Faculty Bibliography

Hemostasis is a major concern during the perioperative period. Changes in platelet aggregation and coagulation factors may contribute to the delicate balance between thrombosis and bleeding. We sought to better understand perioperative hemostasis by investigating the changes in platelet aggregation and coagulation factors during the perioperative period. We performed a prospective cohort analysis of 70 subjects undergoing non-emergent orthopedic surgery of the knee (n = 28), hip (n = 35), or spine (n = 7) between August 2011 and November 2011. Plasma was collected preoperatively (T1), 1-h intraoperatively (T2), 1-h (T3), 24-h (T4) and 48-h (T5) postoperatively. Platelet function testing was performed using whole blood impedance aggregometry. Coagulation assays were performed for factor VII, factor VIII, von Willebrand Factor (vWF), and fibrinogen. Of the 70 patients, mean age was 64.1 +/- 9.8 years, 61 % were female, and 74 % were Caucasian. Platelet activity decreased until 1 h postoperatively and then significantly increased above baseline at 24- and 48-h postoperatively. Compared to baseline, coagulation factors decreased intraoperatively. Factor VII activity continued to decrease, while FVIII, vWF, and fibrinogen all increased above baseline postoperatively. The results of our study indicate significant changes in platelet activity and coagulation factors during the perioperative period. Both platelet activity and markers of coagulation decrease during the intraoperative period and then some increase postoperatively. These changes may contribute to the hypercoagulabity and/or bleeding risk that occurs in the perioperative period. Future prospective studies aimed at correlating hemostatic changes with perioperative outcomes are warranted.

BACKGROUND: Ankle-brachial index (ABI) testing is a simple, noninvasive method to diagnose peripheral artery disease (PAD) and is associated with all-cause mortality. The association of ABI levels and myocardial infarction (MI) and stroke is less certain. We sought to further characterize the association between ABI levels and history of MI and stroke. METHODS: Using data from the Life Line Screening program, 3.6 million self-referred participants from 2003 to 2008 completed a medical questionnaire and had bilateral ABIs performed. Logistic regression was used to estimate the association between ABI cutoff points (ABI <0.90 and ABI >1.40) and ABI levels with history of MI, stroke, and MI or stroke (MI/stroke). Models were adjusted for age, sex, race/ethnicity, smoking, diabetes, hypertension, hypercholesterolemia, physical activity, and family history of cardiovascular disease. Separate sex-specific models were performed. RESULTS: Overall, 155,552 (4.5%) had an ABI <0.90, and 42,890 (1.2%) had an ABI >1.40. An ABI <0.90 was associated with higher odds of MI (adjusted odds ratio [OR] 1.67, 95% CI 1.63-1.71), stroke (OR 1.77, 95% CI 1.72-1.82), and MI/stroke (OR 1.71, 95% CI 1.67-1.74), all P < .001. An ABI >1.40 was also associated with higher odds of MI (OR 1.19, 95% CI 1.14-1.24), stroke (OR 1.30, 95% CI 1.22-1.38), and MI/stroke (OR 1.22, 95% CI 1.17-1.27), all P < .001. The ORs for MI/stroke for different ABI levels formed a reverse J-shaped curve in both women and men. CONCLUSIONS: In a large national screening database, there is a strong, consistent relationship between ABI levels and a history of prevalent MI, stroke, and MI/stroke.

OBJECTIVEThe aim of this study was to investigate the relationship between diabetes and different phenotypes of peripheral vascular disease (lower extremity peripheral artery disease [PAD], carotid artery stenosis [CAS], and abdominal aortic aneurysm [AAA]).RESEARCH DESIGN AND METHODSPrevalence of vascular disease was evaluated in 3,696,778 participants of the Life Line Screening survey between 2003 and 2008. PAD was defined as ankle-brachial pressure index <0.90 or prior revascularization, CAS as >/=50% stenosis or prior revascularization, and AAA as infrarenal aortic diameter >/=3 cm or prior repair. Odds ratios (ORs) and 95% CIs were assessed using logistic regression modeling.RESULTSDiabetes mellitus was present in 10.8% of participants (n = 399,884). Prevalence of PAD, CAS, and AAA were significantly higher (P < 0.0001) in participants with compared with those without diabetes. After multivariate adjustment for baseline demographics and clinical risk factors, a significant interaction existed between diabetes and vascular disease phenotype (P < 0.0001). Diabetes was associated with increased odds of PAD (OR 1.42 [95% CI 1.41-1.4]; P < 0.0001) and CAS (1.45 [1.43-1.47]; P < 0.0001) but decreased odds of AAA (0.86 [0.84-0.88]; P < 0.0001). The strength of association increased with increasing severity of disease in each vascular phenotype, and this association persisted in the population with asymptomatic vascular disease.CONCLUSIONSIn a large population-based study, the association between diabetes and vascular disease differed according to vascular phenotype. Future studies exploring the mechanism for these vascular-specific differences are needed.

Background: While fruit and vegetable (F&V) consumption is associated with reduced risk of stroke and coronary heart disease, there is little data on peripheral artery disease (PAD). We sought to study the association between F&V intake and prevalence of PAD in a large community cohort. Methods: From 2003 - 2008, over 3.5 million self-referred participants at >20,000 US sites completed a medical and lifestyle questionnaire and were evaluated by screening ankle-brachial index <0.9 for PAD. Subjects were queried for frequency of consumption of >3 servings of F&V (<1x/mo, 1x/mo- 1x/wk, 2-3x/wk, 4- 5x/wk, daily). Multivariate logistic regression analysis was used to estimate odds of PAD by F&V intake. Results: Among 3,523,545 individuals, mean age was 63.4 + 10.6 years and 63% were female. F&V intake ranged from 7% (<1x/month) to 29% (daily consumption of >3 servings). After adjustment for age, sex, race, smoking, physical activity, diabetes, hypertension, hyperlipidemia and family history of vascular disease, there was a step-wise inverse association of F&V intake with PAD (P for trend <0.0001; Figure). Compared to subjects with <1x/month consumption of >3 servings of F&V, daily intake was associated with 20% lower odds of PAD (OR 0.800, 95% CI 0.784 - 0.816). Conclusion: We present data from a large community cohort, in which F&V intake exhibited an inverse step-wise relationship with PAD prevalence after correction for multiple established risk factors, suggestive of protective effects in this vascular territory. (Figure Presented)

Background: Immature platelet levels are easily measured, related to platelet RNA, and are a potentially useful biomarker of platelet activity. We investigated the reproducibility, effect of aspirin, and association of immature platelet levels with coronary artery disease (CAD). Methods: Following an overnight fast, 48 controls had 4 weekly blood collections. Aspirin 81mg was used between weeks 3 and 4. Subjects with CAD on aspirin monotherapy were included. Platelet count (PLT), immature platelet fraction (IPF) and immature platelet count (IPC) were investigated. Reproducibility was assessed by coefficient of variation (CV) and intraclass correlation coefficient (ICC). Paired comparison was measured using Wilcoxon signed-rank test and unpaired analysis using Wilcoxon rank-sum test. Results: Reproducibility in PLT (CV=8.0%, ICC=.88), IPF (CV=14%, ICC=.87) and IPC (CV=12%, ICC =.77) measurements were excellent. Aspirin had no significant effect on PLT, IPF or IPC. Subjects with CAD (vs controls) had similar PLT (214 [188-235] vs 208 x 103/muL [185-231], p=0.61) but significantly higher IPF (3.3% [2.2-4.9] vs 4.2% [3.1-5.4], p=0.03) and IPC (6.8 [5.1-9.7] vs 8.3 x 103/muL [6.8-11.3], p=0.03; Figure). Conclusions: Immature platelet levels are reproducible over time and significantly higher in subjects with CAD. Immature platelet levels may be a potentially useful biomarker reflecting platelet activity. Future studies correlating IPF and IPC with incident cardiovascular events are needed. (Figure Presented)

Periprocedural hyperglycemia is an independent predictor of mortality in patients who underwent percutaneous coronary intervention (PCI). However, periprocedural management of blood glucose is not standardized. The effects of routinely continuing long-acting glucose-lowering medications before coronary angiography with possible PCI on periprocedural glycemic control have not been investigated. Patients with diabetes mellitus (DM; n = 172) were randomized to continue (Continue group; n = 86) or hold (Hold group; n = 86) their clinically prescribed long-acting glucose-lowering medications before the procedure. The primary end point was glucose level on procedural access. In a subset of patients (no DM group: n = 25; Continue group: n = 25; and Hold group: n = 25), selected measures of platelet activity that change acutely were assessed. Patients with DM randomized to the Continue group had lower blood glucose levels on procedural access compared with those randomized to the Hold group (117 [97 to 151] vs 134 [117 to 172] mg/dl, p = 0.002). There were two hypoglycemic events in the Continue group and none in the Hold group, and no adverse events in either group. Selected markers of platelet activity differed across the no DM, Continue, and Hold groups (leukocyte platelet aggregates: 8.1% [7.2 to 10.4], 8.7% [6.9 to 11.4], 10.9% [8.6 to 14.7], p = 0.007; monocyte platelet aggregates: 14.0% [10.3 to 16.3], 20.8% [16.2 to 27.0], 22.5% [15.2 to 35.4], p <0.001; soluble p-selectin: 51.9 ng/ml [39.7 to 74.0], 59.1 ng/ml [46.8 to 73.2], 72.2 ng/ml [58.4 to 77.4], p = 0.014). In conclusion, routinely continuing clinically prescribed long-acting glucose-lowering medications before coronary angiography with possible PCI help achieve periprocedural euglycemia, appear safe, and should be considered as a strategy for achieving periprocedural glycemic control.

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.

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.