title: Aspirin increases nitric oxide formation in chronic stable coronary disease.
abstract: BACKGROUND
  There are no published randomized data on secondary prevention in humans about whether aspirin affects nitric oxide (NO) formation. In patients with chronic stable coronary disease, we tested whether aspirin at clinically relevant doses increases NO formation.
  
  
  METHODS
  In a randomized, double-blind trial, 37 patients from 2 cardiology office practices were assigned to daily doses of 81, 162.5, 325, 650, or 1300 aspirin for 12 weeks. Primary prespecified outcome measures were changes in heme oxygenase (HO-1), a downstream target of NO formation, and asymmetrical dimethyl arginine (ADMA), a competitive inhibitor of NO synthase.
  
  
  RESULTS
  There were no significant differences for HO-1 or ADMA between any of the clinically relevant doses of aspirin tested, so all were combined. For HO-1, there was a significant increase (10.29 ± 2.44, P < .001) from baseline (15.37 ± 1.85) to week 12 (25.66 ± 1.57). The mean ratio (MR) of week 12 to baseline for HO-1 was significantly higher than 1.0 (1.67, confidence interval [CI] from 1.60 to 1.74, P < .001). For ADMA, there was a significant decrease (-0.24 ± 0.11, P < .001) from baseline (0.78 ± 0.08) to week 12 (0.54 ± 0.07). The MR of week 12 to baseline for ADMA was significantly lower than 1.0 (0.69, CI from 0.66 to 0.73, P < .001).
  
  
  CONCLUSIONS
  In patients with chronic stable coronary disease, all clinically relevant daily doses of aspirin tested, from 81 to 1300 mg, produce similar and statistically significant increases in HO-1 and decreases in ADMA. These are the first randomized data on secondary prevention patients. These data support the hypothesis that aspirin has additional beneficial effects mediated through NO formation. Further research, including direct randomized comparisons on atherosclerosis using noninvasive techniques as well as on occlusive vascular disease events, is necessary.
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine, Madison, WI, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Hetzel
authors.forename: David
authors.initials: D
authors.lastname: DeMets
authors.forename: Ricky
authors.initials: R
authors.lastname: Schneider
authors.forename: Steven
authors.initials: S
authors.lastname: Borzak
authors.forename: Wendy
authors.initials: W
authors.lastname: Schneider
authors.forename: Victor
authors.initials: V
authors.lastname: Serebruany
authors.forename: Henning
authors.initials: H
authors.lastname: Schröder
authors.forename: Charles H
authors.initials: CH
authors.lastname: Hennekens
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000097:blood; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D051547:Heme Oxygenase-1 / Q000097:blood / Q000737:chemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D013608:Tablets, Enteric-Coated; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D002317:Cardiovascular Agents; D010975:Platelet Aggregation Inhibitors; D013608:Tablets, Enteric-Coated; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D001241:Aspirin