title: The effect of aggressive versus conventional lipid-lowering therapy on markers of inflammatory and oxidative stress.
abstract: OBJECTIVE
  Recent trial results are in favor of aggressive lipid lowering using high dose statins in patients needing secondary prevention. It is unclear whether these effects are solely due to more extensive lipid lowering or the result of the potentially anti-inflammatory properties of statins. We aimed to determine whether aggressive compared with conventional statin therapy is more effective in reducing systemic markers of inflammation and oxidative stress.
  
  
  METHODS
  This was a multi-centre, double-blind, placebo-controlled trial. Patients with previous cardiovascular disease, who did not achieve low density lipoprotein (LDL) cholesterol levels <2.6 mmol/l on conventional statin therapy (simvastatin 40 mg) were randomized to continue with simvastatin 40 mg or to receive atorvastatin 40 mg for 8 weeks and thereafter atorvastatin 80 mg for the final 8 weeks (aggressive treatment). Lipids, C-reactive protein, soluble cellular adhesion molecules, neopterin, von Willebrand Factor, and antibodies against oxidized LDL were measured at baseline and after 16 weeks.
  
  
  RESULTS
  Lipid levels decreased significantly in the aggressive treatment group (LDL-C reduction 20.8%; P < 0.001), whereas a slight increase was observed in the conventional group (LDL-C increase 3.7%; P = 0.037). A significant reduction in antibodies against oxidized LDL was seen in the aggressive (13.4%; P < 0.001) and the conventional (26.8%; P < 0.001) group, but there was no difference between groups (P = 0.25). Furthermore, no significant differences in change in other biomarkers was observed between both groups.
  
  
  CONCLUSIONS
  This study does not support the hypothesis that a more profound reduction in inflammatory and oxidative stress contributes to the benefits of aggressive statin therapy.
authors.affiliation: Department of Internal Medicine, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. udomulder@gmail.com
authors.forename: Douwe J
authors.initials: DJ
authors.lastname: Mulder
authors.forename: Paul L
authors.initials: PL
authors.lastname: van Haelst
authors.forename: Martgriet H
authors.initials: MH
authors.lastname: Wobbes
authors.forename: Rijk O
authors.initials: RO
authors.lastname: Gans
authors.forename: Felix
authors.initials: F
authors.lastname: Zijlstra
authors.forename: Johan F
authors.initials: JF
authors.lastname: May
authors.forename: Andries J
authors.initials: AJ
authors.lastname: Smit
authors.forename: Jan Willem Cohen
authors.initials: JW
authors.lastname: Tervaert
authors.forename: Jasper J
authors.initials: JJ
authors.lastname: van Doormaal
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood; D008077:Lipoproteins, LDL / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D011758:Pyrroles / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D019821:Simvastatin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000906:Antibodies; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011758:Pyrroles; C099252:oxidized low density lipoprotein; D014841:von Willebrand Factor; D019798:Neopterin; D002097:C-Reactive Protein; D000069059:Atorvastatin; D019821:Simvastatin