Reduction of daily life ischaemia by aspirin in patients with angina: underlying link between thromboxane A2 and macrophage colony stimulating factor

Heart. 2004 Apr;90(4):389-93. doi: 10.1136/hrt.2003.015164.

Abstract

Objectives: To evaluate whether aspirin reduces the incidence and frequency of daily life myocardial ischaemia in a cohort of patients with chronic stable coronary artery disease.

Setting: Tertiary referral centre.

Methods: 60 patients with chronic stable coronary artery disease underwent 48 hour Holter monitoring to assess the incidence and frequency of daily life myocardial ischaemia. Those with myocardial ischaemia (40/60) entered a double blind, crossover trial of aspirin (300 mg/day for three weeks) versus placebo. After each treatment arm, 48 hour Holter monitoring was repeated and urinary thromboxane (Tx) B2, 11-dehydro-TxB2, plasma prothrombin fragment F1+2, macrophage colony stimulating factor (MCSF), and interleukin (IL)-6 were measured.

Results: Aspirin reduced the total number and duration of ischaemic episodes from 339 to 251 and from 1765 to 1365 minutes, respectively (p < 0.01 for both). TxB2 was also reduced from 0.2 to 0.1 ng/mg creatinine, 11-dehydro-TxB2 from 3.3 to 1.3 ng/mg creatinine, F1+2 from 1.5 to 1.2 nmol/l, MCSF from 991 to 843 pg/ml, and IL-6 from 3.5 to 2.9 pg/ml (p < 0.05 for all). 11-dehydro-TxB2 excretion with and without aspirin was related to MCSF concentrations (p < 0.01), and the percentage reduction of MCSF by aspirin was related to the reduction of 11-dehydro-TxB2 (p < 0.05) and the reduction of the ischaemic burden compared with placebo (p < 0.05).

Conclusions: In patients with daily life ischaemia, aspirin reduces the incidence and frequency of ischaemic episodes as well as the systemic concentrations of haemostatic/inflammatory markers. Aspirin may prevent transient coronary flow reductions through platelet, thrombin, and cytokine inhibition.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aspirin / therapeutic use*
  • Biomarkers / blood
  • Biomarkers / urine
  • Cohort Studies
  • Coronary Artery Disease / complications
  • Cross-Over Studies
  • Double-Blind Method
  • Electrocardiography, Ambulatory
  • Female
  • Humans
  • Interleukin-6 / urine
  • Macrophage Colony-Stimulating Factor / blood*
  • Male
  • Middle Aged
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / prevention & control*
  • Myocardial Ischemia / urine
  • Peptide Fragments / analysis
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prothrombin / analysis
  • Thromboxane A2 / metabolism*
  • Thromboxane B2 / analogs & derivatives*
  • Thromboxane B2 / urine

Substances

  • Biomarkers
  • Interleukin-6
  • Peptide Fragments
  • Platelet Aggregation Inhibitors
  • prothrombin fragment 1.2
  • Thromboxane B2
  • Thromboxane A2
  • 11-dehydro-thromboxane B2
  • Macrophage Colony-Stimulating Factor
  • Prothrombin
  • Aspirin