Postprandial hemorrheology and apolipoprotein B metabolism in patients with familial hypertriglyceridemia.

Impaired postprandial lipoprotein metabolism has been found to be related to the extent of coronary artery disease. Moreover, since dyslipoproteinemias are associated with impaired hemorrheology, we investigated the effect of postprandial hypertriglyceridemia on hemorrheological parameters before and after triglyceride-lowering therapy. Triglyceride-rich lipoproteins (TRLs) separated by ultracentrifugation (d < 1.006 g/dL) and chylomicrons and chylomicron remnants (quantified by apolipoprotein [apo] B-48 determination) were determined after a fat load in 10 patients with familial hypertriglyceridemia before and after therapy with gemfibrozil (900 mg daily). Lipid and hemorrheological parameters (plasma and whole-blood viscosity [PV and BV], red cell aggregation [RCA], hematocrit, and fibrinogen) were determined at baseline and every hour up to 6 hours postprandially. Fasting total triglycerides and TRL triglycerides significantly decreased with gemfibrozil therapy (P < .01). Total triglycerides postprandially increased from 9.53 +/- 1.72 to 14.47 +/- 2.07 mmol/L (TRL triglycerides by 61%) before therapy (P < .05) and from 4.61 +/- 1.28 to 7.17 +/- 0.99 mmol/L (TRL triglycerides by 57%) after therapy (P < .05). The postprandial TRL apo B increase was reduced with gemfibrozil (from 11.6 +/- 2.8 to 20.7 +/- 5.0 mg/dL with therapy v 19.0 +/- 7.6 to 33.0 +/- 12.5 mg/dL before therapy, P < .05, respectively) with a proportionally greater increase in apo B-48 (119% and 169%, respectively) compared with apo B-100 (64% and 64%, respectively). Fasting RCA was improved with lipid-lowering therapy (P < .05), but PV, BV, RCA, and fibrinogen did not show any statistically significant postprandial changes either before or after lipid-lowering therapy. In summary, we did not find any statistically significant changes in hemorrheological parameters, despite a strong postprandial increase of triglycerides. In particular, these findings were independent of fasting triglyceride levels. We conclude that triglyceride-lowering therapy by gemfibrozil had no substantial beneficial effects with respect to hemorrheology in patients with familial hypertriglyceridemia.

Effects of n-3 fatty acids and fenofibrate on lipid and hemorrheological parameters in familial dysbetalipoproteinemia and familial hypertriglyceridemia.

There is increasing evidence that hemorrheological abnormalities are associated with an enhanced risk of atherosclerosis. The n-3 fatty acids (n-3-FA) have been shown to have beneficial effects on atherosclerosis in patients with dyslipoproteinemias. We studied 23 patients with elevated plasma triglycerides to evaluate the influence of fish oil and fenofibrate therapy on hemorrheological parameters (15 patients with familial hypertriglyceridemia [FHTG] and eight with familial dysbetalipoproteinemia [FDL]). The patients (one woman and 22 men aged 45.7 +/- 2.0 years) were treated with increasing doses of n-3-FA (1.8 to 3.6 g/d: 0.9 to 1.8 g eicosapentaenoic acid and 0.6 to 1.2 g docosahexaenoic acid) for 8 weeks. Lipid parameters, whole-blood viscosity at different shear rates, plasma viscosity, fibrinogen concentration, and red blood cell aggregation (RCA) were measured at baseline and at weeks 2, 4, 8 (end of n-3-FA therapy), and 12. Compliance was ensured by measuring plasma concentrations of eicosapentaenoic acid and docosahexaenoic acid. After 12 weeks, patients began treatment with fenofibrate (250 mg daily); investigations were performed again at week 20. Total triglycerides (from 6.90 +/- 1.70 to 3.61 +/- 0.78 mmol/L in FDL and 7.44 +/- 1.50 to 4.15 +/- 0.55 in FHTG), very-low-density lipoprotein (VLDL) triglycerides, and VLDL cholesterol were significantly decreased with n-3-FA therapy in both groups (P < .05). In FHTG, low-density lipoprotein (LDL) cholesterol increased significantly (from 2.75 +/- 0.28 to 3.97 +/- 0.35 mmol/L, P < .01); in FDL, total cholesterol decreased (from 9.76 +/- 1.32 to 7.34 +/- 1.07 mmol/L, P < .05). No significant changes were observed in hemorrheological parameters, except for reduced RCA with 3.6 g n-3-FA in FHTG. However, with fenofibrate therapy, in addition to comparable lipoprotein changes seen with fish oil, fibrinogen levels and plasma and blood viscosity decreased in patients with FDL. We conclude that n-3-FA and fenofibrate have comparable effects on lipid parameters in patients with FDL and FHTG. Because of additional beneficial effects on hemorrheological parameters, fenofibrate may be preferred for the treatment of FDL.