Fibrinogen catabolism in patients with type II and type IV hyperlipidemia. Effect of dietary and clofibrate treatment on laboratory findings.

Abstract

Fibrinogen catabolism was studied by plasma fibrinogen chromatography and other methods in 99 subjects with hyperlipoproteinemla Types lla, Mb, and IV, and in 24 control subjects with normal blood llpid values. Subjects with either a history of thromboembolic vascular disease or clinical evidence of atherosclerosis were excluded. Type II subjects (I.e., the combined group of Type lla and lib subjects) showed an elevation of plasma high molecular weight fibrinogen complexes, which Is indicative of enhanced fibrin formation. They also showed an elevation of fibrinogenflrst-derivatlve, which Is Indicative of fibrinogenolysls and Increased plasma euglobulin activity. Subjects with Type IV hyperlipoproteinemla showed similar findings to those of Type II except that high molecular weight fibrinogen complex concentration was normal. Subsequently, 36 patients received a fat-controlled, low cholesterol diet and were studied In a blind, random, crossover study of dietary vs clofibrate treatment. T he role of local fibrin deposition in atherosclerosis in humans remains uncertain. Histological evidence supports the view that local fibrin and platelet deposition is an integral pathological feature of progressive atherosclerosis. 1 "* Elevation of plasma fibrinogen has also been shown to be as significantly associated with the development of ischemic heart disease as elevation of cholesterol. 7 Yet studies to demonstrate enhanced fibrin formation in patients with atherosclerosis have seldom been attempted. 8 patients with hyperlipidemia Types II and IV (namely, patients at risk of developing age-accelerated atherosclerosis), is unknown. Although studies with isotopically labeled fibrinogen have failed to show a shortened half-life survival time in the atherosclerotic subject, 9 fibrin formation under physiological conditions accounts for only 2% to 3% of overall fibrinogen catabolism. 10 Consequently, fibrinogen Ti* is an insensitive measure of fibrin formation and deposition, and failure to demonstrate alteration in fibrinogen Tŝ urvival does not exclude substantial change in fibrin formation rates.Plasma fibrinogen chromatography has provided a new approach to the study of fibrinogen catabolism. 11 " 13 This procedure quantifies in plasma the percentage and concentration of high molecular weight fibrinogen complexes (HMWFC), native fibrinogen, and derivatives of fibrinogen smaller than the native molecule, collectively termed "fibrinogen-first-derivative" and mostly composed of fibrinogen fragments X and Y.

Statins Therapy: Effects on Plasma Fibrinogen Levels and Fibrinolysis

“…Different studies have found that bezafibrate reduced fibrinogen levels by 10 to 40% in patients with atherosclerosis [37,38] and 25% in non-insulin-dependent diabetic patients [39]. Clofibrate reduced fibrinogen levels by 26% in patients with peripheral arterial disease [40] and by 9% in patients with thrombotic vascular disease [41]. Fenofibrate and bezafibrate reduced fibrinogen by 9 and 15%, respectively, in patients with primary hypercholesterolemia [34].…”