Relationship Between Apelin and New-onset Atrial Fibrillation After Coronary Artery Bypass Grafting
Condition: Coronary Atherosclerotic Heart Disease
MeSH terms: Atrial Fibrillation; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia
Study type: Observational

Summary: 
      To investigate whether apelin can be used as an indicator to predict postoperative atrial
      fibrillation in patients with coronary atherosclerotic heart disease, and to provide an
      objective basis for the clinical selection of a preventive intervention program for atrial
      fibrillation.
    

Detailed description: 
      Atherosclerosis is a systematic and progressive pathological process, which commonly occurs
      in the intima of large and medium-sized arteries. The disease can lead to degenerative,
      proliferative, non-inflammatory lesions; thickening, hardening, and loss of elasticity of the
      vascular wall, and vascular stenosis; and reduced arterial blood flow. Eventually, organ
      damage occurs. Coronary atherosclerotic heart disease is the most common chronic degenerative
      disease caused by atherosclerosis.

      Coronary artery bypass grafting (CABG) can effectively increase myocardial blood supply,
      prevent myocardial infarction, and improve quality of life, and is associated with low rates
      of surgical complications and mortality. However, new-onset atrial fibrillation is a common
      complication after coronary artery bypass grafting, with an incidence rate of 30%. It induces
      hemodynamic instability, is often accompanied by left-ventricular systolic dysfunction and
      congestive heart failure, and increases the risk of stroke.

      Several studies have shown that the initiation and maintenance of atrial fibrillation is
      strongly associated with inflammation, which affects the electrical and structural remodeling
      of the heart. The role of C-reactive protein (CRP), a marker of inflammation, has been widely
      investigated. C-reactive protein is a non-specific acute-phase protein, and is elevated in
      many cardiovascular diseases, including coronary atherosclerotic heart disease, heart failure
      and hypertension. Elevated C-reactive protein levels are not only associated with simple and
      post-surgical atrial fibrillation, but also with cardioversion and recurrence of atrial
      fibrillation after ablation. However, there is no elevation of C-reactive protein levels in
      lone atrial fibrillation, indicating that inflammation is associated with cardiovascular
      disease, but not with atrial fibrillation per se. One of the aims of the present study is to
      determine how C-reactive protein levels in patients with new-onset atrial fibrillation change
      after coronary artery bypass grafting.

      Apelin has anti-inflammatory effects in different tissues. Ellinor et al. showed that levels
      of apelin-12 were remarkably low in patients with atrial fibrillation. Recurrence of atrial
      fibrillation is high in patients with persistent atrial fibrillation and low apelin-12 levels
      after electrical cardioversion.

      Apelin is an endogenous ligand of the G-protein coupled receptor APJ, and exhibits homology
      to angiotensin II. The signaling system stimulated by apelin regulates many physiological
      functions and pathological processes. The main target of apelin is the cardiovascular system;
      it dilates blood vessels, and has antifibrotic and positive inotropic effects. Falcone et al.
      showed that the risk of recurrence of atrial fibrillation was 3.1 times greater in patients
      with low apelin levels than those with high apelin levels. Furthermore, Yang et al. concluded
      that apelin levels were lower in patients with different types of atrial fibrillation than in
      controls, indicating that apelin might contribute to the initiation and maintenance of atrial
      fibrillation.

      The investigators carried out a literature search on the Web of Science and
      ClinicalTrials.gov, using the search terms "apelin", "coronary artery bypass", and "atrial
      fibrillation". The investigators also searched the Wanfang Database and China National
      Knowledge Infrastructure, using the terms "apelin", "coronary atherosclerotic heart disease",
      "surgery", and "atrial fibrillation"; or "apelin", "coronary atherosclerotic heart disease",
      "coronary artery bypass grafting", and "atrial fibrillation". However, the investigators
      found no clinical studies of the relationship between apelin and atrial fibrillation after
      coronary artery bypass grafting. The investigators therefore designed the present study to
      investigate this relationship.

      In the cohort study, patients with coronary atherosclerotic heart disease scheduled to
      undergo coronary artery bypass grafting will be assigned to high and low apelin groups,
      according to preoperative apelin levels. The incidence of atrial fibrillation will be
      compared between the two groups 7 days postoperatively. In addition, a case-control trial in
      the same patients will compare plasma apelin levels and inflammatory response between those
      patients with and without atrial fibrillation 7 days postoperatively.

      Adverse events Adverse events after coronary artery bypass grafting will be recorded. These
      might include myocardial infarction, myocardial ischemia, bradycardia, hypotension, and stent
      thrombosis. The investigators will provide a detailed record of date of onset,
      treatment-related processing method, and possible relationship with treatment. All adverse
      reactions should be reported to the researcher in charge and clinical Institutional Review
      Board within 24 hours.

      Data collection, management, analysis and open access Data collection: A table will be
      formulated for data collection according to the trial design. Data will be added to an
      electronic database using a double data entry strategy.

      Data management: Accuracy of information will be checked when all recruited patients are
      followed up. The database will be locked by the researcher in charge and will not be altered.
      All information relating to this trial will be preserved by The General Hospital of Shenyang
      Military Region, China.

      Data analysis: The electronic database will be fully disclosed to a statistician for
      statistical analysis.

      Open access: Published data will be available at www.figshare.com.

      Statistical analysis Statistical analysis will be performed by a statistician blinded to
      group assignment, using SPSS 19.0 software. If measurement data are normally distributed,
      data will be expressed as mean ± SD, and count data will be expressed as percentages. P <
      0.05 will be considered statistically significant.

      In the cohort study, the chi-square test will be used to compare the incidence rate of
      new-onset atrial fibrillation after coronary artery bypass grafting in patients with high and
      low apelin levels.

      In the case-control study, paired t-tests will be used to compare plasma apelin, brain
      natriuretic peptide, and high-sensitivity C-reactive protein levels in patients with and
      without atrial fibrillation. Multivariate logistic regression analysis will be applied to
      determine the relationship between plasma apelin levels, cardiac fibrosis and inflammatory
      response with atrial fibrillation after coronary artery bypass grafting.

      Frequency and measures for monitoring trial implementation Trial progression will be reported
      to the Ethics Committee of the General Hospital of Shenyang Military Region every month and
      the trial's status will be updated in the registration database.

      Confidentiality Test data, including medical records, will be saved electronically and in
      hard copy. The electronic data will be preserved in a dedicated password-protected computer
      and managed by a data manager. The paper data will be preserved in a secure, locked place by
      the data manager and researcher in charge for future viewing.
    

Intervention name(s): atrial fibrillation; non-atrial fibrillation
Intervention type(s): Other; Other
Intervention description(s): In the case-control trial, patients with atrial fibrillation 7 days after surgery will be assigned to an atrial fibrillation group.; In the case-control trial, patients without atrial fibrillation 7 days after surgery will be assigned to a non-atrial fibrillation group.
Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Patients with coronary atherosclerotic heart disease, without a history of atrial
        fibrillation, and scheduled to undergo CABG. Their baseline data will be assessed according
        to inclusion and exclusion criteria. Up to 120 patients with coronary atherosclerotic heart
        disease scheduled to undergo coronary artery bypass grafting (CABG) will be recruited from
        the Department of Cardiac Surgery, General Hospital of Shenyang Military Region, China.