Haptoglobin Polymorphism as a Determinant of Adverse Outcome After Cardiac Surgery in Diabetic Patients

NCT02771808 | Completed

• 1 other identifier: 14691
• Study Type: observational
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

Specific aim 1a will test the hypothesis that diabetic patients with 2-2 haptoglobin genotype have higher indices of postoperative myocardial injury (creatine kinase MB isoenzyme , Troponin I ) and renal injury (as indicated by elevated creatinine, cytostatin C and glomerular filtration rate). Of note, significantly elevated levels (\>5 times the upper normal limit) of creatine kinase MB isoenzyme and troponins postoperatively have been associated with postoperative myocardial ischemia/infarction and are a predictor of short-term and long-term mortality after cardiac surgery. 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.

Conditions

Coronary Artery Disease

Keywords

CABG

Outcome Measures

Primary Outcomes (1)

• number of participants with myocardial injury

  number of participants with general markers for myocardial injury

  24 hours post CPB

Secondary Outcomes (2)

• number of participants with renal injury

  24 hrs post CPB

• number of participants with incidence of new onset atrial fibrillation

  day 15

Study Arms (1)

diabetic patients

obtain biomarker samples from diabetic patients and examine for 1-1 \& 1-2 \& 2-2 haptoglobin genotype

Other: biomarker samples

Interventions

biomarker samples OTHER

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)

Also known as: haptoglobin

diabetic patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult diabetic patients scheduled for an elective cardiac surgery on pump at UVA

You may qualify if:

• years of age and older
• Scheduled for an elective cardiac surgery on pump
• Diabetic -type I or type II
• Informed consent

You may not qualify if:

• Patients with chronic hemolytic disorders;
• Patients with hemoglobinopathies
• Enrollment in another interventional clinical trial

Sponsors & Collaborators

• University of Virginia: lead
• International Anesthesia Research Society (IARS): collaborator

Study Sites (1)

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Related Publications (23)

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  PMID: 15607389 BACKGROUND

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  PMID: 17699010 BACKGROUND

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  PMID: 12587082 BACKGROUND

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  PMID: 10320249 BACKGROUND

• Levy AP, Hochberg I, Jablonski K, Resnick HE, Lee ET, Best L, Howard BV; Strong Heart Study. Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: The Strong Heart Study. J Am Coll Cardiol. 2002 Dec 4;40(11):1984-90. doi: 10.1016/s0735-1097(02)02534-2.

  PMID: 12475459 BACKGROUND

• 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.

  PMID: 12941730 BACKGROUND

• 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.

  PMID: 16123372 BACKGROUND

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  PMID: 15662028 BACKGROUND

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  PMID: 16820150 BACKGROUND

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  PMID: 11231444 BACKGROUND

• 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.

  PMID: 19406870 BACKGROUND

• 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.

  PMID: 16242452 BACKGROUND

• Ramsay J, Shernan S, Fitch J, Finnegan P, Todaro T, Filloon T, Nussmeier NA. Increased creatine kinase MB level predicts postoperative mortality after cardiac surgery independent of new Q waves. J Thorac Cardiovasc Surg. 2005 Feb;129(2):300-6. doi: 10.1016/j.jtcvs.2004.06.005.

  PMID: 15678039 BACKGROUND

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  PMID: 17462392 BACKGROUND

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  PMID: 18692657 BACKGROUND

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MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Haptoglobins

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Mucoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Acute-Phase Proteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Alpha-Globulins; Serum Globulins; Globulins

Study Officials

• Jacob Raphael, MD

  UVA Anesthesiology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesiology

Study Record Dates

• First Submitted: September 17, 2010
• First Posted: May 13, 2016
• Study Start: September 1, 2010
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: May 13, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)