Haemostatic and inflammatory alterations in familial hypercholesterolaemia, and the impact of angiotensin II infusion

J Renin Angiotensin Aldosterone Syst. 2015 Jun;16(2):328-38. doi: 10.1177/1470320315575848. Epub 2015 Apr 22.

Abstract

Introduction: 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.

Keywords: Angiotensin II; coagulation; familial hypercholesterolaemia; fibrinolysis; inflammation.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiotensin II / administration & dosage*
  • Angiotensin II / pharmacology*
  • Antifibrinolytic Agents / metabolism
  • Biomarkers / metabolism
  • Blood Pressure / drug effects
  • Calibration
  • Case-Control Studies
  • Demography
  • Female
  • Fibrinolysin / metabolism
  • Heart Rate / drug effects
  • Hemostasis / drug effects*
  • Humans
  • Hyperlipoproteinemia Type II / complications*
  • Hyperlipoproteinemia Type II / pathology*
  • Inflammation / complications*
  • Interleukin-6 / metabolism
  • Leukocytes / metabolism
  • Male
  • Peptide Fragments / metabolism
  • Placebos
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Prothrombin / metabolism

Substances

  • Antifibrinolytic Agents
  • Biomarkers
  • Interleukin-6
  • Peptide Fragments
  • Placebos
  • Plasminogen Activator Inhibitor 1
  • prothrombin fragment 1.2
  • Angiotensin II
  • Prothrombin
  • Fibrinolysin