Circulating thrombomodulin levels are related to latent progression of hypertensive atherosclerosis in patients

The present study was designed to test the hypothesis that circulating levels of thrombomodulin are elevated in patients with hypertension in proportion to the severity of the vascular damage. A cross-sectional study was carried out using a population consisting of 96 patients with essential hypertension without clinically evident cardiovascular disease (mean age: 65 10 years) and 99 healthy normotensive control subjects (64 9 years). Blood was sampled and serum concentrations of soluble thrombomodulin were measured using an enzyme immunoassay method. We calculated the ratio of the concentration of thrombomodulin to that of creatinine, because soluble thrombomodulin is excreted by the kidney and the serum level of thrombomodulin was correlated with that of creatinine (p<0.05). The association between the ratio and other clinical variables was investigated. The ratio of the thrombomodulin to creatinine concentrations was higher in hypertensive (29.3 +/- 10.9) than in control subjects (24.4 +/- 5.9; p<0.0001). Systolic blood pressure was correlated with the ratio but the ratio showed no correlation with serum lipid levels when analyzed using data from all subjects. In hypertensive patients, the ratio correlated with the grade of sclerotic, but not hypertensive, changes in the fundus oculi (Schele's classification, p<0.001). Furthermore, the ratio correlated with brachial-ankle pulse wave velocity (p<0.001). However, no correlation was detected between the ratio and blood pressure. These results suggest that circulating levels of thrombomodulin are elevated in hypertensive patients as compared to normotensive subjects and that the thrombomodulin level may be a molecular marker of the latent progression of atherosclerosis in hypertensive patients.