Haptoglobin Polymorphism as a Determinant of Adverse Outcome After Cardiac Surgery in Diabetic Patients
NCT ID: NCT02771808
Last Updated: 2016-05-13
Study Results
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Basic Information
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COMPLETED
83 participants
OBSERVATIONAL
2010-09-30
2015-05-31
Brief Summary
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Specific aim 1b will evaluate preoperative and postoperative indices of oxidative stress (such as isoprostane f2 alpha and malondialdehyde) and will evaluate whether patients with type 2-2 haptoglobin express increased oxidative stress. The investigators will also try to correlate whether patients with increased oxidative stress are those with elevated indices of myocardial and/or renal injury Specific aim 1c will try to evaluate whether patients with type 2-2 haptoglobin also have increased levels of inflammatory indices (C-reactive protein,\[interleukin\] IL-1, IL-2, IL-6, TNF\[tumor necrosis factor\]) and try to correlate the findings with postoperative myocardial and or renal injury.
The incidence of atrial fibrillation after coronary artery bypass graft ranges from 19% to 27%. The investigators will also look at any correlation of the type 2-2 haptoglobin and the incidence of post-operative atrial fibrillation.
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Detailed Description
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Over the past several years haptoglobin has been identified as a risk factor that predicts the development of cardiovascular complications in diabetics. There are 3 major haplotypes of haptoglobin: 1-1; 1-2 and 2-2. Several studies have demonstrated that diabetic individuals with the 2-2 genotype have up to 5 fold increased risk to develop cardiovascular complications as compared to diabetic patients with a non-2-2 haptoglobin genotype. There is no data in the literature that evaluated whether the haptoglobin 2-2 genotype is a risk factor for increased postoperative morbidity and/or mortality after cardiac surgery in patients with DM.
Therefore, the aims of the study are to evaluate whether diabetic patients with the 2-2 genotype are at increased risk for postoperative morbidity and/or mortality after cardiac surgery.
Preliminary studies in diabetic patients demonstrated that those with haptoglobin 2-2 genotype are at increased risk for cardiovascular complications of diabetes. Moreover, these patients were found to have increased in-hospital mortality after acute MI compared to diabetic individuals that do not have the 2-2 genotype, and they also suffer from increased incidence of post catheterization stent thrombosis compared to diabetics that do not have the 2-2 genotype
Conditions
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Study Design
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CASE_ONLY
PROSPECTIVE
Study Groups
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diabetic patients
obtain biomarker samples from diabetic patients and examine for 1-1 \& 1-2 \& 2-2 haptoglobin genotype
biomarker samples
biomarker samples for haptoglobin genotype (RT-PCR) and phenotype (hemoglobin electrophoresis) general markers for oxidative stress (isoprostane f2 alpha, malondialdehyde) markers of inflammation (CRP, IL-1, 2, 6, 10 and TNF) markers of cardiac injury (CPK, troponins and BNP) markers of kidney injury (cystatin C, creatinine, GFR)
Interventions
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biomarker samples
biomarker samples for haptoglobin genotype (RT-PCR) and phenotype (hemoglobin electrophoresis) general markers for oxidative stress (isoprostane f2 alpha, malondialdehyde) markers of inflammation (CRP, IL-1, 2, 6, 10 and TNF) markers of cardiac injury (CPK, troponins and BNP) markers of kidney injury (cystatin C, creatinine, GFR)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Scheduled for an elective cardiac surgery on pump
* Diabetic -type I or type II
* Informed consent
Exclusion Criteria
* Patients with hemoglobinopathies
* Enrollment in another interventional clinical trial
18 Years
ALL
No
Sponsors
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International Anesthesia Research Society (IARS)
OTHER
University of Virginia
OTHER
Responsible Party
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Jacob Raphael
Associate Professor of Anesthesiology
Principal Investigators
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Jacob Raphael, MD
Role: PRINCIPAL_INVESTIGATOR
UVA Anesthesiology
Locations
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University of Virginia Health System
Charlottesville, Virginia, United States
Countries
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References
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Moreno PR, Fuster V. New aspects in the pathogenesis of diabetic atherothrombosis. J Am Coll Cardiol. 2004 Dec 21;44(12):2293-300. doi: 10.1016/j.jacc.2004.07.060.
Donahoe SM, Stewart GC, McCabe CH, Mohanavelu S, Murphy SA, Cannon CP, Antman EM. Diabetes and mortality following acute coronary syndromes. JAMA. 2007 Aug 15;298(7):765-75. doi: 10.1001/jama.298.7.765.
Bucerius J, Gummert JF, Walther T, Doll N, Falk V, Onnasch JF, Barten MJ, Mohr FW. Impact of diabetes mellitus on cardiac surgery outcome. Thorac Cardiovasc Surg. 2003 Feb;51(1):11-6. doi: 10.1055/s-2003-37280.
Carson JL, Scholz PM, Chen AY, Peterson ED, Gold J, Schneider SH. Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery. J Am Coll Cardiol. 2002 Aug 7;40(3):418-23. doi: 10.1016/s0735-1097(02)01969-1.
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Roguin A, Koch W, Kastrati A, Aronson D, Schomig A, Levy AP. Haptoglobin genotype is predictive of major adverse cardiac events in the 1-year period after percutaneous transluminal coronary angioplasty in individuals with diabetes. Diabetes Care. 2003 Sep;26(9):2628-31. doi: 10.2337/diacare.26.9.2628.
Suleiman M, Aronson D, Asleh R, Kapeliovich MR, Roguin A, Meisel SR, Shochat M, Sulieman A, Reisner SA, Markiewicz W, Hammerman H, Lotan R, Levy NS, Levy AP. Haptoglobin polymorphism predicts 30-day mortality and heart failure in patients with diabetes and acute myocardial infarction. Diabetes. 2005 Sep;54(9):2802-6. doi: 10.2337/diabetes.54.9.2802.
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Muehlschlegel JD, Perry TE, Liu KY, Nascimben L, Fox AA, Collard CD, Avery EG, Aranki SF, D'Ambra MN, Shernan SK, Body SC; CABG Genomics Investigators. Troponin is superior to electrocardiogram and creatinine kinase MB for predicting clinically significant myocardial injury after coronary artery bypass grafting. Eur Heart J. 2009 Jul;30(13):1574-83. doi: 10.1093/eurheartj/ehp134. Epub 2009 Apr 30.
Paparella D, Cappabianca G, Visicchio G, Galeone A, Marzovillo A, Gallo N, Memmola C, Schinosa Lde L. Cardiac troponin I release after coronary artery bypass grafting operation: effects on operative and midterm survival. Ann Thorac Surg. 2005 Nov;80(5):1758-64. doi: 10.1016/j.athoracsur.2005.04.040.
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Fox AA, Shernan SK, Collard CD, Liu KY, Aranki SF, DeSantis SM, Jarolim P, Body SC. Preoperative B-type natriuretic peptide is as independent predictor of ventricular dysfunction and mortality after primary coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2008 Aug;136(2):452-61. doi: 10.1016/j.jtcvs.2007.12.036.
Cuthbertson BH, Croal BL, Rae D, Gibson PH, McNeilly JD, Jeffrey RR, Smith WC, Prescott GJ, Buchan KG, El-Shafei H, Gibson GA, Hillis GS. N-terminal pro-B-type natriuretic peptide levels and early outcome after cardiac surgery: a prospective cohort study. Br J Anaesth. 2009 Nov;103(5):647-53. doi: 10.1093/bja/aep234. Epub 2009 Aug 27.
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Other Identifiers
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14691
Identifier Type: -
Identifier Source: org_study_id
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