Evening aspirin intake results in higher levels of platelet inhibition and a reduction in reticulated platelets - a window of opportunity for patients with cardiovascular disease?

Cardiovascular events occur most frequently in the early morning. Similarly, the release of reticulated platelets (RP) by megakaryocytes has a peak in the late night and early morning. Which aspirin regimen most effectively inhibits platelets during these critical hours is unknown. Hence, the primary objective of this trial was to assess platelet function and RP levels at 8.00 AM, in stable cardiovascular (CVD) patients, during three different aspirin regimens. In this open-label randomized cross-over study subjects were allocated to three sequential aspirin regimens: once-daily (OD) 80 mg morning; OD-evening, and twice-daily (BID) 40 mg. Platelet function was measured at 8.00 AM & 8.00 PM by serum Thromboxane B2 (sTxB2) levels, the Platelet Function Analyzer (PFA)-200® Closure Time (CT), Aspirin Reaction Units (ARU, VerifyNow®), and RP levels. In total, 22 patients were included. At 8.00 AM, sTxB2 levels were the lowest after OD-evening in comparison with OD-morning (p = <0.01), but not in comparison with BID. Furthermore, RP levels were similar at 8.00 AM, but statistically significantly reduced at 8.00 PM after OD-evening (p = .01) and BID (p = .02) in comparison with OD-morning. OD-evening aspirin intake results in higher levels of platelet inhibition during early morning hours and results in a reduction of RP levels in the evening. These findings may, if confirmed by larger studies, be relevant to large groups of patients taking aspirin to reduce cardiovascular risk.

The viewing of a 'Bloodcurdling' horror movie increases platelet reactivity: A randomized cross-over study in healthy volunteers.

BACKGROUND: Epidemiological studies have suggested an increased risk of cardiovascular events (CVE) during acute stressful and/or frightful moments. A possible explanation for this could be an effect of acute stress on hemostasis. A recent study demonstrated an increase in factor VIII after watching a horror movie. Primary hemostasis, however, is thought to play a more prominent role in the etiology of CVE. The objective of this study was therefore to assess the influence of viewing a 'bloodcurdling' horror movie on platelet reactivity in healthy volunteers. METHODS: We performed a randomized cross-over study in healthy adults. Subjects were allocated to two movies in random sequence: a horror and a control movie. Blood was drawn at baseline and after 24 min of viewing time. The primary endpoint was the change in Platelet Function Analyzer® Closure Time (Δ PFA-CT) after watching the movie. RESULTS: In total, 20 participants, aged 18-30 years, completed the study protocol. The delta PFA-CT was statistically significantly shorter with a mean in the delta difference of -9.7 s (SEM 4.0, 95% C.I. -18.0 to -1.3) during the horror movie versus the control movie. The Light Transmission Aggregometry endpoints were in line with the PFA-CT, albeit only the highest level of Arachidonic Acid agonist demonstrated a statistically significant mean difference in the delta of aggregation of 13.15% (SEM 7.0, 95% C.I. 1.6-27.9). CONCLUSION: A 'blood curdling' horror movie increases platelet reactivity. These data are supportive of a role of platelet reactivity in acute stress induced cardiovascular event risk.

Chronic use of low-dose aspirin is not associated with lower bone mineral density in the general population.

BACKGROUND: Low-dose aspirin is the cornerstone of secondary prevention of cardiovascular disease. Previous studies suggested that the use of aspirin is associated with an increased fracture risk. However, there is uncertainty whether this is due to an effect of aspirin on bone mineral density (BMD). METHODS: Between 2008 and 2012, information on medication use and dual X-ray absorptiometry measured vertebral and femoral BMD of 916 participants was collected in the Netherland Epidemiology of Obesity study. The cross-sectional association between chronic low-dose aspirin use and BMD was estimated using linear regression, controlling for demography, body composition, comorbidity and other medication use which could affect BMD. A subgroup analysis in postmenopausal women (n=329) was conducted. RESULTS: After full adjustment, there was no difference between aspirin users and non-users for vertebral BMD (adjusted mean difference: 0.036 (95% CI -0.027 to 0.100) g/cm2) and femoral BMD (adjusted mean difference: 0.001 (-0.067 to 0.069) g/cm2). Also in the subgroup of postmenopausal women, aspirin use was not associated with lower vertebral (adjusted mean difference: 0.069 (-0.046 to 0.184) g/cm2) or femoral BMD (adjusted mean difference: -0.055 (-0.139;0.029) g/cm2). CONCLUSION: Chronic use of low-dose aspirin is not associated with lower BMD in the general population. The increased risk of fractures observed in aspirin users in previous studies is therefore more likely to be the result of common causes of aspirin use and fractures, but not of direct effects of aspirin on BMD.

Effect of aspirin intake at bedtime versus on awakening on circadian rhythm of platelet reactivity. A randomised cross-over trial.

The risk of acute cardiovascular events is highest during morning hours, and platelet activity peaks during morning hours. The effect of timing of aspirin intake on circadian rhythm and morning peak of platelet reactivity is not known. It was our objective to evaluate the effect of timing of aspirin intake on circadian rhythm and morning peak of platelet reactivity. A randomised open-label cross-over trial in healthy subjects (n=14) was conducted. Participants used acetylsalicylic acid (80 mg) on awakening or at bedtime for two periods of two weeks, separated by a four-week wash-out period. At the end of both periods blood was drawn every 3 hours to measure COX-1-dependent (VerifyNow-Aspirin; Serum Thromboxane B2 [STxB2]) and COX-1-independent (flow cytometry surface CD62p expression; microaggregation) platelet activity. VerifyNow platelet reactivity over the whole day was similar with intake on awakening and at bedtime (mean difference: -9 [95 % confidence interval (CI) -21 to 4]). However, the morning increase in COX-1-dependent platelet activity was reduced by intake of aspirin at bedtime compared with on awakening (mean difference VerifyNow: -23 Aspirin Reaction Units [CI -50 to 4]; STxB2: -1.7 ng/ml [CI -2.7 to -0.8]). COX-1-independent assays were not affected by aspirin intake or its timing. Low-dose aspirin taken at bedtime compared with intake on awakening reduces COX-1-dependent platelet reactivity during morning hours in healthy subjects. Future clinical trials are required to investigate whether simply switching to aspirin intake at bedtime reduces the risk of cardiovascular events during the high risk morning hours.

Predicting the need for radiologic imaging in adults with febrile urinary tract infection.

BACKGROUND: Radiologic evaluation of adults with febrile urinary tract infection (UTI) is frequently performed to exclude urological disorders. This study aims to develop a clinical rule predicting need for radiologic imaging. METHODS: We conducted a prospective, observational study including consecutive adults with febrile UTI at 8 emergency departments (EDs) in the Netherlands. Outcomes of ultrasounds and computed tomographs of the urinary tract were classified as "urgent urological disorder" (pyonephrosis or abscess), "nonurgent urologic disorder," "normal," and "incidental nonurological findings." Urgent and nonurgent urologic disorders were classified as "clinically relevant radiologic findings." The data of 5 EDs were used as the derivation cohort, and 3 EDs served as the validation cohort. RESULTS: Three hundred forty-six patients were included in the derivation cohort. Radiologic imaging was performed for 245 patients (71%). A prediction rule was derived, being the presence of a history of urolithiasis, a urine pH ≥7.0, and/or renal insufficiency (estimated glomerular filtration rate, ≤40 mL/min/1.73 m(3)). This rule predicts clinically relevant radiologic findings with a negative predictive value (NPV) of 93% and positive predictive value (PPV) of 24% and urgent urological disorders with an NPV of 99% and a PPV of 10%. In the validation cohort (n = 131), the NPV and PPV for clinically relevant radiologic findings were 89% and 20%, respectively; for urgent urological disorders, the values were 100% and 11%, respectively. Potential reduction of radiologic imaging by implementing the prediction rule was 40%. CONCLUSIONS: Radiologic imaging can selectively be applied in adults with febrile UTI without loss of clinically relevant information by using a simple clinical prediction rule.