IS ASSOCIATED WITH FIBRINOGEN AND DEGRADATION OF CROSS-LINKED FIBRIN

Immunohistochemical studies of human atherosclerotic lesions have demo nstrated the occurrence of fibrin deposition and its degradation in th e arterial wall. We studied fibrinogen, the generation of thrombin, an d the degradation of fibrin in 40 patients with stable peripheral arte rial occlusive disease of varying severity, as assessed by the ankle/b rachial pressure index and duplex ultrasonography and/or angiography. Circulating fibrinogen (functional and immunological), fibrinopeptide A, thrombin-antithrombin III complex, and D-dimer were measured. The s everity of atherosclerosis was associated with both fibrinogen (both f unctional and immunological) and D-dimer (r=.57, P<.0002, and r=.57, P <.0001, respectively). Fibrinogen and D-dimer showed a significant pos itive correlation (r=.50, P<.001). Generation of thrombin was detected in 24 patients (60%) by fibrinopeptide A and levels of thrombin-antit hrombin III complex. As a sign of coagulation activation and fibrinoly sis, we found that thrombin-antithrombin III complex and the degradati on of cross-linked fibrin were progressively associated with the exten t of vascular disease. The plasmin-mediated fibrin breakdown contribut ed to increased levels of circulating fibrinogen, an established risk factor for thrombotic complications. The significant correlations betw een fibrinogen/D-dimer and the severity of atherosclerosis support pre vious pathological studies and imply that local degradation of cross-l inked fibrin is involved in the progression of atherosclerosis.