Cigarette smoking is associated with increased circulating proinflammatory and procoagulant markers in patients with chronic coronary artery disease: Effects of aspirin treatment

Ikonomidis, Ignatios; Lekakis, John; Vamvakou, Georgia; Andreotti, Felicita; Nihoyannopoulos, Petros

doi:10.1016/j.ahj.2004.08.030

« Previous Next »American Heart Journal
Volume 149, Issue 5 , Pages 832-839, May 2005

Cigarette smoking is associated with increased circulating proinflammatory and procoagulant markers in patients with chronic coronary artery disease:

Effects of aspirin treatment

Ignatios Ikonomidis, MD, FESC
- Department of Clinical Therapeutics, University of Athens, Alexandra Hospital, Athens, Greece
- Reprint requests: Ignatios Ikonomidis, MD, FESC, Department of Clinical Therapeutics, University of Athens, Alexandra Hospital, Perikleous 19, N. Chalkidona, Athens, 14343 Greece.
John Lekakis, MD, FESC
- Department of Clinical Therapeutics, University of Athens, Alexandra Hospital, Athens, Greece
Georgia Vamvakou, MD
- Department of Clinical Therapeutics, University of Athens, Alexandra Hospital, Athens, Greece
Felicita Andreotti, MD, PhD, FESC
- Imperial College School of Medicine, National Heart and Lung Institute, Cardiology Department, Hammersmith Hospital, London, United Kingdom
Petros Nihoyannopoulos, MD, FRCP, FACC, FESC
- Imperial College School of Medicine, National Heart and Lung Institute, Cardiology Department, Hammersmith Hospital, London, United Kingdom

Received 27 May 2004; accepted 24 August 2004.

Background

Smoking is associated with endothelial dysfunction. Cytokines released by injured endothelium promote vascular interactions with leukocytes and platelets. We investigated whether (a) cigarette smoking is linked to increased cytokine production, which may mediate platelet activation and thrombin generation in chronic coronary artery disease (CAD), and (b) aspirin treatment inhibits smoking-related changes on cytokines, platelets, and thrombin.

Methods and Results

Plasma macrophage–colony-stimulating factor (M-CSF) and C-reactive protein (CRP) were measured in 100 patients with chronic CAD, 60 of whom were chronic smokers. Prothrombin fragments 1+2 and urinary 11–dehydro-thromboxane B₂ (TXB₂) were additionally measured in 60 of 100 patients (30 of whom were smokers) and in 24 healthy controls. Smokers (n = 20) matched for age, myocardial ischemia, and other risk factors with 20 nonsmokers entered a double-blind crossover trial of aspirin (300 mg/d for 3 weeks) versus placebo. Blood and urine measurements were repeated after each treatment. Compared with nonsmokers, smokers had 3-fold median M-CSF (1499 vs 476 pg/mL), 2-fold CRP (1.5 vs 0.8 mg/L), and higher 11–dehydro-TXB₂ (3.6 vs 2.1 ng/mg creatinine, P < .01 for all comparisons). After aspirin treatment, M-CSF, CRP, 11–dehydro-TXB₂, and prothrombin fragments 1+2 remained higher in smokers compared with nonsmokers despite a significant reduction of these markers by aspirin (P < .05). M-CSF remained related to 11–dehydro-TXB₂ excretion during both treatment phases (P < .01) suggesting that cytokine-mediated thromboxane A₂ production was not altered by aspirin.

Conclusions

Smoking is associated with increased M-CSF, CRP, and platelet activity. Although aspirin treatment reduces the proinflammatory and procoagulant markers in smokers, it does not abolish the proinflammatory effects of smoking in patients with chronic CAD.