title: Hypercholesterolaemia and lipid lowering treatment do not affect the acute endogenous fibrinolytic capacity in vivo.
abstract: 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.
  
  
  METHODS
  Parallel group comparison and double blind randomised crossover.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  METHODS
  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.affiliation: Department of Cardiology, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK. D.E.Newby@ed.ac.uk
authors.forename: D E
authors.initials: DE
authors.lastname: Newby
authors.forename: F N
authors.initials: FN
authors.lastname: Witherow
authors.forename: R A
authors.initials: RA
authors.lastname: Wright
authors.forename: P
authors.initials: P
authors.lastname: Bloomfield
authors.forename: C A
authors.initials: CA
authors.lastname: Ludlam
authors.forename: N A
authors.initials: NA
authors.lastname: Boon
authors.forename: K A A
authors.initials: KA
authors.lastname: Fox
authors.forename: D J
authors.initials: DJ
authors.lastname: Webb
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000502:physiology; D016022:Case-Control Studies; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D017035:Pravastatin / Q000627:therapeutic use*; D013373:Substance P / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D000924:Anticholesteremic Agents; D013373:Substance P; D010959:Tissue Plasminogen Activator; D017035:Pravastatin