title: Severity of peripheral atherosclerosis is associated with fibrinogen and degradation of cross-linked fibrin.
abstract: Immunohistochemical studies of human atherosclerotic lesions have demonstrated the occurrence of fibrin deposition and its degradation in the arterial wall. We studied fibrinogen, the generation of thrombin, and the degradation of fibrin in 40 patients with stable peripheral arterial occlusive disease of varying severity, as assessed by the ankle/brachial 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 severity of atherosclerosis was associated with both fibrinogen (both functional and immunological) and D-dimer (r = .57, P < .0002, and r = .57, P < .0001, respectively). Fibrinogen and D-dimer showed a significant positive correlation (r = .50, P < .001). Generation of thrombin was detected in 24 patients (60%) by fibrinopeptide A and levels of thrombin-antithrombin III complex. As a sign of coagulation activation and fibrinolysis, we found that thrombin-antithrombin III complex and the degradation of cross-linked fibrin were progressively associated with the extent of vascular disease. The plasmin-mediated fibrin breakdown contributed to increased levels of circulating fibrinogen, an established risk factor for thrombotic complications. The significant correlations between fibrinogen/D-dimer and the severity of atherosclerosis support previous pathological studies and imply that local degradation of cross-linked fibrin is involved in the progression of atherosclerosis.
authors.affiliation: Wihuri Research Institute, Helsinki, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Lassila
authors.forename: S
authors.initials: S
authors.lastname: Peltonen
authors.forename: M
authors.initials: M
authors.lastname: Lepäntalo
authors.forename: O
authors.initials: O
authors.lastname: Saarinen
authors.forename: P
authors.initials: P
authors.lastname: Kauhanen
authors.forename: V
authors.initials: V
authors.lastname: Manninen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000990:Antithrombin III / Q000378:metabolism; D001161:Arteriosclerosis / Q000097:blood* / Q000000981:diagnostic imaging; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D005342:Fibrinolysis; D005344:Fibrinopeptide A / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000000981:diagnostic imaging; D011859:Radiography; D014463:Ultrasonography
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D005344:Fibrinopeptide A; D000990:Antithrombin III; D005337:Fibrin; D005340:Fibrinogen; D010447:Peptide Hydrolases