Statin therapy and thromboxane generation in patients with coronary artery disease treated with high-dose aspirin.
Aspirin and statin therapy are mainstay treatments in patients with coronary artery disease (CAD). The relation between statin therapy, in vivo thromboxane (Tx) generation; a marker of inflammation, and blood thrombogenicity has never been explored. Urinary 11-dehydro (dh) TxB2 was determined in patients with suspected CAD on 325 mg daily aspirin therapy prior to undergoing cardiac catheterisation (n=281). Thrombogenicity was estimated by thrombelastographic measurement of thrombin-induced platelet-fibrin clot strength (TIP-FCS) and lipids/lipoproteins were determined by vertical density gradient ultracentrifugation/ELISA. The influence of statin therapy and dose was analysed by the atorvastatin equivalent dose (5-10 mg, 20-40 mg, or 80 mg daily). Statin therapy (n=186) was associated with a dose-dependent reduction in urinary 11-dh TxB2 (p=0.046) that was independent of LDL and apo B100 levels but was strongly related to TIP-FCS (p=0.006). By multivariate analysis, no statin therapy (n=95) and female gender were independently associated with high urinary 11-dh TxB2 [OR=2.95 (0.1.57-5.50, p=0.0007); OR=2.25 (1.24-4.05, p=0.007)], respectively. In aspirin-treated patients, statin therapy was independently and inversely associated with inflammation in a dose-dependent manner. Elevated 11-dh TxB2 was associated with a prothrombotic state indicated by high TIP-FCS. Our data suggest that measurement of urinary 11-dTxB2 may be a useful method to optimise statin dosing in order to reduce thrombotic risk.
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Bliden
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Singla
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Gesheff
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Toth
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Tabrizchi
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Guyer
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Singh
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Franzese
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Stapleton
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Tantry
Paul A. Gurbel, MD, Sinai Center for Thrombosis Research, Cardiac Catheterization Laboratory, Sinai Hospital of Baltimore, 2401 W. Belvedere Ave, Baltimore, MD 21215, USA, Tel.: +1 410 601 9600, Fax: +1 410 601 9601, E-mail: PGURBEL@LIFEBRIDGEHEALTH.ORG.
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D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D015415:Biomarkers / Q000652:urine; D001777:Blood Coagulation / Q000187:drug effects; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000652:urine*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D012307:Risk Factors; D012737:Sex Factors; D013916:Thrombelastography; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine; D016896:Treatment Outcome; D014461:Ultracentrifugation
D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D008055:Lipids; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D001241:Aspirin
Aspirin; coronary artery disease; inflammation; lipids; platelets; statin; urinary 11-dehydrothromboxane B2