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Berezin AE. Predictive value of the systemic immune inflammation index in recurrence of atrial fibrillation after radiofrequency catheter ablation. World J Cardiol 2025; 17:102981. [PMID: 39866209 PMCID: PMC11755125 DOI: 10.4330/wjc.v17.i1.102981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 12/21/2024] [Accepted: 01/02/2025] [Indexed: 01/21/2025] Open
Abstract
The recurrence of atrial fibrillation (AF) in patients after successful radiofrequency catheter ablation (RFCA) appears to be an unresolved clinical issue and needs to be clearly elucidated. There are many factors associated with AF recurrence, such as duration of AF, male sex, concomitant heart failure, hemodynamic parameters, chronic obstructive pulmonary disease, hypertension, obstructive sleep apnea, hyperthyroidism, smoking and obesity. However, the inflammatory changes are strongly associated with electrical and structural cardiac remodeling, cardiac damage, myocardial fibrotic changes, microvascular dysfunction and altered reparative response. In this context, biomarkers reflecting the different stages of AF pathogenesis deserve thorough investigation. The authors of the retrospective study revealed that one-year recurrence rate of non-valvular AF in the high systemic immune inflammation (SII) index group was significantly increased compared to that of the low SII index group and provided additional predictive value to the APPLE. Furthermore, the authors suggest that this biomarker may help physicians to optimize the selection of AF patients and to develop a personalized treatment approach. In conclusion, the SII index may serve as a valuable indicator of recurrent AF in patients after RFCA and may be a biomarker with plausible predictive value for poor clinical outcomes.
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Affiliation(s)
- Alexander E Berezin
- Department of Internal Medicine-II, Paracelsus Medical University Salzburg, Salzburg 5020, Austria.
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Diakantonis A, Verras C, Bezati S, Bistola V, Ventoulis I, Velliou M, Boultadakis A, Ikonomidis I, Parissis JT, Polyzogopoulou E. Predictive Value of N-Terminal Pro B-Type Natriuretic Peptide for Short-Term Outcome of Cardioversion in Patients with First-Diagnosed or Paroxysmal Atrial Fibrillation Presenting to the Emergency Department. Biomedicines 2024; 12:2895. [PMID: 39767800 PMCID: PMC11727096 DOI: 10.3390/biomedicines12122895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 12/12/2024] [Accepted: 12/17/2024] [Indexed: 01/16/2025] Open
Abstract
Background: Atrial fibrillation (AF) is a common arrhythmia in the emergency department (ED). We investigated the role of N-terminal pro b-type natriuretic peptide (NT-proBNP) in predicting both the outcome of AF cardioversion and the risk of AF recurrence or persistence on the 8th (D8) and 30th (D30) day post-cardioversion. Methods: This prospective, observational study evaluated patients with recent-onset AF, managed by either pharmacological (PC) or electrical cardioversion (EC) in the ED. Patients were treated either immediately or electively after 3 weeks of anticoagulation. NT-proBNP assessments were performed prior to cardioversion. Results: Of the 148 patients enrolled, 56% had paroxysmal AF, 85% underwent immediate cardioversion and 72% received EC. Successful cardioversion to sinus rhythm (SR) was achieved in 85% of patients. Patients with successful cardioversion and those who remained free from AF on D8 had lower NT-proBNP levels compared to patients with failed cardioversion or with AF recurrence or persistence on D8 [day of cardioversion, D0: SR vs. non-SR, 387 (127-1095) pg/mL vs. 1262 (595-2295), p = 0.004; D8: SR vs. non-SR, 370 (127-1095) vs. 1366 (718-2295), p = 0.002]. In multivariate analysis, higher logNT-proBNP was associated with higher risk of cardioversion failure [OR, 95%CI: 4.80 (1.58-14.55), p = 0.006] and AF recurrence or persistence on D8 [OR, 95%CI: 3.65 (1.06-12.59), p = 0.041]. ROC analysis confirmed the predictive ability of NT-proBNP for both outcomes (D0: AUC 0.735, p < 0.001; D8: AUC 0.761, p < 0.001). A cut-off value of NT-proBNP > 580 pg/mL was able to predict failure of AF conversion and occurrence of recurrent/persistent AF at D8. Conclusions: NT-proBNP is a promising biomarker for identifying patients presenting to the ED with recent-onset AF who run a greater risk of cardioversion failure and post-discharge AF recurrence/persistence in the immediate and short term.
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Affiliation(s)
- Antonios Diakantonis
- University Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (S.B.); (V.B.); (M.V.); (A.B.); (J.T.P.); (E.P.)
| | - Christos Verras
- University Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (S.B.); (V.B.); (M.V.); (A.B.); (J.T.P.); (E.P.)
| | - Sofia Bezati
- University Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (S.B.); (V.B.); (M.V.); (A.B.); (J.T.P.); (E.P.)
| | - Vasiliki Bistola
- University Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (S.B.); (V.B.); (M.V.); (A.B.); (J.T.P.); (E.P.)
- Second Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Ioannis Ventoulis
- Department of Occupational Therapy, University of Western Macedonia, 50200 Ptolemaida, Greece;
| | - Maria Velliou
- University Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (S.B.); (V.B.); (M.V.); (A.B.); (J.T.P.); (E.P.)
| | - Antonios Boultadakis
- University Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (S.B.); (V.B.); (M.V.); (A.B.); (J.T.P.); (E.P.)
| | - Ignatios Ikonomidis
- Second Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - John T. Parissis
- University Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (S.B.); (V.B.); (M.V.); (A.B.); (J.T.P.); (E.P.)
| | - Effie Polyzogopoulou
- University Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (S.B.); (V.B.); (M.V.); (A.B.); (J.T.P.); (E.P.)
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Guo F, Wang J, Wu M, Yang S, He C, Lu M, Zhao X, Jiang H, Liao Q, Li S. Novel insight into neurofilament light chain and rhythm outcomes after catheter ablation of new-onset atrial fibrillation: A prospective cohort study. Heart Rhythm 2024:S1547-5271(24)03266-1. [PMID: 39197737 DOI: 10.1016/j.hrthm.2024.08.048] [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] [Received: 07/15/2024] [Revised: 08/19/2024] [Accepted: 08/22/2024] [Indexed: 09/01/2024]
Abstract
BACKGROUND Atrial fibrillation (AF) is an age-related disorder closely linked to autonomic nervous system dysfunction. Neurofilament light chain (NFL) protein is a biomarker for neurodegenerative diseases. OBJECTIVE The purpose of this study was to evaluate the predictive value of NFL in forecasting AF recurrence after ablation. METHODS Patients newly diagnosed with AF who underwent catheter ablation were included. Serum NFL levels were measured using enzyme-linked immunosorbent assay. The primary outcome was AF recurrence during follow-up. RESULTS A total of 215 consecutive patients were enrolled, with average follow-up period of 10.69 months. During this period, 29 patients experienced AF recurrence. Multivariate Cox regression analysis revealed that high NFL levels (≥300 pg/mL) were an independent predictor of recurrence risk (adjusted hazard ratio [HR] 3.756; 95% confidence interval [CI] 1.392-10.136). The associations between NFL levels and AF recurrence were consistent across subgroups defined by age (>65 years), gender, hypertension, and paroxysmal AF. Restricted cubic spline analysis showed a consistent linear relationship across the entire range of NFL levels. Furthermore, incorporating NFL into the CHA2DS2-VASc score model significantly improved the prediction of recurrent AF risk, as demonstrated by time-dependent area under the curve and decision curve analysis. Notable enhancements were also observed in terms of net reclassification improvement (HR 0.464; 95% CI 0.226-0.675; P <.05) and integrated discrimination improvement (HR 0.087; 95% CI 0.017-0.183; P = .08). CONCLUSION NFL may serve as an effective biomarker for risk stratification and therapeutic decision-making in patients with new-onset AF who have undergone catheter ablation.
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Affiliation(s)
- Fuding Guo
- Key Laboratory of Cardiovascular Disease of Yunnan Province, Clinical Medicine Center for Cardiovascular Disease of Yunnan Province, Department of Cardiology, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Jun Wang
- Department of Cardiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, People's Republic of China
| | - Min Wu
- Department of Oncology, Third People's Hospital of Honghe Prefecture, Gejiu, Yunnan, People's Republic of China
| | - Seng Yang
- Key Laboratory of Cardiovascular Disease of Yunnan Province, Clinical Medicine Center for Cardiovascular Disease of Yunnan Province, Department of Cardiology, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Chende He
- Key Laboratory of Cardiovascular Disease of Yunnan Province, Clinical Medicine Center for Cardiovascular Disease of Yunnan Province, Department of Cardiology, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Mei Lu
- Key Laboratory of Cardiovascular Disease of Yunnan Province, Clinical Medicine Center for Cardiovascular Disease of Yunnan Province, Department of Cardiology, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Xiaohua Zhao
- Key Laboratory of Cardiovascular Disease of Yunnan Province, Clinical Medicine Center for Cardiovascular Disease of Yunnan Province, Department of Cardiology, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Hong Jiang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, People's Republic of China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, People's Republic of China.
| | - Qiwei Liao
- Key Laboratory of Cardiovascular Disease of Yunnan Province, Clinical Medicine Center for Cardiovascular Disease of Yunnan Province, Department of Cardiology, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
| | - Shaolong Li
- Key Laboratory of Cardiovascular Disease of Yunnan Province, Clinical Medicine Center for Cardiovascular Disease of Yunnan Province, Department of Cardiology, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
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Jannati S, Patnaik R, Banerjee Y. Beyond Anticoagulation: A Comprehensive Review of Non-Vitamin K Oral Anticoagulants (NOACs) in Inflammation and Protease-Activated Receptor Signaling. Int J Mol Sci 2024; 25:8727. [PMID: 39201414 PMCID: PMC11355043 DOI: 10.3390/ijms25168727] [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: 06/16/2024] [Revised: 07/20/2024] [Accepted: 07/22/2024] [Indexed: 09/02/2024] Open
Abstract
Non-vitamin K oral anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs-apixaban, rivaroxaban, edoxaban, and dabigatran-not only as anticoagulants, but also as modulators of inflammation via protease-activated receptor (PAR) signaling. We highlight the unique pharmacotherapeutic properties of each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond their established anticoagulant roles, emerging research suggests that NOACs influence inflammation through PAR signaling pathways, implicating factors such as factor Xa (FXa) and thrombin in the modulation of inflammatory responses. This review synthesizes current evidence on the anti-inflammatory potential of NOACs, exploring their impact on inflammatory markers and conditions like atherosclerosis and diabetes. By delineating the mechanisms by which NOACs mediate anti-inflammatory effects, this work aims to expand their therapeutic utility, offering new perspectives for managing inflammatory diseases. Our findings underscore the broader clinical implications of NOACs, advocating for their consideration in therapeutic strategies aimed at addressing inflammation-related pathologies. This comprehensive synthesis not only enhances understanding of NOACs' multifaceted roles, but also paves the way for future research and clinical applications in inflammation and cardiovascular health.
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Affiliation(s)
- Shirin Jannati
- Yajnavalkaa Banerrji Research Group, College of Medicine and Health Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai Health, Dubai P.O. Box 505055, United Arab Emirates; (S.J.); (R.P.)
| | - Rajashree Patnaik
- Yajnavalkaa Banerrji Research Group, College of Medicine and Health Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai Health, Dubai P.O. Box 505055, United Arab Emirates; (S.J.); (R.P.)
| | - Yajnavalka Banerjee
- Yajnavalkaa Banerrji Research Group, College of Medicine and Health Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai Health, Dubai P.O. Box 505055, United Arab Emirates; (S.J.); (R.P.)
- Centre for Medical Education, University of Dundee, Dundee DD1 4HN, UK
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Vercek G, Jug B, Novakovic M, Antonic M, Djordjevic A, Ksela J. Conventional and Novel Inflammatory Biomarkers in Chronic Heart Failure Patients with Atrial Fibrillation. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1238. [PMID: 39202519 PMCID: PMC11356261 DOI: 10.3390/medicina60081238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 07/24/2024] [Accepted: 07/25/2024] [Indexed: 09/03/2024]
Abstract
(1) Background and Objectives: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased morbidity and mortality both in the general population and heart failure patients. Inflammation may promote the initiation, maintenance and perpetuation of AF, but the impact of inflammatory molecular signaling on the association between AF and heart failure remains elusive. (2) Materials and Methods: In 111 patients with chronic stable heart failure, baseline values of conventional (IL-6 and hsCRP) and selected novel inflammatory biomarkers (IL-10, IL-6/IL-10 ratio, orosomucoid and endocan) were determined. Inflammatory biomarkers were compared with respect to the presenting cardiac rhythm. (3) Results: Patients aged below 75 years with AF had significantly higher values of IL-6 and IL-6/IL-10 ratio; IL-6 levels were a significant predictor of AF in both univariate (OR 1.175; 95%CI 1.013-1.363; p = 0.034) and multivariate logistic regression analysis when accounting for other inflammatory biomarkers (OR 1.327; 95% CI 1.068-1.650; p = 0.011). Conversely, there was no association between other novel inflammatory biomarkers and AF. (4) Conclusions: IL-6 levels and the IL-6/IL-10 ratio are associated with AF in patients with chronic stable heart failure under the age of 75 years, suggesting that inflammatory molecular signaling may play a role in the development of AF in the heart failure population.
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Affiliation(s)
- Gregor Vercek
- Department of Vascular Diseases, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; (G.V.); (B.J.); (M.N.)
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Borut Jug
- Department of Vascular Diseases, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; (G.V.); (B.J.); (M.N.)
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Marko Novakovic
- Department of Vascular Diseases, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; (G.V.); (B.J.); (M.N.)
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Miha Antonic
- Department of Cardiac Surgery, University Medical Centre Maribor, 2000 Maribor, Slovenia; (M.A.); (A.D.)
- Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia
| | - Anze Djordjevic
- Department of Cardiac Surgery, University Medical Centre Maribor, 2000 Maribor, Slovenia; (M.A.); (A.D.)
- Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia
| | - Jus Ksela
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Department of Cardiovascular Surgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
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Ayash B, Malaeb D, Hallit S, Hosseini H. Assessing adherence to treatment guidelines and complications among atrial fibrillation patients in the United Arab Emirates. Front Cardiovasc Med 2024; 11:1359922. [PMID: 39049956 PMCID: PMC11266282 DOI: 10.3389/fcvm.2024.1359922] [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: 12/22/2023] [Accepted: 06/19/2024] [Indexed: 07/27/2024] Open
Abstract
Background Atrial fibrillation (AF), a potential trigger for stroke development, is considered a modifiable condition that can halt complications, decrease mortality, and prevent morbidity. The CHA₂DS₂-VASc and HAS-BLED scores are categorized as risk assessment tools used to estimate the risk of thrombosis development and assess major bleeding among atrial fibrillation patients. Objectives Our study aims to assess the adherence to post-discharge treatment recommendations according to CHA₂DS₂-VASc score risk group and evaluate the impact of CHA₂DS₂-VASc score and HAS-BLED score risk categories on death, length of hospital stay, complications, and hospital readmission among United Arab Emirates (UAE) patients. Methods This was a multicenter retrospective study conducted from November 2022 to April 2023 in the United Arab Emirates. Medical charts for AF patients were assessed for possible enrolment in the study. Results A total number of 400 patients were included with a mean age of 55 (±14.5) years. The majority were females (67.8%), and most had high CHA₂DS₂-VASc and HAS-BLED scores (60% and 57.3%, respectively). Our study showed that adherence to treatment recommendations upon discharge was 71.8%. The bivariate analysis showed that patients with a high CHA₂DS₂-VASc score had a significantly higher risk of death (p-value of 0.001), hospital readmission (p-value of 0.007), and complications (p-value of 0.044) vs. the low and moderate risk group with a p-value of <0.05. Furthermore, our findings showed that the risk of death (0.001), complications (0.057), and mean hospital stay (0.003) were significantly higher in the high HAS-BLED risk score compared to both the low- and moderate-risk categories. Hospital stay was significantly higher in CHA₂DS₂-VASc and HAS-BLED high-risk score categories compared to the low-risk score category with a p-value of <0.001. Conclusion Our study concluded that the adherence to treatment guidelines in atrial fibrillation patients was high and showed that patients received the most effective and patient-centered treatment. In addition, our study concluded that the risk of complications and mortality was higher in high-risk category patients.
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Affiliation(s)
- Bayan Ayash
- College of Pharmacy, Gulf Medical University, Ajman, United Arab Emirates
| | - Diana Malaeb
- College of Pharmacy, Gulf Medical University, Ajman, United Arab Emirates
| | - Souheil Hallit
- School of Medicine and Medical Sciences, Holy Spirit University of Kaslik, Jounieh, Lebanon
- Department of Psychology, College of Humanities, Effat University, Jeddah, Saudi Arabia
- Applied Science Research Center, Applied Science Private University, Amman, Jordan
| | - Hassan Hosseini
- UPEC-University Paris-Est, Creteil, France
- RAMSAY SANTÉ, HPPE, Champigny sur Marne, France
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Zhang S, Xu W, Xu J, Qiu Y, Wan Y, Fan Y. Association of C-reactive protein level with adverse outcomes in patients with atrial fibrillation: A meta-analysis. Am J Med Sci 2024; 367:41-48. [PMID: 37979919 DOI: 10.1016/j.amjms.2023.11.009] [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: 02/14/2023] [Revised: 07/28/2023] [Accepted: 11/09/2023] [Indexed: 11/20/2023]
Abstract
BACKGROUND Studies on the association between C-reactive protein (CRP) level and poor outcomes have been yielded controversial results in patients with atrial fibrillation (AF). This meta-analysis sought to investigate the utility of elevated CRP level in predicting adverse outcomes in AF patients. METHODS Two authors systematically searched PubMed and Embase databases (until December 10, 2022) for studies evaluating the value of elevated CRP level in predicting all-cause mortality, cardiovascular death, stroke, or major adverse cardiovascular events (MACEs) in AF patients. The predictive value of CRP was expressed by pooling adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the highest versus the lowest level or per unit of log-transformed increase. RESULTS Ten studies including 30,345 AF patients satisfied our inclusion criteria. For the highest versus the lowest CRP level, the pooled adjusted HR was 1.57 (95% CI 1.34-1.85) for all-cause mortality, 1.18 (95% CI 0.92-1.50) for cardiovascular death, and 1.57 (95% CI 1.10-2.24) for stroke, respectively. When analyzed the CRP level as continuous data, per unit of log-transformed increase was associated with a 27% higher risk of all-cause mortality (HR 1.27; 95% CI 1.23-1.32) and 16% higher risk of MACEs (HR 1.16; 95% CI 1.05-1.28). CONCLUSIONS Elevated CRP level may be an independent predictor of all-cause mortality, stroke, and MACEs in patients with AF. CRP level at baseline can provide important prognostic information in risk classification of AF patients.
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Affiliation(s)
- Shiqi Zhang
- Department of Gastroenterology, The Suqian Clinical College of Xuzhou Medical University, Suqian, Jiangsu, China
| | - Wei Xu
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Juan Xu
- Department of Oncology, Ganyu District People's Hospital of Lianyungang City, Lianyungang, Jiangsu, China
| | - Yue Qiu
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Yanluan Wan
- Department of Geriatric Disease, Ganyu District People's Hospital of Lianyungang City, Lianyungang, Jiangsu, China
| | - Yu Fan
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China.
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Majdinasab M, Lamy de la Chapelle M, Marty JL. Recent Progresses in Optical Biosensors for Interleukin 6 Detection. BIOSENSORS 2023; 13:898. [PMID: 37754132 PMCID: PMC10526799 DOI: 10.3390/bios13090898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 09/14/2023] [Accepted: 09/18/2023] [Indexed: 09/28/2023]
Abstract
Interleukin 6 (IL-6) is pleiotropic cytokine with pathological pro-inflammatory effects in various acute, chronic and infectious diseases. It is involved in a variety of biological processes including immune regulation, hematopoiesis, tissue repair, inflammation, oncogenesis, metabolic control, and sleep. Due to its important role as a biomarker of many types of diseases, its detection in small amounts and with high selectivity is of particular importance in medical and biological fields. Laboratory methods including enzyme-linked immunoassays (ELISAs) and chemiluminescent immunoassays (CLIAs) are the most common conventional methods for IL-6 detection. However, these techniques suffer from the complexity of the method, the expensiveness, and the time-consuming process of obtaining the results. In recent years, too many attempts have been conducted to provide simple, rapid, economical, and user-friendly analytical approaches to monitor IL-6. In this regard, biosensors are considered desirable tools for IL-6 detection because of their special features such as high sensitivity, rapid detection time, ease of use, and ease of miniaturization. In this review, current progresses in different types of optical biosensors as the most favorable types of biosensors for the detection of IL-6 are discussed, evaluated, and compared.
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Affiliation(s)
- Marjan Majdinasab
- Department of Food Science & Technology, School of Agriculture, Shiraz University, Shiraz 71441-65186, Iran;
| | - Marc Lamy de la Chapelle
- Institut des Molécules et Matériaux du Mans (IMMM—UMR 6283 CNRS), Le Mans Université, Avenue Olivier Messiaen, CEDEX 9, 72085 Le Mans, France;
| | - Jean Louis Marty
- BAE: Biocapteurs-Analyses-Environnement, University of Perpignan Via Domitia, 52 Avenue Paul Alduy, CEDEX 9, 66860 Perpignan, France
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Hubbert L, Mallios P, Karlström P, Papakonstantinou A, Bergh J, Hedayati E. Long-term and real-life incidence of cancer therapy-related cardiovascular toxicity in patients with breast cancer: a Swedish cohort study. Front Oncol 2023; 13:1095251. [PMID: 37152049 PMCID: PMC10154463 DOI: 10.3389/fonc.2023.1095251] [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: 11/10/2022] [Accepted: 04/05/2023] [Indexed: 05/09/2023] Open
Abstract
Background The administration of anticancer drugs in females with comorbidity increases the risk for cancer therapy-related cardiovascular toxicity (CTR-CVT), which in turn contributes to cardiovascular disease (CVD). Furthermore, a pathophysiological connection between cancer and cardiovascular disease may exist. Objective To assess the long-term risks and predictors of CTR-CVT, including clinical hypertension (HT), coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF), as well as all-cause mortality in women diagnosed with early breast cancer (BC) and eligible for adjuvant chemotherapy in Sweden. Methods Data were extracted from Swedish registers and medical records on 433 women, 18-60 years of age, diagnosed 1998-2002 with lymph node-positive BC, and considered for adjuvant chemotherapy. CTR-CVT was defined as HT, CAD, HF, or AF after the diagnosis of BC. Follow-up was from the date of BC diagnosis until November 30, 2021, or death. Prevalence of CTR-CVT and all-cause mortality were calculated. Hazard ratios (HR) were determined for factors associated with CTR-CVT. Results The median age was 50 (interquartile range (IQR) 32) years. 910 CTR-CVT events were diagnosed in 311 women with a median of 19.3 (IQR 15,3) years follow-up. The proportions of CTR-CVT events were: HT 281 (64%); CAD 198 (46%); HF 206 (47%); and AF 225 (51%). The cumulative incidence of CTR-CVT was 71.8%, and 50% of all 433 patients developed CTR-CVT within 11.7 years of BC diagnosis (standard deviation (SD) 0.57, 95% confidence interval (CI) 10.6-12.9). Age was a risk factor for CTR-CVT. Anthracycline increased the risk for HF (p=0,001; HR 2,0; 95%CI 1,4-2,8), CAD (p= 0,002; HR 1,7; 95% CI 1,2-2,4), and AF (p=0,013; HR 1,5; 95% CI 1,0-2,0). At the end of the 24-year study period, 227 of the 433 women were alive, and the total cumulative mortality was 47,6%. Conclusion The prevalence of CTR-CVT and all-cause mortality is high after BC diagnosis and treatment, particularly in older patients and those receiving anthracyclines. These findings and the onset of CTR-CVT support cardio-oncology guidelines recommending initial risk stratification and cardiovascular monitoring during treatment, followed by long-term annual screening for cardiovascular risk factors and CTR-CVT among BC survivors.
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Affiliation(s)
- Laila Hubbert
- Department of Cardiology and Department of Health, Medicine and Caring Sciences, Linköping University, Norrköping, Sweden
| | - Panagiotis Mallios
- Department of Cardiology and Department of Health, Medicine and Caring Sciences, Linköping University, Norrköping, Sweden
| | - Patric Karlström
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Department of Internal Medicine, Ryhov County Hospital, Jönköping, Sweden
| | - Andri Papakonstantinou
- Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
- Medical Unit: Breast, Endocrine Tumors, and Sarcoma, Theme Cancer, Karolinska University Hospital and Comprehensive Cancer Center, Stockholm, Sweden
| | - Jonas Bergh
- Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
- Medical Unit: Breast, Endocrine Tumors, and Sarcoma, Theme Cancer, Karolinska University Hospital and Comprehensive Cancer Center, Stockholm, Sweden
| | - Elham Hedayati
- Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
- Medical Unit: Breast, Endocrine Tumors, and Sarcoma, Theme Cancer, Karolinska University Hospital and Comprehensive Cancer Center, Stockholm, Sweden
- *Correspondence: Elham Hedayati,
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Rafaqat S, Afzal S, Khurshid H, Safdar S, Rafaqat S, Rafaqat S. The Role of Major Inflammatory Biomarkers in the Pathogenesis of Atrial Fibrillation. J Innov Card Rhythm Manag 2022; 13:5265-5277. [PMID: 37293559 PMCID: PMC10246921 DOI: 10.19102/icrm.2022.13125] [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: 05/07/2022] [Accepted: 06/27/2022] [Indexed: 12/01/2023] Open
Abstract
Many studies have reported a relationship between inflammation and atrial fibrillation (AF). According to the literature, inflammation is the key component in pathophysiological processes during the development of AF; the amplification of inflammatory pathways triggers AF, and, at the same time, AF increases the inflammatory state. The plasma levels of several inflammatory biomarkers are elevated in patients with AF; therefore, inflammation might contribute to both the maintenance and occurrence of AF and its thromboembolic complications. Numerous inflammatory markers have been linked to AF, including CD40 ligand, fibrinogen, matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein-1, myeloperoxidase, plasminogen activator inhibitor-1, and serum amyloid A. There are many pathophysiological aspects of AF that are linked to these inflammatory biomarkers, including atrial structural remodeling and atrial dilatation, increased atrial myocyte expression, fluctuations in calcium cycling, cardiac remodeling promotion, increased cardiac myocyte proliferation and terminal differentiation, production of several MMPs, the pathogenesis of atherosclerosis and cardiomyocyte apoptosis, an increased degree of fibrosis in atrial myocardium, and the progression and development of atherogenesis and atherothrombosis. The present review article aims to provide an updated overview and focus on the basic role of different biomarkers of inflammation in the pathophysiological aspects of the pathogenesis of AF.
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Affiliation(s)
- Saira Rafaqat
- Lahore College for Women University, Lahore, Pakistan
| | | | - Huma Khurshid
- Lahore College for Women University, Lahore, Pakistan
| | | | - Sana Rafaqat
- Lahore College for Women University, Lahore, Pakistan
| | - Simon Rafaqat
- Forman Christian College (A Chartered University), Lahore, Pakistan
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11
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Chen S, Luo X, Zhao J, Liang Z, Gu J. Exploring the causality between ankylosing spondylitis and atrial fibrillation: A two-sample Mendelian randomization study. Front Genet 2022; 13:951893. [PMID: 36468019 PMCID: PMC9708899 DOI: 10.3389/fgene.2022.951893] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 11/01/2022] [Indexed: 09/22/2023] Open
Abstract
Objective: To study whether ankylosing spondylitis (AS) has a causal effect on the risk of atrial fibrillation (AF) using two-sample Mendelian randomization (MR) analysis. Methods: Single nucleotide polymorphisms (SNPs) were selected as independent instrumental variables (IVs) from a GWAS study of AS. Summary data from a large-scale GWAS meta-analysis of AF was utilized as the outcome dataset. Inverse-variance weighted (IVW) model was used for the primary analysis. Multiple sensitivity and heterogeneity tests were conducted to confirm the robustness of the results. Results: In total, 18 SNPs were identified as IVs for MR analysis. Five MR methods consistently found that ankylosing spondylitis was not causally associated with atrial fibrillation (IVW: OR = 0.983 (0.894, 1.080), p = 0.718; MR-Egger: OR = 1.190 (0.973, 1.456), p = 0.109; Simple mode: OR = 0.888 (0.718, 1.098), p = 0.287; Weighted mode: OR = 0.989 (0.854, 1.147), p = 0.890; Weight median: OR = 0.963 (0.852, 1.088), p = 0.545). Leave-one-out analysis supported the stability of MR results. Both the MR-Egger intercept and MR-PRESSO method revealed the absence of horizontal pleiotropy. Conclusion: The two-sample MR analysis did not support a causal relationship between AS and the risk of AF.
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Affiliation(s)
- Shuhong Chen
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- The Clinical Medical Research Center for Immune Diseases of Guangdong Province, Guangzhou, China
| | - Xiqing Luo
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- The Clinical Medical Research Center for Immune Diseases of Guangdong Province, Guangzhou, China
| | - Jiaoshi Zhao
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- The Clinical Medical Research Center for Immune Diseases of Guangdong Province, Guangzhou, China
| | - Zhenguo Liang
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- The Clinical Medical Research Center for Immune Diseases of Guangdong Province, Guangzhou, China
| | - Jieruo Gu
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- The Clinical Medical Research Center for Immune Diseases of Guangdong Province, Guangzhou, China
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12
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Wang YF, Jiang C, He L, Pu CY, Du X, Sang CH, Long DY, Tang RB, Dong JZ, Ma CS. Performance of the ABC-bleeding risk score for assessing major bleeding risk in Chinese patients with atrial fibrillation on oral anticoagulation therapy: A real-world study. Front Cardiovasc Med 2022; 9:1019986. [PMID: 36407455 PMCID: PMC9669712 DOI: 10.3389/fcvm.2022.1019986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 10/10/2022] [Indexed: 08/30/2023] Open
Abstract
OBJECTIVE To evaluate performance of the ABC (Age, Biomarkers, Clinical history)-bleeding risk score in estimating major bleeding risk in Chinese patients with atrial fibrillation (AF) on oral anticoagulation (OAC) therapy in real-world practice. METHODS Data were collected from the Chinese Atrial Fibrillation Registry study (CAFR). Patients were stratified into low-, medium-, and high-risk groups based on ABC-bleeding risk score with 1-year major bleeding risk (<1%, 1-2%, and > 2%) and modified HAS-BLED score (≤1, 2, and > 2 points). Cox proportional-hazards (Cox-PH) models were used to determine the association of major bleeding incidence with bleeding scores. Harrell's C-index of the two scores were compared. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) at 1 year were employed to evaluate the reclassification capacity. The calibration curve was plotted to compare the predicted major bleeding risk using ABC-bleeding risk score with the observed annualized event rate. The decision analysis curves (DCA) were performed to show the clinical utilization of two scores in identifying major bleeding events. RESULTS The study included 2,892 AF patients on OAC therapy. After the follow-up of 3.0 years, 48 patients had major bleeding events; the incidence of a bleeding event in the low-, medium-, and high-risk groups according to ABC-bleeding risk score was 0.31% (reference group, HR = 1.00),0.51% (HR = 1.83, 95%CI: 0.91-3.69, P = 0.09), and 1.49% (HR = 4.92, 95%CI: 2.34-10.30, P < 0.001), respectively. Major bleeding incidence had an independent association with growth differentiation factor 15 (GDF-15) level (HR = 2.16, 95%CI: 1.27-3.68, P = 0.005) after adjusting components of the HAS-BLED score and cTnT-hs level. The ABC-bleeding score showed a Harrell's C-index of 0.67 (95%CI: 0.60-0.75) in estimating major bleeding risk, which was non-significant compared to the modified HAS-BLED score (0.67 vs. 0.63; P = 0.38). NRI and IDI also revealed comparable reclassification capacity of ABC-bleeding risk score compared with HAS-BLED score (14.6%, 95%CI: -10.2%, 39.4%, P = 0.25; 0.2%, 95%CI -0.1 to 0.9%, P = 0.64). Cross-tabulation of the two scores showed that the ABC-bleeding score outperformed the HAS-BLED score in identifying patients with a high risk of major bleeding. The calibration curve showed that the ABC-bleeding risk score overestimated the observed major bleeding risk. DCA did not show any difference in net benefit when using either of the scores. CONCLUSION This study verified the value of the ABC-bleeding risk score in assessing major bleeding risk in Chinese patients with AF on OAC therapy in real-world practice. Despite the overestimation of major bleeding risk, ABC-bleeding score performed better in stratifying patients with a high risk than the modified HAS-BLED score. Combining the two scores could be a clinically practical strategy for precisely stratifying AF patients, especially those at a high risk of major bleeding, and further supporting the optimization of OAC treatment.
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Affiliation(s)
- Yu-Feng Wang
- Department of Cardiology, National Clinical Research Centre for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Chao Jiang
- Department of Cardiology, National Clinical Research Centre for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Liu He
- Department of Cardiology, National Clinical Research Centre for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Cun-Ying Pu
- Roche Diagnostics (Shanghai) Limited, Medical and Scientific Affairs, Shanghai, China
| | - Xin Du
- Department of Cardiology, National Clinical Research Centre for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Heart Health Research Center, Beijing, China
- Faculty of Medicine, The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia
| | - Cai-Hua Sang
- Department of Cardiology, National Clinical Research Centre for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - De-Yong Long
- Department of Cardiology, National Clinical Research Centre for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Ri-Bo Tang
- Department of Cardiology, National Clinical Research Centre for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Jian-Zeng Dong
- Department of Cardiology, National Clinical Research Centre for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Centre for Cardiovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China
| | - Chang-Sheng Ma
- Department of Cardiology, National Clinical Research Centre for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
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13
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Aulin J, Hijazi Z, Lindbäck J, Alexander JH, Gersh BJ, Granger CB, Hanna M, Horowitz J, Lopes RD, McMurray JJV, Oldgren J, Siegbahn A, Wallentin L. Biomarkers and heart failure events in patients with atrial fibrillation in the ARISTOTLE trial evaluated by a multi-state model. Am Heart J 2022; 251:13-24. [PMID: 35569564 DOI: 10.1016/j.ahj.2022.03.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 03/04/2022] [Accepted: 03/04/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Atrial fibrillation (AF) and heart failure (HF) often coexist. We investigated the prognostic impact of biomarkers on the development of HF and death in patients with AF and different left ventricular systolic function considering the influence of competing events. METHODS The study included 11,818 patients with AF from the ARISTOTLE trial who at entry had information on history of HF, an estimate of left ventricular function and plasma samples for determination of biomarkers representing cardiorenal dysfunction (NT-proBNP, troponin T, cystatin C) and inflammation (GDF-15, IL-6, CRP). Patients were categorized into: (I) HF with reduced ejection fraction (HFrEF, n = 2,048), (II) HF with preserved ejection fraction (HFpEF, n = 2,520), and (III) No HF (n = 7,250). Biomarker associations with HF hospitalization and death were analyzed using a multi-state model accounting also for repeated events. RESULTS Baseline levels of NT-proBNP, troponin T, cystatin C, GDF-15, IL-6, and CRP were highest in HFrEF and lowest in No HF. During median 1.9 years follow-up, 546 patients were hospitalized at least once for HF and 819 died. Higher levels of all investigated biomarkers were associated with both outcomes (all P< .0001), with highest event rates in HFrEF and lowest in No HF. The associations remained after adjustments and were more pronounced for first than for recurrent events. CONCLUSIONS In anticoagulated patients with AF, biomarkers indicating cardiorenal dysfunction and inflammation improve the identification of patients at risk of developing HF or worsening of already existing HF. These biomarkers might be useful for targeting novel HF therapies in patients with AF.
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Affiliation(s)
- Julia Aulin
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
| | - Ziad Hijazi
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - Johan Lindbäck
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | | | | | | | | | - John Horowitz
- Basil Hetzel Institute, University of Adelaide, Adelaide, SA, Australia
| | - Renato D Lopes
- Duke Clinical Research Institute, Duke Health, Durham, NC
| | - John J V McMurray
- BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom
| | - Jonas Oldgren
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - Agneta Siegbahn
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden
| | - Lars Wallentin
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
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14
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Tan Z, Song T, Huang S, Liu M, Ma J, Zhang J, Yu P, Liu X. Relationship between serum growth differentiation factor 15, fibroblast growth factor-23 and risk of atrial fibrillation: A systematic review and meta-analysis. Front Cardiovasc Med 2022; 9:899667. [PMID: 35990956 PMCID: PMC9386045 DOI: 10.3389/fcvm.2022.899667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 07/11/2022] [Indexed: 11/13/2022] Open
Abstract
Background and objectiveGrowth differentiation factor-15 (GDF-15) and fibroblast growth factor-23 (FGF-23) are considered predictors of the incidence of cardiovascular diseases. The present meta-analysis aimed to elucidate the associations between GDF-15 and FGF-23 in the risk of atrial fibrillation (AF).MethodsAn electronic search was conducted in the Cochrane Library, PubMed, and Embase databases from inception until February 27, 2021. The study protocol was registered in the PROSPERO database (CRD42020182226).ResultsIn total, 15 studies that enrolled 36,017 participants were included. Both serum FGF-23 and GDF-15 were elevated in patients with AF. Analysis of categorical variables showed higher serum FGF-23 levels were associated with an increased risk of AF [relative risk (RR) = 1.28, 95% confidence interval (CI): 1.05–1.56]. In contrast, this association was not found with GDF-15 (RR = 0.91, 95% CI: 0.20–4.04). In dose-response analysis, a linear positive association was noted between serum FGF-23 levels and the risk of AF (P nonlinear = 0.9507), with a RR elevation of 7% for every 20 pg/ml increase in the serum FGF-23 levels (95% CI: 1.02–1.13). No remarkable relationship was found between serum GDF-15 levels and the risk of AF, and the overall RR for the association between a 100 ng/L increment in GDF-15 levels and AF was 1.01 (95% CI: 0.998–1.02).ConclusionOur study showed a positive linear correlation between serum FGF-23 levels and the risk of AF. However, no significant association was found between GDF-15 and the risk of AF. Further studies are warranted to clarify whether serum FGF-23 levels may be considered in predicting the risk of AF.Systematic Review Registration:http:www.york.ac.uk/inst/crd, identifier CRD42020182226.
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Affiliation(s)
- Ziqi Tan
- Department of Endocrine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Tiangang Song
- Department of Endocrine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Shanshan Huang
- Department of Endocrine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Menglu Liu
- Department of Cardiology, Seventh People's Hospital of Zhengzhou, Henan, China
| | - Jianyong Ma
- Department of Pharmacology and Systems Physiology University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Jing Zhang
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Peng Yu
- Department of Endocrine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- *Correspondence: Peng Yu
| | - Xiao Liu
- Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Xiao Liu
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15
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Russo V, Fabiani D. Put out the fire: The pleiotropic anti-inflammatory action of non-vitamin K oral anticoagulants. Pharmacol Res 2022; 182:106335. [PMID: 35781059 DOI: 10.1016/j.phrs.2022.106335] [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] [Received: 05/10/2022] [Revised: 06/15/2022] [Accepted: 06/28/2022] [Indexed: 11/28/2022]
Abstract
Non-vitamin K antagonist oral anticoagulants (NOACs) should be the preferred anticoagulant strategy for preventing ischemic stroke in patients with atrial fibrillation (AF) at increased thromboembolic risk and for treating deep venous thromboembolism (DVT) in the general population. Beyond their inhibiting action on the activated factor X (FXa) or thrombin (FIIa), NOACs showed some pleiotropic anti-inflammatory effects. The present review aimed to describe the role of FXa and FIIa in the inflammation pathway and the potential anti-inflammatory effects of NOACs.
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Affiliation(s)
- Vincenzo Russo
- Cardiology Unit, Department of Medical Translational Sciences, University of Campania "Luigi Vanvitelli" - Monaldi Hospital, Naples, Italy.
| | - Dario Fabiani
- Cardiology Unit, Department of Medical Translational Sciences, University of Campania "Luigi Vanvitelli" - Monaldi Hospital, Naples, Italy
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16
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Ihara K, Sasano T. Role of Inflammation in the Pathogenesis of Atrial Fibrillation. Front Physiol 2022; 13:862164. [PMID: 35492601 PMCID: PMC9047861 DOI: 10.3389/fphys.2022.862164] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 03/21/2022] [Indexed: 12/15/2022] Open
Abstract
Atrial fibrillation (AF) is one of the most common arrhythmias encountered in clinical practice. AF is a major risk factor for stroke, which is associated with high mortality and great disability and causes a significant burden on society. With the development of catheter ablation, AF has become a treatable disease, but its therapeutic outcome has been limited so far. In persistent and long-standing AF, the expanded AF substrate is difficult to treat only by ablation, and a better understanding of the mechanism of AF substrate formation will lead to the development of a new therapeutic strategy for AF. Inflammation is known to play an important role in the substrate formation of AF. Inflammation causes and accelerates the electrical and structural remodeling of the atria via pro-inflammatory cytokines and other inflammatory molecules, and enhances the AF substrate, leading to the maintenance of AF and further inflammation, which forms a vicious spiral, so-called "AF begets AF". Breaking this vicious cycle is expected to be a key therapeutic intervention in AF. In this review, we will discuss the relationship between AF and inflammation, the inflammatory molecules included in the AF-related inflammatory process, and finally the potential of those molecules as a therapeutic target.
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Affiliation(s)
- Kensuke Ihara
- Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Tetsuo Sasano
- Department of Cardiovascular Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
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17
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Alme KN, Ulvik A, Askim T, Assmus J, Mollnes TE, Naik M, Næss H, Saltvedt I, Ueland PM, Knapskog AB. Neopterin and kynurenic acid as predictors of stroke recurrence and mortality: a multicentre prospective cohort study on biomarkers of inflammation measured three months after ischemic stroke. BMC Neurol 2021; 21:476. [PMID: 34879833 PMCID: PMC8653541 DOI: 10.1186/s12883-021-02498-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 11/15/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Chronic low-grade inflammation is associated with both ischemic stroke and sedentary behaviour. The aim of this study was to investigate the predictive abilities of biomarkers of inflammation and immune modulation associated with sedentary behaviour for ischemic stroke recurrence and mortality in a stroke population. METHODS Patients admitted to hospital for acute stroke were recruited to the prospective multicentre cohort study, the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study, from May 2015 until March 2017. Patients with ischemic stroke, blood samples available from the three-month follow-up, and no stroke recurrence before the three-month follow-up were included. Serum was analysed for C-reactive protein (CRP) with high-sensitive technique, and plasma for interleukin-6 (IL-6), neopterin, pyridoxic acid ratio index (PAr-index: 4-pyridoxic acid: [pyrioxal+pyridoxal-5'-phosphate]) and kynurenic acid (KA). Ischemic stroke recurrence and death were identified by the Norwegian Stroke Registry and the Cause of Death Registry until 31 December 2018. RESULTS The study included 354 patients, 57% male, mean age 73 (SD 11) years, mean observation time 2.5 (SD 0.6) years, and median National Institute of Health Stroke Scale of 0 (IQR 1) at three months. CRP was associated with mortality (HR 1.40, CI 1.01, 1.96, p = 0.046), and neopterin was associated with the combined endpoint (recurrent ischemic stroke or death) (HR 1.52, CI 1.06, 2.20, p = 0.023), adjusted for age, sex, prior cerebrovascular disease, modified Rankin Scale, and creatinine. When adding neopterin and KA to the same model, KA was negatively associated (HR 0.57, CI 0.33, 0.97, p = 0.038), and neopterin was positively associated (HR 1.61, CI 1.02, 2.54, p = 0.040) with mortality. Patients with cardioembolic stroke at baseline had higher levels of inflammation at three months. CONCLUSION Neopterin might be a valuable prognostic biomarker in stroke patients. The use of KA as a measure of anti-inflammatory capacity should be investigated further. TRIAL REGISTRATION The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted on 08/01/2016.
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Affiliation(s)
- Katinka Nordheim Alme
- Institute of Clinical Medicine (K1), University of Bergen, Bergen, Norway. .,Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.
| | | | - Torunn Askim
- Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Science, NTNU-Norwegian University of Science and Technology, Trondheim, Norway
| | - Jörg Assmus
- Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway
| | - Tom Eirik Mollnes
- Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway.,Research Laboratory, Nordland Hospital, Bodø, and K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway.,Centre of Molecular Inflammation Research, NTNU-Norwegian University of Science and Technology, Trondheim, Norway
| | - Mala Naik
- Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.,Department of Clinical Science (K2), University of Bergen, Bergen, Norway
| | - Halvor Næss
- Institute of Clinical Medicine (K1), University of Bergen, Bergen, Norway.,Department of Neurology, Haukeland University Hospital, Bergen, Norway.,Centre for age-related medicine, Stavanger University Hospital, Stavanger, Norway
| | - Ingvild Saltvedt
- Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Science, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.,Department of Geriatrics, Clinic of internal medicine, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | | | - Anne-Brita Knapskog
- Department of Geriatric Medicine, Oslo University Hospital. Ullevaal, Oslo, Norway
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18
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Jia X, Cheng X, Wu N, Xiang Y, Wu L, Xu B, Li C, Zhang Z, Tong S, Zhong L, Li Y. Prognostic value of interleukin-6 in atrial fibrillation: A cohort study and meta-analysis. Anatol J Cardiol 2021; 25:872-879. [PMID: 34866581 DOI: 10.5152/anatoljcardiol.2021.69299] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE The prognostic value of interleukin-6 (IL-6) in patients with atrial fibrillation (AF) has not been fully elucidated. Therefore, we conducted a cohort study and a meta-analysis to assess the predictive value of IL-6 for stroke and mortality in patients with AF. METHODS A cohort study was performed in newly diagnosed non-valvular patients with AF. A total of 217 patients with AF were followed up for a mean of 27 months. A multivariate Cox regression analysis was used to evaluate the association between IL-6 and stroke/all-cause mortality. The incremental value was also assessed by adding IL-6 to the CHA2DS2-VASc score. Besides, a meta-analysis of all reported cohort studies and our cohort study was conducted to validate the association of circulating IL-6 and stroke/mortality in patients with AF. RESULTS Our cohort study showed that elevated plasma level of IL-6 was an independent risk factor for predicting stroke [hazard ratio (HR)=3.81; 95% confidence interval (CI), 1.11-13.05; p=0.033] and all-cause mortality (HR=3.11; 95% CI, 1.25-7.72; p=0.015) in patients with AF. Adding IL-6 levels to CHA2DS2-VASc score showed limited improvement of the predictive power for stroke [area under curve (AUC) from 0.81 to 0.88, p=0.006]. Meta-analysis confirmed that increased circulating level of IL-6 was significantly associated with increased risk of stroke (pooled HR=1.97; 95% CI, 1.22-3.17; p=0.006) and all-cause mortality (pooled HR=2.73; 95% CI, 2.29-3.25; p<0.001). CONCLUSION Increased circulating level of IL-6 was significantly associated with greater risk of stroke and all-cause mortality in patients with AF. Adding IL-6 biomarker to the CHA2DS2-VASc score may help to determine the management of AF treatment.
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Affiliation(s)
- Xiaoyue Jia
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China;Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China
| | - Xi Cheng
- Department of Sciences-Education, Chongqing General Hospital, University of Chinese Academy of Sciences; Chongqing-People's Republic of China
| | - Na Wu
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China;Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China
| | - Ying Xiang
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China;Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China
| | - Long Wu
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China;Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China
| | - Bin Xu
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China;Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China
| | - Chengying Li
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China;Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China
| | - Zhihui Zhang
- Department of Cardiology, Southwest Hospital, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China
| | - Shifei Tong
- Cardiovascular Disease Center, Third Affiliated Hospital of Chongqing Medical University; Chongqing-People's Republic of China
| | - Li Zhong
- Cardiovascular Disease Center, Third Affiliated Hospital of Chongqing Medical University; Chongqing-People's Republic of China
| | - Yafei Li
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China;Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University); Chongqing-People's Republic of China
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19
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A Review of the Molecular Mechanisms Underlying Cardiac Fibrosis and Atrial Fibrillation. J Clin Med 2021; 10:jcm10194430. [PMID: 34640448 PMCID: PMC8509789 DOI: 10.3390/jcm10194430] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 09/22/2021] [Accepted: 09/24/2021] [Indexed: 01/03/2023] Open
Abstract
The cellular and molecular mechanism involved in the pathogenesis of atrial fibrosis are highly complex. We have reviewed the literature that covers the effectors, signal transduction and physiopathogenesis concerning extracellular matrix (ECM) dysregulation and atrial fibrosis in atrial fibrillation (AF). At the molecular level: angiotensin II, transforming growth factor-β1, inflammation, and oxidative stress are particularly important for ECM dysregulation and atrial fibrotic remodelling in AF. We conclude that the Ang-II-MAPK and TGF-β1-Smad signalling pathways play a major, central role in regulating atrial fibrotic remodelling in AF. The above signalling pathways induce the expression of genes encoding profibrotic molecules (MMP, CTGF, TGF-β1). An important mechanism is also the generation of reactive oxygen species. This pathway induced by the interaction of Ang II with the AT2R receptor and the activation of NADPH oxidase. Additionally, the interplay between cardiac MMPs and their endogenous tissue inhibitors of MMPs, is thought to be critical in atrial ECM metabolism and fibrosis. We also review recent evidence about the role of changes in the miRNAs expression in AF pathophysiology and their potential as therapeutic targets. Furthermore, keeping the balance between miRNA molecules exerting anti-/profibrotic effects is of key importance for the control of atrial fibrosis in AF.
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20
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Abstract
Conduction disorders and arrhythmias remain difficult to treat and are increasingly prevalent owing to the increasing age and body mass of the general population, because both are risk factors for arrhythmia. Many of the underlying conditions that give rise to arrhythmia - including atrial fibrillation and ventricular arrhythmia, which frequently occur in patients with acute myocardial ischaemia or heart failure - can have an inflammatory component. In the past, inflammation was viewed mostly as an epiphenomenon associated with arrhythmia; however, the recently discovered inflammatory and non-canonical functions of cardiac immune cells indicate that leukocytes can be arrhythmogenic either by altering tissue composition or by interacting with cardiomyocytes; for example, by changing their phenotype or perhaps even by directly interfering with conduction. In this Review, we discuss the electrophysiological properties of leukocytes and how these cells relate to conduction in the heart. Given the thematic parallels, we also summarize the interactions between immune cells and neural systems that influence information transfer, extrapolating findings from the field of neuroscience to the heart and defining common themes. We aim to bridge the knowledge gap between electrophysiology and immunology, to promote conceptual connections between these two fields and to explore promising opportunities for future research.
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21
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Abstract
New therapeutic approaches are required for secondary prevention of residual vascular risk after stroke. Diverse sources of evidence support a causal role for inflammation in the pathogenesis of stroke. Randomized controlled trials of anti-inflammatory agents have reported benefit for secondary prevention in patients with coronary disease. We review the data from observational studies supporting a role for inflammation in pathogenesis of stroke, overview randomized controlled trials of anti-inflammatory therapy in cardiac disease and discuss the potential implications for stroke prevention therapy.
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Affiliation(s)
- Peter J Kelly
- Stroke Service, Mater University Hospital and University College Dublin, Ireland (P.J.K.).,Health Research Board Stroke Clinical Trials Network Ireland (P.J.K.)
| | - Robin Lemmens
- KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, Belgium (R.L.).,VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium (R.L.).,Department of Neurology, University Hospitals Leuven, Belgium (R.L.)
| | - Georgios Tsivgoulis
- Second Department of Neurology, "Attikon" University Hospital, National & Kapodistrian University of Athens, Greece (G.T.)
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22
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Benz AP, Aeschbacher S, Krisai P, Moschovitis G, Blum S, Meyre P, Blum MR, Rodondi N, Di Valentino M, Kobza R, De Perna ML, Bonati LH, Beer JH, Kühne M, Osswald S, Conen D. Biomarkers of Inflammation and Risk of Hospitalization for Heart Failure in Patients With Atrial Fibrillation. J Am Heart Assoc 2021; 10:e019168. [PMID: 33843247 PMCID: PMC8174180 DOI: 10.1161/jaha.120.019168] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Background Hospitalization for heart failure (HF) is very common in patients with atrial fibrillation (AF). We hypothesized that biomarkers of inflammation can identify patients with AF at increased risk of this important complication. Methods and Results Patients with established AF were prospectively enrolled. Levels of hs‐CRP (high‐sensitivity C‐reactive protein) and interleukin‐6 were measured from plasma samples obtained at baseline. We calculated an inflammation score ranging from 0 to 4 (1 point for each biomarker between the 50th and 75th percentile, 2 points for each biomarker above the 75th percentile). Individual associations of biomarkers and the inflammation score with HF hospitalization were obtained from multivariable Cox proportional hazards models. A total of 3784 patients with AF (median age 72 years, 24% prior HF) were followed for a median of 4.0 years. The median (interquartile range) plasma levels of hs‐CRP and interleukin‐6 were 1.64 (0.81–3.69) mg/L and 3.42 (2.14–5.60) pg/mL, respectively. The overall incidence of HF hospitalization was 3.04 per 100 person‐years and increased from 1.34 to 7.31 per 100 person‐years across inflammation score categories. After multivariable adjustment, both biomarkers were significantly associated with the risk of HF hospitalization (per increase in 1 SD, adjusted hazard ratio [HR], 1.22; 95% CI, 1.11–1.34 for log‐transformed hs‐CRP; adjusted HR, 1.48; 95% CI, 1.35–1.62 for log‐transformed interleukin‐6). Similar results were obtained for the inflammation score (highest versus lowest score, adjusted HR, 2.43; 95% CI, 1.80–3.30; P value for trend <0.001). Conclusions Biomarkers of inflammation strongly predicted HF hospitalization in a large, contemporary sample of patients with AF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.
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Affiliation(s)
- Alexander P Benz
- Population Health Research Institute McMaster University Hamilton Canada
| | - Stefanie Aeschbacher
- Division of Cardiology Department of Medicine University Hospital Basel Basel Switzerland.,Cardiovascular Research Institute Basel University Hospital BaselUniversity of Basel Switzerland
| | - Philipp Krisai
- Cardiovascular Research Institute Basel University Hospital BaselUniversity of Basel Switzerland.,Electrophysiology and Ablation Unit and L'Institut de Rythmologie et Modélisation Cardiaque (LIRYC) Centre Hospitalier Universitaire de Bordeaux Bordeaux-Pessac France
| | - Giorgio Moschovitis
- Population Health Research Institute McMaster University Hamilton Canada.,Division of Cardiology Ente Ospedaliero Cantonale (EOC)Ospedale Regionale di Lugano Lugano Ticino Switzerland
| | - Steffen Blum
- Division of Cardiology Department of Medicine University Hospital Basel Basel Switzerland.,Cardiovascular Research Institute Basel University Hospital BaselUniversity of Basel Switzerland
| | - Pascal Meyre
- Division of Cardiology Department of Medicine University Hospital Basel Basel Switzerland.,Cardiovascular Research Institute Basel University Hospital BaselUniversity of Basel Switzerland
| | - Manuel R Blum
- Institute of Primary Health Care (BIHAM) University of Bern Switzerland.,Department of General Internal Medicine, Inselspital Bern University HospitalUniversity of Bern Switzerland
| | - Nicolas Rodondi
- Institute of Primary Health Care (BIHAM) University of Bern Switzerland.,Department of General Internal Medicine, Inselspital Bern University HospitalUniversity of Bern Switzerland
| | - Marcello Di Valentino
- Division of Cardiology Ente Ospedaliero Cantonale (EOC)Ospedale San Giovanni Bellinzona Bellinzona Ticino Switzerland.,Biomedical Sciences Università della Svizzera Italiana Lugano Switzerland
| | - Richard Kobza
- Division of Cardiology Luzerner Kantonsspital Luzern Switzerland
| | - Maria Luisa De Perna
- Division of Cardiology Ente Ospedaliero Cantonale (EOC)Ospedale Regionale di Lugano Lugano Ticino Switzerland
| | - Leo H Bonati
- Department of Neurology and Stroke Center University Hospital Basel Basel Switzerland
| | - Jürg H Beer
- Department of Medicine Cantonal Hospital of Baden Switzerland.,Center for Molecular Cardiology University of Zurich Switzerland
| | - Michael Kühne
- Division of Cardiology Department of Medicine University Hospital Basel Basel Switzerland.,Cardiovascular Research Institute Basel University Hospital BaselUniversity of Basel Switzerland
| | - Stefan Osswald
- Division of Cardiology Department of Medicine University Hospital Basel Basel Switzerland.,Cardiovascular Research Institute Basel University Hospital BaselUniversity of Basel Switzerland
| | - David Conen
- Population Health Research Institute McMaster University Hamilton Canada.,Cardiovascular Research Institute Basel University Hospital BaselUniversity of Basel Switzerland
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23
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Pol T, Hijazi Z, Lindbäck J, Alexander JH, Bahit MC, De Caterina R, Eikelboom JW, Ezekowitz MD, Gersh BJ, Granger CB, Hylek EM, Lopes R, Siegbahn A, Wallentin L. Evaluation of the prognostic value of GDF-15, ABC-AF-bleeding score and ABC-AF-death score in patients with atrial fibrillation across different geographical areas. Open Heart 2021; 8:openhrt-2020-001471. [PMID: 33741689 PMCID: PMC7986788 DOI: 10.1136/openhrt-2020-001471] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 01/26/2021] [Accepted: 03/06/2021] [Indexed: 12/23/2022] Open
Abstract
Objectives Growth differentiation factor 15 (GDF-15) is a biomarker independently associated with bleeding and death in anticoagulated patients with atrial fibrillation (AF). GDF-15 is also used as one component in the more precise biomarker-based ABC (age, biomarkers, clinical history)-AF-bleeding and ABC-AF-death risk scores. Data from large trials indicate a geographic variability in regard to overall outcomes, including bleeding and mortality risk. Our aim was to assess the consistency of the association between GDF-15, ABC-AF-bleeding score and ABC-AF-death score, with major bleeding and death, across world geographic regions. Methods Data were available from 14 767 patients with AF from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and 8651 patients with AF from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial in this cohort study. GDF-15 was analysed from plasma samples obtained at randomisation. The geographical consistency of the associations between outcomes and GDF-15, ABC-AF-bleeding score and ABC-AF-death scores were assessed by Cox-regression models including interactions with predefined geographical region. Results GDF-15 and the ABC-AF-bleeding score were associated with major bleeding in both trials across regions (p<0.0001). Similarly, GDF-15 and the ABC-AF-death score were associated with all-cause mortality in both trials across regions (p<0.0001). Overall, the association between GDF-15, the ABC-AF-bleeding score and ABC-AF-death risk score with major bleeding and death was consistent across regions in both ARISTOTLE and the RE-LY trial cohorts. The ABC-AF-bleeding and ABC-AF-death risk scores were consistent regarding discriminative ability when comparing geographic regions in both trial cohorts. The C-indices ranged from 0.649 to 0.760 for the ABC-AF-bleeding and from 0.677 to 0.806 for the ABC-AF-death score by different geographic regions. Conclusions In patients with AF on anticoagulation, GDF-15 and the biomarker-based ABC-AF-bleeding and ABC-AF-death risk scores are consistently associated with respectively increased risk of major bleeding and death and have similar prognostic value across world geographic regions. Trial registration number ClinicalTrials.gov Registry NCT00412984 and NCT00262600.
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Affiliation(s)
- Tymon Pol
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden .,Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - Ziad Hijazi
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.,Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - Johan Lindbäck
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - John H Alexander
- Duke Clinical Research Institute, Duke Health, Durham, North Carolina, USA
| | - M Cecilia Bahit
- INECO Neurociencias Oroño, Fundación INECO, Rosario, Argentina
| | | | - J W Eikelboom
- Population Health Res Inst, Hamilton, Ontario, Canada
| | - Michael D Ezekowitz
- Thomas Jefferson Medical Coll and the Heart Ctr, Wynnewood, Pennsylvania, USA
| | | | | | | | - Renato Lopes
- Duke Clinical Research Institute, Duke Health, Durham, North Carolina, USA
| | - Agneta Siegbahn
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.,Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden
| | - Lars Wallentin
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.,Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
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24
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Rivera-Caravaca JM, Vílchez JA, Rodríguez-Rojas C, Albadalejo-Otón MD, Gil-Pérez P, Lopez-García C, Veliz-Martínez A, Roldán V, Marín F. Influence of the matrix type over the concentration of GDF-15. J Investig Med 2020; 68:1402-1404. [DOI: 10.1136/jim-2020-001351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/18/2020] [Indexed: 11/04/2022]
Abstract
Growth differentiation factor 15 (GDF-15) has been suggested as a prognostic biomarker for bleeding and mortality in atrial fibrillation (AF). To date, serum and EDTA matrices are standardized for the GDF-15 assay but it is unclear if it can be measured also in citrate. In this study, we aim to investigate if the Elecsys GDF-15 assay (Roche Diagnostics, Mannheim, Germany) can be determined accurately in citrate samples in a cohort of 10 patients with AF and 10 healthy controls. From January 2018 to March 2018, we included healthy controls and patients with AF under vitamin K antagonists in a tertiary hospital. Blood samples were drawn in both groups. We included 10 controls (50% males, mean age 36.4±8.9 years) and 10 patients with AF (80% males, mean age 76.5±16.6 years). The mean GDF-15 levels were increased in patients with AF in comparison to healthy controls, as expected by the presence of a heart-related condition and the higher age of this population. In healthy controls, GDF-15 levels showed an optimal correlation between EDTA-serum (r=0.975; p<0.001), EDTA-citrate (r=0.972; p<0.001), and serum-citrate (r=0.997; p<0.001) samples. This was also observed in patients with AF: EDTA-serum (r=0.975; p<0.001), serum-citrate (r=0.835; p=0.003), and EDTA-citrate (r=0.768; p=0.009). Our results demonstrate that citrate samples may be used for the determination of GDF-15 in AF given the positive and good correlation with EDTA and serum matrices. Further studies should validate these observations.
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25
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Zhou P, Waresi M, Zhao Y, Lin HC, Wu B, Xiong N, Li H, Huang Q, Luo X, Li J. Increased serum interleukin-6 level as a predictive biomarker for atrial fibrillation: A systematic review and meta-analysis. REVISTA PORTUGUESA DE CARDIOLOGIA (ENGLISH EDITION) 2020. [DOI: 10.1016/j.repce.2020.07.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
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26
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Yano M, Egami Y, Ukita K, Kawamura A, Nakamura H, Matsuhiro Y, Yasumoto K, Tsuda M, Okamoto N, Tanaka A, Matsunaga-Lee Y, Shutta R, Nishino M, Tanouchi J. Atrial fibrillation type modulates the clinical predictive value of neutrophil-to-lymphocyte ratio for atrial fibrillation recurrence after catheter ablation. IJC HEART & VASCULATURE 2020; 31:100664. [PMID: 33163615 PMCID: PMC7599425 DOI: 10.1016/j.ijcha.2020.100664] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 10/11/2020] [Accepted: 10/12/2020] [Indexed: 10/31/2022]
Abstract
BACKGROUND The neutrophil-to-lymphocyte ratio (NLR) has been proposed as an indicator of a systemic inflammatory response. There are baseline differences in the inflammation status between paroxysmal atrial fibrillation (PAF) and persistent AF (PerAF). The NLR changes and late recurrences of AF (LRAF) after ablation depending on the AF type remain unknown. METHODS Consecutive AF patients undergoing pulmonary vein isolation (PVI) by radiofrequency catheter ablation were enrolled from September 2014 to June 2018. The peripheral blood leukocyte NLR 1 day before and 36-48 h after PVI were measured. First, the relationship between NLR changes after to before ablation (ΔNLR) and ERAFs/LRAFs in PAF and PerAF patients were investigated to exclude the baseline inflammation status and evaluate catheter ablation induced inflammation. Second, the clinical impact of the NLR for predicting LRAFs was evaluated. RESULTS There hundred sixty-nine PAF and 264 PerAF patients from Osaka Rosai AF registry were enrolled. The ratio of ERAFs/LRAFs in PAF and PerAF patients were 26.8%/22.5% and 39.4%/29.9%, respectively. In PAF and PerAF patients, the ΔNLR was significantly higher with ERAF than no-ERAF (p = 0.022 and p = 0.010, respectively). In PAF patients, the ΔNLR was significantly higher with LRAF than no-LRAF (p = 0.017), while with PerAF, the ΔNLR did not significantly differ between LRAFs and no-LRAFs. In PAF, the ΔNLR was independently and significantly associated with LRAFs after PVI (p = 0.029). CONCLUSION The ΔNLR was significantly higher only in PAF patients with LRAFs than no-LRAFs, but not in PerAF patients. The ΔNLR was useful for predicting LRAFs after PVI in PAF patients.
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Affiliation(s)
- Masamichi Yano
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
| | - Yasuyuki Egami
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
| | - Kohei Ukita
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
| | - Akito Kawamura
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
| | - Hitoshi Nakamura
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
| | - Yutaka Matsuhiro
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
| | - Koji Yasumoto
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
| | - Masaki Tsuda
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
| | - Naotaka Okamoto
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
| | - Akihiro Tanaka
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
| | - Yasuharu Matsunaga-Lee
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
| | - Ryu Shutta
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
| | - Masami Nishino
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
| | - Jun Tanouchi
- Division of Cardiology, Osaka Rosai Hospital, 3-1179 Nagasonecho, Kita-ku, Sakai, Osaka 591-8025, Japan
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27
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Zhou P, Waresi M, Zhao Y, Lin HC, Wu B, Xiong N, Li H, Huang Q, Luo X, Li J. Increased serum interleukin-6 level as a predictive biomarker for atrial fibrillation: A systematic review and meta-analysis. Rev Port Cardiol 2020; 39:723-728. [PMID: 33234354 DOI: 10.1016/j.repc.2020.07.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 07/09/2020] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Atrial fibrillation (AF) is related to a higher risk of thromboembolic events and mortality. Some studies have demonstrated that the inflammatory biomarker interleukin-6 (IL-6) is associated with a higher risk of higher thrombosis in AF patients, but the real effect of IL-6 remains a controversy. METHODS We conducted a systematic review and meta-analysis to investigate the association between IL-6 and thromboembolic events, as well as bleeding events, acute coronary syndrome (ACS) events and all-cause mortality in AF. RESULTS A total of five studies involving 22 928 patients met our inclusion criteria for the systematic review. The higher level of IL-6 in AF patients is related to long-term thromboembolic events including stroke (RR 1.44, CI 95% 1.09-1.90, p=0.01). IL-6 meant a higher risk of long-term bleeding risk (RR 1.36, CI 95% 1.06-1.74, p=0.02), ACS risk (RR 1.81, CI 95% 1.43-2.30, p<0.001) and all-cause mortality (RR 2.35, CI 95% 2.09-2.65, p<0.001). CONCLUSION A higher level of IL-6 may predict a greater number of long-term thromboembolic events and bleeding events, ACS events and mortality in AF patients. Further studies such as the cut-off point of IL-6 need to be conducted in the future.
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Affiliation(s)
- Peng Zhou
- Department of Cardiology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China
| | - Maieryemu Waresi
- Department of Cardiology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China
| | - Yikai Zhao
- Department of Cardiology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China
| | - Hung-Chen Lin
- Department of Cardiology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China
| | - Bangwei Wu
- Department of Cardiology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China
| | - Nanqing Xiong
- Department of Cardiology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China
| | - Huiyang Li
- Department of Cardiology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China
| | - Qingyu Huang
- Department of Cardiology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China
| | - Xinping Luo
- Department of Cardiology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China
| | - Jian Li
- Department of Cardiology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China.
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28
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Affiliation(s)
- Christoph R Sinning
- Department of Cardiology, University Heart & Vascular Center Hamburg Eppendorf, Hamburg, Germany
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29
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Mironova Staroverova AI, Panchenko EP, Kropacheva ES, Zemlyanskaya OA. [Resumption of anticoagulant therapy after major bleeding and recurrence of hemorrhagic complications in patients with atrial fibrillation with a high risk of stroke and thromboembolism (based on the results of 20 years of observation)]. TERAPEVT ARKH 2020; 92:15-23. [PMID: 33346426 DOI: 10.26442/00403660.2020.09.000655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 10/13/2020] [Indexed: 11/22/2022]
Abstract
AIM To analyze the frequency of resumption of anticoagulant therapy (ACT) after major and clinically significant bleeding among AF patients who received oral anticoagulants and were observed in the Department of clinical problems of atherothrombosis from 1999 to 2019 within the retro-prospective register Regata-2, and to search for clinical factors associated with recurrence of hemorrhagic complications among patients who resumed anticoagulant therapy after a bleeding episode. MATERIALS AND METHODS In cohort study of patients with high-risk AF with absolute indications for ACT we enrolled 290 AF patients (130 women and 160 men) aged 32 to 85 years (the average age was 65.188.89 years). During the follow-up period, 92 patients developed hemorrhagic complications, and 73 of them resumed ACT. 35 of the 73 patients who resumed ACT developed a relapse of major/clinically significant bleeding. RESULTS The frequency of resuming ACT after the first hemorrhagic complication increased over time from 75% in the period from 19992003 to 90% in the period 20152019. We were not able to establish an exact relationship between the presence of concomitant pathology and the decision to resume the ACT after bleeding. The only reliable reason for refusing to resume the ACT was the patients categorical reluctance. Among patients who had recurrent hemorrhagic complications, the total score on the Charleson comorbidity scale was significantly higher (4.232.01vs3.521.43;p=0.0425). Patients with recurrent bleeding were significantly more likely to suffer from CKD with a decrease in GFR less than 60 ml/min/1.73 sq. m, and also had a history of erosive and ulcerative lesions of the gastrointestinal tract. There was also a significant Association of recurrent bleeding with the use of proton pump inhibitors. Subgroups of patients who switched from warfarin to taking direct oral anticoagulants after the first bleeding and subsequent recurrent bleeding did not differ in basic clinical characteristics from patients without bleeding after changing the anticoagulant. According to multiple regression analysis, NSAIDs showed a tendency to develop a relapse of B/C bleeding on the background of direct oral anticoagulants in patients who underwent GO on the background of warfarin therapy (b=0.4524,p=0.0530). CONCLUSION During the 20-year follow-up, the frequency of all major and clinically significant bleeding was 2.6/100 patients-years, the frequency of first bleeding was 5.86/100 patients-years, while the frequency of repeated hemorrhagic complications was 7.06/100 patients-years. Patients with a high thromboembolic risk should receive anticoagulants, provided that the modifiable risk factors for bleeding are carefully corrected.
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Affiliation(s)
| | - E P Panchenko
- Myasnikov Institute of Clinical Cardiology, National Medical Research Center for Cardiology
| | - E S Kropacheva
- Myasnikov Institute of Clinical Cardiology, National Medical Research Center for Cardiology
| | - O A Zemlyanskaya
- Myasnikov Institute of Clinical Cardiology, National Medical Research Center for Cardiology
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30
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van Marion DMS, Lanters EAH, Ramos KS, Li J, Wiersma M, Baks-te Bulte L, J. Q. M. Muskens A, Boersma E, de Groot NMS, Brundel BJJM. Evaluating Serum Heat Shock Protein Levels as Novel Biomarkers for Atrial Fibrillation. Cells 2020; 9:E2105. [PMID: 32947824 PMCID: PMC7564530 DOI: 10.3390/cells9092105] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 09/09/2020] [Accepted: 09/14/2020] [Indexed: 02/07/2023] Open
Abstract
Background: Staging of atrial fibrillation (AF) is essential to understanding disease progression and the accompanied increase in therapy failure. Blood-based heat shock protein (HSP) levels may enable staging of AF and the identification of patients with higher risk for AF recurrence after treatment. Objective: This study evaluates the relationship between serum HSP levels, presence of AF, AF stage and AF recurrence following electrocardioversion (ECV) or pulmonary vein isolation (PVI). Methods: To determine HSP27, HSP70, cardiovascular (cv)HSP and HSP60 levels, serum samples were collected from control patients without AF and patients with paroxysmal atrial fibrillation (PAF), persistent (PeAF) and longstanding persistent (LSPeAF) AF, presenting for ECV or PVI, prior to intervention and at 3-, 6- and 12-months post-PVI. Results: The study population (n = 297) consisted of 98 control and 199 AF patients admitted for ECV (n = 98) or PVI (n = 101). HSP27, HSP70, cvHSP and HSP60 serum levels did not differ between patients without or with PAF, PeAF or LSPeAF. Additionally, baseline HSP levels did not correlate with AF recurrence after ECV or PVI. However, in AF patients with AF recurrence, HSP27 levels were significantly elevated post-PVI relative to baseline, compared to patients without recurrence. Conclusions: No association was observed between baseline HSP levels and the presence of AF, AF stage or AF recurrence. However, HSP27 levels were increased in serum samples of patients with AF recurrence within one year after PVI, suggesting that HSP27 levels may predict recurrence of AF after ablative therapy.
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Affiliation(s)
- Denise M. S. van Marion
- Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije University, 1081HV Amsterdam, The Netherlands; (D.M.S.v.M.); (K.S.R.); (J.L.); (M.W.); (L.B.-t.B.)
| | - Eva A. H. Lanters
- Department of Cardiology, Erasmus MC, 3000CA Rotterdam, The Netherlands; (E.A.H.L.); (A.J.Q.M.M.); (E.B.); (N.M.S.d.G.)
| | - Kennedy S. Ramos
- Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije University, 1081HV Amsterdam, The Netherlands; (D.M.S.v.M.); (K.S.R.); (J.L.); (M.W.); (L.B.-t.B.)
- Department of Cardiology, Erasmus MC, 3000CA Rotterdam, The Netherlands; (E.A.H.L.); (A.J.Q.M.M.); (E.B.); (N.M.S.d.G.)
| | - Jin Li
- Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije University, 1081HV Amsterdam, The Netherlands; (D.M.S.v.M.); (K.S.R.); (J.L.); (M.W.); (L.B.-t.B.)
| | - Marit Wiersma
- Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije University, 1081HV Amsterdam, The Netherlands; (D.M.S.v.M.); (K.S.R.); (J.L.); (M.W.); (L.B.-t.B.)
- Netherlands Heart Institute, 3511EP Utrecht, The Netherlands
| | - Luciënne Baks-te Bulte
- Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije University, 1081HV Amsterdam, The Netherlands; (D.M.S.v.M.); (K.S.R.); (J.L.); (M.W.); (L.B.-t.B.)
| | - Agnes J. Q. M. Muskens
- Department of Cardiology, Erasmus MC, 3000CA Rotterdam, The Netherlands; (E.A.H.L.); (A.J.Q.M.M.); (E.B.); (N.M.S.d.G.)
| | - Eric Boersma
- Department of Cardiology, Erasmus MC, 3000CA Rotterdam, The Netherlands; (E.A.H.L.); (A.J.Q.M.M.); (E.B.); (N.M.S.d.G.)
| | - Natasja M. S. de Groot
- Department of Cardiology, Erasmus MC, 3000CA Rotterdam, The Netherlands; (E.A.H.L.); (A.J.Q.M.M.); (E.B.); (N.M.S.d.G.)
| | - Bianca J. J. M. Brundel
- Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije University, 1081HV Amsterdam, The Netherlands; (D.M.S.v.M.); (K.S.R.); (J.L.); (M.W.); (L.B.-t.B.)
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Aulin J, Hijazi Z, Siegbahn A, Andersson U, Alexander JH, Connolly SJ, Ezekowitz MD, Gersh BJ, Granger CB, Horowitz J, Hylek EM, Lopes RD, Yusuf S, Wallentin L, Oldgren J. Serial measurement of interleukin-6 and risk of mortality in anticoagulated patients with atrial fibrillation: Insights from ARISTOTLE and RE-LY trials. J Thromb Haemost 2020; 18:2287-2295. [PMID: 32510737 DOI: 10.1111/jth.14947] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 04/29/2020] [Accepted: 05/29/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND The inflammatory biomarker interleukin-6 (IL-6) is associated with mortality in atrial fibrillation (AF). OBJECTIVE To investigate if repeated IL-6 measurements improve the prognostication for stroke or systemic embolism, major bleeding, and mortality in anticoagulated patients with AF. METHODS IL-6 levels by ELISA were measured at study entry and at 2 months in 4830 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial with 1.8 years median follow-up. In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, IL-6 was measured at study entry, 3, 6, and 12 months in 2559 patients with 2.0 years median follow-up. Associations between a second IL-6 measurement and outcomes, adjusted for baseline IL-6, clinical variables, and other cardiovascular biomarkers, were analyzed by Cox regression. RESULTS Median IL-6 levels were 2.0 ng/L (interquartile range [IQR] 1.30-3.20) and 2.10 ng/L (IQR 1.40-3.40) at the two time-points in ARISTOTLE, and, in RE-LY, 2.5 ng/L (IQR 1.6-4.3), 2.5 ng/L (IQR 1.6-4.2), 2.4 ng/L (IQR 1.6, 3.9), and 2.4 ng/L (IQR 1.5, 3.9), respectively. IL-6 was associated with mortality; hazard ratios per 50% higher IL-6 at 2 or 3 months, respectively, were 1.32 (95% confidence interval, 1.23-1.41; P < .0001) in ARISTOTLE, and 1.11 (1.01-1.22, P = .0290) in RE-LY; with improved C index from 0.74 to 0.76 in ARISTOTLE, but not in the smaller RE-LY cohort. There were no consistent associations with second IL-6 and stroke or systemic embolism, or major bleeding. CONCLUSIONS Persistent systemic inflammatory activity, assessed by repeated IL-6 measurements, is associated with mortality independent of established clinical risk factors and other strong cardiovascular biomarkers in anticoagulated patients with AF.
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Affiliation(s)
- Julia Aulin
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - Ziad Hijazi
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - Agneta Siegbahn
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
- Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden
| | - Ulrika Andersson
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - John H Alexander
- Duke Clinical Research Institute, Duke University Medical Center, Duke Health, Durham, NC, USA
| | - Stuart J Connolly
- Population Health Research Institute, McMaster U and Hamilton Health Sciences, Hamilton, ON, Canada
| | | | | | - Christopher B Granger
- Duke Clinical Research Institute, Duke University Medical Center, Duke Health, Durham, NC, USA
| | | | | | - Renato D Lopes
- Duke Clinical Research Institute, Duke University Medical Center, Duke Health, Durham, NC, USA
| | - Salim Yusuf
- Population Health Research Institute, McMaster U and Hamilton Health Sciences, Hamilton, ON, Canada
| | - Lars Wallentin
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - Jonas Oldgren
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
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32
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Cell-Free Circulating Mitochondrial DNA: A Potential Blood-Based Marker for Atrial Fibrillation. Cells 2020; 9:cells9051159. [PMID: 32397106 PMCID: PMC7290331 DOI: 10.3390/cells9051159] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 04/30/2020] [Accepted: 05/02/2020] [Indexed: 02/06/2023] Open
Abstract
Atrial fibrillation (AF), the most common, progressive tachyarrhythmia is associated with serious complications, such as stroke and heart failure. Early recognition of AF, essential to prevent disease progression and therapy failure, is hampered by the lack of accurate diagnostic serum biomarkers to identify the AF stage. As we previously showed mitochondrial dysfunction to drive experimental and human AF, we evaluated whether cell-free circulating mitochondrial DNA (cfc-mtDNA) represents a potential serum marker. Therefore, the levels of two mtDNA genes, COX3 and ND1, were measured in 84 control patients (C), 59 patients undergoing cardiac surgery without a history of AF (SR), 100 paroxysmal (PAF), 116 persistent (PeAF), and 20 longstanding-persistent (LS-PeAF) AF patients undergoing either cardiac surgery or AF treatment (electrical cardioversion or pulmonary vein isolation). Cfc-mtDNA levels were significantly increased in PAF patients undergoing AF treatment, especially in males and patients with AF recurrence after AF treatment. In PeAF and LS-PeAF, cfc-mtDNA levels gradually decreased. Importantly, cfc-mtDNA in serum may originate from cardiomyocytes, as in vitro tachypaced cardiomyocytes release mtDNA in the medium. The findings suggest that cfc-mtDNA is associated with AF stage, especially in males, and with patients at risk for AF recurrence after treatment.
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Zhou X, Dudley SC. Evidence for Inflammation as a Driver of Atrial Fibrillation. Front Cardiovasc Med 2020; 7:62. [PMID: 32411723 PMCID: PMC7201086 DOI: 10.3389/fcvm.2020.00062] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 03/26/2020] [Indexed: 12/31/2022] Open
Abstract
Atrial fibrillation (AF) is one of the most common types of arrhythmias and increases cardiovascular morbidity and mortality. Current therapeutic approaches to AF that focus on rhythm control have high recurrence rates and no life prolongation value. While possible explanations include toxicity of current therapies, another likely explanation may be that current therapies do not address fundamental mechanisms of AF initiation and maintenance. Inflammation has been shown to affect signaling pathways that lead to the development of AF. This paper reviews the roles of inflammation in the occurrence, development, and mechanisms of AF and reviews the therapeutic implications of the correlation of inflammation and AF.
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Affiliation(s)
- Xiaoxu Zhou
- Division of Cardiology, Department of Medicine, the Lillehei Heart Institute, University of Minnesota at Twin Cities, Minneapolis, MN, United States
| | - Samuel C Dudley
- Division of Cardiology, Department of Medicine, the Lillehei Heart Institute, University of Minnesota at Twin Cities, Minneapolis, MN, United States
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34
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Shinohara T, Takahashi N. High-Sensitivity C-Reactive Protein and Bleeding Events in Atrial Fibrillation Patients Treated With Direct Oral Anticoagulants. Circ J 2020; 84:376-377. [PMID: 32051350 DOI: 10.1253/circj.cj-20-0061] [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: 11/01/2024]
Affiliation(s)
- Tetsuji Shinohara
- Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University
| | - Naohiko Takahashi
- Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University
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35
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Ding WY, Harrison S, Gupta D, Lip GYH, Lane DA. Stroke and Bleeding Risk Assessments in Patients With Atrial Fibrillation: Concepts and Controversies. Front Med (Lausanne) 2020; 7:54. [PMID: 32154260 PMCID: PMC7047213 DOI: 10.3389/fmed.2020.00054] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Accepted: 02/05/2020] [Indexed: 12/20/2022] Open
Abstract
Risk assessments are an important element in the management of patients with atrial fibrillation (AF). In this review, we aim to discuss the concepts and controversies surrounding the various risk factors for stroke and bleeding in AF. Indeed, there are a variety of clinical, electrical, biological, and genetic markers to guide stroke and bleeding risk assessments in AF. The more common factors have been used to formulate risk stratification scores. Some risk factors have shown promise, but others remain less well-defined. Our aim is to discuss concepts and controversies surrounding current evidence of risk factors for stroke and bleeding assessments in AF.
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Affiliation(s)
- Wern Yew Ding
- Liverpool Centre for Cardiovascular Science, Liverpool Heart and Chest Hospital, University of Liverpool, Liverpool, United Kingdom
| | - Stephanie Harrison
- Liverpool Centre for Cardiovascular Science, Liverpool Heart and Chest Hospital, University of Liverpool, Liverpool, United Kingdom
| | - Dhiraj Gupta
- Liverpool Centre for Cardiovascular Science, Liverpool Heart and Chest Hospital, University of Liverpool, Liverpool, United Kingdom
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science, Liverpool Heart and Chest Hospital, University of Liverpool, Liverpool, United Kingdom.,Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Deirdre A Lane
- Liverpool Centre for Cardiovascular Science, Liverpool Heart and Chest Hospital, University of Liverpool, Liverpool, United Kingdom.,Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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36
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Kobalava ZD, Lazarev PV. [Risk of Coronary Events in Atrial Fibrillation]. KARDIOLOGIIA 2020; 60:43-52. [PMID: 32245354 DOI: 10.18087/cardio.2020.1.n828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Accepted: 10/30/2019] [Indexed: 06/11/2023]
Abstract
It has been established that cardiovascular events due to coronary heart disease are highly prevalent in the population of patients with atrial fibrillation. In this review, pathophysiologic mechanisms explaining this association are detailed along with supporting epidemiological evidence. Various methods for the prediction and prevention of coronary events in atrial fibrillation are iscussed, including modification of shared risk factors, antithrombotic therapy and selection of the optimal direct oral anticoagulant in terms of favourable influence on ischemic cardiac outcomes.
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Affiliation(s)
- Zh D Kobalava
- Peoples Friendship University of Russia (RUDN University)
| | - P V Lazarev
- Peoples Friendship University of Russia (RUDN University)
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37
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Safavi-Naeini P, Rasekh A. Thromboembolism in Atrial Fibrillation: Role of the Left Atrial Appendage. Card Electrophysiol Clin 2019; 12:13-20. [PMID: 32067643 DOI: 10.1016/j.ccep.2019.11.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
Atrial fibrillation (AF) is the most common arrhythmia. Patients with AF have a higher risk for thromboembolism than individuals without AF. The left atrial appendage (LAA) is the main source of thromboembolism because of its anatomic, mechanical, and electrophysiologic properties, and accounts for more than 90% of thrombus formation in patients with AF. Advancement in imaging expands knowledge about anatomic and physiologic characteristics of LAA. The risk of thromboembolism events in patients with AF depends on clinical comorbidities and structural and physiologic parameters of atria, especially LAA. This article discusses AF-related thromboembolic events and the role of the LAA.
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Affiliation(s)
- Payam Safavi-Naeini
- Electrophysiology Clinical Research and Innovation, Texas Heart Institute, Houston, TX, USA
| | - Abdi Rasekh
- Cardiology, Baylor College of Medicine, 6624 Fannin Street Suite 2480, Houston, TX 77030, USA; Cardiology, Texas Heart Institute, Houston, TX, USA.
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Huang J, Xiang Y, Zhang H, Wu N, Chen X, Wu L, Xu B, Li C, Zhang Z, Tong S, Zhong L, Li Y. Plasma Level of Interferon-γ Predicts the Prognosis in Patients With New-Onset Atrial Fibrillation. Heart Lung Circ 2019; 29:e168-e176. [PMID: 31813744 DOI: 10.1016/j.hlc.2019.11.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Revised: 10/25/2019] [Accepted: 11/02/2019] [Indexed: 10/25/2022]
Abstract
BACKGROUND Patients with atrial fibrillation are at increased risk of stroke and mortality. It is not clear if inflammatory biomarkers are associated with stroke and mortality in patients with atrial fibrillation. We aimed to evaluate the predictive value of three inflammatory biomarkers (interleukin [IL]-9, IL-10, and interferon [IFN]-γ) for stroke and mortality in atrial fibrillation. METHOD A total of 232 patients with new-onset atrial fibrillation were enrolled and 217 patients were completely followed-up. Peripheral plasma concentrations of cytokines (IL-9, IL-10, and IFN-γ) were measured using Luminex xMAP assays. The association between dichotomous groups of cytokines and outcomes were evaluated by a Cox proportional hazards model. The incremental value of inflammatory biomarkers, in addition to the CHA2DS2-VASc score, was also assessed. RESULTS Patients were followed-up for a median duration of 27 (interquartile range [IQR], 23-30) months. The elevated plasma level of IFN-γ was an independent risk factor for stroke (hazard ratio [HR], 4.02 [IQR, 1.06-15.34]; p=0.042) and all-cause mortality (HR, 3.93 [IQR, 1.43-10.78]; p=0.008) in patients with atrial fibrillation. Adding high IFN-γ to the CHA2DS2-VASc score showed improvement in discrimination and reclassification prediction for stroke and mortality. However, IL-9 and IL-10 had no statistically significant association with stroke and all-cause mortality in patients with atrial fibrillation. CONCLUSIONS In this "real-world" cohort of patients with atrial fibrillation, we have shown for the first time that plasma levels of IFN-γ could provide incremental prognostic value supplementary to that obtained from the CHA2DS2-VASc scores for predicting of stroke and all-cause mortality.
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Affiliation(s)
- Jiaqi Huang
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China
| | - Ying Xiang
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China
| | - Huan Zhang
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China
| | - Na Wu
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China
| | - Xinghua Chen
- Department of Cardiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China
| | - Long Wu
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China
| | - Bin Xu
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China
| | - Chengying Li
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China
| | - Zhihui Zhang
- Department of Cardiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China
| | - Shifei Tong
- Cardiovascular Disease Center, Third Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Li Zhong
- Cardiovascular Disease Center, Third Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Yafei Li
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University), Chongqing, People's Republic of China.
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39
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Alkhouli M, Friedman PA. Ischemic Stroke Risk in Patients With Nonvalvular Atrial Fibrillation: JACC Review Topic of the Week. J Am Coll Cardiol 2019; 74:3050-3065. [PMID: 31865973 DOI: 10.1016/j.jacc.2019.10.040] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 10/16/2019] [Accepted: 10/21/2019] [Indexed: 12/16/2022]
Abstract
The last decade has witnessed remarkable advances in pharmacological and nonpharmacological strategies for stroke prevention in patients with atrial fibrillation. However, the currently available clinical stroke risk prediction models do not account for key nonclinical factors (arrhythmia burden, left atrial physiology and anatomy, chemical and electrocardiographic markers) and other competing clinical risks. Hence, their ability to identify patients who will derive the most benefit from pharmacological and mechanical risk prevention strategies remain limited. In this paper, the authors review the current and evolving ischemic stroke risk prediction schemes in patients with nonvalvular atrial fibrillation, highlight the strengths and weaknesses of the models, and discuss the unmet needs in this field.
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Affiliation(s)
- Mohamad Alkhouli
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.
| | - Paul A Friedman
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota. https://twitter.com/drpaulfriedman
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40
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Demelo-Rodríguez P, Galeano-Valle F, Marcelo-Ayala A, Fernández-Carracedo E, Cuenca-Zarzuela A, Gómez-Morales M, Alvarez-Sala-Walther LA, Bellón-Cano JM, Del-Toro-Cervera J. C-reactive protein level predicts 30-day mortality and bleeding in patients with venous thromboembolism: A prospective single-center study. Med Clin (Barc) 2019; 155:51-56. [PMID: 31787321 DOI: 10.1016/j.medcli.2019.09.024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 09/13/2019] [Accepted: 09/19/2019] [Indexed: 11/24/2022]
Abstract
AIMS The association of on-admission CRP and early adverse outcomes in acute venous thromboembolism (VTE) has not been investigated. We hypothesized that increased on-admission CRP levels would correlate with adverse outcomes in patients with acute VTE. METHOD In this prospective observational study, consecutive patients with acute VTE were enrolled and CRP levels were measured within the first 24h after diagnosis. Mortality, bleeding and recurrence were recorded during a 30-day follow-up. RESULTS 586 patients were included. Higher CRP levels were found in patients with mortality (7.5 vs 4.0mg/dL; p=0.01) and bleeding (7.8 vs 3.9mg/dL; p=0.03). Multivariable logistic regression showed that CRP levels >5mg/dL were associated with higher mortality (OR 6.25; 95% CI, 2.1-18.6) and bleeding (OR 2.7; CI 95% 1.3-5.7). These results were independent to ESC risk score and simplified PESI score for mortality prediction. The predictive capacity of CRP showed an area under the ROC curve - AUC - of .7 (CI 95% .56-.85) for mortality and .65 (CI 95% .54-.75) for bleeding. The prognostic capacity of the ESC risk score and simplified PESI score was improved after adding the CRP cutoff of 5mg/dL (AUC of .87 CI 95% .79-.95). CONCLUSION Our findings suggest that on-admission CRP level may be a simple, widely available and valuable biomarker to identify high-risk VTE patients for early mortality and bleeding. CRP ≥5mg/dL was independently associated with 30-day VTE related death and bleeding.
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Affiliation(s)
- Pablo Demelo-Rodríguez
- Venous Thromboembolism Unit, Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Spain; Instituto de investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - Francisco Galeano-Valle
- Venous Thromboembolism Unit, Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Spain; Instituto de investigación Sanitaria Gregorio Marañón, Madrid, Spain.
| | - Almudena Marcelo-Ayala
- Venous Thromboembolism Unit, Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Eduardo Fernández-Carracedo
- Venous Thromboembolism Unit, Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | | | - Marina Gómez-Morales
- Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Spain
| | - Luis Antonio Alvarez-Sala-Walther
- Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Spain; Instituto de investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - José María Bellón-Cano
- Department of Statistics, Instituto de investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - Jorge Del-Toro-Cervera
- Venous Thromboembolism Unit, Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Spain; Instituto de investigación Sanitaria Gregorio Marañón, Madrid, Spain
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Sideris S, Archontakis S, Latsios G, Lazaros G, Toutouzas K, Tsiamis E, Vavuranakis M, Vlachopoulos C, Gatzoulis K, Tsioufis C, Tousoulis D. Biomarkers Associated with Bleeding Risk in the Setting of Atrial Fibrillation. Curr Med Chem 2019; 26:824-836. [PMID: 28721832 DOI: 10.2174/0929867324666170718124742] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Revised: 11/20/2017] [Accepted: 11/28/2017] [Indexed: 01/19/2023]
Abstract
BACKGROUND Prevention of thromboembolic disease, mainly stroke, with oral anticoagulants remains a major therapeutic goal in patients with atrial fibrillation. Unfortunately, despite the high efficacy, anticoagulant therapy is associated with a significant risk of, frequently catastrophic, and hemorrhagic complications. Among different clinical and laboratory parameters related to an increased risk of bleeding, several biological markers have been recognized and various risk scores for bleeding have been developed. OBJECTIVES/METHODS The aim of the present study is to review current evidence regarding the different biomarkers associated with raised bleeding risk in atrial fibrillation. RESULTS Data originating from large cohorts or the recent large-scale trials of atrial fibrillation have linked numerous individual biomarkers to an increased bleeding risk. Such a relation was revealed for markers of cardiac physiology, such as troponin, BNP and NT-proBNP, markers of renal function, such as GFR and Cystatin or hepatic function, markers involving the system of coagulation, such as D-dimer and Von Willebrand factor, hematologic markers, such as low haemoglobin or low platelets, inflammatory markers, such as interleukin-6, other factors such as GDF-15 and vitamin-E and finally genetic polymorphisms. Many such biomarkers are incorporated in the bleeding risk schemata developed for the prediction of the hemorrhagic risk. CONCLUSIONS Biomarkers were introduced in clinical practice in order to better estimate the potential risk of haemorrhage in these patients and increase the prognostic impact of clinical risk scores. In the last years this concept is gaining significant importance.
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Affiliation(s)
- Skevos Sideris
- 1st Cardiology Department, Athens Medical School, Athens, Greece
| | | | - George Latsios
- 1st Cardiology Department, Athens Medical School, Athens, Greece
| | - George Lazaros
- 1st Cardiology Department, Athens Medical School, Athens, Greece
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Bazal P, Gea A, de la Fuente-Arrillaga C, Barrio-López MT, Martinez-González MA, Ruiz-Canela M. Olive oil intake and risk of atrial fibrillation in the SUN cohort. Nutr Metab Cardiovasc Dis 2019; 29:450-457. [PMID: 30948307 DOI: 10.1016/j.numecd.2019.02.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 02/03/2019] [Accepted: 02/07/2019] [Indexed: 01/08/2023]
Abstract
BACKGROUND AND AIMS A Mediterranean-type diet enriched with extra virgin olive oil has been associated with a reduction in the incidence of atrial fibrillation (AF) in a population at high cardiovascular risk. However, no study has replicated these findings. In our study, we analyzed the association between olive oil consumption and AF in the SUN project, a cohort with young Spanish adults at low cardiovascular risk. METHODS AND RESULTS We included all participants without prevalent AF at baseline (18,118 participants). Incident AF cases were confirmed by a cardiologist following a prespecified protocol. We used multivariable repeated-measurement Cox models adjusted for possible confounders (sex, age, BMI, and several classic cardiovascular risk factors). After a mean follow-up of 10.1 years, 94 AF incident cases were confirmed. Comparing to the lowest category of consumption (<7.9 g/d), the multivariable models showed hazard ratios (IC 95%) of 1.52 (0.93-2.48) for low-to-moderate, 1.44 (0.83-2.47) for moderate-to-high and 1.27 (0.56-2.86) for high olive oil intake. In a subgroup analysis stratified by overweight, an inverse although non-significant association was found only among overweight participants when we compared the highest vs the lowest category of consumption (p for interaction = 0.043). CONCLUSION No association between olive oil and AF was found in this low-risk cohort, although the effect of extra-virgin olive oil on AF prevention especially among people with overweight deserves further investigation.
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Affiliation(s)
- P Bazal
- Servicio Navarro de Salud-Osasunbidea, Pamplona, Spain; Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, IdiSNA, Pamplona, Spain
| | - A Gea
- Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, IdiSNA, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - C de la Fuente-Arrillaga
- Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, IdiSNA, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - M T Barrio-López
- Electrophysiology Laboratory and Arrhythmia Unit, Hospital Monteprincipe, Grupo HM Hospitales, University CEU-San Pablo, Madrid, Spain
| | - M A Martinez-González
- Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, IdiSNA, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Nutrition, Harvard TH Chan School of Public Health, Boston, USA
| | - M Ruiz-Canela
- Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, IdiSNA, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
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Ioannou A, Papageorgiou N, Falconer D, Rehal O, Sewart E, Zacharia E, Toutouzas K, Vlachopoulos C, Siasos G, Tsioufis C, Tousoulis D. Biomarkers Associated with Stroke Risk in Atrial Fibrillation. Curr Med Chem 2019; 26:803-823. [PMID: 28721825 DOI: 10.2174/0929867324666170718120651] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 12/08/2016] [Accepted: 12/16/2016] [Indexed: 11/22/2022]
Abstract
Background:Atrial fibrillation (AF) is associated with an increased risk of cardioembolic stroke. The risk of cardioembolism is not adequately reduced with the administration of oral anticoagulants, since a number of patients continue to experience thromboembolic events despite receiving treatment. Therefore, identification of a circulating biomarker to identify these high-risk patients would be clinically beneficial.Objective:In the present article, we aim to review the available data regarding use of biomarkers to predict cardioembolic stroke in patients with AF.Methods:We performed a thorough search of the literature in order to analyze the biomarkers identified thus far and critically evaluate their clinical significance.Results:A number of biomarkers have been proposed to predict cardioembolic stroke in patients with AF. Some of them are already used in the clinical practice, such as d-dimers, troponins and brain natriuretic peptide. Novel biomarkers, such as the inflammatory growth differentiation factor-15, appear to be promising, while the role of micro-RNAs and genetics appear to be useful as well. Even though these biomarkers are associated with an increased risk for thromboembolism, they cannot accurately predict future events. In light of this, the use of a scoring system, that would incorporate both circulating biomarkers and clinical factors, might be more useful.Conclusions:Recent research has disclosed several biomarkers as potential predictors of cardioembolic stroke in patients with AF. However, further research is required to establish a multifactorial scoring system that will identify patients at high-risk of thromboembolism, who would benefit from more intensive treatment and monitoring.
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Affiliation(s)
| | | | | | - Onkar Rehal
- University College London Hospital, London, United Kingdom
| | - Emma Sewart
- University College London Medical School, London, United Kingdom
| | - Effimia Zacharia
- 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Athens, Greece
| | - Konstantinos Toutouzas
- 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Athens, Greece
| | - Charalambos Vlachopoulos
- 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Athens, Greece
| | - Gerasimos Siasos
- 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Athens, Greece
| | - Costas Tsioufis
- 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Athens, Greece
| | - Dimitris Tousoulis
- 1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Athens, Greece
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Sandhu RK, Ezekowitz JA, Hijazi Z, Westerbergh J, Aulin J, Alexander JH, Granger CB, Halvorsen S, Hanna MS, Lopes RD, Siegbahn A, Wallentin L. Obesity paradox on outcome in atrial fibrillation maintained even considering the prognostic influence of biomarkers: insights from the ARISTOTLE trial. Open Heart 2018; 5:e000908. [PMID: 30487982 PMCID: PMC6242013 DOI: 10.1136/openhrt-2018-000908] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Revised: 09/22/2018] [Accepted: 10/17/2018] [Indexed: 12/25/2022] Open
Abstract
Objective We investigated the association between obesity and biomarkers indicating cardiac or renal dysfunction or inflammation and their interaction with obesity and outcomes. Methods A total of 14 753 patients in the Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation (ARISTOTLE) trial provided plasma samples at randomisation to apixaban or warfarin. Median follow-up was 1.9 years. Body Mass Index (BMI) was measured at baseline and categorised as normal, 18.5–25 kg/m2; overweight, >25 to <30 kg/m2; and obese, ≥30 kg/m2. We analysed the biomarkers high-sensitivity C reactive protein (hs-CRP), interleukin 6 (IL-6), growth differentiation factor-15 (GDF-15), troponin T and N-terminal B-type natriuretic peptide (NT-pro-BNP). Outcomes included stroke/systemic embolism (SE), myocardial infarction (MI), composite (stroke/SE, MI, or all-cause mortality), all-cause and cardiac mortality, and major bleeding. Results Compared with normal BMI, obese patients had significantly higher levels of hs-CRP and IL-6 and lower levels of GDF-15, troponin T and NT-pro-BNP. In multivariable analyses, higher compared with normal BMI was associated with a lower risk of all-cause mortality (overweight: HR 0.73 (95% CI 0.63 to 0.86); obese: 0.67 (0.56 to 0.80), p<0.0001), cardiac death (overweight: HR 0.74 (95% CI 0.60 to 0.93); obese: 0.71 (0.56 to 0.92), p=0.01) and composite endpoint (overweight: 0.80 (0.70 to 0.92); obese: 0.72 (0.62 to 0.84), p<0.0001). Conclusions Regardless of biomarkers indicating inflammation or cardiac or renal dysfunction, obesity was independently associated with an improved survival in anticoagulated patients with AF. Trial registration number NCT00412984.
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Affiliation(s)
- Roopinder K Sandhu
- Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.,Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada
| | - Justin A Ezekowitz
- Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.,Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada
| | - Ziad Hijazi
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.,Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
| | - Johan Westerbergh
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - Julia Aulin
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.,Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
| | - John H Alexander
- Duke Medicine, Duke Clinical Research Institute, Durham, North Carolina, USA
| | | | - Sigrun Halvorsen
- Department of Cardiology B, Oslo University Hospital Ulleval and University of Oslo, Oslo, Norway
| | - Michael S Hanna
- Bristol-Myers Squibb (Former Employee), Princeton, New Jersey, USA
| | - Renato D Lopes
- Duke Medicine, Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Agneta Siegbahn
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.,Department of Medical Sciences, Clinical Chemistry, University Hospital, Uppsala, Sweden
| | - Lars Wallentin
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.,Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
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Clinical utility of circulating interleukin-6 concentrations in the detection of functionally relevant coronary artery disease. Int J Cardiol 2018; 275:20-25. [PMID: 30340850 DOI: 10.1016/j.ijcard.2018.10.029] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 09/06/2018] [Accepted: 10/08/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND Inflammation plays a major role in the pathogenesis of coronary artery disease (CAD). METHODS We hypothesized, that quantifying inflammation by measuring circulating interleukin-6 concentrations help in the diagnosis and/or prediction of functionally relevant CAD. Among consecutive patients with symptoms suggestive of CAD, functionally relevant CAD was adjudicated in two domains: first, diagnosis according to myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography; second, cardiovascular death and all-cause death during 2-years follow-up. Adjudication was done blinded to the interleukin-6 concentrations. RESULTS Among 1553 patients, symptoms were adjudicated to be causally related to CAD in 43% (665/1553). Interleukin-6 concentrations were higher in patients with functionally relevant CAD as compared to those without (1.56 pg/mL versus 1.30 pg/mL, p < 0.001), but overall had only low-to-modest diagnostic accuracy (area under the curve [AUC]: 0.57, 95%CI 0.55-0.61) and were no independent predictor of functionally relevant CAD after multivariable adjustment (p = 0.068). Interleukin-6 concentrations had moderate-to-high accuracy in the prediction of cardiovascular death (AUC 0.75, 95%CI 0.69-0.82) and all-cause death (AUC 0.72, 95%CI 0.66-0.78) at 2-years, and remained a significant predictor after multivariable adjustment (p < 0.001). Compared to patients with interleukin-6 concentrations below the median (1.41 pg/mL), patients with concentrations above the median had a significantly higher cumulative incidence of cardiovascular death (1% vs. 4%, log-rank p < 0.001) and all-cause death (2% vs. 8%, log-rank p < 0.001) at 2 years. CONCLUSION Interleukin-6 concentrations are strong and independent predictors of cardiovascular death and all-cause death.
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Scott L, Li N, Dobrev D. Role of inflammatory signaling in atrial fibrillation. Int J Cardiol 2018; 287:195-200. [PMID: 30316645 DOI: 10.1016/j.ijcard.2018.10.020] [Citation(s) in RCA: 110] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Accepted: 10/03/2018] [Indexed: 01/09/2023]
Abstract
Atrial fibrillation (AF), the most prevalent arrhythmia, is often associated with enhanced inflammatory response. Emerging evidence points to a causal role of inflammatory signaling pathways in the evolution of atrial electrical, calcium handling and structural remodeling, which create the substrate of AF development. In this review, we discuss the clinical evidence supporting the association between inflammatory indices and AF development, the molecular and cellular mechanisms of AF, which appear to involve multiple canonical inflammatory pathways, and the potential of anti-inflammatory therapeutic approaches in AF prevention/treatment.
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Affiliation(s)
- Larry Scott
- Department of Medicine (Section of Cardiovascular Research), Baylor College of Medicine, Houston, TX, USA; Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, USA
| | - Na Li
- Department of Medicine (Section of Cardiovascular Research), Baylor College of Medicine, Houston, TX, USA; Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, USA; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX, USA.
| | - Dobromir Dobrev
- Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany.
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Zuzarte P, Scola G, Duong A, Kostiw K, Figueira ML, Costa-Vitali A. NT-proBNP is a potential mediator between reduced ejection fraction and depression in patients with heart failure. J Psychiatr Res 2018; 104:8-15. [PMID: 29913350 DOI: 10.1016/j.jpsychires.2018.06.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 05/26/2018] [Accepted: 06/08/2018] [Indexed: 01/08/2023]
Abstract
Depression and anxiety are prevalent in patients with heart failure (HF). Reduced ejection fraction (EF) and increased N-terminal-prohormone B-type natriuretic peptide (NT-proBNP) have been shown to be independently associated with depressive symptoms and may therefore increase HF disease progression and mortality. This study evaluated whether NT-proBNP mediated the impact of reduced EF on depressive and anxiety symptoms in patients with HF. Participants (n = 124) were patients with a diagnosis of chronic HF enrolled in the Heart Failure Disease Management Program at Health Sciences North. Subjects were assessed for depressive and anxiety symptoms according to the Hospital Anxiety and Depression Scale questionnaire at enrolment. Ejection fraction, measured through Multigated Acquisition Technique and NT-proBNP, measured through chemiluminescent immunoassay, were obtained at baseline. Patient outcomes were monitored for 12-months after enrollment. Associations were determined using regression and multivariate models. Indirect effects were assessed using mediation analysis. EF and NT-proBNP were highly correlated. Mediation analysis showed no significant direct effect of EF on the levels of depressive and anxiety symptoms, however, there was a significant indirect effect of EF on depression that was mediated by the levels of NT-proBNP, but not for EF and anxiety. Our results suggest that NT-proBNP is a potential mechanism linking reduced EF and depressive symptoms in patients with HF. While results are still preliminary, this study suggests that NT-proBNP may be a potential biomarker in identifying HF patients with reduced EF at high risk for depression, disease progression and mortality.
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Affiliation(s)
- Pedro Zuzarte
- Heart Failure Disease Management Program, Health Sciences North, Sudbury, Ontario, Canada; University of Lisbon, Faculty of Medicine, Lisbon, Portugal.
| | | | | | | | | | - Atilio Costa-Vitali
- Heart Failure Disease Management Program, Health Sciences North, Sudbury, Ontario, Canada; Cardiovascular CRO, Sudbury, ON, Canada
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Carvalho PM, Felício MR, Santos NC, Gonçalves S, Domingues MM. Application of Light Scattering Techniques to Nanoparticle Characterization and Development. Front Chem 2018; 6:237. [PMID: 29988578 PMCID: PMC6026678 DOI: 10.3389/fchem.2018.00237] [Citation(s) in RCA: 161] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 06/04/2018] [Indexed: 01/07/2023] Open
Abstract
Over the years, the scientific importance of nanoparticles for biomedical applications has increased. The high stability and biocompatibility, together with the low toxicity of the nanoparticles developed lead to their use as targeted drug delivery systems, bioimaging systems, and biosensors. The wide range of nanoparticles size, from 10 nm to 1 μm, as well as their optical properties, allow them to be studied using microscopy and spectroscopy techniques. In order to be effectively used, the physicochemical properties of nanoparticle formulations need to be taken into account, namely, particle size, surface charge distribution, surface derivatization and/or loading capacity, and related interactions. These properties need to be optimized considering the final nanoparticle intended biodistribution and target. In this review, we cover light scattering based techniques, namely dynamic light scattering and zeta-potential, used for the physicochemical characterization of nanoparticles. Dynamic light scattering is used to measure nanoparticles size, but also to evaluate their stability over time in suspension, at different pH and temperature conditions. Zeta-potential is used to characterize nanoparticles surface charge, obtaining information about their stability and surface interaction with other molecules. In this review, we focus on nanoparticle characterization and application in infection, cancer and cardiovascular diseases.
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Affiliation(s)
- Patrícia M Carvalho
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Mário R Felício
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Nuno C Santos
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Sónia Gonçalves
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Marco M Domingues
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
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Horjen AW, Ulimoen SR, Norseth J, Svendsen JH, Smith P, Arnesen H, Seljeflot I, Tveit A. High-sensitivity troponin I in persistent atrial fibrillation - relation to NT-proBNP and markers of inflammation and haemostasis. Scandinavian Journal of Clinical and Laboratory Investigation 2018; 78:386-392. [PMID: 29933716 DOI: 10.1080/00365513.2018.1481224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
PURPOSE As cardiac troponins emerge as prognostic markers in atrial fibrillation (AF), it is important to identify mechanisms initiating and perpetuating cardiac troponin release, including its relations to other circulating biomarkers, in AF populations. We studied associations between high-sensitivity troponin I (hs-TnI) and markers representing myocardial wall tension, inflammation and haemostasis in persistent AF. METHODS In a double blind, placebo-controlled study, 171 patients referred for electrical cardioversion for persistent AF were randomised to receive candesartan or placebo for 3-6 weeks before and 6 months after cardioversion. Associations between baseline levels of hs-TnI and other biomarkers were investigated by bivariate non-parametric correlations (Spearman's correlation coefficient denoted rs). RESULTS Baseline levels of hs-TnI correlated significantly, although weakly, with interleukin-6 (rs = 0.260, p = .003), N-terminal pro-B-type natriuretic peptide (rs = 0.251, p = .004), tissue-plasminogen activator antigen (rs = 0.233, p = .008), D-dimer (rs = 0.220, p = .013), E-selectin (rs = 0.207, p = .019), high-sensitivity C-reactive protein (rs = 0.202, p = .022) and vascular cell adhesion molecule-1 (rs = 0.189, p = .032). CONCLUSIONS Hs-TnI correlated weakly with biomarkers representing myocardial wall tension, inflammation and haemostasis in persistent AF. The lack of any strong correlation between hs-TnI and the investigated biomarkers is in concert with the idea that hs-TnI release is an independent process parallel to other pathophysiological mechanisms associated with AF.
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Affiliation(s)
- Anja Wiedswang Horjen
- a Department of Medical Research , Baerum Hospital, Vestre Viken Hospital Trust , Drammen , Norway.,b Faculty of Medicine , University of Oslo , Oslo, Norway
| | - Sara Reinvik Ulimoen
- a Department of Medical Research , Baerum Hospital, Vestre Viken Hospital Trust , Drammen , Norway
| | - Jon Norseth
- c Clinic for Medical Diagnostics, Vestre Viken Hospital Trust , Drammen , Norway
| | - Jesper Hastrup Svendsen
- d Department of Cardiology , Rigshospitalet, University of Copenhagen , Copenhagen Ø , Denmark
| | - Pål Smith
- b Faculty of Medicine , University of Oslo , Oslo, Norway.,e Department of Cardiology , Akershus University Hospital , Lørenskog , Norway
| | - Harald Arnesen
- b Faculty of Medicine , University of Oslo , Oslo, Norway.,f Center for Clinical Heart Research, Department of Cardiology , Oslo University Hospital Ullevål , Oslo , Norway
| | - Ingebjørg Seljeflot
- b Faculty of Medicine , University of Oslo , Oslo, Norway.,f Center for Clinical Heart Research, Department of Cardiology , Oslo University Hospital Ullevål , Oslo , Norway
| | - Arnljot Tveit
- a Department of Medical Research , Baerum Hospital, Vestre Viken Hospital Trust , Drammen , Norway.,b Faculty of Medicine , University of Oslo , Oslo, Norway
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