INCREASED PLASMA-LEVELS OF TISSUE FACTOR PATHWAY INHIBITOR (TFPI) AFTER N-3 POLYUNSATURATED FATTY-ACIDS SUPPLEMENTATION IN PATIENTS WITH CHRONIC ATHEROSCLEROTIC DISEASE

This double-blind, randomised, controlled study examined the effect of a daily dosage of 3 g n-3 polyunsaturated fatty acids (n-3 PUFA) on p lasma lipids and some haemostatic factors in 40 patients with chronic atherosclerotic diseases. Serum lipids, factor VII, tissue factor path way inhibitor (TFPI) and prothrombin activation fragment 1+2 (F-1+2) w ere measured at baseline and after 2, 8, and 16-week supplementation o f either n-3 PUFA or corn oil. Administration of n-3 PUFA promptly low ered serum triglycerides and increased LDL-cholesterol (-32% and +33%, respectively, after 2 weeks of treatment) while a significant increas e (+31%) in HDL-cholesterol was documented at the end of the observati on period. Treatment with n-3 PUFA induced a progressive significant i ncrease of TFPI plasma levels (+21% after 16 weeks; p = 0.029). TFPI a ctivity was significantly correlated with LDL-cholesterol, and multipl e stepwise regression analysis showed that LDL-cholesterol was the mos t important predictor of TFPI activity. Plasma levels of the inhibitor showed also a very high parallelism in their trend over time (ANOVA m odel for homogeneity of slopes) with both HDL-cholesterol (p = 0.82) a nd LDL-cholesterol (p = 0.67). Patients treated with n-PUFA also showe d a significant reduction of F-1+2 plasma levels (p = 0.016) while no significant changes were detected in plasma factor VII clotting activi ty. Lipid and haemostatic parameters were not modified at any study ti me in patients receiving corn oil as placebo. The results of this stud y confirm the effects of n-3 PUFA administration on plasma lipids and show that in patients with chronic atherosclerotic disease a 16-week s upplementation with these compounds induces a small but statistically significant increase of TFPI plasma levels with a parallel down-regula tion of the extrinsic pathway of blood coagulation which may be releva nt to the antithrombotic activity of fish diet and fish oil derivative s.