Increasing plasma fibrinogen, but unchanged levels of intraplatelet cyclicnucleotides, plasma endothelin-1, factor VII, and neopterin during cholesterol lowering with fluvastatin

Lipid-lowering statin treatment reduces cardiovascular morbidity and mortal ity and improves endothelial function in patients with hypercholesterolemia . The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin dur ing lipid lowering. In addition, the endothelial production of platelet ant iaggregatory and vasodilatory factors such as nitric oxide and prostacyclin , and vasoconstrictive factors such as endothelin-1, was assessed. Plasma f ibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet ni tric oxide and prostacyclin mediators cyclic 3'5'-guanosine monophosphate ( cGMP) and cyclic 3'-5'-adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 pati ents (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease o f 1.62 mmol/l [1.26-2.18 (19%); P < 0.01] was noted in levels of total chol esterol, and a decrease of 1.70 mmol/l [1.52-230 (28%); P < 0.01] in levels of low-density lipoprotein cholesterol. Plasma levels of fibrinogen had in creased [from 4.81 g/l (4.26-5.27) to 5.17 g/l (4.81-5.67); P < 0.05], wher eas no significant changes had occurred in intraplatelet levels of cGMP [de crease by 0.05 pmol/10(9) platelets (-0.17 to 0.24); NS], cAMP [decrease by 0.13 pmol/10(9) platelets (-0.37 to 0.86); NS], plasma endothelin-1 [decre ase by 0.05 pg/ml (-0.60 to 0.70); NS], plasma factor Vn [from 1.14 IE/ml ( 0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nm ol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during choles terol-lowering treatment with fluvastatin, plasma levels of fibrinogen incr eased whereas intraplatelet cyclic nucleotide levels and plasma endothelin- 1, factor VII and neopterin levels were unchanged. Blood Coag Fibrinol 10:1 33-140 (C) 1999 Lippincott Williams & Wilkins.