CARDIOVASCULAR MEDICINE

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

D E Newby¹, F N Witherow¹, R A Wright¹, P Bloomfield¹, C A Ludlam², N A Boon¹, K A A Fox¹, D J Webb³

¹ Department of Cardiology, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK
² Department of Haematology, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK
³ Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

Correspondence to:
Correspondence to:
Dr D E Newby, Cardiovascular Research, Department of Cardiology, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, Scotland, UK;
D.E.Newby{at}ed.ac.uk

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.

Keywords: fibrinolytic factors; hypercholesterolaemia; lipid lowering treatment

Abbreviations: ELISA, enzyme linked immunosorbent assay; FBF, forearm blood flow; Hct, Haematocrit; LDL, low density lipoprotein; PAI-1, plasminogen activator inhibitor type 1; t-PA, tissue plasminogen activator; WOSCOPS, west of Scotland coronary prevention study

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