Faculty Bibliography

BACKGROUND AND PURPOSE/OBJECTIVE:Because the diagnosis and treatment of carotid artery disease may reduce the rate of stroke, the aim of this study was to determine whether a diet intervention was associated with incident carotid artery disease. METHODS:Participants were 48 835 postmenopausal women aged 50 to 79 years who were randomly assigned to either the intervention or comparison group in the Women's Health Initiative Diet Modification Trial. Incident carotid artery disease was defined as an overnight hospitalization with either symptoms or a surgical intervention to improve flow. RESULTS:After a mean follow-up of 8.3 years from 1994 to 2005, there were 297 (0.61%) incident carotid artery events. In contrast to the comparison group, the risk of incident carotid disease did not differ from those assigned to the intervention group (hazard ratio, 1.08; 95% confidence interval, 0.9-1.4). In secondary analysis, there was no significant effect of the intervention on the risk for incident carotid disease during the 5 years of postintervention follow-up from 2005 to 2010 (hazard ratio, 1.24; 95% confidence interval, 0.9-1.7) and no significant effect during cumulative follow-up from 1994 to 2010 (hazard ratio, 1.13; 95% confidence interval, 0.9-1.4). CONCLUSIONS:Among postmenopausal women, a dietary intervention aimed at reducing total fat intake and encouraging increased intake of fruit, vegetables, and grains did not significantly change the risk for incident carotid artery disease. CLINICAL TRIAL REGISTRATION URL/BACKGROUND:http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

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: 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)

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.

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.