Faculty Bibliography

A 67-year-old man with a drug-eluting stent in his proximal left anterior descending artery was admitted to the hospital after sustaining a traumatic injury to the skull. Due to persistent bleeding from a subgaleal hematoma, intravenous 1-desamino-8-D-arginine vasopressin (DDAVP) was administered. Five hours later, the patient complained of crushing chest pain. A 12-lead electrocardiogram demonstrated 2 mm ST-segment elevations in the precordial leads with reciprocal depressions in the inferior leads. Emergency cardiac catheterization demonstrated total occlusion of the proximal left anterior descending stent with TIMI 0 flow. Another drug-eluting stent was placed inside the original stent with restoration of TIMI 3 flow. During the catheterization, the patient became progressively hypoxic and hypotensive requiring intubation, dopamine drip, and placement of an intra-aortic balloon pump. The patient's hospitalization was complicated by prolonged shock requiring inotropes and vasopressors. This is the first reported case of an ST-elevation myocardial infarction due to in-stent thrombosis occurring after DDAVP administration. Though DDAVP is well tolerated and efficacious in treating several types of coagulopathies, this case illustrates its potential pro-thrombotic effects. Therefore, DDAVP should be used with caution in patients with known coronary artery disease and coronary stents.

BACKGROUND: Data collected as part of routine clinical practice could be used to detect cardiovascular outcomes in pragmatic clinical trials or clinical registry studies. The reliability of claims data for documenting outcomes is unknown. METHODS AND RESULTS: We linked records of Women's Health Initiative (WHI) participants aged >/=65 years to Medicare claims data and compared hospitalizations that had diagnosis codes for acute myocardial infarction or coronary revascularization with WHI outcomes adjudicated by study physicians. We then compared the hazard ratios for active versus placebo hormone therapy based solely on WHI-adjudicated events with corresponding hazard ratios based solely on claims data for the same hormone trial participants. Agreement between WHI-adjudicated outcomes and Medicare claims was good for the diagnosis of myocardial infarction (kappa, 0.71-0.74) and excellent for coronary revascularization (kappa, 0.88-0.91). The hormone:placebo hazard ratio for clinical myocardial infarction was 1.31 (95% confidence interval, 1.03-1.67) based on WHI outcomes and 1.29 (95% confidence interval, 1.00-1.68) based on Medicare data. The hazard ratio for coronary revascularization was 1.09 (95% confidence interval, 0.88-1.35) based on WHI outcomes and 1.10 (95% confidence interval, 0.89-1.35) based on Medicare data. The differences between hazard ratios derived from WHI and Medicare data were not significant in 1000 bootstrap replications. CONCLUSIONS: Medicare claims may provide useful data on coronary heart disease outcomes among patients aged >/=65 years in clinical research studies. CLINICAL TRIALS REGISTRATION INFORMATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00000611.

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.