Hypercholesterolaemia and lipid lowering treatment do not affect the acute endogenous fibrinolytic capacity in vivo

• Published in: British heart journal 2002-01, Vol.87 (1), p.48-53
• Main Authors: Newby, D E, Witherow, F N, Wright, R A, Bloomfield, P, Ludlam, C A, Boon, N A, Fox, K A A, Webb, D J
• Format: Article
• Language: English
• Subjects: Adult; Anticholesteremic Agents - therapeutic use; Antilipemic agents; Biological and medical sciences; Blood clots; Blood Flow Velocity - drug effects; Blood pressure; Blood Pressure - physiology; Cardiovascular disease; Cardiovascular Medicine; Case-Control Studies; Cholesterol; Cross-Over Studies; Double-Blind Method; Drug dosages; ELISA; Endothelium; enzyme linked immunosorbent assay; FBF; Female; Fibrinolysis - drug effects; fibrinolytic factors; Forearm - blood supply; forearm blood flow; General and cellular metabolism. Vitamins; Haematocrit; Hct; Heart attacks; Humans; hypercholesterolaemia; Hypercholesterolemia; Hypercholesterolemia - drug therapy; Hypercholesterolemia - metabolism; Hypercholesterolemia - physiopathology; LDL; lipid lowering treatment; Lipids; low density lipoprotein; Male; Medical sciences; Nitric oxide; PAI-1; Pharmacology. Drug treatments; Physiological aspects; Plasma; plasminogen activator inhibitor type 1; Pravastatin - therapeutic use; Smoking; Strain gauges; Studies; Substance P - pharmacology; t-PA; Tissue plasminogen activator; Tissue Plasminogen Activator - metabolism; west of Scotland coronary prevention study; WOSCOPS
• ISSN: 1355-6037; 0007-0769; 1468-201X
• DOI: 10.1136/heart.87.1.48

Objective: To assess acute tissue plasminogen activator (t-PA) release in vivo in patients with hypercholesterolaemia in the presence and absence of lipid lowering treatment and in matched normocholesterolaemic controls. Design: Parallel group comparison and double blind randomised crossover. Setting: University hospital. Patients: Eight patients with hypercholesterolaemia (> 7.8 mmol/l) and eight matched normocholesterolaemic controls (< 5.5 mmol/l). Methods: Blood flow and plasma fibrinolytic factors were measured in both forearms during unilateral brachial artery infusions of the endothelium dependent vasodilator substance P (2–8 pmol/min) and the endothelium independent vasodilator sodium nitroprusside (1–4 μg/min). Interventions: In patients, measurements were made on three occasions: at baseline and after six weeks of placebo or pravastatin 40 mg daily administered in a double blind randomised crossover design. Main outcome measures: Acute release of t-PA. Results: Compared with patients, in normocholesterolaemic control subjects substance P caused greater dose dependent increases in forearm blood flow (p < 0.05) but similar increases in plasma t-PA antigen and activity concentrations. During pravastatin treatment in patients, total serum cholesterol fell by 22% from a mean (SEM) of 8.1 (0.3) to 6.4 (0.4) mmol/l (p = 0.002) and substance P induced vasodilatation was no longer significantly impaired in comparison with controls. However, despite reproducible responses, pravastatin treatment was not associated with significant changes in basal or substance P induced t-PA release. Conclusions: Hypercholesterolaemia and lipid lowering treatment cause no demonstrable effects on acute substance P induced t-PA release in vivo. This suggests that the preventative benefits of lipid lowering treatment are unlikely to be mediated by improvements in endogenous fibrinolysis.