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

Completed

• Conditions: Coronary Artery Disease
• Interventions: Other: biomarker samples

• Registration Number: NCT02771808
• Lead Sponsor: University of Virginia

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.

Detailed Description

Diabetes mellitus is a major risk factor for postoperative morbidity and mortality after cardiac surgery, mainly because of accelerated atherosclerosis and target-organ injury that predispose these patients to increased incidence of postoperative morbidity (such as but not limited to, postoperative adverse cardiac events, renal injury or stroke) and mortality.

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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2010-09
• Study First Submitted: 2010-09-17
• Primary Completion: 2015-05
• Study Completion: 2015-05
• Status Verified: 2016-05
• Study First Submitted QC: 2016-05-12
• Last Update Submitted: 2016-05-12
• Study First Posted: 2016-05-13
• Last Update Posted: 2016-05-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 83

Inclusion Criteria

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

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Exclusion Criteria

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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
number of participants with myocardial injury	24 hours post CPB	number of participants with general markers for myocardial injury

Secondary Outcome Measures

Name	Time	Method
number of participants with renal injury	24 hrs post CPB	number of participants with markers of kidney injury (cystatin C, creatinine, GFR)
number of participants with incidence of new onset atrial fibrillation	day 15	incidence of new onset atrial fibrillation will be recorded

Trial Locations

Locations (1)

University of Virginia Health System; 🇺🇸 Charlottesville, Virginia, United States