Faculty Bibliography

Abstract Some studies suggest that mean platelet volume (MPV) correlates with increased risk for cardiovascular morbidity and mortality. In this study, we aim to assess reproducibility, need for standardized measurements, effect of aspirin, and association with other established markers of platelet activity. Following an overnight fast, 48 healthy volunteers had weekly assessment of platelet activity and were administered aspirin 81 mg daily for 7 d between weeks 3 and 4. We investigated the influence of time between phlebotomy and MPV measurement (n = 10). Reproducibility was assessed by coefficient of variation (CV) and intraclass correlation coefficient (ICC). MPV measurements were reproducible (Week 1: 10.6 fL [9.9-11], Week 2: 10.6 fL [10.0-10.9], Week 3: 10.6 fL [9.8-11]). CV was 0.85 (p < 0.001) for each comparison, indicating excellent reproducibility. There was no effect of aspirin on MPV (10.6 fL [9.8-11] versus 10.5 fL [9.9-11]; p = 0.81). MPV significantly increased as time between phlebotomy and MPV measurement increased (Spearman's rho = 0.94, p = 0.001). Increasing MPV tertiles was associated with collagen- and thrombin receptor-activated peptide-induced platelet aggregation but not with ADP- or arachidonic acid-induced or spontaneous platelet aggregation. In conclusion, when standardized, MPV is a reproducible marker of platelet size and not affected by low-dose aspirin. MPV is modestly associated with some, but not all, markers of platelet activity.

Biomarker testing for efficacy of therapy is an accepted way for clinicians to individualize dosing to genetic and/or environmental factors that may be influencing a treatment regimen. Aspirin is used by nearly 43 million Americans on a regular basis to reduce risks associated with various atherothrombotic diseases. Despite its widespread use, many clinicians are unaware of the link between suboptimal response to aspirin therapy and increased risk for inferior clinical outcomes in several disease states, and biomarker testing for efficacy of aspirin therapy is not performed as routinely as efficacy testing in other therapeutic areas. This article reviews the clinical and laboratory aspects of determining whole-body thromboxane production, particularly as it pertains to efficacy assessment of aspirin responsiveness.

OxLDL/beta2GPI complexes have been implicated in the initiation and progression of atherosclerosis and associated with disease severity and adverse outcomes. We investigate the significance of anti-oxLDL/beta2GPI antibodies and oxLDL/beta2GPI complexes in patients with arterial and idiopathic venous disease. A cohort of 61 arterial disease patients, 32 idiopathic venous disease patients, and 53 healthy controls was studied. Because statins influence oxLDL/beta2GPI, these complexes were analyzed on subjects not taking statins. Arterial and venous groups expressed higher levels of IgG anti-oxLDL/beta2GPI antibodies than controls without any other significant clinical association. OxLDL/beta2GPI complexes were significantly elevated in arterial (0.69 U/mL, P = 0.004) and venous disease (0.54 U/mL, P = 0.025) than controls (0.39 U/mL). Among arterial diseases, oxLDL/beta2GPI was 0.85 U/mL for carotid artery disease, 0.72 U/mL for peripheral artery disease, and 0.52 U/mL for abdominal aortic aneurysm. There was a significant association with male gender, age, hypertension, and history of thrombosis. Subjects with oxLDL/beta2GPI above the median (0.25 U/mL) were more likely to have arterial (OR 4.5, P = 0.004) or venous disease (OR 4.1, P = 0.008). Multivariate regression indicated that males (P = 0.021), high cholesterol (P = 0.011), and carotid disease (P = 0.023) were significant predictors of oxLDL/beta2GPI. The coexistence of oxLDL/beta2GPI in arterial and venous disease may suggest a common oxidative mechanism that independently predicts carotid artery disease.

Dual antiplatelet therapy is the cornerstone in the management of patients with acute coronary syndromes (ACS). Ticagrelor, an oral, direct, reversibly binding, P2Y12 receptor antagonist, is approved for the prevention of atherothrombotic events in adult patients with ACS. In the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor was associated with significant reductions in cardiovascular events, cardiovascular mortality, and all-cause mortality compared with clopidogrel. A subanalysis of PLATO trial data identified a geographic region interaction (p = 0.045), indicating reduced efficacy of ticagrelor versus clopidogrel in North American patients. This effect could be due to chance, but may be explained by an interaction of ticagrelor with high aspirin doses, which are commonly used in the United States. In patients taking low-dose maintenance aspirin, ticagrelor was more effective than clopidogrel in decreasing cardiovascular events regardless of the geographic region. A proposed hypothetical mechanism for the interaction between ticagrelor and higher aspirin dose is linked to the level of P2Y12 inhibition and the potential prothrombotic effects of high-dose aspirin through the suppression of prostacyclin. A review of data regarding aspirin use for secondary prevention of events in ACS demonstrated that low aspirin doses (75 to 160 mg/day) are consistently favored for short- and long-term use because of the lack of a dose-response relationship between increasing aspirin dose and improved efficacy, and a higher incidence of gastrointestinal bleeding with increasing aspirin dose. The use of low aspirin doses reflects good clinical practice and is encouraged in current guidelines.