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

Abstract

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 1ϩ2 (F1ϩ2), 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. F1ϩ2 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 F1ϩ2, those in the upper tertile (Ͼ0.55 nmol/L) showed significantly higher IMT (PϽ0.01). In correlation analysis, a positive relationship was found between plasma F1ϩ2 and carotid IMT. F1ϩ2 also correlated positively with cholesterol (PϽ0.008) and low-density lipoprotein cholesterol (PϽ0.005), but not with blood pressure or body mass index. In the multivariate analysis, the association of F1ϩ2 with carotid IMT remained significant (PϽ0.001) 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 F1ϩ2 were significantly associated with carotid IMT, suggesting a relationship between thrombin generation and the development atherosclerosis.

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“…The reproducibility of IMT measurements between and within sonographers had previously been checked in 20 individuals who returned 2 weeks later for a second examination. 9 The between-observer intraclass correlation coefficient was 0.76 (PϽ0.001) and the betweensubject repeatability was 0.82 (PϽ0.001). The corresponding coefficients of variance were 5% and 10%, respectively.…”

“…In all subjects, carotid ultrasonography was performed to determine IMT, as previously described. 9,11 Subjects were examined by the same 2 sonographers blinded to all clinical information. The reproducibility of IMT measurements between and within sonographers had previously been checked in 20 individuals who returned 2 weeks later for a second examination.…”

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“…Las mediciones se hicieron con un transductor lineal de 5-12 MHz (ATL 500 HDI). Las variabilidades intraobservador e interobservador de los ecografistas ha sido validada en estudios previos de nuestro grupo [24][25][26] . El punto de la medició n fue 1 cm proximal del bulbo de cada arteria caró tida comú n, en zonas libres de placa.…”

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“…From each individual, the IMT was determined as the average of near- and far-wall measurements of each CCA. Carotid artery IMT has been shown to be reproducible [12,19].…”