Prothrombin fragment 1+2 is associated with carotid intima-media thickness in subjects free of clinical cardiovascular disease.
OBJECTIVE
Thrombin, a central enzyme in the clotting cascade, plays a role not only in thrombosis but also in the progression of atherosclerosis. We studied the relationship between prothrombin fragment 1+2 (F1+2), a specific marker of thrombin generation in vivo, and carotid intima-media thickness (IMT), an index of subclinical atherosclerosis.


METHODS
We examined 181 asymptomatic middle-aged subjects (mean age 55.6 years, 76.7% men) free of overt clinical atherosclerotic disease. F1+2 was measured by enzyme-linked immunosorbent assay and IMT by duplex ultrasonography of carotid artery. Multiple linear regression analysis was used to assess the relationship between the 2 parameters.


RESULTS
Compared with individuals in the lowest tertile of F1+2, those in the upper tertile (>0.55 nmol/L) showed significantly higher IMT (P<0.01). In correlation analysis, a positive relationship was found between plasma F1+2 and carotid IMT. F1+2 also correlated positively with cholesterol (P<0.008) and low-density lipoprotein cholesterol (P<0.005), but not with blood pressure or body mass index. In the multivariate analysis, the association of F1+2 with carotid IMT remained significant (P<0.001) after adjustment for age, sex, body mass index, systolic blood pressure, cholesterol, diabetes, and smoking.


CONCLUSIONS
In a population sample of adults without clinically overt atherosclerotic disease, the plasma levels of F1+2 were significantly associated with carotid IMT, suggesting a relationship between thrombin generation and the development atherosclerosis.
Páramo
J A
JA
Atherosclerosis Research, University Clinic, School of Medicine, University of Navarra, Pamplona, Spain. japaramo@unav.es
Orbe
J
J
Beloqui
O
O
Benito
A
A
Colina
I
I
Martinez-Vila
E
E
Diez
J
J
D001161:Arteriosclerosis / Q000209:etiology; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D002340:Carotid Artery Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011516:Prothrombin; D012044:Regression Analysis; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology*; D018616:Ultrasonography, Doppler, Duplex / Q000706:statistics & numerical data
D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D011516:Prothrombin