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
- 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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