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1.  Use of Medicare Data to Identify Coronary Heart Disease Outcomes In the Women's Health Initiative (WHI) 
Data collected as part of routine clinical practice could be used to detect cardiovascular outcomes in pragmatic clinical trials, or in 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 and older to Medicare claims data, and compared hospitalizations that had diagnosis codes for acute myocardial infarction (MI) 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 for MI (kappa = 0.71 to 0.74), and excellent for coronary revascularization (kappa=0.88 to 0.91). The hormone:placebo hazard ratio for clinical MI was 1.31 (95% confidence interval (CI) 1.03 to 1.67) based on WHI outcomes, and 1.29 (CI 1.00 to 1.68) based on Medicare data. The hazard ratio for coronary revascularization was 1.09 (CI 0.88 to 1.35) based on WHI outcomes and 1.10 (CI 0.89 to 1.35) based on Medicare data. The differences between hazard ratios derived from WHI and Medicare data were not significant in 1,000 bootstrap replications.
Medicare claims may provide useful data on coronary heart disease outcomes among patients aged 65 years and older in clinical research studies.
Clinical Trials Registration Information, Trial Number NCT00000611
PMCID: PMC4548886  PMID: 24399330
outcomes research; research design; randomized controlled trials
2.  Greater Frequency of Nut Consumption is Associated with Lower Prevalence of, Peripheral Arterial Disease 
Preventive medicine  2014;72:15-18.
Nut consumption has been associated with lower risk of coronary heart disease and all-cause mortality. The association between nut intake and peripheral arterial disease (PAD) is uncertain.
We sought to investigate the association between nut consumption and presence of prevalent PAD in a large cross-sectional sample.
Self-referred participants at >20,000 US sites who completed a medical and lifestyle questionnaire were evaluated by screening ankle brachial indices for PAD. Multivariable logistic regression analysis was used to estimate odds of PAD in different nut consumption categories.
Among 3,312,403 individuals, mean age was 63.6 ±10.6 years and 62.8% were female. There were 219,527 cases of PAD. After multivariable adjustment there was an inverse association of nut intake with PAD. Compared to subjects with consumption of nuts
These observations suggest the need for more rigorous testing evaluating the role of nuts in PAD prevention.
PMCID: PMC4518851  PMID: 25532677
peripheral arterial disease; nuts; nutrition
While the relationship between physical activity and coronary heart disease is well characterized, a paucity of data exists regarding physical activity and vascular disease in other arterial territories. This study examined the prevalence of peripheral artery disease (PAD) and carotid artery stenosis (CAS) in association with physical activity.
Approach and Results
The association between physical activity and vascular disease was examined in more than 3 million self-referred US participants in the United States from 2003–2008 who completed a medical and lifestyle questionnaire in the Life Line screening program. All subjects were evaluated by screening ankle brachial indices <0.90 for PAD and ultrasound imaging for CAS >50%. Multivariable logistic regression modeling was used to estimate odds of disease. Among 3,250,350 subjects, 63% of the population engaged in some leisure time vigorous physical activity. After adjustment for age, sex, race/ethnicity, hypertension, hypercholesterolemia, smoking status, diabetes, body mass index and family history of cardiovascular disease, subjects who reported any physical activity had a significantly lower odds of PAD (OR 0.64, 95% CI 0.63 – 0.65) and CAS (OR 0.80, 95% CI 0.79 – 0.81). The association between physical activity with PAD and CAS was robust when stratified by sex, race and age categories. Physical activity intensity frequency was associated with lower PAD and CAS in a graded manner (p trend <0.0001 for both). Findings appeared unaffected by confounding by comorbidity or indication.
In a large population based study, higher levels of physical activity were independently associated with lower odds of vascular disease in the lower extremities and carotid arteries.
PMCID: PMC4518860  PMID: 25359858
Diabetes Care  2014;37(6):1636-1642.
The 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]).
Prevalence 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.
Diabetes mellitus was present in 10.8% of participants (n = 399,884). Prevalence of PAD, CAS, and AAA was 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.
In 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.
PMCID: PMC4030086  PMID: 24705616
Background and Purpose
Since 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.
Participants were 48,835 postmenopausal women aged 50 to 79 years who were randomly assigned to either the intervention or comparison group in the WHI Diet Modification Trial. Incident carotid artery disease was defined as an overnight hospitalization with either symptoms or a surgical intervention to improve flow.
After a mean follow-up of 8.3 years from 1994 – 2005, there were 297 (0.61%) incident carotid artery events. Contrasted to the comparison group, the risk of incident carotid disease did not differ from those assigned to the intervention group (HR: 1.08, 95% CI: 0.9 - 1.4). In secondary analysis, there was no significant effect of the intervention on the risk for incident carotid disease during the five years of post-intervention follow-up from 2005 to 2010 (1.24, 0.9 - 1.7) and no significant effect during cumulative follow-up from 1994 to 2010 (1.13, 0.9 – 1.4).
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.
PMCID: PMC4259099  PMID: 24743440
diet; carotid artery disease; trial; women
The primary aim of the present study was to determine the cumulative effect of a set of peripheral artery disease (PAD) risk factors among age, gender and race/ethnicity groups in the United States.
We examined data from a nationally representative sample of the US population (National Health and Nutrition Examination Survey [NHANES], 1999–2004). A total of 7058 subjects 40 years or older that completed the interview, medical examination and had ankle–brachial index (ABI) measurements were included in this study.
The age- and sex-standardized prevalence of PAD was 4.6 % (standard error [SE] 0.3%).The highest prevalence of PAD was observed among elderly, non-Hispanic Blacks and women. In a multivariable age-, gender- and race/ethnicity-adjusted model hypertension, diabetes, chronic kidney disease, and smoking were retained as PAD risk factors (p ≤ 0.05 for each). The odds of PAD increased with each additional risk factor present from a non-significant 1.5-fold increase (O.R 1.5, 95% confidence interval [CI] 0.9–2.6) in the presence of one risk factor, to more than ten-fold (OR 10.2, 95% CI 6.4–16.3) in the presence of three or more risk factors. In stratified analysis, non-Hispanic Blacks (OR 14.7, 95% CI 2.1–104.1) and women (OR 18.6, 95% CI 7.1–48.7) were particularly sensitive to this cumulative effect.
In a large nationally representative sample, an aggregate set of risk factors that included diabetes mellitus, chronic kidney disease, hypertension and smoking significantly increase the likelihood of prevalent PAD. A cumulative risk factor analysis highlights important susceptibility differences among different population groups and provides additional evidence to redefine screening strategies in PAD.
PMCID: PMC4436703  PMID: 22739687
Peripheral arterial disease; risk assessment; traditional cardiovascular risk factors; NHANES
The American journal of cardiology  2014;113(9):1474-1480.
Peri-procedural hyperglycemia is an independent predictor of mortality in patients undergoing percutaneous coronary intervention (PCI). However, peri-procedural management of blood glucose is not standardized. The effects of routinely continuing long-acting glucose-lowering medications prior to coronary angiography with possible PCI on peri-procedural 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 prior to procedure. The primary endpoint 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 [97–151] vs 134 [117–172] mg/dL, p=0.002). There were 2 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% [7.2–10.4], 8.7% [6.9–11.4], 10.9% [8.6–14.7], p=0.007; monocyte platelet aggregates: 14.0% [10.3–16.3], 20.8% [16.2–27.0], 22.5% [15.2–35.4], p<0.001; soluble p-selectin: 51.9ng/mL [39.7–74.0], 59.1ng/mL [46.8–73.2], 72.2ng/mL [58.4–77.4], p=0.014). In conclusion, routinely continuing clinically prescribed long-acting glucose-lowering medications prior to coronary angiography with possible PCI helps achieve peri-procedural euglycemia, appears safe, and should be considered as a strategy for achieving peri-procedural glycemic control.
PMCID: PMC4018663  PMID: 24630791
hyperglycemia; diabetes mellitus; coronary angiography; percutaneous coronary intervention
Journal of Immunology Research  2014;2014:234316.
OxLDL/β2GPI 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/β2GPI antibodies and oxLDL/β2GPI 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/β2GPI, these complexes were analyzed on subjects not taking statins. Arterial and venous groups expressed higher levels of IgG anti-oxLDL/β2GPI antibodies than controls without any other significant clinical association. OxLDL/β2GPI 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/β2GPI 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/β2GPI 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/β2GPI. The coexistence of oxLDL/β2GPI in arterial and venous disease may suggest a common oxidative mechanism that independently predicts carotid artery disease.
PMCID: PMC4227323  PMID: 25405208
Journal of the American College of Cardiology  2013;62(9):10.1016/j.jacc.2013.03.080.
This study sought to perform a systematic review and meta-analysis to understand the role of stress cardiac magnetic resonance imaging (CMR) in assessing cardiovascular prognosis in patients with known or suspected coronary artery disease (CAD).
Although stress CMR is excellent for the diagnosis of obstructive CAD, the prognostic value of stress CMR has been less well described.
PubMed, Cochrane CENTRAL, and metaRegister of Controlled Trials were searched for stress CMR studies with >6 months of prognostic data. Primary endpoints were cardiovascular death, myocardial infarction (MI), and a composite outcome of cardiovascular death or MI during follow-up. Summary effect estimates were generated with random-effects modeling, and annualized event rates were assessed.
Nineteen studies (14 vasodilator, 4 dobutamine, and 1 that used both) involved a total of 11,636 patients with a mean follow-up of 32 months. Patients had a mean age of 63 ± 12 years, 63% were male, and 26% had previous MI; mean left ventricular ejection fraction was 61 ± 12%; and late gadolinium enhancement was present in 29% and ischemia in 32%. Patients with ischemia had a higher incidence of MI (odds ratio [OR]: 7.7; p < 0.0001), cardiovascular death (OR: 7.0; p < 0.0001), and the combined endpoint (OR: 6.5; p < 0.0001) compared with those with a negative study. The combined outcome annualized events rates were 4.9% for a positive versus 0.8% for a negative stress CMR (p < 0.0001), 2.8% versus 0.3% for cardiovascular death (p < 0.0001), and 2.6% versus 0.4% for MI (p < 0.0005). The presence of late gadolinium enhancement was also significantly associated with a worse prognosis.
A negative stress CMR study is associated with very low risk of cardiovascular death and MI. Stress CMR has excellent prognostic characteristics and may help guide risk stratification of patients with known or suspected CAD.
PMCID: PMC3863376  PMID: 23727209
late gadolinium enhancement; myocardial perfusion; prognosis; stress cardiac MRI
Mechanisms for increased cardiovascular risk in HIV-1-infected adults are incompletely understood, but platelet activation and immune activation leading to a prothrombotic state have been proposed as significant contributors. Aspirin has antiplatelet and immunomodulatory properties. We explored whether 1 week of low-dose aspirin attenuates platelet activation and immune activation in HIV-1-infected and virologically suppressed adults on antiretroviral therapy.
Platelet activation and immune activation were measured in HIV-1-infected subjects virologically suppressed on antiretroviral therapy and controls before and after 1 week of low-dose aspirin.
Compared with control subjects, HIV-1-infected subjects had increased platelet activation, as measured by spontaneous platelet aggregation and aggregation in response to adenosine diphosphate, collagen, and arachidonic acid. After aspirin therapy, percent aggregation decreased similarly in both HIV-1-infected and control subjects to all platelet agonists tested except aggregation in response to arachidonic acid, which remained elevated in the HIV-1-infected group. HIV-1-infected subjects exhibited increased markers of T-cell activation (CD38 and HLA-DR) and monocyte activation (sCD14), which decreased after 1 week of aspirin therapy. Moreover, leukocyte responses to Toll-like receptor stimulation were enhanced after 1 week of aspirin therapy. In vitro studies showed that HIV-1 plasma could activate healthy platelets, which in turn activated monocytes, implicating a direct role for activated platelets in immune activation.
Our data demonstrate that heightened platelet activation and immune activation in treated HIV-1 disease are attenuated by 1 week of aspirin therapy. Aspirin should be further studied for its antithrombotic and immunomodulatory benefits in treated HIV-1 disease.
PMCID: PMC3756489  PMID: 23406976
platelets; HIV-1; aspirin; immune activation; aggregation
Platelets  2013;25(3):188-192.
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 ≤4% and ICC>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.
PMCID: PMC3809021  PMID: 23786366
Aspirin; mean platelet volume; platelet aggregation
American heart journal  2013;165(3):427-433.e1.
Thrombotic and bleeding complications are major concerns during orthopedic surgery. Given the frequency of orthopedic surgical procedures and the limited data in the literature, we sought to investigate the incidence and risk factors for thrombotic (myocardial necrosis and infarction) and bleeding events in patients undergoing orthopedic surgery.
Methods and Results
We performed a retrospective cohort analysis of 3,082 consecutive subjects ≥ 21 years of age undergoing hip, knee, or spine surgery between November 1, 2008, and December 31, 2009. Patient characteristics were ascertained using ICD-9 diagnosis coding and retrospective review of medical records, and laboratory/blood bank databases. In-hospital outcomes included myocardial necrosis (elevated troponin), major bleeding, coded myocardial infarction (MI), and coded hemorrhage as defined by ICD-9 coding. Of the 3,082 subjects, mean age was 60.8 ± 13.3 years and 59% were female. Myocardial necrosis, coded MI, major bleeding, and coded hemorrhage occurred in 179 (5.8%), 20 (0.7%), 165 (5.4%), and 26 (0.8%) subjects, respectively. Increasing age (P<0.001), CAD (P<0.001), cancer (P=0.004), and chronic kidney disease (P=0.01) were independent predictors of myocardial necrosis, while procedure type (P<0.001), cancer (P<0.001), female sex (P<0.001), CAD (P<0.001), and COPD (P=0.01) were independent predictors of major bleeding.
There is a delicate balance between thrombotic and bleeding events in the perioperative period following orthopedic surgery. Perioperative risk of both thrombosis and bleeding deserve careful attention in preoperative evaluation and future prospective studies aimed at attenuating this risk are warranted.
PMCID: PMC3595114  PMID: 23453114
arterial thrombosis; major bleeding; perioperative management
The American journal of cardiology  2012;111(2):185-189.
Increased platelet activity is associated with adverse cardiovascular events. Mean platelet volume (MPV) correlates with platelet activity but the relationship between MPV and long-term mortalityin patients undergoing percutaneous coronary intervention(PCI) is not well established. Furthermore, the role of change in MPV over time has not been previously evaluated. We evaluatedMPV at baseline, 30 days, 60 days, 90 days, 1 year, 2 years, and 3 years post-procedure in 1,512 patients who underwent PCI. The speed of change in MPV was estimated using slope of linear regression. Mortality was determined by query of social security death index. Over a median of 8.7 years, mortality was 49.3% post-PCI. There was no significant difference in mortality when stratified by MPV quartiles (1stquartile 50.1%, 2nd quartile 47.7%, 3rd quartile 51.3%, 4thquartile 48.3%, p=0.74). In patients with available data to determine a change in MPV over time post-PCI (n=839), mortality was 49.1% and significantly higher in patients with an increase (52.9%) compared to those with a decrease (44.2%) or no change (49.1%) in MPV over time (p<0.0001). In conclusion, there was no association between baseline MPV and long-term mortality in patients undergoing PCI. However, there was increased mortality when MPV increasedover time post-PCI. Monitoring MPV after coronary revascularization may play a role in risk stratification.
PMCID: PMC3538911  PMID: 23102880
Mean platelet volume; percutaneous coronary intervention; long-term mortality
Thrombosis and haemostasis  2012;109(1):85-92.
The mechanism underlying a hyperreactive platelet phenotype remains unknown. Since serotonin has been shown to influence platelet biology and atherothrombosis, we sought to investigate the association of platelet serotonin transporter number, binding affinity, and uptake kinetics to platelet aggregation. A total of 542 healthy volunteers had light transmittance platelet aggregometry measured in response to varying concentrations of epinephrine, serotonin, epinephrine plus serotonin, ADP and collagen. Transporter-dependent serotonin uptake rate was determined (Vmax), as were serotonin transporter number (Bmax) and binding affinity (Kd) using 3H paroxetine binding in a homologous displacement assay, nonlinear regression and validated algorithms for kinetic modeling. Stimulation with submaximal (2 μM) epinephrine concentration elicited a distinct, bimodal pattern of platelet aggregation in this population. In contrast, subjects exhibited minimal aggregation in response to serotonin alone. Co-stimulation with submaximal epinephrine and serotonin induced platelet aggregation to a level beyond that observed with either agonist alone and maintained a bimodal response distribution. Subjects with heightened (>60%) platelet aggregation to both epinephrine alone and epinephrine plus serotonin exhibited increased platelet serotonin uptake, and transporter number and affinity. In a population of healthy subjects, co-stimulation with submaximal concentrations of epinephrine and serotonin identifies a subset of individuals with a hyperreactive platelet aggregation profile that is associated with changes in platelet serotonin function.
PMCID: PMC3582386  PMID: 23223800
Platelets; platelet activity; serotonin; epinephrine; transporter
The role of residents as teachers has grown over time. Programs have been established within various specialties to formally develop these skills. Anesthesiology residents are frequently asked to provide supervision for novice learners and have numerous opportunities for teaching skills and clinical decision making. Yet, there are no educational programs described in the literature to train anesthesiology residents to teach novice learners.
To explore whether a resident-as-teacher program would increase anesthesiology residents' self-reported teaching skills.
An 8-session interactive Anesthesiology Residents-as-Teachers (ART) Program was developed to emphasize 6 key teaching skills. During a 2-year period, 14 anesthesiology residents attended the ART program. The primary outcome measure was resident self-assessment of their teaching skills across 14 teaching domains, before and 6 months after the ART program. Residents also evaluated the workshops for quality with a 9-item, postworkshop survey. Paired t testing was used for analysis.
Resident self-assessment led to a mean increase in teaching skills of 1.04 in a 5-point Likert scale (P < .001). Residents reported the greatest improvement in writing/using teaching objectives (+1.29, P < .001), teaching at the bedside (+1.57, P  =  .002), and leading case discussions (+1.64, P  =  .001). Residents rated the workshops 4.2 out of 5 (3.9–4.7).
Residents rated their teaching skills as significantly improved in 13 of 14 teaching domains after participation in the ART program. The educational program required few resources and was rated highly by residents.
PMCID: PMC3546586  PMID: 24294434
American heart journal  2011;161(5):972-978.
Subjects with peripheral artery disease (PAD) are at increased risk of cardiovascular morbidity and mortality, perhaps in part, related to increased levels of inflammation, platelet activity, and lipids. We therefore sought to investigate the relationship between PAD and levels of inflammatory, platelet, and lipid biomarkers and the treatment effect of darapladib, a novel lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor.
This is a post hoc analysis of the 959 patients with coronary disease or their risk equivalent receiving atorvastatin who were randomized to receive darapladib or placebo to examine the effects of an Lp-PLA2 inhibitor on the biomarkers of cardiovascular risk. We conducted an exploratory analysis evaluating the levels of biomarkers in subjects with PAD (n = 172) compared with those without PAD (n = 787).
After adjustment for age, sex, smoking, body mass index, and diabetes, subjects with PAD had greater levels of matrix metalloproteinase-9 (between group comparisons 22%, 95% confidence interval [10–31], P < .01), myeloperoxidase (12% [2–20], P = .01), interleukin-6 (13% [4–21], P = .01), adiponectin (17% [7–26], P < .01), intercellular adhesion molecule-1 (7% [2–11], P < .01), osteoprotegrin (6% [1–10], P = .02), CD40 ligand (15% [1–28], P = .04), high-sensitivity C-reactive protein (17% [1–31], P = .04), and triglycerides (11% [0.2–21], P = .05). No significant difference was detected for Lp-PLA2 activity, P-selectin, urinary 11-dehydrothroboxane B2, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol between subjects with and without PAD. Darapladib produced highly significant inhibition of Lp-PLA2 activity when compared with placebo at weeks 4 and 12 (P < .01) in patients with and without PAD.
Subjects with PAD had elevated levels of matrix metalloproteinase-9, myeloperoxidase, interleukin-6, adiponectin, intercellular adhesion molecule-1, osteoprotegrin, CD40 ligand, high-sensitivity C-reactive protein, and triglycerides compared with those without PAD. Darapladib, a novel Lp-PLA2 inhibitor, was equally effective in reducing Lp-PLA2 activity levels in subjects with and without PAD.
PMCID: PMC3750980  PMID: 21570531
Atherosclerosis  2010;213(2):586-591.
We sought to determine whether mean platelet volume (MPV) is associated with the prevalence of peripheral artery disease (PAD).
Platelets play a pivotal role in the pathogenesis of atherosclerosis and PAD. MPV, a measure of platelet size available in every blood count, is increasingly recognized as an important marker of platelet activity.
We analyzed data from 6354 participants aged 40 years and older from the 1999 to 2004 National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US population. PAD was defined as an ankle brachial index ≤0.90 in either leg. Odds ratios and 95% confidence intervals were estimated by logistic regression.
The prevalence of PAD in the cohort was 5.7%. MPV was significantly associated with PAD prevalence (tertile 1 – 4.4%, tertile 2 – 6.1%, tertile 3 – 7.0%, P for trend = 0.003). After adjustment for age, sex, and race, the odds ratio of PAD comparing the highest tertile to the lowest tertile was 1.57 (95% confidence interval 1.15–2.13). After further adjustment for smoking status, hypertension, hypercholesterolemia, diabetes, glomerular filtration rate, body mass index, and platelet count the corresponding odds ratio was 1.58 (95% confidence interval 1.14–2.19). The addition of triglycerides, hemoglobin A1c, and C-reactive protein did not affect the results. The significant association between MPV and PAD was unchanged when MPV was used as a continuous variable.
Mean platelet volume is independently associated with PAD. These findings support the hypothesis that platelet size is an independent predictor of increased risk for PAD.
PMCID: PMC3739454  PMID: 20940069
Mean platelet volume; Platelets; Peripheral artery disease; Epidemiology
Diabetes Care  2012;35(5):1074-1078.
The association between platelet activity, diabetes, and glucometabolic control is uncertain. We aim to investigate mean platelet volume (MPV), a marker of platelet size and platelet activity, with the prevalence of diabetes, metabolic syndrome, and degree of glycemic control.
This is a retrospective analysis of 13,021 participants in the National Health and Nutrition Examination Survey from 1999 to 2004. Prevalence of diabetes was defined as nonfasting glucose >200 mg/dL, fasting glucose ≥126 mg/dL, or treatment with hypoglycemic agents. Presence of metabolic syndrome was determined by the National Cholesterol Education Program Adult Treatment Panel III definition. Odds ratios and 95% CIs were estimated by logistic regression.
MPV was significantly higher in subjects with diabetes (8.20 vs. 8.06 femtoliter [fL], P < 0.01) but not in subjects with metabolic syndrome (8.09 vs. 8.07 fL, P = 0.24). For the metabolic syndrome components, MPV was significantly higher in abdominal obesity (P = 0.03) and low HDL (P = 0.04), and not different in high blood pressure (P = 0.07), abnormal glucose metabolism (P = 0.71), or hypertriglyceridemia (P = 0.46). There was a significant correlation between MPV and glucose (P < 0.0001) and between MPV and hemoglobin A1c (P < 0.0001) in subjects with diabetes. These correlations were no longer significant in those without diabetes. The adjusted odds of diabetes rose with increasing MPV levels and were most pronounced in subjects with MPV levels exceeding the 90th percentile (≥9.31 fL). The association between MPV and diabetes was most apparent in those with the poorest glucose control.
Mean platelet volume is strongly and independently associated with the presence and severity of diabetes.
PMCID: PMC3329806  PMID: 22410814
Few studies simultaneously investigated lipids and lipoprotein biomarkers as predictors of ischemic stroke. The value of these biomarkers as independent predictors of ischemic stroke remains controversial.
We conducted a prospective nested case-control study among postmenopausal women from the Women’s Health Initiative Observational Study to assess the relationship between fasting lipids (total cholesterol, LDL-C, HDL-C, and triglycerides), lipoproteins (LDL, HDL and VLDL particle number and size, IDL particle number, and lipoprotein [a]) and risk of ischemic stroke. Among women free of stroke at baseline, 774 ischemic stroke patients were matched according to age and race to controls using a 1:1 ratio.
In bivariate analysis, baseline triglycerides (P<0.001), IDL particles (P<0.01), LDL particles (P<0.01), VLDL triglyceride (P<0.001), VLDL particles (P<0.01), VLDL size (P<0.001), LDL size (P=0.03), and total/HDL cholesterol ratio (P<0.01) were significantly higher among women with incident ischemic stroke, while levels of HDL-C (P<0.01) and HDL size (P<0.01) were lower. No significant baseline difference for total cholesterol (P=0.15), LDL-C (P=0.47), and lipoprotein (a) (P=0.11) was observed. In multivariable analysis, triglycerides, (OR for the highest vs lowest quartile, 1.56; 95% CI, 1.13-2.17, P for trend =0.02), VLDL size (OR 1.59, 95% CI, 1.10-2.28, P for trend =0.03) and IDL particle number (OR 1.46, 95% CI, 1.04-2.04, P for trend =0.02) were significantly associated with ischemic stroke.
Among a panel of lipid and lipoprotein biomarkers, baseline triglycerides, VLDL size and IDL particle number were significantly associated with incident ischemic stroke in postmenopausal women.
PMCID: PMC3547588  PMID: 22308251
Lipids; Lipoproteins; Ischemic Stroke; Women; Triglycerides
Light transmission aggregometry (LTA) is considered the gold-standard for investigating platelet activity ex vivo. However, LTA protocols are not standardized and differences in LTA procedure are a potential source of variance in results. Centrifugation speed is an essential component of platelet preparation in LTA, has yet to be standardized, and may affect platelet aggregation results. We sought to investigate the effect of relative centrifugal force (RCF) intensity on LTA results.
Ten healthy controls had venous blood drawn and centrifuged at 150g, 200g, 300g, and 500g for 10 minutes. Cell counts in whole blood and PRP were measured using a hematology analyzer. LTA was performed using 1.0uM ADP and 0.4uM epinephrine as an agonist. Aggregation (%) was compared at 60, 120, 180, and 300 seconds (s) and at maximum aggregation.
Centrifugation speed was associated with decreasing platelet count (P<0.001) and decreasing MPV (P<0.001) in platelet rich plasma. Maximum aggregation decreased with increasing speeds for ADP 1.0uM (150g-89%, 200g-93%, 300g-71%, 500g-17%; P<0.001). Similar findings were noted at 120s (150g-69%, 200g-50%, 300g-35%, 500g-12%; P<0.001), 180s (150g-82%, 200g-74%, 300g-44%, 500g-13%; P<0.001), and 300s (150g-85%, 200g-88%, 300g-55%, 500g-14%; P<0.001). Consistently, platelet aggregation in response to epinephrine 0.4uM decreased significantly with increasing centrifuge RCF at 60s, 120s, 180s, 300s, and at maximum aggregation (P<0.05 for each comparison).
Our data demonstrate the importance of centrifugation speed in the interpretation of LTA results, supporting the need for standardization of centrifugation RCF in LTA protocols.
PMCID: PMC3209490  PMID: 21794095
Light transmission aggregometry; Methodology; Centrifuge; Platelets
PMCID: PMC3839141  PMID: 24282710
The Accreditation Council for Graduate Medical Education requires residency programs to teach 6 core competencies and to provide evidence of effective standardized training through objective measures. George Washington University's Department of Anesthesiology and Critical Care Medicine implemented a pilot program to address the interpersonal and communication skill competency. In this program, we aimed to pilot the Relationship Express model, a series of exercises in experiential learning to teach anesthesiology residents to build effective relationships with patients in time-limited circumstances. The purpose of this paper is to describe the application of this model for anesthesiology training.
A total of 7 first-year clinical anesthesiology residents participated in this pilot study, and 4 residents completed the entire program for analysis purposes. Relationship Express was presented in three 1.5-hour sessions: (1) introduction followed by 2-case, standardized patient pretest with feedback to residents from faculty observers; (2) interpersonal and communication skills didactic workshop with video behavior modeling; and (3) review discussion followed by 2-case, standardized patient posttest and evaluation.
Modified Brookfield comments revealed the following themes: (1) time constraints were realistic compared with clinical practice; (2) admitting errors with patients was difficult; (3) patients were more aware of body language than anticipated; (4) residents liked the group discussions and the video interview; (5) standardized patients were convincing; and (6) residents found the feedback from faculty and standardized patients helpful.
Resident retrospective self-assessment and learning comments confirm the potential value of the Relationship Express model. This program will require further assessment and refinement with a larger number of residents.
PMCID: PMC3010947  PMID: 22132285

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