Influence of cyclooxygenase-1 genotype on ex vivo aspirin response in patients at risk for stroke.

BACKGROUND: We sought to determine whether cyclooxygenase-1 (PTGS1) genotype is associated with the ability of aspirin to inhibit platelet aggregation in patients at risk for stroke. METHODS: Blood and urine samples were collected from 60 subjects, including 28 African Americans, who were taking aspirin for primary or secondary stroke prevention. Samples were analyzed for the PTGS1 A-707G, PTGS1 P17L, and glycoprotein IIIa (ITGB3)P1(A1/A2) genotypes, ex-vivo platelet aggregation, serum cholesterol, plasma salicylate levels, and urinary 11-dehydrothromboxane B(2) (11-dhTxB(2)) concentrations. The association between PTGS1 A-707G and P17L genotypes and aspirin response, as assessed by ex vivo studies and 11-dhTxB(2) concentrations, was evaluated by statistical testing and nonlinear mapping. RESULTS: Salicylate concentrations, ITGB3 genotype distribution and 11-dhTxB(2) concentrations were similar among PTGS1 genotype groups. More subjects with the PTGS1 17PP versus PL genotype had incomplete ex-vivo inhibition of platelet aggregation by aspirin (57 vs. 20%; p = 0.04). Fifty-nine percent of subjects homozygous for both the PTGS -707A and 17P alleles, but none with both the PTGS1 -707G and 17L alleles had incomplete inhibition with aspirin; p = 0.04. Similarly, nonlinear mapping showed a direct relationship between the PTGS1 17P allele and decreased aspirin response. When analyzed separately by ethnicity, the association with the P17L genotype and aspirin response persisted in African Americans, but not Caucasians. CONCLUSIONS: Our data suggest that the PTGS1 P17L genotype contributes to response to aspirin as assessed by ex-vivo platelet aggregation. Our data further suggest that the association between PTGS1 genotype and aspirin response might vary by ethnicity.

Platelet aggregation and recruitment with aspirin-clopidogrel therapy.

BACKGROUND: Aspirin-clopidogrel combination therapy inhibits platelet aggregation. The effect on platelet recruitment is unknown. METHODS: Thirty chronic ischemic stroke patients taking aspirin alone followed by aspirin-clopidogrel combined therapy had platelet reactivity tests performed over 3 months: ex vivo platelet aggregation, platelet recruitment and urinary 11-dehydro-thromboxane B(2) (11-dhTxB(2))excretion. Statistical analysis of variance compared platelet aggregation and recruitment between aspirin alone and aspirin-clopidogrel, and longitudinal regression analysis estimated platelet recruitment over time. Nonlinear mapping defined variable connections in each patient. RESULTS: Statistically significant differences were found between aspirin alone and aspirin-clopidogrel for (1) adenosine-diphosphate- and collagen-induced platelet aggregation and maximum inhibition of platelet recruitment and (2) increasing inhibition of platelet recruitment over time. Urinary 11-dhTxB(2) excretion did not predict platelet aggregation response. Nonlinear mapping showed patient-unique variable interconnections. CONCLUSIONS: Platelet inhibition with aspirin-clopidogrel may increase over time, and future studies should focus on this finding in the context of vascular complications.

Coca tea consumption causes positive urine cocaine assay.

BACKGROUND: Coca tea, derived from the same plant that is used to synthesize cocaine, is commonly consumed in South America and easily obtained in the United States. OBJECTIVES: To determine whether consumption of coca tea would result in a positive urine toxicology screen for cocaine metabolites. METHODS: Five healthy adult volunteers consumed coca tea and underwent serial quantitative urine testing for cocaine metabolites by fluorescence polarization immunoassay. The cutoff for a positive assay was chosen at 300 ng/ml, the National Institute on Drug Abuse standard. RESULTS: Each participant's urine cocaine assay was positive (level exceeding 300 ng/ml) by 2 h after ingestion. Three out of five participants' samples remained positive at 36 h. Mean urine benzoylecgonine concentrations in all postconsumption samples was 1777 ng/ml (95% confidence interval: 1060-2495). CONCLUSIONS: Coca tea ingestion resulted in a positive urine assay for cocaine metabolite. Healthcare professionals should consider a history of coca tea ingestion when interpreting urine toxicology results.

Sex difference in the antiplatelet effect of aspirin in patients with stroke.

BACKGROUND: There is substantial interpatient variability in response to aspirin after an ischemic stroke or transient ischemic attack (TIA), as assessed by ex vivo effects of aspirin on platelet aggregation. The factors contributing to this variability are not well defined. OBJECTIVE: To determine whether demographic, social, or clinical characteristics are associated with ex vivo response to aspirin in patients with a history of stroke or TIA. METHODS: Eighty-one patients who were taking aspirin for secondary stroke prevention and underwent ex vivo platelet aggregation studies were identified. The medical records of eligible patients were reviewed by clinicians who specialize in the management of stroke patients. Characteristics were compared between 45 patients who had a complete response to aspirin and 36 patients who exhibited an incomplete (partial) response to aspirin based on the results of platelet aggregation testing. RESULTS: The median (range) aspirin dose was similar in complete (325; 81-1950 mg/day) and partial (325; 81-1300 mg/day) responders. There was no association between aspirin response and age, race, body mass index, medical history, smoking status, or use of statin or hormone replacement therapy. However, sex was significantly associated with response to aspirin, with more women in the partial versus complete responder group (75% vs 49%; p = 0.02). CONCLUSIONS: Our data suggest that aspirin may be less effective at inhibiting platelet aggregation in women compared with men who have a history of ischemic stroke or TIA.

Cardiovascular benefits of garlic (Allium sativum L).

Although garlic is believed to have health-promoting benefits, many of the claimed benefits are not supported by good scientific studies. This review critically examined current scientific literature concerning claims of cardiovascular benefits from regular consumption of garlic or garlic preparations. The vast majority of recent randomized, placebo-controlled studies do not support a role for garlic in lowering blood lipids. There also is insufficient evidence to support a role in reducing blood pressure. While there have been indications of antiatherosclerotic effects associated with garlic consumption, there are insufficient data in humans. Investigation of antithrombotic effects of garlic consumption appears to hold promise, but too few data exist to draw firm conclusions.