Resistin is one of the components of epicardial tissue. It is studied in terms of various correlations, both in systemic and local aspects . The correlation between serum resistin levels and the patient mortality rate has yet to be fully determined. It is presumed that resistin levels in plasma do not reflect the levels in PVAT [18, 19].
According to the obtained results, the median values of PVAT resistin levels in the AF group and the non-AF group were significantly different (Spearman’s test), and they were higher in the AF group than in the non-AF group, which may indicate a significant influence of adipose tissue on the occurrence of postoperative complications.
Based on the literature on the subject, the values of the plasma resistin level in healthy persons range between 7 and 22 ng/mL, and the mean level is 15 ng/mL. In diabetic patients, the mean resistin level is estimated at 40 ng/mL . For PVAT resistin levels, reference values have not been definitively developed. Previous publications compared resistin levels in PVAT sampled intraoperatively with obtained results .
No similar reports were found in the literature comparing resistin levels in tissue and peripheral blood. Previously published studies have mainly concentrated on determining resistin levels in peripheral blood . Other researchers, in turn, assessed its presence in PVAT . From a practical point of view, the publication was rather a scientific report, as it is currently impossible to analyze the composition of PVAT without its surgical collection, e.g., during cardiac surgery. Due to greater sample availability, the values of resistin levels in peripheral blood are better described in the literature, as opposed to the less frequently studied resistin levels in tissue. No publications in the literature refer to the simultaneous correlation of concentrations of potential markers of AF occurrence, such as resistin in PVAT tissue and patient plasma.
The present study also assessed the correlation between resistin and the concentration of inflammatory markers before CABG (IL-6, hsCRP, troponin). A moderate correlation appeared between PVAT resistin and hsCRP measured before surgery and plasma resistin and IL-6 before CABG. The difference between the AF and non-AF groups was not significant.
The analysis of the ROC curves showed that the highest predictive value of the compared parameters of postoperative atrial fibrillation was the level of PVAT resistin, followed by the plasma resistin level. Thus, the demonstrated correlation between these parameters confirms the usefulness of determining the plasma resistance level in patients before CABG surgery to predict the potential risk of postoperative complications.
According to Zhang et al., elevated resistin levels correlate with other inflammatory cytokines (interleukin 1 beta [IL-1 beta], IL-6, and tumor necrosis factor-alpha [TNF-alpha]). The authors experimented on an animal model and found that the development of coronary artery disease involves changes in blood flowing through the vessels as well as changes in the vessels and perivascular tissues. An explanation for this phenomenon is the penetration of proinflammatory substances circulating in plasma into the arterial wall and perivascular tissues, mainly PVAT, where the inflammatory process is likely to be localized. The same mechanism may apply to the course of atherosclerosis in humans .
The proinflammatory effect of resistin in plasma is linked to more frequent incidents of atrial fibrillation in the general population. The Framingham Offspring Study, in a long-term observation of a population of 2480 patients, assessed the impact of resistin concentrations on the occurrence of paroxysmal AF in the general population . The correlation was present for traditional etiological factors of AF. The obtained results were similar to those in a study of postmenopausal women. Ozcan et al. and Ermakov et al. demonstrated that plasma resistin levels in patients with paroxysmal atrial fibrillation were higher than in patients without that complication [15, 22]. The role of adipocytokines as markers of inflammation was demonstrated in the example of chronic inflammatory diseases with exacerbations .
Similar correlations with the onset of AF were also demonstrated by Gungor et al. in a group of 40 cardiac surgery patients; however, despite the potential possibility of sampling, the study was limited to the investigation of plasma resistin levels . The above papers [24, 25] present an assessment of plasma resistin concentrations and their correlation with AF. The authors do not address the potentially simultaneous relationship of plasma resistin and PVAT concentrations and possible correlations with AF.
Mazurek et al. demonstrated that the presence of inflammatory mediators in PVAT can amplify vascular inflammation, and atherosclerotic plaque instability via apoptosis (TNF-α), and neovascularization . In animal studies, the adventitial application of endotoxins in vivo in pigs, monocyte chemotactic protein-1 (MCP-1), IL-1β, or oxidized LDL, induced an influx of inflammatory cells into the arterial wall, coronary vasospasm, or damage to the internal membrane, suggesting that bioactive molecules from perivascular tissues may alter arterial homeostasis . The cited study provides a new method of assessing risk factors for atrial fibrillation before its onset using measurements of pro-inflammatory molecule concentrations at intravascular and extravascular levels in homogenates.
A similar paracrine effect may characterize adipocyte activity in the left atrial wall. Adipose infiltration of the atrial wall and gradual induction of inflammation lead to atrial fibrosis, which may contribute to the generation of arrhythmia .
According to the literature, resistin increases the production of reactive oxygen (ROS) . Excessive production of ROS leads to damage to myocardial cells and the heart conduction system. According to Ren et al., ROS-induced oxidative stress links gradual atrial remodeling and paroxysmal AF . Oxidative stress is generated after procedures utilizing extracorporeal circulation, such as CABG, and markers of this condition, such as myeloperoxidase (MPO), and inflammatory markers, such as IL-6, correlate with increased resistin levels after cardiac surgery. This study determined plasma resistin levels before surgery to assess the baseline concentrations and the environment in which arrhythmia may develop. Laurikka et al. found a correlation between resistin levels and IL-6 after CABG surgery, reaching its peak at 24 hours .
Reports suggest that plasma resistin levels are reduced by simvastatin . The study by Grosso et al. showed that relatively prolonged, three-month administration of a statin with pioglitazone caused a reduction in plasma resistin levels in patients awaiting CABG surgery compared to a group of patients who did not receive such treatment. However, this therapeutic effect in circulating blood and plasma can only be achieved after prolonged treatment . The presented observation suggests the advisability of determining plasma resistin levels before CABG surgery to determine the risk of postoperative AF.
In addition to qualitative studies, there are also quantitative studies of adipose tissue. Available methods make it possible to assess the thickness of adipose tissue using ultrasound, computed tomography, and MRI. For the presented group, this study was limited to the measurement of epicardial adipose tissue, which showed no significant differences in perioperative examination (Table 1).
The above observations may contribute to the deepening knowledge of AF pathogenesis and the impact of elevated resistin levels on its formation. They indicate the potential directions of therapeutic measures and interventions that may influence the composition of PVAT. It is possible to formulate a further hypothesis related to the clinical benefits, in certain patients, of reducing oxidative stress caused by extracorporeal circulation. In the future, it may be possible to design a strategy in which patients with elevated resistin levels would be recommended a revascularisation procedure utilizing off-pump technology instead of extracorporeal circulation. Thus, reducing the cardiovascular risk and the likelihood of AF.
It should be noted that new prophylactic drug therapies can be used for patients at risk of developing postoperative AF. They aim to mitigate the inflammatory response. Type 2 diabetic acute myocardial infarction (AMI) patients receiving sodium-glucose cotransporter 2 inhibitors (SGLT2-I) exhibited a significantly reduced inflammatory response. The inflammatory response occurring in AMI has been proposed as a potential pharmacological target . In this regard, recent evidence presented in the AMI-PROTECT trial suggests that using SGLT2 in the perioperative phase of myocardial infarction may attenuate the inflammatory response and reduce the risk of arrhythmic events . However, patients undergoing CABG surgery from both study groups were not taking oral SGLT2 antidiabetic drugs during the described follow-up period or before surgery. Therefore, the effect of treatment with SGLT2 inhibitors on resistin levels or IL-6 was not analyzed. An assessment of such a relationship could be included in subsequent studies.
The strengths of the study
The strength of the paper is, in our opinion, the unique, previously unpublished study comparing plasma resistin levels with tissue resistin levels in PVAT. Such unique opportunities are only available with cardiac surgery. Once these were compared, concentrations could be related to the specific clinical problem in cardiology which is atrial fibrillation. The number of patients included in the study - 108 - is also a definite strength of the publication.
In the future, a more detailed description of adipose tissue should be obtained with imaging tests – CT (computer tomography) and MRI (magnetic resonance imaging).
The present study did not assess the level of vitamin D3 in patients and its impact on their condition, which may contribute to a more in-depth observation of the causes of coronary atherosclerosis.
In this study, the analysis was carried out on a relatively small group of 108 patients; a more significant number would allow a more accurate assessment of the phenomenon.
The analysis of other adipocytokines present in PVAT would allow broadening of the spectrum of this research.
The presented results indicate the usefulness of determining plasma resistin levels, which reflect the condition of epicardial adipose tissue. Furthermore, this marker may aid in identifying patients at risk for postoperative atrial fibrillation before myocardial revascularisation.