title: Haemostatic and inflammatory alterations in familial hypercholesterolaemia, and the impact of angiotensin II infusion.
abstract: BACKGROUND
  We examined potential prothrombotic and proinflammatory effects of angiotensin II in 16 otherwise healthy familial hypercholesterolaemia subjects and 16 matched controls.
  
  
  METHODS
  Markers of fibrinolysis, thrombin generation and inflammation were assessed in plasma before, during and 1h after a 3h intravenous infusion of angiotensin II. In addition, placebo experiments with saline infusion were carried out.
  
  
  RESULTS
  Baseline plasminogen activator inhibitor type-1 activity and plasmin-antiplasmin-complex concentrations were similar in FH and controls, as were interleukin-6, leukocyte counts and C-reactive protein. Fibrinogen levels were higher in FH, and we observed a greater thrombin generating potential in FH (calibrated automated thrombogram), but no signs of elevated thrombin generation in vivo (prothrombin fragment 1+2). During angiotensin infusion plasminogen activator inhibitor type-1 activity decreased and plasmin-antiplasmin-complex concentrations increased similarly in FH and controls. Total and maximal amount of thrombin generated was unchanged, as were prothrombin-fragment-1+2 levels. Interleukin-6 and leukocyte counts increased similarly in both groups during angiotensin infusion, while fibrinogen tended to increase in FH and increased in controls. During saline infusion plasminogen activator inhibitor type-1 activity and prothrombin fragment 1+2 concentrations fell, whereas other markers were unchanged.
  
  
  CONCLUSIONS
  FH exhibits an increased thrombin generation potential, an intact fibrinolysis, and has no convincing signs of inflammation. Angiotensin has proinflammatory effects, and might have minor profibrinolytic and procoagulatory effects.
authors.affiliation: Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Stockholm, Sweden Department of Internal Medicine, Ryhov County Hospital, Jönköping, Sweden mikael.ekholm@ki.se.
authors.forename: Mikael
authors.initials: M
authors.lastname: Ekholm
authors.affiliation: Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kahan
authors.affiliation: Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Division of Internal Medicine, Stockholm, Sweden.
authors.forename: Gun
authors.initials: G
authors.lastname: Jörneskog
authors.affiliation: Department of Medicine, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Brinck
authors.affiliation: Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Stockholm, Sweden.
authors.forename: N Håkan
authors.initials: NH
authors.lastname: Wallén
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage* / Q000494:pharmacology*; D000933:Antifibrinolytic Agents / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002138:Calibration; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications* / Q000473:pathology*; D007249:Inflammation / Q000150:complications*; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D010919:Placebos; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism
chemical_list: D000933:Antifibrinolytic Agents; D015415:Biomarkers; D015850:Interleukin-6; D010446:Peptide Fragments; D010919:Placebos; D017395:Plasminogen Activator Inhibitor 1; C045879:prothrombin fragment 1.2; D000804:Angiotensin II; D011516:Prothrombin; D005341:Fibrinolysin
keywords: Angiotensin II; coagulation; familial hypercholesterolaemia; fibrinolysis; inflammation