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

May 12, 2016 updated by: Jacob Raphael, University of Virginia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Observational

Enrollment (Actual)

83

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
diabetic patients
obtain biomarker samples from diabetic patients and examine for 1-1 & 1-2 & 2-2 haptoglobin genotype
Other: 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 Names:
  • haptoglobin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
number of participants with myocardial injury
Time Frame: 24 hours post CPB
number of participants with general markers for myocardial injury
24 hours post CPB

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Virginia

Collaborators

International Anesthesia Research Society (IARS)

Investigators

  • Principal Investigator: Jacob Raphael, MD, UVA Anesthesiology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (Actual)

May 1, 2015

Study Completion (Actual)

May 1, 2015

Study Registration Dates

First Submitted

September 17, 2010

First Submitted That Met QC Criteria

May 12, 2016

First Posted (Estimate)

May 13, 2016

Study Record Updates

Last Update Posted (Estimate)

May 13, 2016

Last Update Submitted That Met QC Criteria

May 12, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14691

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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