Aspirin increases nitric oxide formation in chronic stable coronary disease

Scott Hetzel, David DeMets, Ricky Schneider, Steven Borzak, Wendy Schneider, Victor Serebruany, Henning Schröder, Charles H. Hennekens

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Introduction: 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. Materials and 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.

Original languageEnglish (US)
Pages (from-to)217-221
Number of pages5
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Issue number3
StatePublished - May 2013

Bibliographical note

Funding Information:
This trial was funded as an investigator-initiated grant to Florida Atlantic University (FAU), with Charles H. Hennekens, MD, DrPH, and Sir Richard Doll, Research Professor, as the principal Investigators, by Bayer. The funding source, Bayer, had no role in the design, conduct, analysis, interpretation, preparation of the manuscript, or the decisions about whether or where to submit the manuscript for publication.


  • Aspirin
  • Atherosclerosis (4 limit = 5)
  • Nitric oxide


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