Fibrinogen plasma levels as a marker of thrombin activation: new insights on the role of fibrinogen as a cardiovascular risk factor.
Fibrinogen has recently emerged as a major risk factor for atherothrombosis. However, the pathophysiologic mechanism linking high fibrinogen concentration to cardiovascular disease is unclear. In this study 136 subjects (75 males, 61 females, age 51.7 +/- 14.4 years, mean +/- standard deviation, range 17-82) were tested for total and HDL-cholesterol, total triglycerides, apolipoprotein AI, apolipoprotein B, fibrinogen, prothrombin fragment and D-dimer. Moreover, 5 subjects who had hyperfibrinogenemia (range 450 to 950 mg/dl) for at least 6 months by repeated measurements, were treated with a short 7-day course of heparin 12,500 U/day subcutaneously. The effect of heparin on all the above mentioned parameters was observed at the end of treatment and after 7 days of wash-out. Simple regression analysis detected a positive correlation between fibrinogen and age, prothrombin fragment and D-dimer, and a negative correlation between fibrinogen and HDL-cholesterol and apolipoprotein AI. A direct correlation between age and both prothrombin fragment and D-dimer was also demonstrated. Multivariate analysis showed a persistent correlation between fibrinogen and prothrombin fragment, D-dimer and age, that was not influenced by sex, smoking habit and body mass index. In the 5 hyperfibrinogenemic subjects, heparin administration significantly reduced fibrinogen (625.4 +/- 211.1 vs 455.2 +/- 112.3 mg/dl, p < 0.03), prothrombin fragment (0.97 +/- 0.1 vs 0.63 +/- 0.2 nM, p < 0.002) and D-dimer (336 +/- 101.8 vs 275.2 +/- 78.5 ng/ml, p < 0.03). All these parameters returned to baseline after 7 days of wash-out (fibrinogen 632.5 +/- 198.2 mg/dl, prothrombin fragment 0.96 +/- 0.2 nM, D-dimer 325.8 +/- 98.65 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Ceriello
A
A
Department of Clinic and Experimental Pathology, University of Udine, Italy.
Pirisi
M
M
Giacomello
R
R
Stel
G
G
Falleti
E
E
Motz
E
E
Lizzio
S
S
Gonano
F
F
Bartoli
E
E
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis*; D004789:Enzyme Activation; D005260:Female; D005340:Fibrinogen / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D012044:Regression Analysis; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism*
D015415:Biomarkers; D005340:Fibrinogen; D013917:Thrombin