title: Relation of interleukin-6, C-reactive protein, and the prothrombotic state to transesophageal echocardiographic findings in atrial fibrillation.
abstract: Atrial fibrillation (AF) is a major cause of morbidity and mortality from stroke due to thromboembolism from the fibrillating left atrium, including its appendage. We hypothesized that indexes of inflammation (as indicated by C-reactive protein and interleukin-6) and indexes of the prothrombotic state in AF that represent platelet activation (soluble P-selectin levels), endothelial damage or dysfunction (von Willebrand factor), coagulation (tissue factor and fibrinogen), and hemorrheology (plasma viscosity and hematocrit) would be related to the presence of thromboembolic predictors on transesophageal echocardiography in patients with long-term AF. To test this hypothesis, we recruited 37 patients with long-term AF who were receiving warfarin therapy with an international normalized ratio of > or =2.0 for > or =3 weeks before transesophageal echocardiography. Twenty-two patients had dense spontaneous echo contrast (SEC) visible in the left atrium or left atrial appendage, 10 had complex atheromatous plaque in the descending aorta, 11 had peak left atrial appendage velocities < or =0.2 m/s, and 3 had thrombus visible in the left atrial appendage. Twenty-eight patients had > or =1 transesophageal echocardiographic (TEE) risk factor for thromboembolism. Plasma levels of C-reactive protein (p = 0.03) and soluble P-selectin (p = 0.04) and hematocrit (p = 0.004) were higher among patients with AF with dense SEC than among those without. No significant associations were found for other TEE risk factors. Hematocrit was the only variable significantly associated with the presence of > or =1 TEE risk factor among patients with AF (p = 0.007) and the only independent associate of dense SEC after multivariate analysis (relative risk 1.4, 95% confidence interval 1.1 to 1.6) per 1% increase in hematocrit (p = 0.003, r(2) = 0.22). Although hematocrit was the only independent associate of dense SEC and > or =1 TEE risk factor, significant associations between dense SEC and the 2 indexes, C-reactive protein and soluble P-selectin, may indicate that mechanisms other than stasis are present with dense SEC. These observations support an "inflammatory hypothesis" in the pathogenesis of SEC that may have implications for thrombogenesis in AF.
authors.affiliation: Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, United Kingdom.
authors.forename: Dwayne S G
authors.initials: DS
authors.lastname: Conway
authors.forename: Peter
authors.initials: P
authors.lastname: Buggins
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hughes
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000097:blood* / Q000000981:diagnostic imaging* / Q000188:drug therapy; D002097:C-Reactive Protein / Q000032:analysis*; D016022:Case-Control Studies; D017548:Echocardiography, Transesophageal; D005260:Female; D006400:Hematocrit; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D015999:Multivariate Analysis; D019007:P-Selectin / Q000097:blood; D010865:Pilot Projects; D015539:Platelet Activation; D012307:Risk Factors; D013923:Thromboembolism / Q000453:epidemiology; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D015850:Interleukin-6; D019007:P-Selectin; D014859:Warfarin; D002097:C-Reactive Protein