Relationship Between Apelin and New-onset Atrial Fibrillation After Coronary Artery Bypass Grafting

2016-06-21 19:08:22 | BioPortfolio


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.


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, 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

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.

Study Design

Observational Model: Case Control, Time Perspective: Retrospective


Coronary Atherosclerotic Heart Disease


atrial fibrillation, non-atrial fibrillation




General Hospital of Shenyang Military Region

Results (where available)

View Results


Published on BioPortfolio: 2016-06-21T19:08:22-0400

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Medical and Biotech [MESH] Definitions

Rapid, irregular atrial contractions caused by a block of electrical impulse conduction in the right atrium and a reentrant wave front traveling up the inter-atrial septum and down the right atrial free wall or vice versa. Unlike ATRIAL FIBRILLATION which is caused by abnormal impulse generation, typical atrial flutter is caused by abnormal impulse conduction. As in atrial fibrillation, patients with atrial flutter cannot effectively pump blood into the lower chambers of the heart (HEART VENTRICLES).

Long-term changes in the electrophysiological parameters and/or anatomical structures of the HEART ATRIA that result from prolonged changes in atrial rate, often associated with ATRIAL FIBRILLATION or long periods of intense EXERCISE.

A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666)

Impaired or delayed impulse conduction between the right and left HEART ATRIA. Advanced interatrial blocks are often associated with arrhythmias (e.g., ATRIAL FLUTTER; and ATRIAL FIBRILLATION), direct conduction block via the Bachmann's bundle and concomitant left atrial enlargement. Syndrome of advanced interatrial block associated with SUPRAVENTRICULAR TACHYCARDIA is referred to as Bayes syndrome.

Developmental abnormalities in any portion of the ATRIAL SEPTUM resulting in abnormal communications between the two upper chambers of the heart. Classification of atrial septal defects is based on location of the communication and types of incomplete fusion of atrial septa with the ENDOCARDIAL CUSHIONS in the fetal heart. They include ostium primum, ostium secundum, sinus venosus, and coronary sinus defects.

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