Cheryl D Bushnell
Wake Forest University Health Sciences
Project start date: 2008-02-15
Project end date: 2013-01-31
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Sex Differences In Vascular Markers Of Stroke Risk
Cheryl D Bushnell, Associate Professor
Neurologywake Forest University Health Sciences
Grant 5K02NS058760-02 from National Institute Of Neurological Disorders And Stroke IRG: NST
Abstract: The cause of stroke in women is frequently unknown, despite recognition of cardiovascular risk factors and appropriate prevention treatment. The reason may be related to unrecognized subclinical disease, which may be manifested by ongoing thrombin generation, inflammation, endothelial dysfunction, and abnormal responses to vascular stresses. In addition, endogenous hormones such as estradiol and sex hormone binding globulin, as well as menopausal status impact cardiovascular risk. The aims of this K02 project are to 1) Identify biological and physiological markers associated with ischemic stroke in women, and 2) Establish which biological and physiological markers are influenced by sex hormones and/or menopausal status in women with stroke. The working hypotheses are that women with ischemic stroke will have evidence of ongoing inflammation, thrombin generation, endothelial dysfunction, quantified by functional responses to forearm ischemia and measures of arterial stiffness, low sex hormone binding globulin, or a combination of the above processes. Using a case-control cohort design, 75 women with an ischemic stroke and 75 without ischemic stroke matched by age 2 years, menopausal status, and cardiovascular risk factors will be enrolled. Biological markers include tissue factor, matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule-1 (VCAM-1), von Willebrand Factor (vWF), and thrombin-antithrombin III complex (TAT). Vascular studies include brachial artery flow-mediated dilation (measure of endothelial response to ischemia), carotid-femoral pulse wave velocity (measure of arterial stiffness), and ankle-brachial index (measure of peripheral vascular disease). Estradiol, testosterone, sex hormone binding globulin, and follicle stimulating hormone (for menopausal status determination) will also be measured. The significance of each marker will be assessed by plotting ROC curves for each marker, and then entering the significant markers into a multivariable model to determine the best combination of markers of stroke. Both groups of women will be followed for a minimum of two years after enrollment for any vascular outcomes, such as stroke, TIA, or acute coronary syndromes. The expected outcomes of this study will be the discovery of novel biological and vascular markers for stroke, and how endogenous sex hormones impact those markers. This could naturally lead to development of a predictive panel of markers for future stroke risk
Project start date: 2008-02-15
Project end date: 2013-01-31
Grants awarded to Cheryl D Bushnell
Advancing The Study Of Stroke In Women
Cheryl D Bushnell, Associate In Medicine
Duke University 2200 W. Main St. Durham, Nc 27705
Grant 1R13NS052015-01 from National Institute Of Neurological Disorders And Stroke IRG: ZNS1
Abstract: The conference entitled "Advancing the Study of Stroke in Women" will take place Aug 25-26, 2005 in Durham, NC near Duke University. The purpose of this multidisciplinary conference is to generate new ideas for clinical, experimental, and translational studies that will be designed to improve the understanding of stroke risk and prevention for women. This objective will be addressed by assembling panels of distinguished basic science and clinical researchers who will develop a strategic plan for future research related to stroke in women. The Specific Aims of the conference are 1) to summarize estrogen s actions at the level of the neurovascular unit, 2) to design studies that will determine how estrogen may increase the risk of stroke from the clinical, preclinical, and translational perspective, 3) to organize multicenter, multidisciplinary collaborations for these new studies, and 4) to foster junior investigators interest in pursuing research in the field of stroke and women s health. Young investigators with an interest in this field will be encouraged to submit s of ongoing research pertinent to these topics. Every effort will be made to include women, minorities, and those with disabilities. The conference will review estrogen s known actions at the neurovascular unit and with small workshops, experts will discuss the discrepancies among the results of observational and randomized studies, the gaps in knowledge between preclinical and clinical studies of estrogen and stroke, and improved methods of identifying women who are at risk of stroke with short term hormone therapy use for perimenopausal symptoms. The goal for each workgroup will be to summarize the current knowledge of the topic and to propose clinical, experimental, or translational studies that will improve the understanding of estrogen and stroke risk. A poster session for junior and senior investigators with ongoing research will be scheduled. The conference proceedings, including original s, will be published in a neurology journal supplement. This conference is timely based on the results of Women s Health Initiative (WHI) study showing an increased risk of stroke with hormone therapy. By expanding the study of estrogen and stroke, the conference will ultimately lead to improvement of women s health.
Keywords: meeting /conference /symposium, stroke, women s health
Project start date: 2005-06-01
Project end date: 2006-05-31
1R13NS052015-01 (2005): $15000
Hormone Replacement Therapy And Ischemic Stroke Severity
Cheryl D Bushnell, Associate In Medicine
Duke University 2200 W. Main St. Durham, Nc 27705
Grant 5K23NS041929-05 from National Institute Of Neurological Disorders And Stroke IRG: NST
Abstract: Experimental studies in laboratory animals have shown that estrogen reduces stroke severity, but the impact of hormone replacement therapy (HRT) on ischemic stroke severity in humans is not known. There are 2 broad, longterm objectives of this project. The first objective is to determine whether there are differences in stroke severity and outcome between women who are HRT users and women who are nonHRT users. The second objective is to determine whether any difference in these 2 groups is related to enhanced fibrinolysis. The Specific Aims of this proposal are 1) to compare the initial stroke severity in women who are users and nonusers of HRT, 2) to measure any differences in markers of the coagulation and fibrinolytic systems in the acute stroke period, and 3) to assess stroke outcomes in women based on poststroke use or nonuse of HRTs. Subjects for this prospective, observational study will be women admitted with acute ischemic stroke to an academic medical center. In the acute stroke period, initial stroke severity will be assessed using the NIHSS and markers of coagulation (prothrombin fragment F1,2 and thrombinantithrombin III complex) and fibrinolysis (plasminogen activator inhibitor type I) will be measured. Relevant historical and demographic data will be collected. At 3 months poststroke, neurologic impairment (NIHSS), functional status (Barthel Index and Modified Rankin), and quality of life (Stroke Impact Scale) will be assessed. The differences in initial stroke severity will be analyzed accounting for co-variates, and the 3month outcomes will be adjusted for initial stroke severity. This work will provide critical information for physicians prescribing HRT for women at risk for stroke and address whether it is safe to continue these medications in the sub-acute period after stroke. As a K23 proposal, this project will not only provide important clinical information, but is a natural extension of the candidate s previous experience with coagulopathies and stroke, now combined with the commitment to study the impact of stroke in women. This proposal will also provide critical transitional support in a mentored environment leading to the candidate s complete independence as a clinical investigator.
Keywords: estrogen, hormone therapy, human therapy evaluation, neuroprotectant, patient oriented research, stroke, stroke therapy, biomarker, blood coagulation, cardiovascular disorder epidemiology, cerebral ischemia /hypoxia, clinical trial, disease /disorder proneness /risk, endocrine disorder, fibrinolysis, functional ability, longitudinal human study, nervous system disorder, outcomes research, quality of life, remission /regression, female, human subject
Project start date: 2001-09-30
Project end date: 2007-07-31
5K23NS041929-05 (2005): $125658
5K23NS041929-04 (2004): $125658
5K23NS041929-03 (2003): $125658
5K23NS041929-02 (2002): $125469
1K23NS041929-01 (2001): $125334