title: Varespladib methyl in cardiovascular disease.
abstract: BACKGROUND
  The high risk of recurrent cardiovascular events amongst patients with cardiovascular disease receiving evidence-based therapies has prompted investigations into complimentary treatments that may reduce residual risk. Analyses of clinical trials in statin-treated patients demonstrate that elevated lipid levels and an activated systemic inflammatory state are associated with a higher risk of recurrent cardiovascular events.
  
  
  METHODS
  This article reviews evidence supporting the causal role for secretory phospholipase A(2) (sPLA(2)) in experimental atherosclerosis, the involvement of various sPLA(2) isozymes as mediators of pro-atherogenic lipoprotein remodeling and participants in vascular and systemic inflammatory responses, and the evidence that sPLA(2) inhibition reduces atherosclerosis in experimental models and biomarkers associated with cardiovascular events in coronary heart disease (CHD) patients.
  
  
  RESULTS
  The experimental basis for sPLA(2) inhibition with varespladib methyl as a potential candidate for lowering recurrent cardiovascular events particularly in acute coronary syndrome patients is discussed.
  
  
  CONCLUSIONS
  Varespladib methyl therapy reduces atherogenic lipoprotein concentrations and systemic inflammatory markers in CHD patients. The future role of varespladib methyl in CHD patients awaits the results of ongoing clinical trials.
authors.affiliation: Mount Sinai School of Medicine, New York, NY 10029, USA. robert.rosenson@mssm.edu
authors.forename: Robert S
authors.initials: RS
authors.lastname: Rosenson
authors.forename: Heather
authors.initials: H
authors.lastname: Fraser
authors.forename: Joaquim
authors.initials: J
authors.lastname: Trias
authors.forename: Colin
authors.initials: C
authors.lastname: Hislop
mesh_terms: D000085:Acetates / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D007249:Inflammation / Q000503:physiopathology; D007651:Keto Acids; D008297:Male; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000085:Acetates; D015415:Biomarkers; D008078:Cholesterol, LDL; D007211:Indoles; D007651:Keto Acids; C545088:varespladib methyl; D054497:Phospholipases A2, Secretory