Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial.

There is increasing evidence that aspirin initiates biosynthesis of novel antiinflammatory mediators by means of interactions between endothelial cells and leukocytes. These mediators are classified as aspirin-triggered 15-epi-lipoxins. Such compounds may account at least in part for aspirin's clinical benefits, which are distinct from the well appreciated action of aspirin as a platelet inhibitor. Here, we addressed whether aspirin-triggered 15-epilipoxinA4 (ATL) formation is aspirin-dependent in humans and its relationship to aspirin's antiplatelet activity. We conducted a randomized clinical trial among 128 healthy subjects allocated to placebo or to 81-, 325-, or 650-mg daily doses of aspirin for 8 weeks. Plasma thromboxane (TX)B2, an indicator of platelet reactivity, and ATL were assessed from blood collected at baseline and at 8 weeks. Plasma ATL levels significantly increased in the 81-mg aspirin group (0.25 +/- 0.63 ng/ml, P = 0.04), with borderline increases in the 325-mg group (0.16 +/- 0.71 ng/ml) and no apparent significant changes in the 650-mg group (0.01 +/- 0.75 ng/ml, P = 0.96). When ATL and TXB2 were compared, levels changed in a statistically significant and opposite direction (P < 0.01) for all three aspirin doses. These results demonstrated that low-dose aspirin (81 mg daily) initiates production of antiinflammatory ATL opposite to the inhibition of TX. Monitoring ATL may represent a simple clinical parameter to verify an individual's vascular leukocyte antiinflammatory response with low-dose aspirin treatment. These results also emphasize the importance of cell-cell interactions in the modulation of hemostatic, thrombotic, and inflammatory processes.

Cardiac arrest associated with intravenous propofol during transesophageal echocardiography before DC cardioversion.

Transesophageal echocardiography (TEE)-guided cardioversion has been utilized as a feasible alternative to conventional anticoagulation strategies in the management of patients with atrial fibrillation. As such, the use of intravenous sedation protocols using relatively short-acting anesthetics, such as propofol, have gained popularity in the outpatient and inpatient settings for such procedures. The authors report a case of cardiac arrest and electromechanical dissociation associated with the use of intravenous propofol during TEE before direct current cardioversion for atrial fibrillation.

Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women.

OBJECTIVE: Interleukin-6 (IL-6) and C-reactive protein (CRP) are markers of systemic vascular inflammation that herald atherothrombosis and may have important interrelationships with traditional cardiovascular risk factors. METHODS AND RESULTS: We conducted a cross-sectional analysis among 340 apparently healthy women enrolled in the Women's Health Study. In unadjusted analyses, higher levels of IL-6 and CRP were seen with increasing body mass index (BMI), systolic and diastolic blood pressure, and smoking exposure. IL-6 levels were related to the frequency of alcohol intake (P=0.002) and showed an inverse relationship with exercise frequency and hormone replacement therapy (P<0.0001 for both). CRP levels increased with hormone replacement therapy (P=0.0002). Associations among IL-6, CRP, and lipid levels were minimal. Overall, mean levels of IL-6 and CRP increased with increasing numbers of clinical risk factors (P<0.0001). In multivariate analyses, independent relationships were seen between levels of IL-6 and age, BMI, smoking, systolic blood pressure, alcohol use, presence of diabetes, and frequency of exercise. CRP was associated with age, BMI, systolic blood pressure, high density lipoprotein, smoking, and hormone replacement therapy in adjusted analyses. CONCLUSIONS: Plasma levels of IL-6 and CRP are independently related to several clinical cardiovascular risk factors in women.

C-reactive protein, statins, and the primary prevention of atherosclerotic cardiovascular disease.

Emerging data implicate inflammation as integral to atherosclerosis and its complications. From a clinical perspective, the inflammatory biomarker C-reactive protein has demonstrated consistent predictive value in the detection of individuals at high risk for cardiovascular disease. Therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduces C-reactive protein as well as low-density lipoprotein cholesterol, thus providing a potential additional mechanism for the reduction in cardiovascular events associated with the use of these agents. Evidence from the Air Force/Texas Coronary Atherosclerosis Prevention Study suggests that statin therapy may be effective in reducing incident coronary events among those with elevated levels of C-reactive protein but normal levels of low-density lipoprotein cholesterol. These data, along with accumulating laboratory data, support a potential anti-inflammatory benefit of statins. Large-scale, randomized trials in the primary prevention of acute coronary events among individuals without overt hyperlipidemia but with evidence of elevated C-reactive protein are now needed to directly test this hypothesis.