Women undergoing coronary artery bypass graft (CABG) surgery have a higher operative mortality rate, longer hospitalizations, and higher hospital cost compared with men. A large proportion of this excess morbidity and mortality of surgery for women is due to perioperative neurologic injury. Estrogens have been consistently shown to reduce the extent of neurologic injury in a variety of in vitro and animal experimental stroke models. These data together strongly suggest that the higher risk for perioperative neurologic complications for elderly women may relate to their estrogen deficient state. In this randomized, placebo controlled study, we will test the hypothesis that perioperative estrogen replacement in postmenopausal women reduces the risk for neurologic injury after CABG surgery. Three hundred thirty four women undergoing CABG surgery will be prospectively randomized to receive either 17beta-estradiol or placebo in a double-blind fashion beginning the day before surgery and continued for 5 days after surgery. Patients will be assessed for neurocognitive dysfunction, the most common manifestation of neurologic injury from cardiac surgery. Neurocognitive testing will be performed 1-2 days before surgery, 4 to 6 weeks postoperatively, and 6- months after surgery. The primary endpoint will be neurocognitive function 4 to 6 weeks after surgery for women who received 17beta- estradiol compared with placebo perioperatively. We will also evaluate for the importance of postoperative cognitive decline on measures of cognitive function and quality of life 6 months after surgery and whether perioperative 17beta-estradiol treatment improves these latter outcomes. The results of this study will evaluate the efficacy and safety of an easily implemented therapy for improving neurologic outcome and quality of life after CABG surgery for postmenopausal women.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL064600-02
Application #
6537761
Study Section
Special Emphasis Panel (ZRG1-RPHB-3 (01))
Program Officer
Desvigne-Nickens, Patrice
Project Start
2001-06-01
Project End
2006-05-31
Budget Start
2002-06-01
Budget End
2003-05-31
Support Year
2
Fiscal Year
2002
Total Cost
$540,979
Indirect Cost
Name
Washington University
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Mitter, Nanhi; Shah, Ashish; Yuh, David et al. (2010) Renal injury is associated with operative mortality after cardiac surgery for women and men. J Thorac Cardiovasc Surg 140:1367-73
Stearns, Joshua D; Dávila-Román, Victor G; Barzilai, Benico et al. (2009) Prognostic value of troponin I levels for predicting adverse cardiovascular outcomes in postmenopausal women undergoing cardiac surgery. Anesth Analg 108:719-26
Freedland, Kenneth E; Skala, Judith A; Carney, Robert M et al. (2009) Treatment of depression after coronary artery bypass surgery: a randomized controlled trial. Arch Gen Psychiatry 66:387-96
Hogue, Charles W; Fucetola, Robert; Hershey, Tamara et al. (2008) Risk factors for neurocognitive dysfunction after cardiac surgery in postmenopausal women. Ann Thorac Surg 86:511-6
Grogan, Kelly; Stearns, Joshua; Hogue, Charles W (2008) Brain protection in cardiac surgery. Anesthesiol Clin 26:521-38
Rade, Jeffrey J; Hogue Jr, Charles W (2008) Noncardiac surgery for patients with coronary artery stents: timing is everything. Anesthesiology 109:573-5
Hogue, Charles W; Gottesman, Rebecca F; Stearns, Joshua (2008) Mechanisms of cerebral injury from cardiac surgery. Crit Care Clin 24:83-98, viii-ix
Hogue Jr, Charles W; Palin, Christopher A; Kailasam, Rajagopal et al. (2006) C-reactive protein levels and atrial fibrillation after cardiac surgery in women. Ann Thorac Surg 82:97-102
Hogue Jr, Charles W; Hershey, Tamara; Dixon, David et al. (2006) Preexisting cognitive impairment in women before cardiac surgery and its relationship with C-reactive protein concentrations. Anesth Analg 102:1602-8; table of contents
Hogue, Charles W; Lillie, Rema; Hershey, Tamara et al. (2003) Gender influence on cognitive function after cardiac operation. Ann Thorac Surg 76:1119-25

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