Clinical trial NCT02771808: Haptoglobin Polymorphism as a Determinant of Adverse Outcome After Cardiac Surgery in Diabetic Patients
Official title: Haptoglobin Polymorphism as a Determinant of Adverse Outcome After Cardiac Surgery in Diabetic Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Disease
Keywords: CABG
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: International Anesthesia Research Society (IARS)
First posted: 2016-05-13
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult diabetic patients scheduled for an elective cardiac surgery on pump at UVA

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

Eligibility criteria: 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

Primary outcomes:
measure: number of participants with myocardial injury
timeFrame: 24 hours post CPB
Secondary outcomes:
measure: number of participants with renal injury
timeFrame: 24 hrs post CPB
measure: number of participants with incidence of new onset atrial fibrillation
timeFrame: day 15
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: UVA Anesthesiology
name: Jacob Raphael, MD
role: PRINCIPAL_INVESTIGATOR
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