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 microg/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.
RCT Entities:
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 microg/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.
Authors: Alan C Cameron; Kelly McMahon; Mark Hall; Karla B Neves; Francisco J Rios; Augusto C Montezano; Paul Welsh; Ashita Waterston; Jeff White; Patrick B Mark; Rhian M Touyz; Ninian N Lang Journal: JACC CardioOncol Date: 2020-09
Authors: Jehangir N Din; Jaydeep Sarma; Scott A Harding; Karin Lyall; David E Newby; Andrew D Flapan Journal: BMJ Open Date: 2013-09-25 Impact factor: 2.692