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

• Published in: The American heart journal Vol. 149; no. 5; pp. 832 - 839
• Main Authors: IKONOMIDIS, Ignatios, LEKAKIS, John, VAMVAKOU, Georgia, ANDREOTTI, Felicita, NIHOYANNOPOULOS, Petros
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier 01-05-2005; Elsevier Limited
• Subjects: Adult; Age; Aged; Aspirin; Aspirin - therapeutic use; Biological and medical sciences; Blood platelets; C-Reactive Protein - drug effects; C-Reactive Protein - metabolism; Cardiology. Vascular system; Cardiovascular disease; Cigarettes; Coronary Disease - blood; Coronary Disease - drug therapy; Coronary Disease - urine; Coronary heart disease; Cytokines; Double-Blind Method; Drug therapy; Enzymes; Female; Heart; Heart attacks; Humans; Immunoassay; Ischemia; Macrophage Colony-Stimulating Factor - blood; Macrophage Colony-Stimulating Factor - drug effects; Male; Medical sciences; Middle Aged; Peptide Fragments - blood; Prospective Studies; Prothrombin; Risk factors; Smoking; Smoking - adverse effects; Studies; Thromboxane B2 - analogs & derivatives; Thromboxane B2 - urine; Tobacco, tobacco smoking; Toxicology; Values; Human; Chronic; Association; Treatment; Tobacco smoking; Biological marker; Cardiovascular disease; Acetylsalicylic acid; Circulatory system; Cardiology; Coronary heart disease; Phlebology
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2004.08.030

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.
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-TXB 2 (3.6 vs 2.1 ng/mg creatinine, P < .01 for all comparisons). After aspirin treatment, M-CSF, CRP, 11-dehydro-TXB 2 , 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-TXB 2 excretion during both treatment phases (P < .01) suggesting that cytokine-mediated thromboxane A 2 production was not altered by aspirin.
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.