Published Online
on March 11, 2004

A more recent version of this article appeared on May 1, 2004

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Submitted on October 6, 2003
Revised on December 29, 2003
Accepted on January 15, 2004

Prothrombin Fragment 1+2 Is Associated With Carotid Intima-Media Thickness in Subjects Free of Clinical Cardiovascular Disease

J. A. Páramo MD, PhD^*; J. Orbe PhD; O. Beloqui MD, PhD; A. Benito MD, PhD; I. Colina MD, PhD; E. Martinez-Vila MD, PhD; and J. Diez MD, PhD

From Atherosclerosis Research (J.A.P., J.O.), Division of Cardiovascular Pathophysiology (J.A.P., J.O., J.D.), Internal Medicine (O.B., I.C.), Radiology (A.B.), and Neurology (E.M.-V.), University Clinic, School of Medicine, University of Navarra, Pamplona, Spain.

^* To whom correspondence should be addressed. E-mail: japaramo{at}unav.es.

Background and Purpose--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.

Key words: prothrombin • atherosclerosis • carotid arteries • intima-media thickness • thrombin

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