CARDIOVASCULAR MEDICINE

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

I Ikonomidis¹, F Andreotti², P Nihoyannopoulos³

¹ University of Athens, Department of Clinical Therapeutics, Alexandra Hospital, Athens, Greece
² The Institute of Cardiology, Catholic University Medical School, Rome, Italy
³ Cardiology Department, Imperial College School of Medicine, National Heart and Lung Institute, Hammersmith Hospital, London, UK

Correspondence to:
Correspondence to:
Dr Ignatios Ikonomidis
University of Athens, Department of Clinical Therapeutics, Alexandra Hospital, Perikleous 19, N Chalkidona, Athens 14343, Greece; ignoik{at}otenet.gr

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.

Keywords: myocardial ischaemia; aspirin; platelets; cytokines

Abbreviations: F1+2, plasma prothrombin fragment F1+2; IL, interleukin; MCSF, macrophage colony stimulating factor; Tx, thromboxane

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