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Hypercholesterolaemia and lipid lowering treatment do not affect the acute endogenous fibrinolytic capacity in vivo
  1. D E Newby1,
  2. F N Witherow1,
  3. R A Wright1,
  4. P Bloomfield1,
  5. C A Ludlam2,
  6. N A Boon1,
  7. K A A Fox1,
  8. D J Webb3
  1. 1Department of Cardiology, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK
  2. 2Department of Haematology, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK
  3. 3Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
  1. Correspondence to:
    Dr D E Newby, Cardiovascular Research, Department of Cardiology, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, Scotland, 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.

  • fibrinolytic factors
  • hypercholesterolaemia
  • lipid lowering treatment
  • 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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