title: Persisting thrombin activity in elderly patients with atrial fibrillation on oral anticoagulation is decreased by anti-inflammatory therapy with intensive cholesterol-lowering treatment.
abstract: BACKGROUND
  It has been demonstrated that the occurrence of ischemic stroke is more prevalent in AF patients, when increased levels of inflammatory markers are present.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the effect of intensive cholesterol lowering therapy on inflammatory markers and evidence of thrombotic in elderly AF patients treated with OAC.
  
  
  METHODS
  34 elderly patients (69-85 yrs) were randomized to double blind treatment with atorvastatin 40 mg plus ezetimibe 10 mg (n = 17) or double placebo (n = 17) for one year. All were anticoagulated with warfarin (target INR 2.5-3.5). Every 3 months inflammatory markers and parameters for evaluation of haemostatic and fibrinolytic activity were measured.
  
  
  RESULTS
  Anti-inflammatory effects in the treatment arm were reflected by a significant decrease from baseline in hs-CRP, FGF, G-CSF, GM-CSF, IL-1ra, IL-9, IL-13, IL-17 and interferon-γ (P < .05). There was no significant decrease in the control group. Endogenous thrombin potential was still present and active but decreased during treatment (P = .0005) compared to the placebo group. After 12 months treatment, a significant correlation was found between changes in endogenous thrombin potential and hs-CRP, interferon-γ and G-CSF, respectively. No hemorrhagic complications occurred.
  
  
  CONCLUSIONS
  Intensive cholesterol lowering significantly reduced inflammation and was accompanied by reduced thrombin generation. Larger clinical studies should determine which inflammatory markers are most specific and sensitive for estimating the inflammatory burden in these patients and at which corresponding thrombin activity level it is beneficial and safe to add intensive cholesterol lowering therapy even if normal cholesterol levels are present.
authors.affiliation: Department of Cardiology, Radboud University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Janet
authors.initials: J
authors.lastname: van Kuilenburg
authors.forename: Knut Tore
authors.initials: KT
authors.lastname: Lappegård
authors.forename: Joe
authors.initials: J
authors.lastname: Sexton
authors.forename: Izabela
authors.initials: I
authors.lastname: Plesiewicz
authors.forename: Paul
authors.initials: P
authors.lastname: Lap
authors.forename: Leon
authors.initials: L
authors.lastname: Bouwels
authors.forename: Tom
authors.initials: T
authors.lastname: Sprong
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
authors.forename: Freek
authors.initials: F
authors.lastname: Verheugt
authors.forename: Waander L
authors.initials: WL
authors.lastname: van Heerde
authors.forename: Gheorghe A
authors.initials: GA
authors.lastname: Pop
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D000069059:Atorvastatin; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D001384:Azetidines / Q000008:administration & dosage / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D010865:Pilot Projects; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use; D013917:Thrombin / Q000378:metabolism*; D013927:Thrombosis / Q000188:drug therapy
chemical_list: D000893:Anti-Inflammatory Agents; D000924:Anticholesteremic Agents; D000925:Anticoagulants; D001384:Azetidines; D015415:Biomarkers; D005343:Fibrinolytic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D013917:Thrombin; D000069438:Ezetimibe