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Pugliese NR, Paneni F, Tricò D, Bacca AV, De Biase N, Dalpiaz H, Mengozzi A, Virdis A, Ghiadoni L, Taddei S, Kreutz R, Tsioufis K, Masi S. Refining the link between obesity and heart failure: insights from GLP-1 receptor agonist trials and studies adopting direct adiposity measures. Cardiovasc Diabetol 2025; 24:224. [PMID: 40405237 PMCID: PMC12096527 DOI: 10.1186/s12933-025-02778-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Accepted: 05/06/2025] [Indexed: 05/24/2025] Open
Abstract
Overweight and obesity are major risk factors for heart failure (HF), contributing to its development through metabolic, neurohormonal, haemodynamic, and inflammatory alterations. While overweight/obesity increases the risk of developing HF, its impact on patient outcomes remains complex. The "obesity paradox" suggests that a higher BMI may be associated with improved survival in patients with established HF. However, recent GLP-1 receptor agonist (GLP-1 RA) trials suggest that intentional weight loss positively influences outcomes in overweight/obese patients with HF. This seemingly contradictory evidence highlights the need for a deeper understanding of the mechanisms linking adiposity to HF outcomes. A more precise characterization of adiposity phenotypes using alternative and accurate measures of pathological fat accumulation is crucial in identifying individuals who may benefit most from anti-obesity treatments. In this context, recent research underscores the role of epicardial adipose tissue (EAT) in HF pathophysiology, as it directly influences cardiac function and structure through inflammatory, metabolic, and mechanical effects. This narrative review summarises current evidence on the impact of weight loss on HF outcomes, focusing on recent GLP-1 RA trial results. Additionally, it highlights epidemiological and molecular data supporting EAT as a novel adiposity measure that might allow refining patient selection for pharmacological weight-loss treatments. Finally, it emphasizes the need for future research to identify causal pathways linking alternative measures of visceral fat accumulation to HF outcomes. These efforts will be essential in optimizing the benefits of novel weight-loss treatments, ensuring effective and individualized therapeutic strategies for overweight or obese patients with HF.
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Affiliation(s)
- Nicola Riccardo Pugliese
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy
| | - Francesco Paneni
- Center for Translational and Experimental Cardiology (CTEC), University Hospital Zurich and University of Zurich, Zurich, Switzerland
- Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
| | - Domenico Tricò
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy
| | | | - Nicolò De Biase
- PhD Program in Clinical and Translational Science, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Hermann Dalpiaz
- Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy
| | - Alessandro Mengozzi
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy
| | - Agostino Virdis
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy
| | - Lorenzo Ghiadoni
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy
| | - Stefano Taddei
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy
| | - Reinhold Kreutz
- Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Konstantinos Tsioufis
- Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Stefano Masi
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy.
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Kazeminasab F, Mahboobi MH, Mohebinejad M, Nojoumi M, Belyani S, Camera DM, Moradi S, Bagheri R. The Impact of Exercise Training Plus Dietary Interventions on Ectopic Fat in Population with Overweight/Obesity with and without Chronic Disease: A Systematic Review, Meta-analysis, and Metaregression of Randomized Clinical Trials. Curr Dev Nutr 2025; 9:104574. [PMID: 40182739 PMCID: PMC11964600 DOI: 10.1016/j.cdnut.2025.104574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 02/04/2025] [Accepted: 02/16/2025] [Indexed: 04/05/2025] Open
Abstract
Background The growing prevalence of obesity and related chronic diseases has led to increased interest in interventions targeting ectopic fat reduction to which its accumulation is linked to metabolic dysfunction. Objectives This study aimed to evaluate the effects of combined exercise training combined with dietary interventions compared with dietary interventions alone on ectopic fat [visceral fat area (VFA), liver fat, intramuscular fat (IMF), pancreatic fat, renal sinus fat, and pericardial and epicardial fats] in adults with overweight and obesity, both with and without chronic diseases. Methods Web of Science, Scopus, and PubMed were searched for original articles up to 1 March, 2024, that included exercise compared with control interventions on body weight and ectopic fat in adults with overweight or obesity. Weighted mean differences (WMD) for body weight, liver fat, pancreatic fat, and renal sinus fat and standardized mean differences (SMD) for VFA, IMF, pericardial and epicardial fats, and 95% confidence intervals were determined using random-effects models. Results Thirty-two studies, including 1488 participants and 38 intervention groups, met the inclusion criteria. The combined intervention of exercise and diet did not reduce body weight (WMD = -0.23 kg, P = 0.180), liver fat (WMD = 0.05%, P = 0.730), IMF (SMD = -0.08, P = 0.640), pericardial and epicardial fats (SMD = -0.12, P = 0.280), pancreatic fat (WMD = -0.24%, P = 0.370), and renal sinus fat (WMD = 0.01 cm2, P = 0.170) when compared with a diet-only group. Interestingly, exercise combined with diet significantly reduced VFA in participants with obesity (SMD = -0.12, P = 0.040) and healthy males (SMD = -0.33, P = 0.001) when compared with a diet-only group. Conclusions The findings suggest that combined exercise and dietary interventions did not lead to significant reductions in most ectopic fat depots when compared with diet alone. However, a modest reduction in VFA was observed in participants with obesity and healthy males. These results highlight the nuanced impact of exercise in combination with dietary interventions and the need to consider specific fat depots and participant characteristics in obesity management strategies.The trial was registered at PROSPERO as CRD42024546770.
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Affiliation(s)
- Fatemeh Kazeminasab
- Department of Physical Education and Sports Science, Faculty of Humanities, University of Kashan, Kashan, Iran
| | - Mohammad Hossein Mahboobi
- Department of Physical Education and Sports Science, Faculty of Humanities, University of Kashan, Kashan, Iran
| | - Motahareh Mohebinejad
- Department of Physical Education and Sports Science, Faculty of Humanities, University of Kashan, Kashan, Iran
| | - Maedeh Nojoumi
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Saba Belyani
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH, United States
| | - Donny M Camera
- Department of Health and Biostatistics, Swinburne University, Melbourne, Australia
| | - Sajjad Moradi
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, USA
- Department of Nutrition and Food Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Reza Bagheri
- Department of Exercise Physiology, University of Isfahan, Isfahan, Iran
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Whitman J, Kozaily E, Michos ED, Silverman DN, Fudim M, Mentz RJ, Tedford RJ, Rao VN. Epicardial Fat in Heart Failure and Preserved Ejection Fraction: Novel Insights and Future Perspectives. Curr Heart Fail Rep 2025; 22:13. [PMID: 40106059 PMCID: PMC11922990 DOI: 10.1007/s11897-025-00700-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/05/2025] [Indexed: 03/22/2025]
Abstract
PURPOSE OF REVIEW Cardiovascular effects of obesity may be driven, in part, by the distribution of fat. More recently, epicardial adipose tissue (EAT) has gained recognition as an adverse visceral fat impacting cardiac dysfunction in heart failure with preserved ejection fraction (HFpEF). RECENT FINDINGS EAT can be identified and measured using several non-invasive imaging techniques, including transthoracic echocardiography, computed tomography, and cardiac magnetic resonance. The presence of EAT is associated with increased risk of HFpEF and worse clinical outcomes among patients with established HFpEF, independent of total adiposity. EAT may serve a pivotal role in the pathogenesis of HFpEF by worsening volume distribution, enhancing pericardial restraint and ventricular interaction, worsening right ventricular dysfunction, and diminishing exercise tolerance. No large trials have tested the effects of reducing fat in specific areas of the body on cardiovascular outcomes, but some studies that followed people in communities and trials over time have suggested that drug and non-drug treatments that lower EAT could improve the risk factors for heart problems in patients with HFpEF. Further understanding the role that pathogenic fat depots play in HFpEF incidence and progression may provide future therapeutic targets in treating the obese-HFpEF phenotype.
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Affiliation(s)
- Jacob Whitman
- Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Elie Kozaily
- Division of Cardiology, Medical University of South Carolina, 30 Courtenay Drive, MSC Code: 592, Charleston, SC, 29425, USA
| | - Erin D Michos
- Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Daniel N Silverman
- Division of Cardiology, Medical University of South Carolina, 30 Courtenay Drive, MSC Code: 592, Charleston, SC, 29425, USA
- Division of Cardiology, Ralph H. Johnson Department of Veterans Affairs Heath Care System, Charleston, SC, USA
| | - Marat Fudim
- Division of Cardiology and Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
| | - Robert J Mentz
- Division of Cardiology and Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
| | - Ryan J Tedford
- Division of Cardiology, Medical University of South Carolina, 30 Courtenay Drive, MSC Code: 592, Charleston, SC, 29425, USA
| | - Vishal N Rao
- Division of Cardiology, Medical University of South Carolina, 30 Courtenay Drive, MSC Code: 592, Charleston, SC, 29425, USA.
- Division of Cardiology, Ralph H. Johnson Department of Veterans Affairs Heath Care System, Charleston, SC, USA.
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Karaaslan H, İnan H, Elmas AN. The Association Between Epicardial Adipose Tissue Thickness and the Triglyceride-glucose Index in Prediabetic Obese Patients. Angiology 2025:33197251320147. [PMID: 39982028 DOI: 10.1177/00033197251320147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2025]
Abstract
Obesity and pre-diabetes are metabolic disorders associated with insulin resistance (IR). Excess epicardial adipose tissue is also associated with increased IR. The triglyceride-glucose index (TyG) has been evaluated as an alternative measure of the IR in a variety of metabolic and cardiovascular disorders. However, its relationship with EAT thickness has not been studied yet. The study included 176 prediabetic and obese patients. EAT thickness was assessed using echocardiography. EAT thickness, TyG index, anthropometric obesity indices (body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR)), homeostatic model assessment (HOMA-IR), and biochemical parameters were compared. The following correlations between EAT thickness and related parameters were observed: WC (r = .529), BMI (r = .514), ALT (r = .358), TyG index (r = .338), and HOMA-IR (r = .322; P < .001 for all). Multiple regression analysis showed that WC (Beta = .428; P = .004), age (Beta = .223; P < .001), BMI (Beta = .196; P = .029), ALT (Beta = .168; P = .012), and TyG index (Beta = .128; P = .049) were the strongest independent variables correlated with EAT thickness. A model based on WC, BMI, age, TyG index, and ALT provided the best R-square (.387) for estimating EAT thickness (P < .001). The TyG index showed a significant and independent relationship with EAT, suggesting that it may be useful as an indicator of EAT thickness.
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Affiliation(s)
- Hüseyin Karaaslan
- School of Medicine, Department of Endocrinology, Harran University, Sanliurfa, Turkey
| | - Hasan İnan
- School of Medicine, Department of Internal Medicine, Harran University, Sanliurfa, Turkey
| | - Ali Nizami Elmas
- School of Medicine, Department of Cardiology, Harran University, Sanliurfa, Turkey
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Khidr SS, Bakeer BM, Helmy HAR, El-Naggar HM. Cardiac magnetic resonance quantified epicardial fat volume is associated with complex coronary artery disease among diabetics. Cardiovasc Diabetol 2025; 24:64. [PMID: 39920759 PMCID: PMC11806836 DOI: 10.1186/s12933-025-02606-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 01/20/2025] [Indexed: 02/09/2025] Open
Abstract
BACKGROUND Epicardial and pericardial adipose tissues are two distinct types of visceral fat in close adherence to the heart and were found to be increased among diabetics. AIM To investigate the correlation between cardiac magnetic resonance (CMR)-quantified epicardial (EFV) and pericardial fat (PFV) volumes and the complexity of coronary artery disease (CAD) among diabetic and non-diabetic patients. METHODS This was a cross-sectional study that included 111 patients having CAD as indicated by coronary angiography and who underwent CMR. Epicardial and pericardial fat volumes were measured along short-axis CMR-derived images. CAD severity and complexity were evaluated using the syntax score (SS). Patients were classified into diabetic and non-diabetic groups based on their HbA1c and were compared regarding clinical, angiographic, and CMR data. Those with high SS were compared against low/intermediate SS. The correlation of measured EFV and PFV with the SS was evaluated, and possible predictors for high-SS were assessed. RESULTS Diabetic patients (n = 64, 57.7%) had significantly high syntax scores, and significantly larger absolute and indexed EFV and PFV compared to non-diabetics. Both EFV and PFV showed a significant positive correlation with HbA1c and SS. EFV ≥ 119.55 ml significantly predicted high-SS (AUC = 0.84, 95%CI = 0.76-0.91, sensitivity = 77% and specificity = 82.5%) among the study population. Different cutoff points of EFV significantly predicted high SS among diabetics and non-diabetics with respective reasonable sensitivity and specificity. Age and EFV were consistently predictive of high SS on different multivariable regression models. CONCLUSION Increased epicardial adipose tissue was a significant independent predictor of severe and complex CAD, representing a possible risk marker and potential therapeutic target, particularly among diabetics.
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Affiliation(s)
- Shimaa Sayed Khidr
- Department of Cardiovascular Medicine, Assiut University Heart Hospital, Assiut, 71526, Egypt.
| | - Bakeer Mohamed Bakeer
- Department of Cardiovascular Medicine, Assiut University Heart Hospital, Assiut, 71526, Egypt
| | | | - Heba Mahmoud El-Naggar
- Department of Cardiovascular Medicine, Assiut University Heart Hospital, Assiut, 71526, Egypt
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Abusnina W, Merdler I, Cellamare M, Chitturi KR, Chaturvedi A, Feuerstein IM, Zhang C, Ozturk ST, Deksissa T, Sawant V, Lopez K, Lupu L, Haberman D, Ben‐Dor I, Satler LF, Waksman R, Hashim HD, Case BC. Epicardial Fat Tissue: A Potential Marker for Coronary Microvascular Dysfunction. J Am Heart Assoc 2025; 14:e038484. [PMID: 39895522 PMCID: PMC12074709 DOI: 10.1161/jaha.124.038484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 10/28/2024] [Indexed: 02/04/2025]
Abstract
BACKGROUND Coronary microvascular dysfunction (CMD), which mimics symptoms of obstructive coronary artery disease, has significant prognostic implications. While epicardial adipose tissue normally has a protective role, increased epicardial adipose tissue is associated with inflammation and may contribute to CMD. However, a direct correlation remains unclear. We aimed to investigate this association. METHODS AND RESULTS The CMDR (Coronary Microvascular Disease Registry) is a prospective, 2-center registry that is enrolling patients with angina and nonobstructive coronary artery disease who underwent invasive hemodynamic assessment of the coronary microvasculature. Patients with chest computed tomography within 1 year of CMD evaluation were included. We measured epicardial fat volume (EFV) and calculated the EFV index. Logistic regression analysis was used to investigate the association between EFV and EFV index to CMD. Our study included 130 CMDR patients with associated chest CT; 35 were diagnosed with CMD. The CMD-negative patients were younger than the CMD-positive patients (58.52±11.97 versus 63.37±9.56 years; P=0.033), with numerically fewer women (64.2% versus 74.3%; P=0.279). Univariate regression analysis demonstrated a statistically significant association between EFV index and CMD diagnosis (odds ratio, 1.037 [95% CI, 1.014-1.063]; P=0.003), while no significance was observed for EFV (odds ratio, 1.006 [95% CI, 0.995-1.017]; P=0.292). CONCLUSIONS Our results suggest a strong association between EFV index (a significant risk factor) and the presence of CMD. Future studies involving larger cohorts are needed to confirm the association of epicardial adipose tissue with CMD and investigate therapeutic targets to prevent CMD. REGISTRATION URL: https://www.clinicaltrials.gov; unique identifier: NCT05960474.
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Affiliation(s)
- Waiel Abusnina
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Ilan Merdler
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Matteo Cellamare
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Kalyan R. Chitturi
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Abhishek Chaturvedi
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | | | - Cheng Zhang
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Sevket Tolga Ozturk
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Teshome Deksissa
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Vaishnavi Sawant
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Kassandra Lopez
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Lior Lupu
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Dan Haberman
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Itsik Ben‐Dor
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Lowell F. Satler
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Ron Waksman
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Hayder D. Hashim
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
| | - Brian C. Case
- Section of Interventional CardiologyMedStar Washington Hospital CenterWashingtonDCUSA
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Ahmad I, Gupta S, Thomas M, Cai JJ, Heaps CL, Newell-Fugate AE. Aerobic exercise decreases the number and transcript expression of inflammatory M1 macrophages and CD8+ T cells in the epicardial adipose tissue of female pigs. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.02.02.635562. [PMID: 39975127 PMCID: PMC11838430 DOI: 10.1101/2025.02.02.635562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
Background Epicardial adipose tissue (EAT) regulates coronary artery function via lipid metabolism and immune cell recruitment. Increased EAT is a risk factor for coronary artery disease (CAD), but aerobic exercise mitigates CAD. The effect of aerobic exercise on immune cells in EAT is unknown. We hypothesized that aerobic exercise creates an anti-inflammatory environment characterized by increased M2 macrophages and up-regulation of anti-inflammatory cytokine transcripts in EAT. Methods Female Yucatan pigs (n=7) were allocated to sedentary or exercised groups. To mimic CAD, a coronary artery was chronically occluded or remained non-occluded. EAT samples were processed for bulk and single nuclei transcriptomic sequencing. Results Sub-clustering identified immune, endothelial, smooth muscle, adipocytes, adipocyte progenitor cells (APSCs), and neuronal cells, with adipocytes and APSCs being dominant. Non-occluded sedentary EAT had the largest percentage of M1 macrophages and CD8+ T cells. Irrespective of occlusion, sedentary EAT had the largest fraction of cells expressing genes in the tumor necrosis factor (TNF) superfamily. Irrespective of occlusion, exercise upregulated peroxisome proliferator-activated receptor (PPAR) gamma (G) expression and enriched PPAR signaling pathways in adipocytes, macrophages, and T cells. However, PPARG expression was lowest in CD8+ T cells from non-occluded exercised EAT. The greatest number of significant cell-cell communications between adipocytes and immune cells via growth factors and adhesion molecules occurred in occluded sedentary EAT. Conclusion Aerobic exercise mitigates the proinflammatory nature of EAT in CAD via modulation of immune cell subpopulations, decreased TNF superfamily and increased PPARG gene expression, and decreased growth factor communication between adipocytes and immune cells.
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Affiliation(s)
- Irshad Ahmad
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
| | - Shreyan Gupta
- Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
| | - Micah Thomas
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
| | - James J. Cai
- Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
| | - Cristine L. Heaps
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
| | - Annie E. Newell-Fugate
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
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Chartrand DJ, Larose E, Poirier P, Mathieu P, Alméras N, Pibarot P, Lamarche B, Rhéaume C, Lemieux I, Després JP, Piché ME. Visceral adiposity: A major mediator of the relationship between epicardial adiposity and cardiorespiratory fitness in adults. Nutr Metab Cardiovasc Dis 2025; 35:103740. [PMID: 39455333 DOI: 10.1016/j.numecd.2024.09.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 09/10/2024] [Accepted: 09/13/2024] [Indexed: 10/28/2024]
Abstract
BACKGROUND AND AIMS Epicardial adiposity has been positively associated with visceral adipose tissue (VAT). Few studies have examined the association between cardiorespiratory fitness (CRF) and epicardial adiposity. Furthermore, whether this relationship was independent of VAT remains unexplored. Our purpose was to investigate the contribution of VAT in the relationships between CRF, physical activity (PA) and epicardial adipose tissue (EAT) in asymptomatic women and men. METHODS AND RESULTS We examined the associations between EAT and VAT measured by magnetic resonance imaging, CRF measured by cardiopulmonary exercise testing, and PA assessed using pedometers and a 3-day PA journal in 239 apparently healthy adults (43 % women). Participants were compared according to EAT tertiles and CRF level in both sexes. Participants with the highest EAT level presented more VAT (p < 0.001), lower CRF (p < 0.01), and a more deteriorated cardiometabolic health score (p < 0.01) than those with the lowest EAT level. CRF was negatively associated with EAT in both sexes (p < 0.01). No significant relationship was found with PA (p = NS). Stepwise multivariable regression analyses showed that VAT explained most of the variance in EAT in women and men. Mediation analyses confirmed that VAT was a mediator of the association between CRF and EAT in both sexes. CONCLUSION In women and men, VAT appears as a major mediator of the association between CRF and EAT thereby suggesting that managing VAT by improving CRF could help in the prevention of cardiometabolic disorders related to excess EAT.
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Affiliation(s)
- Dominic J Chartrand
- Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Québec, QC, Canada; Faculty of Medicine, Université Laval, Québec, QC, Canada
| | - Eric Larose
- Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Québec, QC, Canada; Faculty of Medicine, Université Laval, Québec, QC, Canada
| | - Paul Poirier
- Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Québec, QC, Canada; Faculty of Pharmacy, Université Laval, Québec, QC, Canada
| | - Patrick Mathieu
- Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Québec, QC, Canada; Faculty of Medicine, Université Laval, Québec, QC, Canada
| | - Natalie Alméras
- Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Québec, QC, Canada; Faculty of Medicine, Université Laval, Québec, QC, Canada
| | - Philippe Pibarot
- Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Québec, QC, Canada; Faculty of Medicine, Université Laval, Québec, QC, Canada
| | - Benoît Lamarche
- Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Université Laval, Québec, QC, Canada; School of Nutrition, Université Laval, Québec, QC, Canada
| | - Caroline Rhéaume
- Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Québec, QC, Canada; Faculty of Medicine, Université Laval, Québec, QC, Canada; VITAM - Centre de recherche en santé durable, CIUSSS de la Capitale-Nationale, Québec, QC, Canada
| | - Isabelle Lemieux
- Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Québec, QC, Canada
| | - Jean-Pierre Després
- Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Québec, QC, Canada; Faculty of Medicine, Université Laval, Québec, QC, Canada; VITAM - Centre de recherche en santé durable, CIUSSS de la Capitale-Nationale, Québec, QC, Canada
| | - Marie-Eve Piché
- Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Québec, QC, Canada; Faculty of Medicine, Université Laval, Québec, QC, Canada.
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Bai J, Li X, Shi Z, Pan H, Wang S, Gao C, Zhao M, Yue X, Yang K, Zhang X, Liu C, Wang W, Zhang T. Changes in the Structure, Function, and Fat Content of the Heart in Patients with Obesity After Bariatric Surgery-A Prospective Magnetic Resonance Imaging Study. Obes Surg 2025; 35:9-18. [PMID: 39643784 DOI: 10.1007/s11695-024-07254-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 04/24/2024] [Accepted: 04/24/2024] [Indexed: 12/09/2024]
Abstract
BACKGROUND Changes in myocardial fat in addition to changes in cardiac structure and function have not been accurately evaluated in obese patients following surgery. MATERIALS AND METHODS Forty-four obese patients who underwent sleeve gastrectomy and completed preoperative and postoperative cardiac magnetic resonance imaging (CMR) before surgery and at 1, 3, and 6 months after surgery were enrolled, and their clinical and laboratory data were collected. The differences and correlations between clinical, laboratory, and CMR parameters between the preoperative and postoperative groups were analysed. RESULTS The left ventricular mass (LVM), left ventricle cardiac output (LVCO), pericardial adipose tissue volume (PATV), and myocardial proton density fat fraction (M-PDFF) decreased after surgery (all P < 0.05). The left ventricle global longitudinal strain increased at 6 months after surgery (P = 0.004). A decrease in BMI was positively correlated with the LVCO (r = 0.58, P < 0.001) at 3 months after surgery and was positively correlated with the LVM and PATV (r = 0.54, P < 0.05) at 6 months after surgery. Six months after surgery, the changes in PATV were positively correlated with the changes in triglycerides (r = 0.61, P < 0.01). There was a moderately positive correlation between the decrease in the LVM and PATV (r = 0.54 ~ 0.71, P < 0.02) after surgery. CONCLUSION After surgery, the cardiac structure and function of obese patients significantly improved, the PATV and M-PDFF decreased, and there was a correlation between the structure and function of the heart and several clinical and laboratory indicators.
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Affiliation(s)
- Jinquan Bai
- Department of Radiology, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, YiYuan Street, NanGang District, Harbin, Heilongjiang, 150001, China
| | - Xiaolu Li
- Department of Radiology, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, YiYuan Street, NanGang District, Harbin, Heilongjiang, 150001, China
| | - Zhenzhou Shi
- Department of Radiology, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, YiYuan Street, NanGang District, Harbin, Heilongjiang, 150001, China
| | - Hong Pan
- Department of Radiology, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, YiYuan Street, NanGang District, Harbin, Heilongjiang, 150001, China
| | - Shuting Wang
- Department of Radiology, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, YiYuan Street, NanGang District, Harbin, Heilongjiang, 150001, China
| | - Chao Gao
- Department of Radiology, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, YiYuan Street, NanGang District, Harbin, Heilongjiang, 150001, China
| | - Min Zhao
- Pharmaceutical Diagnostics, GE Healthcare, No. 1, Tongji South Road, Beijing, 100176, Daxing District, China
| | - Xiuzheng Yue
- Philips Healthcare, Tower No. 2, The World Profit Centre, No. 16, Tianze Road, Beijing, 100600, Chaoyang District, China
| | - Kai Yang
- Department of Bariatric and Metabolic Surgery, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, YiYuan Street, NanGang District, Harbin, Heilongjiang, 150001, China
| | - Xia Zhang
- Department of Bariatric and Metabolic Surgery, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, YiYuan Street, NanGang District, Harbin, Heilongjiang, 150001, China
| | - Chang Liu
- Department of Bariatric and Metabolic Surgery, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, YiYuan Street, NanGang District, Harbin, Heilongjiang, 150001, China
| | - Wei Wang
- The MRI Room, The First Affliated Hospital of Harbin Medical University, No. 23, YouZheng Street, NanGang District, Harbin, Heilongjiang, 150001, China.
| | - Tong Zhang
- Department of Radiology, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, YiYuan Street, NanGang District, Harbin, Heilongjiang, 150001, China
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10
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Asteria C, Secchi F, Morricone L, Malavazos AE, Simona, Francesconi 1, Milani V, Giovanelli A. Open-bore MRI Scanner Assessment of Epicardial Adipose Tissue after Bariatric Surgery: A Pilot Study. Endocr Metab Immune Disord Drug Targets 2025; 25:173-188. [PMID: 39171595 PMCID: PMC11826907 DOI: 10.2174/0118715303310680240607114244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 04/18/2024] [Accepted: 04/27/2024] [Indexed: 08/23/2024]
Abstract
BACKGROUND The recognition of epicardial adipose tissue (EAT) as a cardiac risk factor has increased the interest in strategies that target cardiac adipose tissue. AIM The effect of bariatric and metabolic surgery (BMS)-induced weight loss on EAT volume was evaluated in this study. METHODS Fifteen bariatric patients, with (MS) or without (wMS) Metabolic Syndrome, underwent magnetic resonance imaging (MRI) using an open-bore scanner to assess EAT volume, visceral adipose tissue (VAT) thickness, and other cardiac morpho-functional parameters at baseline and 12 months after BMS. Nine patients underwent laparoscopic sleeve gastrectomy (LSG), and 6 patients underwent Roux-en-Y Gastric Bypass (RYGBP). RESULTS EAT volume significantly decreased in all the patients 12 months post-BMS from 91.6 cm3 to 67.1 cm3; p = 0.0002 in diastole and from 89.4 cm3 to 68.2 cm3; p = 0.0002 in systole. No significant difference was found between the LSG and RYGBP group. Moreover, EAT volume was significantly reduced among wMS compared with MS. In particular, EAT volume in diastole was significantly reduced from 80.9 cm3 to 54.4 cm3; p = 0.0156 in wMS and from 98.3 cm3 to 79.5 cm3; p = 0.031 in MS. The reduction was also confirmed in systole from 81.2 cm3 to 54.1 cm3; p = 0.0156 in wMS and from 105.7 cm3 to 75.1 cm3; p = 0.031 in MS. Finally, a positive correlation was found between EAT loss, BMI (r = 0.52; p = 0.0443) and VAT (r = 0.66; p = 0.008) reduction after BMS. CONCLUSION These findings suggest that EAT reduction may be a fundamental element for improving the cardio-metabolic prognosis of bariatric patients. Moreover, this is the first study performed with an open-bore MRI scanner to measure EAT volume.
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Affiliation(s)
- Carmela Asteria
- National Institute of Obesity Cure (INCO)-Bariatric Unit, IRCCS, Policlinico San Donato, Piazza Edmondo Malan, 2, 20097, San Donato Milanese, Milan, Italy
| | - Francesco Secchi
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Via Mangiagalli 31, 20133, Milano, Italy
- Department of Radiology, IRCCS Policlinico San Donato, piazza Edmondo Malan, 2, 20097, San Donato Milanese, Italy
- Head of Cardiovascular Imaging, IRCCS Multimedica, via Milanese, 300, Sesto San Giovanni, 20099, Milan, Italy
| | - Lelio Morricone
- Metabolic Diseases Service, Palazzo della Salute, Gruppo San Donato (GSD), via Teodorico, 25, 20149, Milan, Italy
| | - Alexis Elias Malavazos
- Endocrinology Unit, Clinical Nutrition and Cardiovascular Prevention Service, IRCCS, Policlinico San Donato, piazza Edmondo Malan, 2, 20097, San Donato Milanese, Milan, Italy
| | - Simona
- National Institute of Obesity Cure (INCO)-Bariatric Unit, IRCCS, Policlinico San Donato, Piazza Edmondo Malan, 2, 20097, San Donato Milanese, Milan, Italy
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Via Mangiagalli 31, 20133, Milano, Italy
- Department of Radiology, IRCCS Policlinico San Donato, piazza Edmondo Malan, 2, 20097, San Donato Milanese, Italy
- Head of Cardiovascular Imaging, IRCCS Multimedica, via Milanese, 300, Sesto San Giovanni, 20099, Milan, Italy
- Metabolic Diseases Service, Palazzo della Salute, Gruppo San Donato (GSD), via Teodorico, 25, 20149, Milan, Italy
- Endocrinology Unit, Clinical Nutrition and Cardiovascular Prevention Service, IRCCS, Policlinico San Donato, piazza Edmondo Malan, 2, 20097, San Donato Milanese, Milan, Italy
- Laboratory of Biostatistics and Data Management, Scientific Directorate, IRCCS, Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy
| | - Francesconi1
- National Institute of Obesity Cure (INCO)-Bariatric Unit, IRCCS, Policlinico San Donato, Piazza Edmondo Malan, 2, 20097, San Donato Milanese, Milan, Italy
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Via Mangiagalli 31, 20133, Milano, Italy
- Department of Radiology, IRCCS Policlinico San Donato, piazza Edmondo Malan, 2, 20097, San Donato Milanese, Italy
- Head of Cardiovascular Imaging, IRCCS Multimedica, via Milanese, 300, Sesto San Giovanni, 20099, Milan, Italy
- Metabolic Diseases Service, Palazzo della Salute, Gruppo San Donato (GSD), via Teodorico, 25, 20149, Milan, Italy
- Endocrinology Unit, Clinical Nutrition and Cardiovascular Prevention Service, IRCCS, Policlinico San Donato, piazza Edmondo Malan, 2, 20097, San Donato Milanese, Milan, Italy
- Laboratory of Biostatistics and Data Management, Scientific Directorate, IRCCS, Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy
| | - Valentina Milani
- Laboratory of Biostatistics and Data Management, Scientific Directorate, IRCCS, Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy
| | - Alessandro Giovanelli
- National Institute of Obesity Cure (INCO)-Bariatric Unit, IRCCS, Policlinico San Donato, Piazza Edmondo Malan, 2, 20097, San Donato Milanese, Milan, Italy
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11
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Dronkers J, van Veldhuisen DJ, van der Meer P, Meems LMG. Heart Failure and Obesity: Unraveling Molecular Mechanisms of Excess Adipose Tissue. J Am Coll Cardiol 2024; 84:1666-1677. [PMID: 39415402 DOI: 10.1016/j.jacc.2024.07.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 07/01/2024] [Accepted: 07/11/2024] [Indexed: 10/18/2024]
Abstract
Obesity is an ongoing pandemic and is associated with the development of heart failure (HF), and especially HF with preserved ejection fraction. The definition of obesity is currently based on anthropometric measurements but neglects the location and molecular properties of excess fat. Important depots associated with HF development are subcutaneous adipose tissue and visceral adipose tissue, both located in the abdominal region, and epicardial adipose tissue (EAT) surrounding the myocardium. However, mechanisms linking these different adipose tissue depots to HF development are incompletely understood. EAT in particular is of great interest because of its close proximity to the heart. In this review, we therefore focus on the characteristics of different adipose tissue depots and their response to obesity. In addition, we evaluate how different mechanisms associated with EAT expansion potentially contribute to HF and in particular HF with preserved ejection fraction development.
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Affiliation(s)
- Just Dronkers
- University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands
| | - Dirk J van Veldhuisen
- University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands
| | - Peter van der Meer
- University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands
| | - Laura M G Meems
- University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
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12
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Abe I, Takahashi N. Premature Ventricular Complexes and Epicardial Adipose Tissue - A Fatty and Funny Relationship. Circ J 2024; 88:1055-1056. [PMID: 38092412 DOI: 10.1253/circj.cj-23-0825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/28/2024]
Affiliation(s)
- Ichitaro Abe
- Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine
| | - Naohiko Takahashi
- Department of Cardiology and Clinical Examination, Oita University Faculty of Medicine
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13
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Folli F, Centofanti L, Magnani S, Tagliabue E, Bignotto M, La Sala L, Pontiroli AE. Obesity effect on newly diagnosed and recurrent post-ablation atrial fibrillation: a systematic review and meta-analysis. J Endocrinol Invest 2024; 47:1051-1066. [PMID: 37962809 DOI: 10.1007/s40618-023-02225-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 10/11/2023] [Indexed: 11/15/2023]
Abstract
BACKGROUND AND AIMS The role of overweight and obesity in the development of atrial fibrillation (AF) is well established; however, the differential effect on the occurrence and recurrence of AF remains uncertain. The aim of this review is to compare the effect of underweight and varying degrees of obesity on onset of AF and in recurrent post-ablation AF, and, when possible, in relation to sex. METHODS A systematic literature search was conducted in PubMed, Embase, and Cochrane Library from inception to January 31, 2023. Studies reporting frequency of newly-diagnosed AF and of recurrent post-ablation AF in different BMI categories, were included. 3400 records were screened and 50 met the inclusion criteria. Standardized data search and abstraction were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. Data were extracted from the manuscripts and were analyzed using a random effect model. The outcome was the occurrence of AF in population studies and in patients undergoing ablation. RESULTS Data from 50 studies were collected, of which 27 for newly-diagnosed AF and 23 for recurrent post-ablation AF, for a total of 15,134,939 patients, of which 15,115,181 in studies on newly-diagnosed AF and 19,758 in studies on recurrent post-ablation AF. Compared to normal weight, the increase in AF was significant (p < 0.01) for overweight, obese, and morbidly obese patients for newly-diagnosed AF, and for obese and morbidly obese patients for recurrent post-ablation AF. Newly-diagnosed AF was more frequent in obese female than obese male patients. CONCLUSION The effect of increased BMI was greater on the onset of AF, and obese women were more affected than men.
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Affiliation(s)
- F Folli
- Department of Health Sciences, University of Milan, Via A. Di Rudinì 8, 20142, Milan, Italy.
| | - L Centofanti
- Department of Health Sciences, University of Milan, Via A. Di Rudinì 8, 20142, Milan, Italy
| | - S Magnani
- Division of Cardiology, Ospedale San Paolo, 20142, Milan, Italy
| | - E Tagliabue
- Laboratory of Cardiovascular and Dysmetabolic Diseases, PST-Via Fantoli 18/15, 20138, Milan, Italy and Value-Based Healthcare Unit, IRCCS MultiMedica, 20099, Sesto San Giovanni, Milan, Italy
| | - M Bignotto
- Department of Health Sciences, University of Milan, Via A. Di Rudinì 8, 20142, Milan, Italy
| | - L La Sala
- Laboratory of Cardiovascular and Dysmetabolic Diseases, PST-Via Fantoli 18/15, 20138, Milan, Italy and Value-Based Healthcare Unit, IRCCS MultiMedica, 20099, Sesto San Giovanni, Milan, Italy
| | - A E Pontiroli
- Department of Health Sciences, University of Milan, Via A. Di Rudinì 8, 20142, Milan, Italy.
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14
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Förster CY, Künzel SR, Shityakov S, Stavrakis S. Synergistic Effects of Weight Loss and Catheter Ablation: Can microRNAs Serve as Predictive Biomarkers for the Prevention of Atrial Fibrillation Recurrence? Int J Mol Sci 2024; 25:4689. [PMID: 38731908 PMCID: PMC11083177 DOI: 10.3390/ijms25094689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 04/23/2024] [Accepted: 04/23/2024] [Indexed: 05/13/2024] Open
Abstract
In atrial fibrillation (AF), multifactorial pathologic atrial alterations are manifested by structural and electrophysiological changes known as atrial remodeling. AF frequently develops in the context of underlying cardiac abnormalities. A critical mechanistic role played by atrial stretch is played by abnormal substrates in a number of conditions that predispose to AF, including obesity, heart failure, hypertension, and sleep apnea. The significant role of overweight and obesity in the development of AF is known; however, the differential effect of overweight, obesity, cardiovascular comorbidities, lifestyle, and other modifiable risk factors on the occurrence and recurrence of AF remains to be determined. Reverse remodeling of the atrial substrate and subsequent reduction in the AF burden by conversion into a typical sinus rhythm has been associated with weight loss through lifestyle changes or surgery. This makes it an essential pillar in the management of AF in obese patients. According to recently published research, microRNAs (miRs) may function as post-transcriptional regulators of genes involved in atrial remodeling, potentially contributing to the pathophysiology of AF. The focus of this review is on their modulation by both weight loss and catheter ablation interventions to counteract atrial remodeling in AF. Our analysis outlines the experimental and clinical evidence supporting the synergistic effects of weight loss and catheter ablation (CA) in reversing atrial electrical and structural remodeling in AF onset and in recurrent post-ablation AF by attenuating pro-thrombotic, pro-inflammatory, pro-fibrotic, arrhythmogenic, and male-sex-associated hypertrophic remodeling pathways. Furthermore, we discuss the promising role of miRs with prognostic potential as predictive biomarkers in guiding approaches to AF recurrence prevention.
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Affiliation(s)
- Carola Y. Förster
- Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University of Würzburg, 97080 Würzburg, Germany
| | - Stephan R. Künzel
- Institute for Transfusion Medicine, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany;
- Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, 01307 Dresden, Germany
| | - Sergey Shityakov
- Laboratory of Chemoinformatics, Infochemistry Scientific Center, ITMO University, 197101 Saint-Petersburg, Russia;
| | - Stavros Stavrakis
- Cardiovascular Section, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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15
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Jalil JE, Gabrielli L, Ocaranza MP, MacNab P, Fernández R, Grassi B, Jofré P, Verdejo H, Acevedo M, Cordova S, Sanhueza L, Greig D. New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review. Int J Mol Sci 2024; 25:4407. [PMID: 38673991 PMCID: PMC11049921 DOI: 10.3390/ijms25084407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 04/02/2024] [Accepted: 04/07/2024] [Indexed: 04/28/2024] Open
Abstract
This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation of visceral adipose tissue, and increased pericardial/epicardial adipose tissue (contributing to an increase in myocardial fat content and interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the enteroendocrine L-cells in the gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, and promoting the proliferation and differentiation of β-cells. GLP-1 regulates gastric emptying and appetite, and GLP-1 RA is currently indicated for treating type 2 diabetes (T2D), obesity, and metabolic syndrome (MS). Recent evidence indicates that GLP-1 RA may play a significant role in preventing HFpEF in patients with obesity, MS, or obese T2D. This effect may be due to activating cardioprotective mechanisms (the endogenous counter-regulatory renin angiotensin system and the AMPK/mTOR pathway) and by inhibiting deleterious remodeling mechanisms (the PKA/RhoA/ROCK pathway, aldosterone levels, and microinflammation). However, there is still a need for further research to validate the impact of these mechanisms on humans.
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Affiliation(s)
- Jorge E. Jalil
- Pontificia Universidad Católica de Chile, School of Medicine, Division of Cardiovascular Diseases, Santiago 8330055, Chile; (L.G.); (P.M.); (R.F.); (H.V.); (M.A.); (S.C.); (L.S.); (D.G.)
| | - Luigi Gabrielli
- Pontificia Universidad Católica de Chile, School of Medicine, Division of Cardiovascular Diseases, Santiago 8330055, Chile; (L.G.); (P.M.); (R.F.); (H.V.); (M.A.); (S.C.); (L.S.); (D.G.)
| | - María Paz Ocaranza
- Pontificia Universidad Católica de Chile, School of Medicine, Division of Cardiovascular Diseases, Santiago 8330055, Chile; (L.G.); (P.M.); (R.F.); (H.V.); (M.A.); (S.C.); (L.S.); (D.G.)
| | - Paul MacNab
- Pontificia Universidad Católica de Chile, School of Medicine, Division of Cardiovascular Diseases, Santiago 8330055, Chile; (L.G.); (P.M.); (R.F.); (H.V.); (M.A.); (S.C.); (L.S.); (D.G.)
| | - Rodrigo Fernández
- Pontificia Universidad Católica de Chile, School of Medicine, Division of Cardiovascular Diseases, Santiago 8330055, Chile; (L.G.); (P.M.); (R.F.); (H.V.); (M.A.); (S.C.); (L.S.); (D.G.)
| | - Bruno Grassi
- Pontificia Universidad Católica de Chile, School of Medicine, Department of Nutrition and Diabetes, Santiago 8330055, Chile; (B.G.); (P.J.)
| | - Paulina Jofré
- Pontificia Universidad Católica de Chile, School of Medicine, Department of Nutrition and Diabetes, Santiago 8330055, Chile; (B.G.); (P.J.)
| | - Hugo Verdejo
- Pontificia Universidad Católica de Chile, School of Medicine, Division of Cardiovascular Diseases, Santiago 8330055, Chile; (L.G.); (P.M.); (R.F.); (H.V.); (M.A.); (S.C.); (L.S.); (D.G.)
| | - Monica Acevedo
- Pontificia Universidad Católica de Chile, School of Medicine, Division of Cardiovascular Diseases, Santiago 8330055, Chile; (L.G.); (P.M.); (R.F.); (H.V.); (M.A.); (S.C.); (L.S.); (D.G.)
| | - Samuel Cordova
- Pontificia Universidad Católica de Chile, School of Medicine, Division of Cardiovascular Diseases, Santiago 8330055, Chile; (L.G.); (P.M.); (R.F.); (H.V.); (M.A.); (S.C.); (L.S.); (D.G.)
| | - Luis Sanhueza
- Pontificia Universidad Católica de Chile, School of Medicine, Division of Cardiovascular Diseases, Santiago 8330055, Chile; (L.G.); (P.M.); (R.F.); (H.V.); (M.A.); (S.C.); (L.S.); (D.G.)
| | - Douglas Greig
- Pontificia Universidad Católica de Chile, School of Medicine, Division of Cardiovascular Diseases, Santiago 8330055, Chile; (L.G.); (P.M.); (R.F.); (H.V.); (M.A.); (S.C.); (L.S.); (D.G.)
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16
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Fang W, Xie S, Deng W. Epicardial Adipose Tissue: a Potential Therapeutic Target for Cardiovascular Diseases. J Cardiovasc Transl Res 2024; 17:322-333. [PMID: 37848803 DOI: 10.1007/s12265-023-10442-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 09/27/2023] [Indexed: 10/19/2023]
Abstract
With increased ageing of the population, cardiovascular disease (CVD) has become the most important factor endangering human health worldwide. Although the treatment of CVD has become increasingly advanced, there are still a considerable number of patients with conditions that have not improved. According to the latest clinical guidelines of the European Cardiovascular Association, obesity has become an independent risk factor for CVD. Adipose tissue includes visceral adipose tissue and subcutaneous adipose tissue. Many previous studies have focused on subcutaneous adipose tissue, but visceral adipose tissue has been rarely studied. However, as a type of visceral adipose tissue, epicardial adipose tissue (EAT) has attracted the attention of researchers because of its unique anatomical and physiological characteristics. This review will systematically describe the physiological characteristics and evaluation methods of EAT and emphasize the important role and treatment measures of EAT in CVD.
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Affiliation(s)
- Wenxi Fang
- Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China
- Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, People's Republic of China
| | - Saiyang Xie
- Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China
- Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, People's Republic of China
| | - Wei Deng
- Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.
- Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, People's Republic of China.
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17
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Kotha S, Plein S, Greenwood JP, Levelt E. Role of epicardial adipose tissue in diabetic cardiomyopathy through the lens of cardiovascular magnetic resonance imaging - a narrative review. Ther Adv Endocrinol Metab 2024; 15:20420188241229540. [PMID: 38476217 PMCID: PMC10929063 DOI: 10.1177/20420188241229540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 01/14/2024] [Indexed: 03/14/2024] Open
Abstract
Accumulating evidence suggests that ectopic/visceral adiposity may play a key role in the pathogenesis of nonischaemic cardiovascular diseases associated with type 2 diabetes. Epicardial adipose tissue (EAT) is a complex visceral fat depot, covering 80% of the cardiac surface with anatomical and functional contiguity to the myocardium and coronary arteries. EAT interacts with the biology of the underlying myocardium by secreting a wide range of adipokines. Magnetic resonance imaging (MRI) is the reference modality for structural and functional imaging of the heart. The technique is now also emerging as the reference imaging modality for EAT quantification. With this narrative review, we (a) surveyed contemporary clinical studies that utilized cardiovascular MRI to characterize EAT (studies published 2010-2023); (b) listed the clinical trials monitoring the response to treatment in EAT size as well as myocardial functional and structural parameters and (c) discussed the potential pathophysiological role of EAT in the development of diabetic cardiomyopathy. We concluded that increased EAT quantity and its inflammatory phenotype correlate with early signs of left ventricle dysfunction and may have a role in the pathogenesis of cardiac disease in diabetes with and without coronary artery disease.
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Affiliation(s)
- Sindhoora Kotha
- Department of Biomedical Imaging Science, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
- Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Sven Plein
- Department of Biomedical Imaging Science, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
- Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - John P. Greenwood
- Department of Biomedical Imaging Science, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
- Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Eylem Levelt
- Department of Biomedical Imaging Science, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UK
- Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds LS1 3EX, UK
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18
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Calcaterra V, Cena H, Garella V, Loperfido F, Chillemi C, Manuelli M, Mannarino S, Zuccotti G. Assessment of Epicardial Fat in Children: Its Role as a Cardiovascular Risk Factor and How It Is Influenced by Lifestyle Habits. Nutrients 2024; 16:420. [PMID: 38337703 PMCID: PMC10857556 DOI: 10.3390/nu16030420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 01/26/2024] [Accepted: 01/29/2024] [Indexed: 02/12/2024] Open
Abstract
Epicardial adipose tissue (EAT) stands out as a distinctive repository of visceral fat, positioned in close anatomical and functional proximity to the heart. EAT has emerged as a distinctive reservoir of visceral fat, intricately interlinked with cardiovascular health, particularly within the domain of cardiovascular diseases (CVDs). The aim of our overview is to highlight the role of EAT as a marker for cardiovascular risk in children. We also explore the influence of unhealthy lifestyle habits as predisposing factors for the deposition of EAT. The literature data accentuate the consequential impact of lifestyle choices on EAT dynamics, with sedentary behavior and unwholesome dietary practices being contributory to a heightened cardiovascular risk. Lifestyle interventions with a multidisciplinary approach are therefore pivotal, involving a nutritionally balanced diet rich in polyunsaturated and monounsaturated fatty acids, regular engagement in aerobic exercise, and psychosocial support to effectively mitigate cardiovascular risks in children. Specific interventions, such as high-intensity intermittent training and circuit training, reveal favorable outcomes in diminishing the EAT volume and enhancing cardiometabolic health. Future clinical studies focusing on EAT in children are crucial for advancing our understanding and developing targeted strategies for cardiovascular risk management in this population.
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Affiliation(s)
- Valeria Calcaterra
- Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milan, Italy;
| | - Hellas Cena
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (H.C.); (F.L.)
- Clinical Nutrition and Dietetics Service, Unit of Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy;
| | - Vittoria Garella
- Pediatric Cardiology Unit, “V. Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.G.); (C.C.); (S.M.)
| | - Federica Loperfido
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (H.C.); (F.L.)
| | - Claudia Chillemi
- Pediatric Cardiology Unit, “V. Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.G.); (C.C.); (S.M.)
| | - Matteo Manuelli
- Clinical Nutrition and Dietetics Service, Unit of Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy;
| | - Savina Mannarino
- Pediatric Cardiology Unit, “V. Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.G.); (C.C.); (S.M.)
| | - Gianvincenzo Zuccotti
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milan, Italy;
- Department of Biomedical and Clinical Science “L. Sacco”, University of Milan, 20157 Milan, Italy
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19
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Ishikawa H, Sugiyama T, Otsuka K, Yamaura H, Hojo K, Kono Y, Ito A, Yamazaki T, Shimada K, Kasayuki N, Fukuda D. Impact of epicardial adipose tissue on diastolic dysfunction in patients with chronic coronary syndrome and preserved left ventricular ejection fraction. EUROPEAN HEART JOURNAL. IMAGING METHODS AND PRACTICE 2024; 2:qyae056. [PMID: 39224094 PMCID: PMC11367961 DOI: 10.1093/ehjimp/qyae056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Accepted: 05/29/2024] [Indexed: 09/04/2024]
Abstract
Aims This study aims to investigate the association between left ventricular diastolic dysfunction (LVDD) and epicardial adipose tissue (EAT) accumulation in patients with chronic coronary syndrome (CCS) and preserved left ventricular ejection fraction (LVEF). Methods and results The study included 314 patients with preserved LVEF who underwent coronary computed tomographic angiography (CCTA) and thoracic tissue Doppler echocardiography (TTDE). The EAT volume was measured using CCTA. LVDD was categorized into three groups: absent LVDD, undetermined LVDD, and LVDD. Multivariate logistic regression analysis was performed to assess the association between the clinical parameters, TTDE and CCTA findings, and LVDD. Patients (mean age: 66 ± 13 years; 52% men) were divided into LVDD present (30 patients, 9.6%), LVDD absent (219 patients, 69.7%), and LVDD undetermined (65 patients, 20.7%) groups. CCTA showed that patients with LVDD had a significantly higher coronary artery calcium (CAC) score and % plaque volume (%PV) than those without LVDD, whereas the prevalence of obstructive coronary artery disease was comparable between the groups. The EAT volume index correlated with each LVDD diagnostic component, except for tricuspid regurgitation velocity. A multivariate model showed that age [odds ratio (OR), 1.13; P < 0.001] and EAT volume index (OR, 1.02; P = 0.038) were independently associated with LVDD, even after adjusting for left ventricular mass index (OR, 1.05; P = 0.005). There was no significant association between the CAC score and %PV or LVDD. Conclusion This study demonstrated that EAT volume index and left ventricular mass index were robust predictors of LVDD; however, there was no independent association between coronary atherosclerotic disease burden and LVDD.
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Affiliation(s)
- Hirotoshi Ishikawa
- Department of Cardiovascular Medicine, Kashibaseiki Hospital, 3300-3 Anamusi, Kashiba, Nara 639-0252, Japan
| | - Takatoshi Sugiyama
- Department of Cardiovascular Medicine, Kashibaseiki Hospital, 3300-3 Anamusi, Kashiba, Nara 639-0252, Japan
| | - Kenichiro Otsuka
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahicho, Abenoku, Osaka 545-8585, Japan
| | - Hiroki Yamaura
- Department of Cardiovascular Medicine, Kashibaseiki Hospital, 3300-3 Anamusi, Kashiba, Nara 639-0252, Japan
| | - Kana Hojo
- Department of Cardiovascular Medicine, Kashibaseiki Hospital, 3300-3 Anamusi, Kashiba, Nara 639-0252, Japan
| | - Yasushi Kono
- Department of Cardiovascular Medicine, Kashibaseiki Hospital, 3300-3 Anamusi, Kashiba, Nara 639-0252, Japan
| | - Asahiro Ito
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahicho, Abenoku, Osaka 545-8585, Japan
| | - Takanori Yamazaki
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahicho, Abenoku, Osaka 545-8585, Japan
| | - Kenei Shimada
- Department of Cardiovascular Medicine, Kashibaseiki Hospital, 3300-3 Anamusi, Kashiba, Nara 639-0252, Japan
| | - Noriaki Kasayuki
- Department of Cardiovascular Medicine, Kashibaseiki Hospital, 3300-3 Anamusi, Kashiba, Nara 639-0252, Japan
| | - Daiju Fukuda
- Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahicho, Abenoku, Osaka 545-8585, Japan
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20
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Ernault AC, de Winter R, Fabrizi B, Bracht JW, Hau C, van Amersfoorth SC, Meulendijks ER, Tijsen AJ, Cócera Ortega L, van der Made I, Gasecka A, Driessen AH, Nieuwland R, Boukens BJ, van der Pol E, de Groot JR, Coronel R. MicroRNAs in extracellular vesicles released from epicardial adipose tissue promote arrhythmogenic conduction slowing. Heart Rhythm O2 2023; 4:805-814. [PMID: 38204457 PMCID: PMC10774655 DOI: 10.1016/j.hroo.2023.10.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2024] Open
Abstract
Background Patients with excess epicardial adipose tissue (EAT) are at increased risk of developing cardiac arrhythmias. EAT promotes arrhythmias by depolarizing the resting membrane of cardiomyocytes, which slows down conduction and facilitates re-entrant arrhythmias. We hypothesized that EAT slows conduction by secreting extracellular vesicles (EVs) and their microRNA (miRNA) cargo. Objective We aimed to determine the role of EAT-derived EVs and their miRNA cargo in conduction slowing. Methods EAT and subcutaneous adipose tissue (SAT) were collected from patients with atrial fibrillation. Adipose tissue explants were incubated in culture medium and secretome was collected. The numbers of EVs in the EAT and SAT secretome were measured by calibrated flow cytometry. EVs in the EAT secretome were isolated by size exclusion chromatography and miRNAs were sequenced. Pathway analysis was performed to predict candidates involved in cardiac electrophysiology. The candidates were validated in the EAT and SAT by quantitative real-time polymerase chain reaction. Finally, miRNA candidates were overexpressed in neonatal rat ventricular myocytes. Results The EV concentration was higher in the EAT secretome than in the SAT and control secretomes. miRNA sequencing of EAT-derived EVs detected a total of 824 miRNAs. Pathway analysis led to the identification of 7 miRNAs potentially involved in regulation of cardiac resting membrane potential. Validation of those miRNA candidates showed that they were all expressed in EAT, and that miR-1-3p and miR-133a-3p were upregulated in EAT in comparison with SAT. Overexpression of miR-1-3p and miR-133a-3p in neonatal rat ventricular myocytes led to conduction slowing and reduced Kcnj2 and Kcnj12 expression. Conclusion miR-1-3p and miR-133a-3p are potential mediators of EAT arrhythmogenicity.
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Affiliation(s)
- Auriane C. Ernault
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Rosan de Winter
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Benedetta Fabrizi
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Jillian W.P. Bracht
- Laboratory of Experimental Clinical Chemistry, Amsterdam UMC, location AMC, Amsterdam, the Netherlands
- Vesicle Observation Center, Amsterdam UMC, location AMC, Amsterdam, the Netherlands
| | - Chi Hau
- Laboratory of Experimental Clinical Chemistry, Amsterdam UMC, location AMC, Amsterdam, the Netherlands
- Vesicle Observation Center, Amsterdam UMC, location AMC, Amsterdam, the Netherlands
| | - Shirley C.M. van Amersfoorth
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Eva R. Meulendijks
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Anke J. Tijsen
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Lucía Cócera Ortega
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Ingeborg van der Made
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Aleksandra Gasecka
- Laboratory of Experimental Clinical Chemistry, Amsterdam UMC, location AMC, Amsterdam, the Netherlands
- Vesicle Observation Center, Amsterdam UMC, location AMC, Amsterdam, the Netherlands
- Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
| | - Antoine H. Driessen
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Rienk Nieuwland
- Laboratory of Experimental Clinical Chemistry, Amsterdam UMC, location AMC, Amsterdam, the Netherlands
- Vesicle Observation Center, Amsterdam UMC, location AMC, Amsterdam, the Netherlands
| | - Bastiaan J. Boukens
- Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
- Department of Medical Biology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
| | - Edwin van der Pol
- Laboratory of Experimental Clinical Chemistry, Amsterdam UMC, location AMC, Amsterdam, the Netherlands
- Vesicle Observation Center, Amsterdam UMC, location AMC, Amsterdam, the Netherlands
- Biomedical Engineering and Physics, Amsterdam UMC, location AMC, Amsterdam, the Netherlands
| | - Joris R. de Groot
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Ruben Coronel
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
- Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
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21
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Song Y, Tan Y, Deng M, Shan W, Zheng W, Zhang B, Cui J, Feng L, Shi L, Zhang M, Liu Y, Sun Y, Yi W. Epicardial adipose tissue, metabolic disorders, and cardiovascular diseases: recent advances classified by research methodologies. MedComm (Beijing) 2023; 4:e413. [PMID: 37881786 PMCID: PMC10594046 DOI: 10.1002/mco2.413] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 09/12/2023] [Accepted: 09/25/2023] [Indexed: 10/27/2023] Open
Abstract
Epicardial adipose tissue (EAT) is located between the myocardium and visceral pericardium. The unique anatomy and physiology of the EAT determines its great potential in locally influencing adjacent tissues such as the myocardium and coronary arteries. Classified by research methodologies, this study reviews the latest research progress on the role of EAT in cardiovascular diseases (CVDs), particularly in patients with metabolic disorders. Studies based on imaging techniques demonstrated that increased EAT amount in patients with metabolic disorders is associated with higher risk of CVDs and increased mortality. Then, in-depth profiling studies indicate that remodeled EAT may serve as a local mediator of the deleterious effects of cardiometabolic conditions and plays a crucial role in CVDs. Further, in vitro coculture studies provided preliminary evidence that the paracrine effect of remodeled EAT on adjacent cardiomyocytes can promote the occurrence and progression of CVDs. Considering the important role of EAT in CVDs, targeting EAT might be a potential strategy to reduce cardiovascular risks. Several interventions have been proved effective in reducing EAT amount. Our review provides valuable insights of the relationship between EAT, metabolic disorders, and CVDs, as well as an overview of the methodological constructs of EAT-related studies.
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Affiliation(s)
- Yujie Song
- Department of Cardiovascular SurgeryXijing HospitalThe Fourth Military Medical UniversityXi'anChina
| | - Yanzhen Tan
- Department of Cardiovascular SurgeryXijing HospitalThe Fourth Military Medical UniversityXi'anChina
| | - Meng Deng
- Department of General MedicineXijing HospitalThe Fourth Military Medical UniversityXi'anChina
| | - Wenju Shan
- Department of General MedicineXijing HospitalThe Fourth Military Medical UniversityXi'anChina
| | - Wenying Zheng
- Department of Cardiovascular SurgeryXijing HospitalThe Fourth Military Medical UniversityXi'anChina
| | - Bing Zhang
- Department of Cardiovascular SurgeryXijing HospitalThe Fourth Military Medical UniversityXi'anChina
| | - Jun Cui
- Department of Cardiovascular SurgeryXijing HospitalThe Fourth Military Medical UniversityXi'anChina
| | - Lele Feng
- Department of Cardiovascular SurgeryXijing HospitalThe Fourth Military Medical UniversityXi'anChina
| | - Lei Shi
- Department of Cardiovascular SurgeryXijing HospitalThe Fourth Military Medical UniversityXi'anChina
| | - Miao Zhang
- Department of Cardiovascular SurgeryXijing HospitalThe Fourth Military Medical UniversityXi'anChina
| | - Yingying Liu
- Department of Cardiovascular SurgeryXijing HospitalThe Fourth Military Medical UniversityXi'anChina
| | - Yang Sun
- Department of General MedicineXijing HospitalThe Fourth Military Medical UniversityXi'anChina
| | - Wei Yi
- Department of Cardiovascular SurgeryXijing HospitalThe Fourth Military Medical UniversityXi'anChina
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22
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Dai G, Li M, Xu H, Quan N. Status of Research on Sestrin2 and Prospects for its Application in Therapeutic Strategies Targeting Myocardial Aging. Curr Probl Cardiol 2023; 48:101910. [PMID: 37422038 DOI: 10.1016/j.cpcardiol.2023.101910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Accepted: 06/27/2023] [Indexed: 07/10/2023]
Abstract
Cardiac aging is accompanied by changes in the heart at the cellular and molecular levels, leading to alterations in cardiac structure and function. Given today's increasingly aging population, the decline in cardiac function caused by cardiac aging has a significant impact on quality of life. Antiaging therapies to slow the aging process and attenuate changes in cardiac structure and function have become an important research topic. Treatment with drugs, including metformin, spermidine, rapamycin, resveratrol, astaxanthin, Huolisu oral liquid, and sulforaphane, has been demonstrated be effective in delaying cardiac aging by stimulating autophagy, delaying ventricular remodeling, and reducing oxidative stress and the inflammatory response. Furthermore, caloric restriction has been shown to play an important role in delaying aging of the heart. Many studies in cardiac aging and cardiac aging-related models have demonstrated that Sestrin2 has antioxidant and anti-inflammatory effects, stimulates autophagy, delays aging, regulates mitochondrial function, and inhibits myocardial remodeling by regulation of relevant signaling pathways. Therefore, Sestrin2 is likely to become an important target for antimyocardial aging therapy.
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Affiliation(s)
- Gaoying Dai
- Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, China
| | - Meina Li
- Department of Infection Control, The First Hospital of Jilin University, Changchun, China
| | - He Xu
- Department of Integrative Medicine, Lequn Branch, The First Hospital of Jilin University, Changchun, China
| | - Nanhu Quan
- Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, China.
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23
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Pereira JPS, Calafatti M, Martinino A, Ramnarain D, Stier C, Parmar C, Weiner S, Dekker LR, Hasenberg T, Wolf O, Pouwels S. Epicardial Adipose Tissue Changes After Bariatric and Metabolic Surgery: a Systematic Review and Meta-analysis. Obes Surg 2023; 33:3636-3648. [PMID: 37801237 DOI: 10.1007/s11695-023-06848-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 09/09/2023] [Accepted: 09/24/2023] [Indexed: 10/07/2023]
Abstract
Epicardial adipose tissue (EAT) is a visceral fat depot located between the myocardium and visceral epicardium. Emerging evidence suggests that excessive EAT is linked to increased risk of cardiovascular conditions and other metabolic diseases. A literature search was conducted from the earliest studies to the 26th of November 2022 on PubMed, Embase, and the Cochrane. All the studies evaluating changes in EAT, pericardial adipose tissue (PAT), or total cardiac fat loss before and after BS were included. From 623 articles, 35 were eventually included in the systematic review. Twenty-one studies showed a significant reduction of EAT after BS, and only one study showed a non-significant reduction (p = 0.2).
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Affiliation(s)
| | - Matteo Calafatti
- Faculty of Medicine, Università la Sapienza di Roma, Rome, Italy
| | | | - Dharmanand Ramnarain
- Department of Intensive Care Medicine, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands
- Department of Intensive Care Medicine, Saxenburgh Medical Centre, Hardenberg, The Netherlands
| | - Christine Stier
- Department of Surgical Endoscopy, Sana Hospitals, Germany and Obesity Center NRW, Huerth, Germany
| | - Chetan Parmar
- Department of Surgery, Whittington Health NHS Trust, London, UK
- Apollo Hospitals Education and Research Foundation, Hyderabad, India
| | - Sylvia Weiner
- Department of Bariatric and Metabolic Surgery, Sana Klinikum, Offenbach am Main, Hessen, Germany
| | - Lukas R Dekker
- Department of Cardiology, Catharina Hospital, Eindhoven, The Netherlands
| | - Till Hasenberg
- Helios Obesity Center West, Helios St. Elisabeth Hospital Oberhausen, Oberhausen, NRW, Germany
- Helios University Hospital Wuppertal, Wuppertal, NRW, Germany
- Faculty of Health, University of Witten/Herdecke, Witten, Germany
| | - Olga Wolf
- Department of Plastic, Reconstructive and Aesthetic Surgery, Florence Nightingale Hospital, Düsseldorf, Germany
| | - Sjaak Pouwels
- Department of Intensive Care Medicine, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands.
- Faculty of Health, University of Witten/Herdecke, Witten, Germany.
- Department of General, Abdominal Surgery and Coloproctology, Helios St. Elisabeth Klinik, Josefstraße 3, 46045, Oberhausen, NRW, Germany.
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24
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Zain S, Shamshad T, Kabir A, Khan AA. Epicardial Adipose Tissue and Development of Atrial Fibrillation (AFIB) and Heart Failure With Preserved Ejection Fraction (HFpEF). Cureus 2023; 15:e46153. [PMID: 37900360 PMCID: PMC10612538 DOI: 10.7759/cureus.46153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/28/2023] [Indexed: 10/31/2023] Open
Abstract
Epicardial adipose tissue (EAT) has been associated with the development of many cardiovascular abnormalities, of which the development of atrial fibrillation (AFIB) in this group of patients is not an uncommon finding. Several mechanisms have been proposed to explain the role of EAT in the development of AFIB. It involves cardiac remodeling owing to the underlying fatty infiltration and the subsequent inflammation and fibrosis. This leads to the formation of ectopic foci that can lead to AFIB. Some studies propose that structural and valvular heart disease and increased hemodynamic stress further augment the development of AFIB in patients with underlying EAT. The degree of development of AFIB is also related to EAT thickness and volume. Therefore, EAT quantification can be used as an imaging technique to predict cardiovascular outcomes in these patients. Obesity also plays an important role in the development of AFIB both as an independent factor and by leading to adipose tissue deposition on the epicardial tissue. Understanding the pathophysiology of EAT is important as it can lead to the development of therapies that can target obesity as a risk factor for preventing AFIB. Some promising therapies have already been investigated for decreasing the risk of AFIB in patients with EAT. Dietary changes and weight loss have been shown to reduce the deposition of fat on epicardial tissue. Antidiabetic drugs and statin therapy have also shown promising results. Bariatric surgery has been shown to decrease EAT volume on echocardiography in obese patients.
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Affiliation(s)
- Sarmad Zain
- Internal Medicine, Nishtar Medical University, Multan, PAK
| | - Talha Shamshad
- Internal Medicine, Nishtar Medical University, Multan, PAK
| | - Ahmad Kabir
- Internal Medicine, Nishtar Medical University, Multan, PAK
- Pulmonology & Critical Care, Ch. Pervaiz Elahi Institute of Cardiology Multan, Multan, PAK
| | - Ahmad Ali Khan
- Cardiology, Ch. Pervaiz Elahi Institute of Cardiology Multan, Multan, PAK
- Internal Medicine, Nishtar Medical University, Multan, PAK
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25
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Shi YJ, Dong GJ, Guo M. Targeting epicardial adipose tissue: A potential therapeutic strategy for heart failure with preserved ejection fraction with type 2 diabetes mellitus. World J Diabetes 2023; 14:724-740. [PMID: 37383601 PMCID: PMC10294070 DOI: 10.4239/wjd.v14.i6.724] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/10/2023] [Accepted: 04/24/2023] [Indexed: 06/14/2023] Open
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various comorbidities, multiple cardiac and extracardiac pathophysiologic abnormalities, and diverse phenotypic presentations. Since HFpEF is a heterogeneous disease with different phenotypes, individualized treatment is required. HFpEF with type 2 diabetes mellitus (T2DM) represents a specific phenotype of HFpEF, with about 45%-50% of HFpEF patients suffering from T2DM. Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM, which is intimately related to the expansion and dysfunction (inflammation and hypermetabolic activity) of epicardial adipose tissue (EAT). EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms. Therefore, suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM. Although there is no treatment specifically for EAT, lifestyle management, bariatric surgery, and some pharmaceutical interventions (anti-cytokine drugs, statins, proprotein convertase subtilisin/kexin type 9 inhibitors, metformin, glucagon-like peptide-1 receptor agonists, and especially sodium-glucose cotransporter-2 inhibitors) have been shown to attenuate the inflammatory response or expansion of EAT. Importantly, these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF. Accordingly, well-designed randomized controlled trials are needed to validate the efficacy of current therapies. In addition, more novel and effective therapies targeting EAT are needed in the future.
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Affiliation(s)
- Yu-Jiao Shi
- Department of Cardiovascular Medicine, Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100091, China
| | - Guo-Ju Dong
- Department of Cardiovascular Medicine, Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100091, China
| | - Ming Guo
- Department of Cardiovascular Medicine, Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100091, China
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26
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Li C, Liu X, Adhikari BK, Chen L, Liu W, Wang Y, Zhang H. The role of epicardial adipose tissue dysfunction in cardiovascular diseases: an overview of pathophysiology, evaluation, and management. Front Endocrinol (Lausanne) 2023; 14:1167952. [PMID: 37260440 PMCID: PMC10229094 DOI: 10.3389/fendo.2023.1167952] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 04/21/2023] [Indexed: 06/02/2023] Open
Abstract
In recent decades, the epicardial adipose tissue (EAT) has been at the forefront of scientific research because of its diverse role in the pathogenesis of cardiovascular diseases (CVDs). EAT lies between the myocardium and the visceral pericardium. The same microcirculation exists both in the epicardial fat and the myocardium. Under physiological circumstances, EAT serves as cushion and protects coronary arteries and myocardium from violent distortion and impact. In addition, EAT acts as an energy lipid source, thermoregulator, and endocrine organ. Under pathological conditions, EAT dysfunction promotes various CVDs progression in several ways. It seems that various secretions of the epicardial fat are responsible for myocardial metabolic disturbances and, finally, leads to CVDs. Therefore, EAT might be an early predictor of CVDs. Furthermore, different non-invasive imaging techniques have been proposed to identify and assess EAT as an important parameter to stratify the CVD risk. We also present the potential therapeutic possibilities aiming at modifying the function of EAT. This paper aims to provide overview of the potential role of EAT in CVDs, discuss different imaging techniques to assess EAT, and provide potential therapeutic options for EAT. Hence, EAT may represent as a potential predictor and a novel therapeutic target for management of CVDs in the future.
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Affiliation(s)
- Cheng Li
- Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Xinyu Liu
- School of Basic Medical Sciences, Changchun University of Chinese Medicine, Changchun, Jilin, China
| | | | - Liping Chen
- Department of Echocardiography, Cardiovascular Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Wenyun Liu
- Department of Radiology, The First Hospital of Jilin University, Jilin Provincial Key Laboratory of Medical Imaging and Big Data, Changchun, Jilin, China
| | - Yonggang Wang
- Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Huimao Zhang
- Department of Radiology, The First Hospital of Jilin University, Jilin Provincial Key Laboratory of Medical Imaging and Big Data, Changchun, Jilin, China
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27
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Thapa S, Selvaraj BS, Davis PN, Smith B, Givan AH, Perez-Rivera JA, Woodard P, Klingensmith JD, Fernandez-del-Valle M. Vigorous-intensity exercise as a modulator of cardiac adipose tissue in women with obesity: a cross-sectional and randomized pilot study. Front Endocrinol (Lausanne) 2023; 14:1104441. [PMID: 37223011 PMCID: PMC10200876 DOI: 10.3389/fendo.2023.1104441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 03/28/2023] [Indexed: 05/25/2023] Open
Abstract
Cardiac adipose tissue (CAT) has become an important target for the reduction of disease risk. Supervised exercise programs have shown potential to "significantly" reduce CAT; however, the impact of different exercise modalities is not clear, and the relationships between CAT, physical activity (PA) levels and fitness (PFit) remain unknown. Therefore, the purpose of this study was to analyze the relationships between CAT, PA and PFit, and to explore the effects of different exercise modalities in a group of women with obesity. A total of 26 women (age: 23.41 ± 5.78 years-old) were enrolled in the cross-sectional study. PA, cardiorespiratory fitness, muscular strength, body composition and CAT were evaluated. The pilot intervention included 16 women randomized to a control (CON, n=5), high intensity interval training (HIIT, n = 5) and high-intensity circuit training (HICT, n=6) groups. Statistical analysis showed negative correlations between CAT and vigorous PA (VPA) (r s=-0.41, p=0.037); and between percent body fat (%BF), fat mass (FM), and all PA levels (r s=-0.41- -0.68, p<0.05); while muscle mass was positively associated with moderate-to-vigorous PA, and upper-body lean mass with all PA levels (r s =0.40-0.53, p<0.05). The HICT intervention showed significant improvements (p<0.05) in %BF, FM, fat free mass, and whole-body and lower extremities lean mass and strength after three weeks; however, only leg strength and upper extremities' FM improved significantly compared to CON and HICT. In conclusion, although all types of PA showed a positive influence on body fat content, only VPA significantly impacted on CAT volume. Moreover, three weeks of HICT induced positive changes in PFit in women with obesity. Further research is needed to explore VPA levels and high-intensity exercise interventions for short- and long-term CAT management.
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Affiliation(s)
- Sumsen Thapa
- Department of Applied Health, Southern Illinois University Edwardsville, Edwardsville, IL, United States
| | - Bharath S. Selvaraj
- Department of Applied Health, Southern Illinois University Edwardsville, Edwardsville, IL, United States
- Iowa Digestive Disease Center, Heartland Medical Research, Inc., Clive, IA, United States
| | - Paige N. Davis
- Department of Applied Health, Southern Illinois University Edwardsville, Edwardsville, IL, United States
- Department of Cardiopulmonary Rehabilitation, Charleston Area Medical Center (CAMC) Memorial Hospital at West Virginia, Charleston, WV, United States
| | - Bryan Smith
- Department of Applied Health, Southern Illinois University Edwardsville, Edwardsville, IL, United States
| | - Amy H. Givan
- Department of Applied Health, Southern Illinois University Edwardsville, Edwardsville, IL, United States
- Division of Rehabilitation Sciences, University of Texas Medical Branch at Galveston, Galveston, TX, United States
| | - Jose A. Perez-Rivera
- Department of Cardiology, University Hospital of Burgos, Burgos, Spain
- Facultad de Ciencias de la Salud, Universidad Isabel I, Isabel, Spain
| | - Pamela K. Woodard
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
| | - Jon D. Klingensmith
- Department of Electrical and Computer Engineering, Southern Illinois University Edwardsville, Edwardsville, IL, United States
| | - Maria Fernandez-del-Valle
- Department of Applied Health, Southern Illinois University Edwardsville, Edwardsville, IL, United States
- Department of Functional Biology, University of Oviedo, Oviedo, Spain
- Health Research Institute of the Principality of Asturias (ISPA), Oviedo, Spain
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28
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Pugliese NR, Pellicori P, Filidei F, De Biase N, Maffia P, Guzik TJ, Masi S, Taddei S, Cleland JGF. Inflammatory pathways in heart failure with preserved left ventricular ejection fraction: implications for future interventions. Cardiovasc Res 2023; 118:3536-3555. [PMID: 36004819 PMCID: PMC9897694 DOI: 10.1093/cvr/cvac133] [Citation(s) in RCA: 63] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 07/26/2022] [Accepted: 08/10/2022] [Indexed: 02/07/2023] Open
Abstract
Many patients with symptoms and signs of heart failure have a left ventricular ejection fraction ≥50%, termed heart failure with preserved ejection fraction (HFpEF). HFpEF is a heterogeneous syndrome mainly affecting older people who have many other cardiac and non-cardiac conditions that often cast doubt on the origin of symptoms, such as breathlessness, or signs, such as peripheral oedema, rendering them neither sensitive nor specific to the diagnosis of HFpEF. Currently, management of HFpEF is mainly directed at controlling symptoms and treating comorbid conditions such as hypertension, atrial fibrillation, anaemia, and coronary artery disease. HFpEF is also characterized by a persistent increase in inflammatory biomarkers. Inflammation may be a key driver of the development and progression of HFpEF and many of its associated comorbidities. Detailed characterization of specific inflammatory pathways may provide insights into the pathophysiology of HFpEF and guide its future management. There is growing interest in novel therapies specifically designed to target deregulated inflammation in many therapeutic areas, including cardiovascular disease. However, large-scale clinical trials investigating the effectiveness of anti-inflammatory treatments in HFpEF are still lacking. In this manuscript, we review the role of inflammation in HFpEF and the possible implications for future trials.
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Affiliation(s)
| | - Pierpaolo Pellicori
- Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, Glasgow G12 8QQ, UK
| | - Francesco Filidei
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy
| | - Nicolò De Biase
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy
| | - Pasquale Maffia
- Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK
- Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples 80138, Italy
| | - Tomasz J Guzik
- Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
- Department of Internal and Agricultural Medicine, Jagiellonian University, Collegium Medicum, Krakow 31-008, Poland
| | - Stefano Masi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy
| | - Stefano Taddei
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy
| | - John G F Cleland
- Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, Glasgow G12 8QQ, UK
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29
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Sheikhbahaei E, Tavassoli Naini P, Agharazi M, Pouramini A, Rostami S, Bakhshaei S, Valizadeh R, Heshmat Ghahdarijani K, Shiravi A, Shahabi S. Cardiac fat pat change after laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis. Surg Obes Relat Dis 2022; 19:653-664. [PMID: 36681624 DOI: 10.1016/j.soard.2022.12.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 11/08/2022] [Accepted: 12/01/2022] [Indexed: 12/23/2022]
Abstract
Cardiac fat pad is a metabolically active organ that plays a role in energy homeostasis and cardiovascular diseases and generates inflammatory cytokines. Many studies have shown remarkable associations between cardiac fat thickness and cardiovascular diseases, making it a valuable target for interventions. Our meta-analysis aimed to investigate the effects of the 2 most popular bariatric surgeries (sleeve gastrectomy [SG] and Roux-en-Y gastric bypass [RYGB]) in cardiac fat pad reduction. A systematic review of the literature was done by searching in Scopus, Web of Science, Cochrane, and PubMed for articles published by September 16, 2022. This review followed the meta-analysis rules based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Nineteen studies met the inclusion criteria out of 128 potentially useful studies, including a total number of 822 patients. The results of subgroup analysis on the type of surgery showed that bariatric surgeries decreased the mean fat pad diameter, but the reduction was greater in SG than in RYGB. Epicardial and pericardial fat type showed a significant decrease of fat pad diameter. The results of subgroup analysis indicated RYGB had a significant reduction in mean fat pad volume. Computed tomography scan and cardiac magnetic resonance imaging showed a significant reduction of the mean cardiac fat pad volume. Epicardial and paracardial fat type showed a significant decrease in volume. The cardiac fat pad diameter and volume were significantly reduced after bariatric surgeries. SG showed greater reduction in fat pad diameter in comparison with RYGB, and RYGB had a significant reduction in mean fat pad volume.
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Affiliation(s)
- Erfan Sheikhbahaei
- Isfahan Minimally Invasive Surgery and Obesity Research Center, Alzahra University Hospital, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Mohammad Agharazi
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Alireza Pouramini
- Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Sepehr Rostami
- Student Research Committee, Dnipro Medical Institute of Conventional and Traditional Medicine, Dnipro, Ukraine
| | | | - Rohollah Valizadeh
- Department of Epidemiology and Biostatistics, School of Public Health, Urmia University of Medical Sciences, Urmia, Iran
| | - Kiyan Heshmat Ghahdarijani
- Isfahan Cardiovascular Research Center, Chamran University Hospital, Department of Cardiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amirabbas Shiravi
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Shahab Shahabi
- Department of Surgery, Minimally Invasive Surgery Research Center, Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran.
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30
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van Woerden G, van Veldhuisen DJ, Westenbrink BD, de Boer RA, Rienstra M, Gorter TM. Connecting epicardial adipose tissue and heart failure with preserved ejection fraction: mechanisms, management and modern perspectives. Eur J Heart Fail 2022; 24:2238-2250. [PMID: 36394512 PMCID: PMC10100217 DOI: 10.1002/ejhf.2741] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 10/19/2022] [Accepted: 11/16/2022] [Indexed: 11/19/2022] Open
Abstract
Obesity is very common in patients with heart failure with preserved ejection fraction (HFpEF) and it has been suggested that obesity plays an important role in the pathophysiology of this disease. While body mass index defines the presence of obesity, this measure provides limited information on visceral adiposity, which is probably more relevant in the pathophysiology of HFpEF. Epicardial adipose tissue is the visceral fat situated directly adjacent to the heart and recent data demonstrate that accumulation of epicardial adipose tissue is associated with the onset, symptomatology and outcome of HFpEF. However, the mechanisms by which epicardial adipose tissue may be involved in HFpEF remain unclear. It is also questioned whether epicardial adipose tissue may be a specific target for therapy for this disease. In the present review, we describe the physiology of epicardial adipose tissue and the pathophysiological transformation of epicardial adipose tissue in response to chronic inflammatory diseases, and we postulate conceptual mechanisms on how epicardial adipose tissue may be involved in HFpEF pathophysiology. Lastly, we outline potential treatment strategies, knowledge gaps and directions for further research.
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Affiliation(s)
- Gijs van Woerden
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Dirk J van Veldhuisen
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - B Daan Westenbrink
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Rudolf A de Boer
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Michiel Rienstra
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Thomas M Gorter
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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31
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Sawyer MKL, Gould PA, Ng ACT, Wang WYS. What is the Relationship Between Epicardial Adipose Tissue, Left Atrial Low Voltage Zones and Atrial Fibrillation? Heart Lung Circ 2022; 31:1429-1431. [PMID: 36436840 DOI: 10.1016/j.hlc.2022.09.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Michael K L Sawyer
- Department of Cardiology, Princess Alexandra Hospital, Brisbane, Qld, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Qld, Australia
| | - Paul A Gould
- Department of Cardiology, Princess Alexandra Hospital, Brisbane, Qld, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Qld, Australia
| | - Arnold C T Ng
- Department of Cardiology, Princess Alexandra Hospital, Brisbane, Qld, Australia
| | - William Y S Wang
- Department of Cardiology, Princess Alexandra Hospital, Brisbane, Qld, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Qld, Australia.
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32
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Sung E, Prakosa A, Zhou S, Berger RD, Chrispin J, Nazarian S, Trayanova NA. Fat infiltration in the infarcted heart as a paradigm for ventricular arrhythmias. NATURE CARDIOVASCULAR RESEARCH 2022; 1:933-945. [PMID: 36589896 PMCID: PMC9802586 DOI: 10.1038/s44161-022-00133-6] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 08/17/2022] [Indexed: 01/03/2023]
Abstract
Infiltrating adipose tissue (inFAT) has been recently found to co-localize with scar in infarcted hearts and may contribute to ventricular arrhythmias (VAs), a life-threatening heart rhythm disorder. However, the contribution of inFAT to VA has not been well-established. We investigated the role of inFAT versus scar in VA through a combined prospective clinical and mechanistic computational study. Using personalized computational heart models and comparing the results from simulations of VA dynamics with measured electrophysiological abnormalities during the clinical procedure, we demonstrate that inFAT, rather than scar, is a primary driver of arrhythmogenic propensity and is frequently present in critical regions of the VA circuit. We determined that, within the VA circuitry, inFAT, as opposed to scar, is primarily responsible for conduction slowing in critical sites, mechanistically promoting VA. Our findings implicate inFAT as a dominant player in infarct-related VA, challenging existing paradigms and opening the door for unexplored anti-arrhythmic strategies.
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Affiliation(s)
- Eric Sung
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
- Alliance for Cardiovascular Diagnostic and Treatment Innovation, Johns Hopkins University, Baltimore, MD, USA
| | - Adityo Prakosa
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
- Alliance for Cardiovascular Diagnostic and Treatment Innovation, Johns Hopkins University, Baltimore, MD, USA
| | - Shijie Zhou
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
- Alliance for Cardiovascular Diagnostic and Treatment Innovation, Johns Hopkins University, Baltimore, MD, USA
| | - Ronald D Berger
- Alliance for Cardiovascular Diagnostic and Treatment Innovation, Johns Hopkins University, Baltimore, MD, USA
- Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Jonathan Chrispin
- Alliance for Cardiovascular Diagnostic and Treatment Innovation, Johns Hopkins University, Baltimore, MD, USA
- Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Saman Nazarian
- Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Natalia A Trayanova
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
- Alliance for Cardiovascular Diagnostic and Treatment Innovation, Johns Hopkins University, Baltimore, MD, USA.
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33
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Poggi AL, Gaborit B, Schindler TH, Liberale L, Montecucco F, Carbone F. Epicardial fat and atrial fibrillation: the perils of atrial failure. Europace 2022; 24:1201-1212. [PMID: 35274140 DOI: 10.1093/europace/euac015] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 01/27/2022] [Indexed: 12/18/2022] Open
Abstract
Obesity is a heterogeneous condition, characterized by different phenotypes and for which the classical assessment with body mass index may underestimate the real impact on cardiovascular (CV) disease burden. An epidemiological link between obesity and atrial fibrillation (AF) has been clearly demonstrated and becomes even more tight when ectopic (i.e. epicardial) fat deposition is considered. Due to anatomical and functional features, a tight paracrine cross-talk exists between epicardial adipose tissue (EAT) and myocardium, including the left atrium (LA). Alongside-and even without-mechanical atrial stretch, the dysfunctional EAT may determine a pro-inflammatory environment in the surrounding myocardial tissue. This evidence has provided a new intriguing pathophysiological link with AF, which in turn is no longer considered a single entity but rather the final stage of atrial remodelling. This maladaptive process would indeed include structural, electric, and autonomic derangement that ultimately leads to overt disease. Here, we update how dysfunctional EAT would orchestrate LA remodelling. Maladaptive changes sustained by dysfunctional EAT are driven by a pro-inflammatory and pro-fibrotic secretome that alters the sinoatrial microenvironment. Structural (e.g. fibro-fatty infiltration) and cellular (e.g. mitochondrial uncoupling, sarcoplasmic reticulum fragmentation, and cellular protein quantity/localization) changes then determine an electrophysiological remodelling that also involves the autonomic nervous system. Finally, we summarize how EAT dysfunction may fit with the standard guidelines for AF. Lastly, we focus on the potential benefit of weight loss and different classes of CV drugs on EAT dysfunction, LA remodelling, and ultimately AF onset and recurrence.
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Affiliation(s)
- Andrea Lorenzo Poggi
- Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
| | - Bénédicte Gaborit
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, Marseille, France
- Aix Marseille Univ, INSERM, INRAE, C2VN Marseille, France
| | - Thomas Hellmut Schindler
- Department of Radiology, Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO, USA
| | - Luca Liberale
- Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
- Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy
| | - Fabrizio Montecucco
- Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
- Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy
| | - Federico Carbone
- Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
- Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy
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34
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Association between depressive symptoms and pericardial fat in healthy older men and women. Sci Rep 2022; 12:13959. [PMID: 35978037 PMCID: PMC9385858 DOI: 10.1038/s41598-022-17888-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 08/02/2022] [Indexed: 12/02/2022] Open
Abstract
Depressive symptoms are associated with increased risk for cardiovascular disease (CVD), and inflammation may contribute to this relationship. Pericardial fat, a highly metabolically active fat depot, is implicated in the pathogenesis of CVD, but its association with depressive symptoms is unclear. This study examined the cross-sectional and longitudinal association between depressive symptoms and pericardial fat over a three-year period. Participants were 543 healthy men and women (mean age = 62.9 years) without history or objective signs of coronary heart disease from the Whitehall II cohort. In men, depressive symptoms were positively associated with pericardial fat at baseline after adjustment for sociodemographics, waist to hip ratio and conventional cardiovascular risk factors. Inflammation, indexed by plasma interleukin 6 concentration, accounted for 17% of this association. Longitudinally, depressive symptoms did not predict pericardial fat three years later in men once baseline levels of pericardial fat were accounted for. No significant associations between depressive symptoms and pericardial fat were found in women. Overall, our findings suggest that greater pericardial fat might be a mechanism by which depressive symptoms are associated with increased risk for CVD in men, and inflammation may also lie on this pathway.
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35
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Walker R, Ramasamy V, Sturgiss E, Dunbar J, Boyle J. Shared medical appointments for weight loss: a systematic review. Fam Pract 2022; 39:710-724. [PMID: 34536073 DOI: 10.1093/fampra/cmab105] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
PURPOSE Shared medical appointments (SMAs) may help mitigate some of the barriers for managing obesity in primary care. The primary aim of this systematic review was to measure the effect of weight loss SMAs. METHODS Systematic searches using keywords and Medical Subject Headings for overweight, obesity, and SMAs were conducted in the CENTRAL, Medline Complete, PsycINFO, Scopus, CINAHL, EMBASE, and Web of Science databases with no date limits. Risk of bias was assessed using the Effective Health Practice Project Quality Assessment Tool for Quantitative Studies. RESULTS Fifteen studies involving weight loss SMAs in adults and children were identified. Six studies had controls. Inconsistency in reporting weight loss or weight change in controlled studies meant that data could not be pooled for meta-analysis. Results from individual studies indicated that SMAs can support adult patients to achieve significant weight loss. Women and older adults were more likely to take up SMA invitations. Results from the 5 studies involving children were less conclusive. Studies involving participants of a higher socioeconomic status tended to report lower attrition than studies involving participants who experienced disadvantage. These findings should be interpreted with caution as all but 1 included study was assessed as being weak in quality. CONCLUSIONS Overall, SMAs may be of benefit to address obesity in primary care, particularly for women and older adults. Appropriately designed prospective and controlled studies are required to engage their target audience and to assess whether SMAs are superior to other weight loss options in primary care.
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Affiliation(s)
- Ruth Walker
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Australia
| | - Vijayanand Ramasamy
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Australia
| | - Elizabeth Sturgiss
- Department of General Practice, School of Public Health and Preventive Medicine, Monash University, Notting Hill, Australia
| | - James Dunbar
- Deakin Rural Health, School of Medicine, Deakin University, Warrnambool, Australia
| | - Jacqueline Boyle
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Australia
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36
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Conte M, Petraglia L, Cabaro S, Valerio V, Poggio P, Pilato E, Attena E, Russo V, Ferro A, Formisano P, Leosco D, Parisi V. Epicardial Adipose Tissue and Cardiac Arrhythmias: Focus on Atrial Fibrillation. Front Cardiovasc Med 2022; 9:932262. [PMID: 35845044 PMCID: PMC9280076 DOI: 10.3389/fcvm.2022.932262] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/13/2022] [Indexed: 01/02/2023] Open
Abstract
Atrial Fibrillation (AF) is the most frequent cardiac arrhythmia and its prevalence increases with age. AF is strongly associated with an increased risk of stroke, heart failure and cardiovascular mortality. Among the risk factors associated with AF onset and severity, obesity and inflammation play a prominent role. Numerous recent evidence suggested a role of epicardial adipose tissue (EAT), the visceral fat depot of the heart, in the development of AF. Several potential arrhythmogenic mechanisms have been attributed to EAT, including myocardial inflammation, fibrosis, oxidative stress, and fat infiltration. EAT is a local source of inflammatory mediators which potentially contribute to atrial collagen deposition and fibrosis, the anatomical substrate for AF. Moreover, the close proximity between EAT and myocardium allows the EAT to penetrate and generate atrial myocardium fat infiltrates that can alter atrial electrophysiological properties. These observations support the hypothesis of a strong implication of EAT in structural and electrical atrial remodeling, which underlies AF onset and burden. The measure of EAT, through different imaging methods, such as echocardiography, computed tomography and cardiac magnetic resonance, has been proposed as a useful prognostic tool to predict the presence, severity and recurrence of AF. Furthermore, EAT is increasingly emerging as a promising potential therapeutic target. This review aims to summarize the recent evidence exploring the potential role of EAT in the pathogenesis of AF, the main mechanisms by which EAT can promote structural and electrical atrial remodeling and the potential therapeutic strategies targeting the cardiac visceral fat.
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Affiliation(s)
- Maddalena Conte
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Casa di Cura San Michele, Maddaloni, Italy
| | - Laura Petraglia
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Serena Cabaro
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | | | | | - Emanuele Pilato
- Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy
| | - Emilio Attena
- Department of Cardiology, Monaldi Hospital, Naples, Italy
| | - Vincenzo Russo
- Chair of Cardiology, Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli” – Monaldi and Cotugno Hospital, Naples, Italy
| | - Adele Ferro
- Institute of Biostructure and Bioimaging, Consiglio Nazionale delle Ricerche, Naples, Italy
| | - Pietro Formisano
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Dario Leosco
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Valentina Parisi
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
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Yamaura H, Otsuka K, Ishikawa H, Shirasawa K, Fukuda D, Kasayuki N. Determinants of Non-calcified Low-Attenuation Coronary Plaque Burden in Patients Without Known Coronary Artery Disease: A Coronary CT Angiography Study. Front Cardiovasc Med 2022; 9:824470. [PMID: 35463764 PMCID: PMC9021435 DOI: 10.3389/fcvm.2022.824470] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 02/28/2022] [Indexed: 12/21/2022] Open
Abstract
Background Although epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD), it is unclear whether EAT volume (EAV) can be used to diagnose high-risk coronary plaque burden associated with coronary events. This study aimed to investigate (1) the prognostic impact of low-attenuation non-calcified coronary plaque (LAP) burden on patient level analysis, and (2) the association of EAV with LAP volume in patients without known CAD undergoing coronary computed tomography angiography (CCTA). Materials and Methods This retrospective study consisted of 376 patients (male, 57%; mean age, 65.2 ± 13 years) without known CAD undergoing CCTA. Percent LAP volume (%LAP, <30 HU) was calculated as the LAP volume divided by the vessel volume. EAT was defined as adipose tissue with a CT attenuation value ranging from −250 to −30 HU within the pericardial sac. The primary endpoint was a composite event of death, non-fatal myocardial infarction, and unstable angina and worsening symptoms requiring unplanned coronary revascularization >3 months after CCTA. The determinants of %LAP (Q4) were analyzed using a multivariable logistic regression model. Results During the follow-up period (mean, 2.2 ± 0.9 years), the primary endpoint was observed in 17 patients (4.5%). The independent predictors of the primary endpoint were %LAP (Q4) (hazard ratio [HR], 3.05; 95% confidence interval [CI], 1.09–8.54; p = 0.033] in the Cox proportional hazard model adjusted by CAD-RADS category. Cox proportional hazard ratio analysis demonstrated that %LAP (Q4) was a predictor of the primary endpoint, independnet of CAD severity, Suita score, EAV, or CACS. The independent determinants of %LAP (Q4) were CACS ≥218.3 (p < 0.0001) and EAV ≥125.3 ml (p < 0.0001). The addition of EAV to CACS significantly improved the area under the curve (AUC) to identify %LAP (Q4) than CACS alone (AUC, EAV + CACS vs. CACS alone: 0.728 vs. 0.637; p = 0.013). Conclusions CCTA-based assessment of EAV, CACS, and LAP could help improve personalized cardiac risk management by administering patient-suited therapy.
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Affiliation(s)
- Hiroki Yamaura
- Department of Cardiovascular Medicine, Kashibaseiki Hospital, Kashiba, Japan
| | - Kenichiro Otsuka
- Department of Cardiovascular Medicine, Kashibaseiki Hospital, Kashiba, Japan.,Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hirotoshi Ishikawa
- Department of Cardiovascular Medicine, Kashibaseiki Hospital, Kashiba, Japan.,Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kuniyuki Shirasawa
- Department of Cardiovascular Medicine, Kashibaseiki Hospital, Kashiba, Japan
| | - Daiju Fukuda
- Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Noriaki Kasayuki
- Department of Cardiovascular Medicine, Kashibaseiki Hospital, Kashiba, Japan
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Scarano Pereira JP, Owen E, Martinino A, Akmal K, Abouelazayem M, Graham Y, Weiner S, Sakran N, Dekker LR, Parmar C, Pouwels S. Epicardial adipose tissue, obesity and the occurrence of atrial fibrillation: an overview of pathophysiology and treatment methods. Expert Rev Cardiovasc Ther 2022; 20:307-322. [PMID: 35443854 DOI: 10.1080/14779072.2022.2067144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Obesity is a chronic disease, which has significant health consequences and is a staggering burden to health care systems. Obesity can have harmful effects on the cardiovascular system, including heart failure, hypertension, coronary heart disease, and atrial fibrillation (AF). One of the possible substrates might be epicardial adipose tissue (EAT), which can be the link between AF and obesity. EAT is a fat deposit located between the myocardium and the visceral pericardium. Numerous studies have demonstrated that EAT plays a pivotal role in this relationship regarding atrial fibrillation. AREAS COVERED This review will focus on the role of obesity and the occurrence of atrial fibrillation (AF) and examine the connection between these and epicardial adipose tissue (EAT). The first part of this review will explain the pathophysiology of EAT and its association with the occurrence of AF. Secondly, we will review bariatric and metabolic surgery and its effects on EAT and AF. EXPERT COMMENTARY In this review, the epidemiology, pathophysiology, and treatments methods of AF are explained. Secondly the effects on EAT were elucidated. Due to the complex pathophysiological link between EAT, AF, and obesity, it is still uncertain which treatment strategy is superior.
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Affiliation(s)
| | - Eloise Owen
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | | | - Kiran Akmal
- Faculty of Medicine, Brighton and Sussex Medical School, Brighton, United Kingdom
| | - Mohamed Abouelazayem
- Department of Surgery, Royal Free London Hospitals NHS Foundation, London, United Kingdom
| | - Yitka Graham
- Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland, United Kingdom.,Facultad de Psucologia, Universidad Anahuac Mexico, Mexico City, Mexico
| | - Sylvia Weiner
- Department of Bariatric and Metabolic Surgery, Krankenhaus Nordwest, Frankfurt am Main, Germany
| | - Nasser Sakran
- Department of Surgery, Holy Family Hospital, Nazareth, Israel.,Azrieli, Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Lukas R Dekker
- Department of Cardiology, Catharina Hospital, Eindhoven, The Netherlands
| | - Chetan Parmar
- Department of Surgery, Whittington Health NHS Trust, London, United Kingdom
| | - Sjaak Pouwels
- Department of Intensive Care Medicine, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands
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39
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Doukbi E, Soghomonian A, Sengenès C, Ahmed S, Ancel P, Dutour A, Gaborit B. Browning Epicardial Adipose Tissue: Friend or Foe? Cells 2022; 11:991. [PMID: 35326442 PMCID: PMC8947372 DOI: 10.3390/cells11060991] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/04/2022] [Accepted: 03/09/2022] [Indexed: 02/08/2023] Open
Abstract
The epicardial adipose tissue (EAT) is the visceral fat depot of the heart which is highly plastic and in direct contact with myocardium and coronary arteries. Because of its singular proximity with the myocardium, the adipokines and pro-inflammatory molecules secreted by this tissue may directly affect the metabolism of the heart and coronary arteries. Its accumulation, measured by recent new non-invasive imaging modalities, has been prospectively associated with the onset and progression of coronary artery disease (CAD) and atrial fibrillation in humans. Recent studies have shown that EAT exhibits beige fat-like features, and express uncoupling protein 1 (UCP-1) at both mRNA and protein levels. However, this thermogenic potential could be lost with age, obesity and CAD. Here we provide an overview of the physiological and pathophysiological relevance of EAT and further discuss whether its thermogenic properties may serve as a target for obesity therapeutic management with a specific focus on the role of immune cells in this beiging phenomenon.
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Affiliation(s)
- Elisa Doukbi
- INSERM, INRAE, C2VN, Aix-Marseille University, F-13005 Marseille, France; (E.D.); (A.S.); (S.A.); (P.A.); (A.D.)
| | - Astrid Soghomonian
- INSERM, INRAE, C2VN, Aix-Marseille University, F-13005 Marseille, France; (E.D.); (A.S.); (S.A.); (P.A.); (A.D.)
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, F-13005 Marseille, France
| | - Coralie Sengenès
- Stromalab, CNRS ERL5311, EFS, INP-ENVT, INSERM U1031, University of Toulouse, F-31100 Toulouse, France;
- Institut National de la Santé et de la Recherche Médicale, University Paul Sabatier, F-31100 Toulouse, France
| | - Shaista Ahmed
- INSERM, INRAE, C2VN, Aix-Marseille University, F-13005 Marseille, France; (E.D.); (A.S.); (S.A.); (P.A.); (A.D.)
| | - Patricia Ancel
- INSERM, INRAE, C2VN, Aix-Marseille University, F-13005 Marseille, France; (E.D.); (A.S.); (S.A.); (P.A.); (A.D.)
| | - Anne Dutour
- INSERM, INRAE, C2VN, Aix-Marseille University, F-13005 Marseille, France; (E.D.); (A.S.); (S.A.); (P.A.); (A.D.)
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, F-13005 Marseille, France
| | - Bénédicte Gaborit
- INSERM, INRAE, C2VN, Aix-Marseille University, F-13005 Marseille, France; (E.D.); (A.S.); (S.A.); (P.A.); (A.D.)
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, F-13005 Marseille, France
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40
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Turkmen K, Ozer H, Kusztal M. The Relationship of Epicardial Adipose Tissue and Cardiovascular Disease in Chronic Kidney Disease and Hemodialysis Patients. J Clin Med 2022; 11:1308. [PMID: 35268399 PMCID: PMC8911356 DOI: 10.3390/jcm11051308] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/14/2022] [Accepted: 02/25/2022] [Indexed: 11/16/2022] Open
Abstract
Cardiovascular diseases remain the most common cause of morbidity and mortality in chronic kidney disease patients undergoing hemodialysis. Epicardial adipose tissue (EAT), visceral fat depot of the heart, was found to be associated with coronary artery disease in cardiac and non-cardiac patients. Additionally, EAT has been proposed as a novel cardiovascular risk in the general population and in end-stage renal disease patients. It has also been shown that EAT, more than other subcutaneous adipose tissue deposits, acts as a highly active organ producing several bioactive adipokines, and proinflammatory and proatherogenic cytokines. Therefore, increased visceral adiposity is associated with proinflammatory activity, impaired insulin sensitivity, increased risk of atherosclerosis, and high morbidity and mortality in hemodialysis patients. In the present review, we aimed to demonstrate the role of EAT in the pathophysiological mechanisms of increased cardiovascular morbidity and mortality in hemodialysis patients.
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Affiliation(s)
- Kultigin Turkmen
- Division of Nephrology, Department of Internal Medicine, Meram Medical Faculty, Necmettin Erbakan University, Konya 42090, Turkey;
| | - Hakan Ozer
- Division of Nephrology, Department of Internal Medicine, Meram Medical Faculty, Necmettin Erbakan University, Konya 42090, Turkey;
| | - Mariusz Kusztal
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland;
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41
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Konwerski M, Gąsecka A, Opolski G, Grabowski M, Mazurek T. Role of Epicardial Adipose Tissue in Cardiovascular Diseases: A Review. BIOLOGY 2022; 11:355. [PMID: 35336728 PMCID: PMC8945130 DOI: 10.3390/biology11030355] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/19/2022] [Accepted: 02/21/2022] [Indexed: 02/01/2023]
Abstract
Cardiovascular diseases (CVDs) are the leading causes of death worldwide. Epicardial adipose tissue (EAT) is defined as a fat depot localized between the myocardial surface and the visceral layer of the pericardium and is a type of visceral fat. EAT is one of the most important risk factors for atherosclerosis and cardiovascular events and a promising new therapeutic target in CVDs. In health conditions, EAT has a protective function, including protection against hypothermia or mechanical stress, providing myocardial energy supply from free fatty acid and release of adiponectin. In patients with obesity, metabolic syndrome, or diabetes mellitus, EAT becomes a deleterious tissue promoting the development of CVDs. Previously, we showed an adverse modulation of gene expression in pericoronary adipose tissue in patients with coronary artery disease (CAD). Here, we summarize the currently available evidence regarding the role of EAT in the development of CVDs, including CAD, heart failure, and atrial fibrillation. Due to the rapid development of the COVID-19 pandemic, we also discuss data regarding the association between EAT and the course of COVID-19. Finally, we present the potential therapeutic possibilities aiming at modifying EAT's function. The development of novel therapies specifically targeting EAT could revolutionize the prognosis in CVDs.
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Affiliation(s)
| | | | | | | | - Tomasz Mazurek
- 1st Chair and Department of Cardiology, Medical University of Warsaw, 02-097 Warszawa, Poland; (M.K.); (A.G.); (G.O.); (M.G.)
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42
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Dysregulated Epicardial Adipose Tissue as a Risk Factor and Potential Therapeutic Target of Heart Failure with Preserved Ejection Fraction in Diabetes. Biomolecules 2022; 12:biom12020176. [PMID: 35204677 PMCID: PMC8961672 DOI: 10.3390/biom12020176] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/12/2022] [Accepted: 01/18/2022] [Indexed: 02/01/2023] Open
Abstract
Cardiovascular (CV) disease and heart failure (HF) are the leading cause of mortality in type 2 diabetes (T2DM), a metabolic disease which represents a fast-growing health challenge worldwide. Specifically, T2DM induces a cluster of systemic metabolic and non-metabolic signaling which may promote myocardium derangements such as inflammation, fibrosis, and myocyte stiffness, which represent the hallmarks of heart failure with preserved ejection fraction (HFpEF). On the other hand, several observational studies have reported that patients with T2DM have an abnormally enlarged and biologically transformed epicardial adipose tissue (EAT) compared with non-diabetic controls. This expanded EAT not only causes a mechanical constriction of the diastolic filling but is also a source of pro-inflammatory mediators capable of causing inflammation, microcirculatory dysfunction and fibrosis of the underlying myocardium, thus impairing the relaxability of the left ventricle and increasing its filling pressure. In addition to representing a potential CV risk factor, emerging evidence shows that EAT may guide the therapeutic decision in diabetic patients as drugs such as metformin, glucagon-like peptide‑1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 inhibitors (SGLT2-Is), have been associated with attenuation of EAT enlargement.
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43
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Min J, Putt ME, Yang W, Bertoni A, Ding J, Lima JA, Allison MA, Barr RG, Al-Naamani N, Patel RB, Beussink-Nelson L, Kawut S, Shah SJ, Freed BH. Association of Pericardial Fat with Cardiac Structure, Function and Mechanics: the Multi-Ethnic Study of Atherosclerosis. J Am Soc Echocardiogr 2022; 35:579-587.e5. [DOI: 10.1016/j.echo.2022.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 12/18/2021] [Accepted: 01/06/2022] [Indexed: 11/24/2022]
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44
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Rasmussen IKB, Zobel EH, Ripa RS, von Scholten BJ, Curovic VR, Jensen JK, Kjaer A, Hansen TW, Rossing P. Liraglutide reduces cardiac adipose tissue in type 2 diabetes: A secondary analysis of the LIRAFLAME randomized placebo-controlled trial. Diabetes Obes Metab 2021; 23:2651-2659. [PMID: 34387408 DOI: 10.1111/dom.14516] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 07/13/2021] [Accepted: 07/28/2021] [Indexed: 01/13/2023]
Abstract
AIM To test the hypothesis that treatment with liraglutide can reduce cardiac adipose tissue. MATERIALS AND METHODS LIRAFLAME is a randomized placebo-controlled, double-blind, parallel clinical study. Participants with type 2 diabetes were randomized to treatment with liraglutide 1.8 mg/d or placebo for 26 weeks. Computed tomography was performed at baseline and at end of treatment to evaluate the cardiac adipose tissue volume, quantified automatically. We report the results of a secondary endpoint evaluating changes in cardiac adipose tissue. RESULTS A total of 102 participants were randomly assigned to liraglutide (n = 51) or placebo (n = 51). At baseline, the mean (SD) cardiac adipose tissue volume was comparable between the liraglutide and the placebo group (232.6 [112.8] vs. 227.0 [103.2] mL; P = 0.80). The mean change in body weight was -3.7 (-4.8, -2.6) kg in the liraglutide and -0.18 (-0.76, 0.40) kg in the placebo group. From baseline to end of treatment the mean cardiac adipose tissue change was -11.5 (95% confidence interval -17.6, -5.4) mL in the liraglutide (P < 0.001) and -0.01 (-5.3, 5.3) mL in the placebo (P = 1.00) groups. The reduction in cardiac adipose tissue was significantly greater in the liraglutide compared to the placebo group (mean difference -11.4 [-19.4, -3.3] mL; P = 0.006), but significance was lost after adjustment for changes in body mass index (P = 0.46). CONCLUSION Treatment with liraglutide for 26 weeks was associated with a reduction in cardiac adipose tissue compared to placebo. The reduction was not independent of weight loss, suggesting that this is not a drug-specific effect.
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Affiliation(s)
| | | | - Rasmus S Ripa
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet, Kobenhavn, Denmark
- University of Copenhagen, Copenhagen, Denmark
| | - Bernt J von Scholten
- Steno Diabetes Centre Copenhagen, Gentofte, Denmark
- Novo Nordisk A/S, Søborg, Denmark
| | | | - Jacob K Jensen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet, Kobenhavn, Denmark
- University of Copenhagen, Copenhagen, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet, Kobenhavn, Denmark
- University of Copenhagen, Copenhagen, Denmark
| | | | - Peter Rossing
- Steno Diabetes Centre Copenhagen, Gentofte, Denmark
- University of Copenhagen, Copenhagen, Denmark
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Nyawo TA, Pheiffer C, Mazibuko-Mbeje SE, Mthembu SXH, Nyambuya TM, Nkambule BB, Sadie-Van Gijsen H, Strijdom H, Tiano L, Dludla PV. Physical Exercise Potentially Targets Epicardial Adipose Tissue to Reduce Cardiovascular Disease Risk in Patients with Metabolic Diseases: Oxidative Stress and Inflammation Emerge as Major Therapeutic Targets. Antioxidants (Basel) 2021; 10:1758. [PMID: 34829629 PMCID: PMC8614861 DOI: 10.3390/antiox10111758] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 10/29/2021] [Accepted: 11/01/2021] [Indexed: 12/25/2022] Open
Abstract
Excess epicardial adiposity, within a state of obesity and metabolic syndrome, is emerging as an important risk factor for the development of cardiovascular diseases (CVDs). Accordingly, increased epicardial fat thickness (EFT) implicates the exacerbation of pathological mechanisms involving oxidative stress and inflammation within the heart, which may accelerate the development of CVDs. This explains increased interest in targeting EFT reduction to attenuate the detrimental effects of oxidative stress and inflammation within the setting of metabolic syndrome. Here, we critically discuss clinical and preclinical evidence on the impact of physical exercise on EFT in correlation with reduced CVD risk within a setting of metabolic disease. This review also brings a unique perspective on the implications of oxidative stress and inflammation as major pathological consequences that link increased EFT to accelerated CVD risk in conditions of metabolic disease.
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Affiliation(s)
- Thembeka A. Nyawo
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7505, South Africa; (T.A.N.); (C.P.); (S.X.H.M.)
- Centre for Cardiometabolic Research in Africa (CARMA), Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa; (H.S.-V.G.); (H.S.)
| | - Carmen Pheiffer
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7505, South Africa; (T.A.N.); (C.P.); (S.X.H.M.)
- Centre for Cardiometabolic Research in Africa (CARMA), Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa; (H.S.-V.G.); (H.S.)
- Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa
| | | | - Sinenhlanhla X. H. Mthembu
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7505, South Africa; (T.A.N.); (C.P.); (S.X.H.M.)
- Department of Biochemistry, North-West University, Mafikeng Campus, Mmabatho 2735, South Africa;
| | - Tawanda M. Nyambuya
- Department of Health Sciences, Faculty of Health and Applied Sciences, Namibia University of Science and Technology, Windhoek 9000, Namibia;
| | - Bongani B. Nkambule
- School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa;
| | - Hanél Sadie-Van Gijsen
- Centre for Cardiometabolic Research in Africa (CARMA), Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa; (H.S.-V.G.); (H.S.)
| | - Hans Strijdom
- Centre for Cardiometabolic Research in Africa (CARMA), Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa; (H.S.-V.G.); (H.S.)
| | - Luca Tiano
- Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy;
| | - Phiwayinkosi V. Dludla
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7505, South Africa; (T.A.N.); (C.P.); (S.X.H.M.)
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Scarano-Pereira JP, Martinino A, Manicone F, Pouwels S. Response to: "Recent advances in the mechanisms underlying the beneficial effects of bariatric and metabolic surgery". Surg Obes Relat Dis 2021; 18:297-298. [PMID: 34742652 DOI: 10.1016/j.soard.2021.10.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 10/10/2021] [Indexed: 11/18/2022]
Affiliation(s)
| | | | - Francesca Manicone
- Università la Sapienza di Roma, Facoltà di Medicina e Odontoiatria, Rome, Italy
| | - Sjaak Pouwels
- Department of Intensive Care Medicine, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands
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47
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Bonou M, Kapelios CJ, Protogerou AD, Mavrogeni S, Aggeli C, Markousis-Mavrogenis G, Psichogiou M, Barbetseas J. Cardiac adiposity as a modulator of cardiovascular disease in HIV. HIV Med 2021; 22:879-891. [PMID: 34514685 DOI: 10.1111/hiv.13166] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 08/02/2021] [Accepted: 08/13/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND With the number of people living with human immunodeficiency virus (HIV) steadily increasing, cardiovascular disease has emerged as a leading cause of non-HIV related mortality. People living with HIV (PLWH) appear to be at increased risk of coronary artery disease and heart failure (HF), while the underlying mechanism appears to be multifactorial. In the general population, ectopic cardiac adiposity has been highlighted as an important modulator of accelerated coronary artery atherosclerosis, arrhythmogenesis and HF with preserved ejection fraction (HFpEF). Cardiac adiposity is also strongly linked with obesity, especially with visceral adipose tissue accumulation. AIMS This review aims to summarize the possible role of cardiac fat depositions, assessed by imaging modalities,as potential contributors to the increased cardiac morbidity and mortality seen in PLWH, as well as therapeutic targets in the current ART era. MATERIALS & METHODS Review of contemporary literature on this topic. DISCUSSION Despite antiretroviral therapy (ART), PLWH have evidence of persistent, HIV-related systemic inflammation and body fat alterations. Cardiac adiposity can play an additional role in the pathogenesis of cardiovascular disease in the HIV setting. Imaging modalities such as echocardiography, cardiac multidetector computed tomography and cardiac magnetic resonance have demonstrated increased adipose tissue. Studies show that high cardiac fat depots play an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. Systemic inflammation due to HIV infection, metabolic adverse effects of ART, adipose alterations in the ageing HIV population, inflammation and immune activation are likely important mechanisms for adipose dysfunction and disproportionately occurrence of ectopic fat depots in the heart among PLWH. CONCLUSIONS High cardiac adiposity seems to plays an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. The underlying mechanisms are multiple and warrant further investigation. Improved understanding of the regulating mechanisms that increase cardiovascular risk in HIV infection may give rise to more tailored therapeutic strategies targeting cardiac fat depots.
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Affiliation(s)
- Maria Bonou
- Department of Cardiology, Laiko General Hospital, Athens, Greece
| | - Chris J Kapelios
- Department of Cardiology, Laiko General Hospital, Athens, Greece
| | - Athanase D Protogerou
- Cardiovascular Prevention & Research Unit, Clinic and Laboratory of Pathophysiology, National and Kapodistrian University Athens School of Medicine, Athens, Greece
| | - Sophie Mavrogeni
- Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece
| | - Constantina Aggeli
- First Department of Cardiology, Hippokration General Hospital, National and Kapodistrian University Athens School of Medicine, Athens, Greece
| | | | - Mina Psichogiou
- First Department of Internal Medicine, Laiko General Hospital, National and Kapodistrian University Athens School of Medicine, Athens, Greece
| | - John Barbetseas
- Department of Cardiology, Laiko General Hospital, Athens, Greece
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48
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Couselo-Seijas M, Rodríguez-Mañero M, González-Juanatey JR, Eiras S. Updates on epicardial adipose tissue mechanisms on atrial fibrillation. Obes Rev 2021; 22:e13277. [PMID: 34002458 DOI: 10.1111/obr.13277] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 04/19/2021] [Indexed: 02/06/2023]
Abstract
Obesity is a well-known risk factor for atrial fibrillation (AF). Local epi-myocardial or intra-myocardial adiposity caused by aging, obesity, or cardiovascular disease (CVD) is considered to be a better predictor of the risk of AF than general adiposity. Some of the described mechanisms suggest that epicardial adipose tissue (EAT) participates in structural remodeling owing to its endocrine activity or its infiltration between cardiomyocytes. Epicardial fat also wraps up the ganglionated plexi that reach the myocardium. Although the increment of volume/thickness and activity of EAT might modify autonomic activity, autonomic system dysfunction might also change the endocrine activity of epicardial fat in a feedback response. As a result, new preventive therapeutic strategies are focused on reducing adiposity and weight loss before AF ablation or inhibiting autonomic neurotransmitter secretion on fat pads during open-heart surgery to reduce the recurrence or postoperative risk of AF. In this manuscript, we review some of the novel findings regarding the pathophysiology and associated risk factors of AF, with special emphasis on the role of EAT in the electrical, structural, and molecular mechanisms of AF initiation and maintenance. In addition, we have included a brief note provided on epicardial fat preclinical models that could be useful for identifying new therapeutic targets.
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Affiliation(s)
- Marinela Couselo-Seijas
- Translational Cardiology group, Health Research Institute, Santiago de Compostela, Spain
- University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Moisés Rodríguez-Mañero
- Translational Cardiology group, Health Research Institute, Santiago de Compostela, Spain
- CIBERCV, Madrid, Spain
- Cardiovascular Department, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - José R González-Juanatey
- University of Santiago de Compostela, Santiago de Compostela, Spain
- CIBERCV, Madrid, Spain
- Cardiovascular Department, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
- Cardiology group, Health Research Institute, Santiago de Compostela, Spain
| | - Sonia Eiras
- Translational Cardiology group, Health Research Institute, Santiago de Compostela, Spain
- CIBERCV, Madrid, Spain
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Abstract
BACKGROUND Both visceral adipose tissue and epicardial adipose tissue (EAT) have pro-inflammatory properties. The former is associated with Coronavirus Disease 19 (COVID-19) severity. We aimed to investigate whether an association also exists for EAT. MATERIAL AND METHODS We retrospectively measured EAT volume using computed tomography (CT) scans (semi-automatic software) of inpatients with COVID-19 and analyzed the correlation between EAT volume and anthropometric characteristics and comorbidities. We then analyzed the clinicobiological and radiological parameters associated with severe COVID-19 (O2 [Formula: see text] 6 l/min), intensive care unit (ICU) admission or death, and 25% or more CT lung involvement, which are three key indicators of COVID-19 severity. RESULTS We included 100 consecutive patients; 63% were men, mean age was 61.8 ± 16.2 years, 47% were obese, 54% had hypertension, 42% diabetes, and 17.2% a cardiovascular event history. Severe COVID-19 (n = 35, 35%) was associated with EAT volume (132 ± 62 vs 104 ± 40 cm3, p = 0.02), age, ferritinemia, and 25% or more CT lung involvement. ICU admission or death (n = 14, 14%) was associated with EAT volume (153 ± 67 vs 108 ± 45 cm3, p = 0.015), hypertension and 25% or more CT lung involvement. The association between EAT volume and severe COVID-19 remained after adjustment for sex, BMI, ferritinemia and lung involvement, but not after adjustment for age. Instead, the association between EAT volume and ICU admission or death remained after adjustment for all five of these parameters. CONCLUSIONS Our results suggest that measuring EAT volume on chest CT scans at hospital admission in patients diagnosed with COVID-19 might help to assess the risk of disease aggravation.
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50
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Saco-Ledo G, Valenzuela PL, Castillo-García A, Arenas J, León-Sanz M, Ruilope LM, Lucia A. Response to Letter to the Editor. Obes Rev 2021; 22:e13253. [PMID: 33825320 DOI: 10.1111/obr.13253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 03/22/2021] [Indexed: 11/28/2022]
Affiliation(s)
- Gonzalo Saco-Ledo
- Bioenergy and Motion Analysis Laboratory, National Research Center on Human Evolution (CENIEH), Burgos, Spain
| | | | | | - Joaquín Arenas
- Physiology, Health and Physical Activity, Research Institute of the Hospital Universitario 12 de Octubre ("imas12"), Madrid, Spain
| | - Miguel León-Sanz
- Physiology, Health and Physical Activity, Research Institute of the Hospital Universitario 12 de Octubre ("imas12"), Madrid, Spain.,Clinical Nutrition Unit, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Luis M Ruilope
- Physiology, Health and Physical Activity, Research Institute of the Hospital Universitario 12 de Octubre ("imas12"), Madrid, Spain.,Hypertension Unit and Cardiorenal Translational Laboratory, Hospital 12 de Octubre, Madrid, Spain
| | - Alejandro Lucia
- Physiology, Health and Physical Activity, Research Institute of the Hospital Universitario 12 de Octubre ("imas12"), Madrid, Spain.,Faculty of Sport Sciences, Universidad Europea de Madrid, Madrid, Spain
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