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Pamies A, Vallvé JC, Paredes S. New Cardiovascular Risk Biomarkers in Rheumatoid Arthritis: Implications and Clinical Utility-A Narrative Review. Biomedicines 2025; 13:870. [PMID: 40299461 PMCID: PMC12025197 DOI: 10.3390/biomedicines13040870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 03/28/2025] [Accepted: 04/02/2025] [Indexed: 04/30/2025] Open
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease that not only causes joint inflammation but also significantly increases the risk of cardiovascular disease (CVD), leading to a higher morbidity and mortality. RA patients face an accelerated progression of atherosclerosis, attributed to both traditional cardiovascular risk factors and systemic inflammation. This review focuses on emerging biomarkers for cardiovascular risk assessment in RA, aiming to enhance early detection and treatment strategies. Specifically, we examine the roles of interleukin-32 (IL-32), Dickkopf-1 (DKK-1), galectin-3 (Gal-3), catestatin (CST), and fetuin-A (Fet-A) as potential markers for CVD in this patient population. IL-32, a proinflammatory cytokine, is elevated in RA patients and plays a significant role in inflammation and endothelial dysfunction, both of which contribute to atherosclerosis. DKK-1, a Wnt signaling pathway inhibitor, has been associated with both synovial inflammation and the development of atherosclerotic plaques. Elevated DKK-1 levels have been linked to an increased CV mortality and could serve as a marker for CVD progression in RA. Gal-3 is involved in immune modulation and fibrosis, with elevated levels in RA patients correlating with disease activity and cardiovascular outcomes. Catestatin, a peptide derived from chromogranin A, has protective anti-inflammatory and antioxidative properties, though its role in RA-related CVD remains under investigation. Finally, Fet-A, a glycoprotein involved in vascular calcification, shows potential as a biomarker for CV events in RA, though data on its role remain conflicting. These biomarkers provide deeper insights into the pathophysiology of RA and its cardiovascular comorbidities. Although some biomarkers show promise in improving CV risk stratification, further large-scale studies are required to validate their clinical utility. Currently, these biomarkers are in the research phase and are not yet implemented in standard care. Identifying and incorporating these biomarkers into routine clinical practice could lead to the better management of cardiovascular risk in RA patients, thus improving outcomes in this high-risk population. This review highlights the importance of continued research to establish reliable biomarkers that can aid in both diagnosis and the development of targeted therapies for cardiovascular complications in RA.
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Affiliation(s)
- Anna Pamies
- Secció de Reumatologia, Hospital de Tortosa Verge de la Cinta, 43500 Tortosa, Catalonia, Spain;
| | - Joan-Carles Vallvé
- Unitat de Recerca en Lípids i Arterioesclerosi, Universitat Rovira i Virgili, 43204 Reus, Catalonia, Spain;
- Institut Investigació Sanitaria Pere Virgili, 43204 Reus, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Silvia Paredes
- Unitat de Recerca en Lípids i Arterioesclerosi, Universitat Rovira i Virgili, 43204 Reus, Catalonia, Spain;
- Institut Investigació Sanitaria Pere Virgili, 43204 Reus, Catalonia, Spain
- Secció de Reumatologia, Hospital Universitari Sant Joan de Reus, 43204 Reus, Catalonia, Spain
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Kulpa J, Paduch J, Szczepanik M, Gorący-Rosik A, Rosik J, Tchórz M, Pawlik A, Gorący J. Catestatin in Cardiovascular Diseases. Int J Mol Sci 2025; 26:2417. [PMID: 40141061 PMCID: PMC11942146 DOI: 10.3390/ijms26062417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/03/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Cardiovascular diseases are one of the leading causes of mortality and morbidity worldwide. The pathogenesis of this group of disorders is highly complex and involves interactions between various cell types and substances, among others, catestatin (CTS). In recent years, numerous researchers have expanded our knowledge about CTS's role in development and its potential for the treatment of a variety of diseases. In this review, the authors discuss CTS's importance in the pathogenesis of arterial hypertension, coronary artery disease, and heart failure. Moreover, we present CTS's influence on heart and vessel function.
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Affiliation(s)
- Joanna Kulpa
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (J.K.); (J.P.); (M.S.); (M.T.); (A.P.)
| | - Jarosław Paduch
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (J.K.); (J.P.); (M.S.); (M.T.); (A.P.)
| | - Marcin Szczepanik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (J.K.); (J.P.); (M.S.); (M.T.); (A.P.)
| | - Anna Gorący-Rosik
- Independent Laboratory of Invasive Cardiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (A.G.-R.); (J.G.)
| | - Jakub Rosik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (J.K.); (J.P.); (M.S.); (M.T.); (A.P.)
| | - Magdalena Tchórz
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (J.K.); (J.P.); (M.S.); (M.T.); (A.P.)
| | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (J.K.); (J.P.); (M.S.); (M.T.); (A.P.)
| | - Jarosław Gorący
- Independent Laboratory of Invasive Cardiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (A.G.-R.); (J.G.)
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Pàmies A, Llop D, Ibarretxe D, Rosales R, Girona J, Masana L, Vallvé JC, Paredes S. Enhanced Association of Novel Cardiovascular Biomarkers Fetuin-A and Catestatin with Serological and Inflammatory Markers in Rheumatoid Arthritis Patients. Int J Mol Sci 2024; 25:9910. [PMID: 39337398 PMCID: PMC11431854 DOI: 10.3390/ijms25189910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 09/09/2024] [Accepted: 09/11/2024] [Indexed: 09/30/2024] Open
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with increased cardiovascular disease (CVD) risk and mortality. This work aimed to evaluate the serum levels of the novel CV biomarkers fetuin-A (fet-A), Dickkopf-1 (DKK-1), galectin-3 (Gal-3), interleukin-32 (IL-32), and catestatin (CST) in RA patients and their associations with RA parameters and CVD markers. A cohort of 199 RA patients was assessed for traditional CVD risk factors, RA disease activity, and biomarker levels. Carotid ultrasound was used to measure carotid intima-media thickness (cIMT) and carotid plaque presence (cPP). Multivariate analyses examined correlations between biomarkers and RA parameters, serological markers, and CVD markers. Adjusted models showed that elevated CST expression levels were associated with rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity (OR = 2.45, p = 0.0001 and OR = 1.48, p = 0.04, respectively) in the overall cohort and for RF in men and women, respectively. In addition, fet-A concentration was inversely associated with the erythrocyte sedimentation rate (ESR) in the overall cohort (β = -0.15, p = 0.038) and in women (β = -0.25, p = 0.004). Fet-A levels were also negatively correlated with disease activity (DAS28-ESR) scores (β = -0.29, p = 0.01) and fibrinogen concentration (β = -0.22, p = 0.01) in women. No adjusted associations were observed for Gal-3, DKK-1 or IL32 concentration. The study revealed no significant associations between the biomarkers and cIMT or cPP. The measurement of CST and fet-A levels could enhance RA patient management and prognosis. However, the utility of biomarkers for evaluating CV risk via traditional surrogate markers is limited, highlighting the need for continued investigations into their roles in RA.
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Affiliation(s)
- Anna Pàmies
- Secció de Reumatologia, Hospital Verge de la Cinta, 43500 Tortosa, Spain;
| | - Dídac Llop
- Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, 43201 Reus, Spain; (D.L.); (D.I.); (R.R.); (J.G.); (L.M.); (S.P.)
- Institut Investigació Sanitaria Pere Virgili, 43204 Reus, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Daiana Ibarretxe
- Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, 43201 Reus, Spain; (D.L.); (D.I.); (R.R.); (J.G.); (L.M.); (S.P.)
- Institut Investigació Sanitaria Pere Virgili, 43204 Reus, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
- Unitat Medicina Vascular i Metabolisme, Hospital Universitari Sant Joan de Reus, 43204 Reus, Spain
| | - Roser Rosales
- Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, 43201 Reus, Spain; (D.L.); (D.I.); (R.R.); (J.G.); (L.M.); (S.P.)
- Institut Investigació Sanitaria Pere Virgili, 43204 Reus, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Josefa Girona
- Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, 43201 Reus, Spain; (D.L.); (D.I.); (R.R.); (J.G.); (L.M.); (S.P.)
- Institut Investigació Sanitaria Pere Virgili, 43204 Reus, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Lluís Masana
- Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, 43201 Reus, Spain; (D.L.); (D.I.); (R.R.); (J.G.); (L.M.); (S.P.)
- Institut Investigació Sanitaria Pere Virgili, 43204 Reus, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
- Unitat Medicina Vascular i Metabolisme, Hospital Universitari Sant Joan de Reus, 43204 Reus, Spain
| | - Joan-Carles Vallvé
- Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, 43201 Reus, Spain; (D.L.); (D.I.); (R.R.); (J.G.); (L.M.); (S.P.)
- Institut Investigació Sanitaria Pere Virgili, 43204 Reus, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Silvia Paredes
- Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, 43201 Reus, Spain; (D.L.); (D.I.); (R.R.); (J.G.); (L.M.); (S.P.)
- Institut Investigació Sanitaria Pere Virgili, 43204 Reus, Spain
- Secció de Reumatologia, Hospital Universitari Sant Joan de Reus, 43204 Reus, Spain
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Zito A, Restivo A, Ciliberti G, Laborante R, Princi G, Romiti GF, Galli M, Rodolico D, Bianchini E, Cappannoli L, D'Oria M, Trani C, Burzotta F, Cesario A, Savarese G, Crea F, D'Amario D. Heart failure management guided by remote multiparameter monitoring: A meta-analysis. Int J Cardiol 2023; 388:131163. [PMID: 37429443 DOI: 10.1016/j.ijcard.2023.131163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 07/01/2023] [Accepted: 07/05/2023] [Indexed: 07/12/2023]
Abstract
BACKGROUND Several implant-based remote monitoring strategies are currently tested to optimize heart failure (HF) management by anticipating clinical decompensation and preventing hospitalization. Among these solutions, the modern implantable cardioverter-defibrillator and cardiac resynchronization therapy devices have been equipped with sensors allowing continuous monitoring of multiple preclinical markers of worsening HF, including factors of autonomic adaptation, patient activity, and intrathoracic impedance. OBJECTIVES We aimed to assess whether implant-based multiparameter remote monitoring strategy for guided HF management improves clinical outcomes when compared to standard clinical care. METHODS A systematic literature research for randomized controlled trials (RCTs) comparing multiparameter-guided HF management versus standard of care was performed on PubMed, Embase, and CENTRAL databases. Incidence rate ratios (IRRs) and associated 95% confidence intervals (CIs) were calculated using the Poisson regression model with random study effects. The primary outcome was a composite of all-cause death and HF hospitalization events, whereas secondary endpoints included the individual components of the primary outcome. RESULTS Our meta-analysis included 6 RCTs, amounting to a total of 4869 patients with an average follow-up time of 18 months. Compared with standard clinical management, the multiparameter-guided strategy reduced the risk of the primary composite outcome (IRR 0.83, 95%CI 0.71-0.99), driven by statistically significant effect on both HF hospitalization events (IRR 0.75, 95%CI 0.61-0.93) and all-cause death (IRR 0.80, 95%CI 0.66-0.96). CONCLUSION Implant-based multiparameter remote monitoring strategy for guided HF management is associated with significant benefit on clinical outcomes compared to standard clinical care, providing a benefit on both hospitalization events and all-cause death.
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Affiliation(s)
- Andrea Zito
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Attilio Restivo
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Giuseppe Ciliberti
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Renzo Laborante
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Giuseppe Princi
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Giulio Francesco Romiti
- Department of Translational and Precision Medicine, Sapienza - University of Rome, Rome, Italy
| | - Mattia Galli
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy; Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy
| | - Daniele Rodolico
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Emiliano Bianchini
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Luigi Cappannoli
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy
| | - Marika D'Oria
- Open Innovation Unit, Scientific Directorate, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Carlo Trani
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy; Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Francesco Burzotta
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy; Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Alfredo Cesario
- Open Innovation Unit, Scientific Directorate, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; CEO, Gemelli Digital Medicine & Health Srl, Rome, Italy
| | - Gianluigi Savarese
- Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Filippo Crea
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy; Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Domenico D'Amario
- Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Department of Translational Medicine, University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy.
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Qiu Z, Fan Y, Wang Z, Huang F, Li Z, Sun Z, Hua S, Jin W, Chen Y. Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species Generation. J Am Heart Assoc 2023; 12:e029470. [PMID: 37119063 PMCID: PMC10227223 DOI: 10.1161/jaha.123.029470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 03/30/2023] [Indexed: 04/30/2023]
Abstract
Background Catestatin has been reported as a pleiotropic cardioprotective peptide. Heart failure with preserved ejection fraction (HFpEF) was considered a heterogeneous syndrome with a complex cause. We sought to investigate the role of catestatin in HFpEF and diastolic dysfunction. METHODS AND RESULTS Administration of recombinant catestatin (1.5 mg/kg/d) improved diastolic dysfunction and left ventricular chamber stiffness in transverse aortic constriction mice with deoxycorticosterone acetate pellet implantation, as reflected by Doppler tissue imaging and pressure-volume loop catheter. Less cardiac hypertrophy and myocardial fibrosis was observed, and transcriptomic analysis revealed downregulation of mitochondrial electron transport chain components after catestatin treatment. Catestatin reversed mitochondrial structural and respiratory chain component abnormality, decreased mitochondrial proton leak, and reactive oxygen species generation in myocardium. Excessive oxidative stress induced by Ru360 abolished catestatin treatment effects on HFpEF-like cardiomyocytes in vitro, indicating the beneficial role of catestatin in HFpEF as a mitochondrial ETC modulator. The serum concentration of catestatin was tested among 81 patients with HFpEF and 76 non-heart failure controls. Compared with control subjects, serum catestatin concentration was higher in patients with HFpEF and positively correlated with E velocity to mitral annular e' velocity ratio, indicating a feedback compensation role of catestatin in HFpEF. Conclusions Catestatin protects against diastolic dysfunction in HFpEF through attenuating mitochondrial electron transport chain-derived reactive oxygen species generation. Serum catestatin concentration is elevated in patients with HFpEF, probably as a relatively insufficient but self-compensatory mechanism.
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Affiliation(s)
- Zeping Qiu
- Department of Cardiovascular Medicine, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
- Institute of Cardiovascular DiseasesShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
| | - Yingze Fan
- Department of Cardiovascular Medicine, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
- Institute of Cardiovascular DiseasesShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
| | - Zhiyan Wang
- Department of Cardiovascular Medicine, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
- Institute of Cardiovascular DiseasesShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
| | - Fanyi Huang
- Department of Cardiovascular Medicine, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
- Institute of Cardiovascular DiseasesShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
| | - Zhuojin Li
- Department of Cardiovascular Medicine, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
- Institute of Cardiovascular DiseasesShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
| | - Zhihong Sun
- Department of Cardiovascular Medicine, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
- Institute of Cardiovascular DiseasesShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
| | - Sha Hua
- Institute of Cardiovascular DiseasesShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
- Heart Failure Center, Ruijin Hospital, & Lu Wan BranchShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Wei Jin
- Department of Cardiovascular Medicine, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
- Institute of Cardiovascular DiseasesShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
- Heart Failure Center, Ruijin Hospital, & Lu Wan BranchShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Yanjia Chen
- Department of Cardiovascular Medicine, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
- Institute of Cardiovascular DiseasesShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
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Serum Catestatin Concentrations Are Increased in Patients with Atrial Fibrillation. J Cardiovasc Dev Dis 2023; 10:jcdd10020085. [PMID: 36826581 PMCID: PMC9965955 DOI: 10.3390/jcdd10020085] [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: 12/11/2022] [Revised: 01/25/2023] [Accepted: 02/14/2023] [Indexed: 02/19/2023] Open
Abstract
The autonomic nervous system is crucial in initiating and maintaining atrial fibrillation (AF). Catestatin is a multipurpose peptide that regulates cardiovascular systems and reduces harmful, excessive activity of the sympathetic nervous system by blocking the release of catecholamines. We aimed to determine whether serum catestatin concentrations are associated with AF severity, duration indices, and various clinical and laboratory indicators in these individuals to better define the clinical value of catestatin in patients with AF. The present single center study enrolled 73 participants with AF and 72 healthy age-matched controls. Serum catestatin concentrations were markedly higher in AF patients than controls (14.11 (10.21-26.02) ng/mL vs. 10.93 (5.70-20.01) ng/mL, p = 0.013). Furthermore, patients with a more severe form of AF had significantly higher serum catestatin (17.56 (12.80-40.35) vs. 10.98 (8.38-20.91) ng/mL, p = 0.001). Patients with higher CHA2DS2-VASc scores (17.58 (11.89-37.87) vs. 13.02 (8.47-22.75) ng/mL, p = 0.034) and higher NT-proBNP levels (17.58 (IQR 13.91-34.62) vs. 13.23 (IQR 9.04-22.61), p = 0.036) had significantly higher serum catestatin concentrations. Finally, AF duration correlated negatively with serum catestatin levels (r = -0.348, p = 0.003). The results of the present study implicate the promising role of catestatin in the intricate pathophysiology of AF, which should be explored in future research.
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Alieva AM, Teplova NV, Reznik EV, Ettinger OA, Faradzhov RA, Khachirova EA, Kovtiukh IV, Kotikova IA, Sysoeva DA, Bigushev IR, Nikitin IG. Catestanin – a promising biological marker for heart failure: A review. CONSILIUM MEDICUM 2022. [DOI: 10.26442/20751753.2022.10.201873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The epidemic of heart failure (HF) is one of the problems that the global health system has been facing for decades. HF is a multicomponent clinical syndrome caused by dysfunction of the heart and its pathological remodeling. In addition to the well-known natriuretic peptides, a number of cardiovascular biological markers have now been identified that provide clinicians with additional opportunities in diagnosing, classifying, predicting, and monitoring the effectiveness of treating patients with HF. From the position of establishing the sympathetic load in patients with HF, it seems very promising to assess the concentrations of catestatin. The presented data of our literature review suggest that catestatin is probably a reliable biological marker of the activity of the sympathetic division of the autonomic nervous system, and its elevated concentrations in patients with HF reflect the severity of the pathological process. However, despite the reliable results of studies, the clinical significance of assessing the values of this marker both separately and in the framework of a multimarker model requires further study in larger prospective clinical studies.
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Cosgriff CV, Miano TA, Mathew D, Huang AC, Giannini HM, Kuri-Cervantes L, Pampena MB, Ittner CAG, Weisman AR, Agyekum RS, Dunn TG, Oniyide O, Turner AP, D'Andrea K, Adamski S, Greenplate AR, Anderson BJ, Harhay MO, Jones TK, Reilly JP, Mangalmurti NS, Shashaty MGS, Betts MR, Wherry EJ, Meyer NJ. Validating a Proteomic Signature of Severe COVID-19. Crit Care Explor 2022; 4:e0800. [PMID: 36479446 PMCID: PMC9722553 DOI: 10.1097/cce.0000000000000800] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
COVID-19 is a heterogenous disease. Biomarker-based approaches may identify patients at risk for severe disease, who may be more likely to benefit from specific therapies. Our objective was to identify and validate a plasma protein signature for severe COVID-19. DESIGN Prospective observational cohort study. SETTING Two hospitals in the United States. PATIENTS One hundred sixty-seven hospitalized adults with COVID-19. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS We measured 713 plasma proteins in 167 hospitalized patients with COVID-19 using a high-throughput platform. We classified patients as nonsevere versus severe COVID-19, defined as the need for high-flow nasal cannula, mechanical ventilation, extracorporeal membrane oxygenation, or death, at study entry and in 7-day intervals thereafter. We compared proteins measured at baseline between these two groups by logistic regression adjusting for age, sex, symptom duration, and comorbidities. We used lead proteins from dysregulated pathways as inputs for elastic net logistic regression to identify a parsimonious signature of severe disease and validated this signature in an external COVID-19 dataset. We tested whether the association between corticosteroid use and mortality varied by protein signature. One hundred ninety-four proteins were associated with severe COVID-19 at the time of hospital admission. Pathway analysis identified multiple pathways associated with inflammatory response and tissue repair programs. Elastic net logistic regression yielded a 14-protein signature that discriminated 90-day mortality in an external cohort with an area under the receiver-operator characteristic curve of 0.92 (95% CI, 0.88-0.95). Classifying patients based on the predicted risk from the signature identified a heterogeneous response to treatment with corticosteroids (p = 0.006). CONCLUSIONS Inpatients with COVID-19 express heterogeneous patterns of plasma proteins. We propose a 14-protein signature of disease severity that may have value in developing precision medicine approaches for COVID-19 pneumonia.
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Affiliation(s)
- Christopher V Cosgriff
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Todd A Miano
- Department of Epidemiology, Biostatistics, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Divij Mathew
- Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Alexander C Huang
- Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Parker Institute for Cancer Immunotherapy, Philadelphia, PA
- Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
| | - Heather M Giannini
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Leticia Kuri-Cervantes
- Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - M Betina Pampena
- Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Caroline A G Ittner
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Ariel R Weisman
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Roseline S Agyekum
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Thomas G Dunn
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Oluwatosin Oniyide
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Alexandra P Turner
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Kurt D'Andrea
- Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Sharon Adamski
- Immune Health Project, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Allison R Greenplate
- Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Immune Health Project, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Brian J Anderson
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Michael O Harhay
- Department of Epidemiology, Biostatistics, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Tiffanie K Jones
- Department of Epidemiology, Biostatistics, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - John P Reilly
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Nilam S Mangalmurti
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Lung Biology Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Michael G S Shashaty
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Michael R Betts
- Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - E John Wherry
- Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Parker Institute for Cancer Immunotherapy, Philadelphia, PA
| | - Nuala J Meyer
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Center for Translational Lung Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Lung Biology Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
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9
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Mohan IK, Baba KSSS, Iyyapu R, Thirumalasetty S, Satish OS. Advances in congestive heart failure biomarkers. Adv Clin Chem 2022; 112:205-248. [PMID: 36642484 DOI: 10.1016/bs.acc.2022.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Congestive heart failure (CHF) is the leading cause of morbidity and mortality in the elderly worldwide. Although many biomarkers associated with in heart failure, these are generally prognostic and identify patients with moderate and severe disease. Unfortunately, the role of biomarkers in decision making for early and advanced heart failure remains largely unexplored. Previous studies suggest the natriuretic peptides have the potential to improve the diagnosis of heart failure, but they still have significant limitations related to cut-off values. Although some promising cardiac biomarkers have emerged, comprehensive data from large cohort studies is lacking. The utility of multiple biomarkers that reflect various pathophysiologic pathways are increasingly being explored in heart failure risk stratification and to diagnose disease conditions promptly and accurately. MicroRNAs serve as mediators and/or regulators of renin-angiotensin-induced cardiac remodeling by directly targeting enzymes, receptors and signaling molecules. The role of miRNA in HF diagnosis is a promising area of research and further exploration may offer both diagnostic and prognostic applications and phenotype-specific targets. In this review, we provide insight into the classification of different biochemical and molecular markers associated with CHF, examine clinical usefulness in CHF and highlight the most clinically relevant.
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Affiliation(s)
| | - K S S Sai Baba
- Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad, Telangana, India
| | - Rohit Iyyapu
- Katuri Medical College & Hospital, Guntur, Andhra Pradesh, India
| | | | - O Sai Satish
- Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad, Telangana, India
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10
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Zalewska E, Kmieć P, Sworczak K. Role of Catestatin in the Cardiovascular System and Metabolic Disorders. Front Cardiovasc Med 2022; 9:909480. [PMID: 35665253 PMCID: PMC9160393 DOI: 10.3389/fcvm.2022.909480] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 04/25/2022] [Indexed: 12/19/2022] Open
Abstract
Catestatin is a multifunctional peptide that is involved in the regulation of the cardiovascular and immune systems as well as metabolic homeostatis. It mitigates detrimental, excessive activity of the sympathetic nervous system by inhibiting catecholamine secretion. Based on in vitro and in vivo studies, catestatin was shown to reduce adipose tissue, inhibit inflammatory response, prevent macrophage-driven atherosclerosis, and regulate cytokine production and release. Clinical studies indicate that catestatin may influence the processes leading to hypertension, affect the course of coronary artery diseases and heart failure. This review presents up-to-date research on catestatin with a particular emphasis on cardiovascular diseases based on a literature search.
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11
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Simac P, Perkovic D, Bozic I, Matijas M, Gugo K, Martinovic D, Bozic J. Serum catestatin levels in patients with rheumatoid arthritis. Sci Rep 2022; 12:3812. [PMID: 35264632 PMCID: PMC8907353 DOI: 10.1038/s41598-022-07735-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Accepted: 02/24/2022] [Indexed: 02/07/2023] Open
Abstract
Catestatin (CST) is an important peptide that influences various inflammatory diseases. Our goal was to investigate CST concentrations in patients with RA compared to healthy subjects. This cross-sectional observational study included 80 patients with RA and 80 healthy control subjects. Demographic characteristics and laboratory parameters were recorded. Serum CST levels were determined by an enzyme-linked immunosorbent assay (ELISA). Serum CST levels were significantly higher in RA patients than in the control group (10.53 ± 3.90 vs 5.24 ± 2.37 ng/mL, p < 0.001). In RA patients, there was a statistically significant correlation between CST and patient age (r = 0.418, p < 0.001) and both DAS28 (r = 0.469, p < 0.001) and HAQ scores (r = 0.483, p < 0.001). There was a statistically significant correlation between serum CST levels and RA duration (r = 0.583, p < 0.001). Multiple linear regression analysis showed that serum CST levels retained a significant association with RA duration (β ± SE, 0.13 ± 0.04, p = 0.002) and DAS28 score (0.94 ± 0.45, p = 0.039) after model adjustment for age, body mass index (BMI) and HAQ score, with serum CST levels as a dependent variable. These findings imply that CST is possibly associated with RA complex pathophysiology and disease activity. However, future larger multicentric longitudinal studies are necessary to define the role of CST in RA.
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Affiliation(s)
- Petra Simac
- Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, University Hospital of Split, Split, Croatia.
| | - Dijana Perkovic
- Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, University Hospital of Split, Split, Croatia
| | - Ivona Bozic
- Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, University Hospital of Split, Split, Croatia
| | - Marijana Matijas
- Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, University Hospital of Split, Split, Croatia
| | - Katarina Gugo
- Department of Medical Laboratory Diagnostics, University Hospital of Split, 21000, Split, Croatia
| | - Dinko Martinovic
- Department of Pathophysiology, School of Medicine, University of Split, 21000, Split, Croatia
| | - Josko Bozic
- Department of Pathophysiology, School of Medicine, University of Split, 21000, Split, Croatia
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12
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Xu WX, Fan YY, Song Y, Liu X, Liu H, Guo LJ. Prognostic differences of catestatin among young and elderly patients with acute myocardial infarction. World J Emerg Med 2022; 13:169-174. [PMID: 35646208 PMCID: PMC9108920 DOI: 10.5847/wjem.j.1920-8642.2022.055] [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: 12/20/2021] [Accepted: 03/16/2022] [Indexed: 01/20/2024] Open
Abstract
BACKGROUND Previous studies have reported inconsistent findings regarding the association between catestatin and outcomes of acute myocardial infarction (AMI). This study aims to investigate the prognostic value of catestatin for long-term outcomes in patients with AMI. METHODS One hundred and sixty-five patients with AMI were enrolled in this series. The plasma catestatin levels at baseline and clinical data were collected. All patients were followed up for four years to investigate whether there were major adverse cardiovascular events (MACEs), including cardiovascular death, recurrent AMI, rehospitalization for heart failure, and revascularization. RESULTS There were 24 patients who had MACEs during the follow-up period. The MACEs group had significantly lower plasma catestatin levels (0.74±0.49 ng/mL vs. 1.10±0.79 ng/mL, P=0.033) and were older (59.0±11.4 years old vs. 53.2±12.8 years old, P=0.036). The rate of MACEs was significantly higher in the elderly group (≥60 years old) than in the young group (<60 years old) (23.8% [15/63] vs. 8.8% [9/102], P=0.008). The catestatin level was significantly lower in the MACEs group than that in the non-MACEs group (0.76±0.50 ng/mL vs. 1.31±0.77 ng/mL, P=0.012), and catestatin was significantly associated with MACEs (Kaplan Meier, P=0.007) among the elderly group, but not in the young group (Kaplan Meier, P=0.893). In the Cox proportional hazards regression, high catestatin was one of the independent factors for predicting MACEs after adjustment for other risk factors (hazard ratio 0.19, 95% confidence interval 0.06-0.62, P=0.006) among elderly patients. CONCLUSIONS Elderly AMI patients with lower plasma catestatin levels are more likely to develop MACEs. Catestatin may be a novel marker for the long-term prognosis of AMI, especially in elderly patients.
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Affiliation(s)
- Wei-xian Xu
- Department of Cardiology, Peking University Third Hospital, Beijing 100191, China
| | - Yuan-yuan Fan
- Department of Cardiology, Peking University Third Hospital, Beijing 100191, China
| | - Yao Song
- Department of Cardiology, Peking University Third Hospital, Beijing 100191, China
| | - Xin Liu
- Department of Cardiology, Peking University Third Hospital, Beijing 100191, China
| | - Hui Liu
- Department of Cardiology, Peking University Third Hospital, Beijing 100191, China
| | - Li-jun Guo
- Department of Cardiology, Peking University Third Hospital, Beijing 100191, China
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13
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Vasostatin-1 as a potential novel circulating biomarker in patients with chronic systolic heart failure: A pilot study. Clin Chim Acta 2021; 526:49-54. [PMID: 34973182 DOI: 10.1016/j.cca.2021.12.024] [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: 11/17/2021] [Revised: 12/20/2021] [Accepted: 12/26/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND AND AIMS Previous studies have shown that circulating chromogranin A (CgA) increases in patients with chronic systolic heart failure (HF). Aim of the present study is to evaluate the potential role of circulating vasostatin-1 (VS-1), a cardioregulatory fragment of CgA, as prognostic marker in patients with chronic HF. MATERIALS AND METHODS The plasma levels of CgA and VS-1 were determined in 80 patients with chronic systolic HF. Patients were followed-up to evaluate the occurrence of cardiovascular (CV) events. RESULTS CgA and VS-1 plasma levels were significantly higher in patients with CV events at follow-up. VS-1, but not CgA, was associated to NT-proBNP. No significant association of CgA and VS-1 with left ventricular ejection fraction (LVEF) was observed. CgA, NT-proBNP and age, but not VS-1, were independent predictors of CV events. CONCLUSION In patients with chronic systolic HF those who experienced CV events had higher levels of VS-1 and CgA. Given its established effect on cardiac cells, the association of VS-1 levels with NT-proBNP levels but not with LVEF, suggests that this fragment might provide complementary information to NT-proBNP and CgA in HF patients.
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14
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Rezar R, Paar V, Seelmaier C, Pretsch I, Schwaiger P, Kopp K, Kaufmann R, Felder TK, Prinz E, Gemes G, Pistulli R, Hoppe UC, Wernly B, Lichtenauer M. Soluble suppression of tumorigenicity 2 as outcome predictor after cardiopulmonary resuscitation: an observational prospective study. Sci Rep 2021; 11:21756. [PMID: 34741120 PMCID: PMC8571342 DOI: 10.1038/s41598-021-01389-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 10/27/2021] [Indexed: 11/09/2022] Open
Abstract
Prognostication after cardiopulmonary resuscitation (CPR) is complex. Novel biomarkers like soluble suppression of tumorigenicity 2 (sST2) may provide an objective approach. A total of 106 post-CPR patients were included in this single-center observational prospective study. Serum sST2 levels were obtained 24 h after admission. Individuals were assigned to two groups: patients below and above the overall cohort’s median sST2 concentration. Primary outcome was a combined endpoint at 6 months (death or Cerebral Performance Category > 2); secondary endpoint 30-day mortality. A uni- and multivariate logistic regression analysis were conducted. Elevated sST2-levels were associated with an increased risk for the primary outcome (OR 1.011, 95% CI 1.004–1.019, p = 0.004), yet no patients with poor neurological outcome were observed at 6 months. The optimal empirical cut-off for sST2 was 46.15 ng/ml (sensitivity 81%, specificity 53%, AUC 0.69). Levels above the median (> 53.42 ng/ml) were associated with higher odds for both endpoints (death or CPC > 2 after 6 months: 21% vs. 49%, OR 3.59, 95% CI 1.53–8.45, p = 0.003; death after 30 days: 17% vs. 43.3%, OR 3.75, 95% CI 1.52–9.21, p = 0.003). A positive correlation of serum sST2 after CPR with mortality at 30 days and 6 months after cardiac arrest could be demonstrated.
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Affiliation(s)
- Richard Rezar
- Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, Salzburg, Austria.
| | - Vera Paar
- Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Clemens Seelmaier
- Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Ingrid Pretsch
- Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Philipp Schwaiger
- Department of Anaesthesiology, Perioperative Medicine and Intensive Care Medicine, Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Kristen Kopp
- Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Reinhard Kaufmann
- Department of Radiology, Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Thomas K Felder
- Department of Laboratory Medicine, Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Erika Prinz
- Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Geza Gemes
- Department of Anaesthesiology and Intensive Care Medicine, Krankenhaus Der Barmherzigen Brüder Graz, Graz, Austria
| | - Rudin Pistulli
- Department of Cardiology I-Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Münster, Münster, Germany
| | - Uta C Hoppe
- Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Bernhard Wernly
- Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, Salzburg, Austria.,Department of Anaesthesiology, Perioperative Medicine and Intensive Care Medicine, Paracelsus Medical University of Salzburg, Salzburg, Austria.,Center for Public Health and Healthcare Research, Paracelsus Medical University of Salzburg, Salzburg, Austria
| | - Michael Lichtenauer
- Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, Salzburg, Austria
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15
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A Novel Paradigm Based on ST2 and Its Contribution towards a Multimarker Approach in the Diagnosis and Prognosis of Heart Failure: A Prospective Study during the Pandemic Storm. Life (Basel) 2021; 11:life11101080. [PMID: 34685450 PMCID: PMC8539225 DOI: 10.3390/life11101080] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Revised: 10/03/2021] [Accepted: 10/09/2021] [Indexed: 02/07/2023] Open
Abstract
Background: Acute heart failure (HF) represents an increasingly common and challenging presentation in the emergency room, also inducing a great socio-economic burden. Extensive research was conducted toward finding an ideal biomarker of acute HF, both in terms of sensitivity and specificity, but today practicians’ interest has shifted towards a more realistic multimarker approach. Natriuretic peptides (NPs) currently represent the gold standard for diagnosing HF in routine clinical practice, but novel molecules, such as sST2, emerge as potentially useful biomarkers, providing additional diagnostic and prognostic value. Methods: We conducted a prospective, single-center study that included 120 patients with acute HF and 53 controls with chronic HF. Of these, 13 patients (eight with acute HF, five from the control group) associated the coronavirus-19 disease (COVID-19). The diagnosis of HF was confirmed by a complete clinical, biological and echocardiographic approach. Results: The serum levels of all studied biomarkers (sST2, NT-proBNP, cardiac troponin) were significantly higher in the group with acute HF. By area under the curve (AUC) analysis, we noticed that NT-proBNP (AUC: 0.976) still had the best diagnostic performance, closely followed by sST2 (AUC: 0.889). However, sST2 was a significantly better predictor of fatal events, showing positive correlations for both in-hospital and at 1-month mortality rates. Moreover, sST2 was also associated with other markers of poor prognosis, such as the use of inotropes or high lactate levels, but not with left ventricle ejection fraction, age, body mass index or mean arterial pressure. sST2 levels were higher in patients with a positive history of COVID-19 as compared with non-COVID-19 patients, but the differences were statistically significant only within the control group. Bivariate regression showed a positive and linear relationship between NT-proBNP and sST2 (r(120) = 0.20, p < 0.002). Conclusions: we consider that sST2 has certain qualities worth integrating in a future multimarker test kit alongside traditional biomarkers, as it provides similar diagnostic value as NT-proBNP, but is emerging as a more valuable prognostic factor, with a better predictive value of fatal events in patients with acute HF.
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16
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Reina-Couto M, Pereira-Terra P, Quelhas-Santos J, Silva-Pereira C, Albino-Teixeira A, Sousa T. Inflammation in Human Heart Failure: Major Mediators and Therapeutic Targets. Front Physiol 2021; 12:746494. [PMID: 34707513 PMCID: PMC8543018 DOI: 10.3389/fphys.2021.746494] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 09/20/2021] [Indexed: 12/28/2022] Open
Abstract
Inflammation has been recognized as a major pathophysiological contributor to the entire spectrum of human heart failure (HF), including HF with reduced ejection fraction, HF with preserved ejection fraction, acute HF and cardiogenic shock. Nevertheless, the results of several trials attempting anti-inflammatory strategies in HF patients have not been consistent or motivating and the clinical implementation of anti-inflammatory treatments for HF still requires larger and longer trials, as well as novel and/or more specific drugs. The present work reviews the different inflammatory mechanisms contributing to each type of HF, the major inflammatory mediators involved, namely tumor necrosis factor alpha, the interleukins 1, 6, 8, 10, 18, and 33, C-reactive protein and the enzymes myeloperoxidase and inducible nitric oxide synthase, and their effects on heart function. Furthermore, several trials targeting these mediators or involving other anti-inflammatory treatments in human HF are also described and analyzed. Future therapeutic advances will likely involve tailored anti-inflammatory treatments according to the patient's inflammatory profile, as well as the development of resolution pharmacology aimed at stimulating resolution of inflammation pathways in HF.
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Affiliation(s)
- Marta Reina-Couto
- Departamento de Biomedicina – Unidade de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
- Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto (MedInUP), Porto, Portugal
- Departamento de Medicina Intensiva, Centro Hospitalar e Universitário São João, Porto, Portugal
| | - Patrícia Pereira-Terra
- Departamento de Biomedicina – Unidade de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
| | - Janete Quelhas-Santos
- Departamento de Biomedicina – Unidade de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
| | - Carolina Silva-Pereira
- Departamento de Biomedicina – Unidade de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
- Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto (MedInUP), Porto, Portugal
| | - António Albino-Teixeira
- Departamento de Biomedicina – Unidade de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
- Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto (MedInUP), Porto, Portugal
| | - Teresa Sousa
- Departamento de Biomedicina – Unidade de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
- Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto (MedInUP), Porto, Portugal
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17
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Günther F, Straub RH, Hartung W, Luchner A, Fleck M, Ehrenstein B. Increased Serum Levels of soluble ST2 as a Predictor of Disease Progression in Systemic Sclerosis. Scand J Rheumatol 2021; 51:315-322. [PMID: 34474647 DOI: 10.1080/03009742.2021.1929457] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVE Interleukin-33 (IL-33) has been investigated as a mediator in the pathogenesis of fibrosis in lung, liver, and heart. There is accumulating evidence for the involvement of the IL-33/IL-33 receptor ST2L signalling pathway in systemic sclerosis (SSc). Little is known about the role of serum sST2 in SSc, which is the subject of the present investigation. METHOD Serum levels of sST2 were measured in 49 patients with SSc, recruited prospectively between November 2017 and March 2019. Patients were divided into those with progressive and those with stable disease. Receiver operating characteristics (ROC) curve analysis was applied to study sST2 as a marker for identifying patients with progressive disease. We used multivariate logistic regression analysis to evaluate the predictive value of sST2 for progressive disease after adjustment for potential confounding factors. RESULTS Serum sST2 levels in patients with progressive disease were significantly elevated compared with patients with stable disease (mean ± sem: 50.4 ± 4.7 ng/mL vs 29.2 ± 2.97 ng/mL, p < 0.001). ROC curve analysis identified an sST2 cut-off value of 37.8 ng/mL as optimal for discriminating patients with progressive disease from those with stable disease (sensitivity 80.0%, specificity 79.3%, area under the curve 0.80). After controlling for potential confounding factors (age, gender, C-reactive protein, pro-brain natriuretic peptide, and sum of internal medicine comorbidities), sST2 remained predictive of progressive disease (odds ratio 1.070, 95% confidence interval 1.017-1.126, p < 0.009). CONCLUSION In the present study, sST2 serum levels were predictive of disease progression in patients with SSc.
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Affiliation(s)
- F Günther
- Department of Rheumatology and Clinical Immunology, Asklepios Clinic, Bad Abbach, Germany
| | - R H Straub
- Department of Internal Medicine I, University Medical Center, Regensburg, Germany
| | - W Hartung
- Department of Rheumatology and Clinical Immunology, Asklepios Clinic, Bad Abbach, Germany
| | - A Luchner
- Department of Cardiology, Barmherzige Brüder Hospital, Regensburg, Germany
| | - M Fleck
- Department of Rheumatology and Clinical Immunology, Asklepios Clinic, Bad Abbach, Germany.,Department of Internal Medicine I, University Medical Center, Regensburg, Germany
| | - B Ehrenstein
- Department of Rheumatology and Clinical Immunology, Asklepios Clinic, Bad Abbach, Germany.,Department of Internal Medicine I, University Medical Center, Regensburg, Germany
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18
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Kumric M, Ticinovic Kurir T, Borovac JA, Bozic J. Role of novel biomarkers in diabetic cardiomyopathy. World J Diabetes 2021; 12:685-705. [PMID: 34168722 PMCID: PMC8192249 DOI: 10.4239/wjd.v12.i6.685] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 01/22/2021] [Accepted: 03/18/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetic cardiomyopathy (DCM) is commonly defined as cardiomyopathy in patients with diabetes mellitus in the absence of coronary artery disease and hypertension. As DCM is now recognized as a cause of substantial morbidity and mortality among patients with diabetes mellitus and clinical diagnosis is still inappropriate, various expert groups struggled to identify a suitable biomarker that will help in the recognition and management of DCM, with little success so far. Hence, we thought it important to address the role of biomarkers that have shown potential in either human or animal studies and which could eventually result in mitigating the poor outcomes of DCM. Among the array of biomarkers we thoroughly analyzed, long noncoding ribonucleic acids, soluble form of suppression of tumorigenicity 2 and galectin-3 seem to be most beneficial for DCM detection, as their plasma/serum levels accurately correlate with the early stages of DCM. The combination of relatively inexpensive and accurate speckle tracking echocardiography with some of the highlighted biomarkers may be a promising screening method for newly diagnosed diabetes mellitus type 2 patients. The purpose of the screening test would be to direct affected patients to more specific confirmation tests. This perspective is in concordance with current guidelines that accentuate the importance of an interdisciplinary team-based approach.
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Affiliation(s)
- Marko Kumric
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
| | - Tina Ticinovic Kurir
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
- Department of Endocrinology, University Hospital of Split, Split 21000, Croatia
| | - Josip A Borovac
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
- Emergency Medicine, Institute of Emergency Medicine of Split-Dalmatia County, Split 21000, Croatia
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
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Miftode RS, Petriș AO, Onofrei Aursulesei V, Cianga C, Costache II, Mitu O, Miftode IL, Șerban IL. The Novel Perspectives Opened by ST2 in the Pandemic: A Review of Its Role in the Diagnosis and Prognosis of Patients with Heart Failure and COVID-19. Diagnostics (Basel) 2021; 11:diagnostics11020175. [PMID: 33530550 PMCID: PMC7911622 DOI: 10.3390/diagnostics11020175] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/01/2021] [Accepted: 01/22/2021] [Indexed: 02/07/2023] Open
Abstract
The increasing incidence of coronavirus disease 19 (COVID-19) and its polymorphic clinical manifestations due to local and systemic inflammation represent a high burden for many public health systems. Multiple evidence revealed the interdependence between the presence of cardiovascular comorbidities and a severe course of COVID-19, with heart failure (HF) being incriminated as an independent predictor of mortality. Suppression of tumorigenicity-2 ST2 has emerged as one of the most promising biomarkers in assessing the evolution and prognosis of patients with HF. The uniqueness of ST2 is determined by its structural particularities. Its transmembrane isoform exerts cardioprotective effects, while the soluble isoform (sST2), which is detectable in serum, is associated with myocardial fibrosis and poor outcome in patients with HF. Some recent data also suggested the potential role of sST2 as a marker of inflammation, while other studies highlighted it as a valuable prognostic factor in patients with COVID-19. In this review, we summarized the pathways by which sST2 is related to myocardial injury and its connection to the severity of inflammation in patients with COVID-19. Also, we reviewed possible perspectives of using it as a dual cardio-inflammatory biomarker, for both early diagnosis, risk stratification and prognosis assessment of patients with concomitant HF and COVID-19.
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Affiliation(s)
- Radu-Stefan Miftode
- Department of Internal Medicine I (Cardiology), Faculty of Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania; (R.-S.M.); (A.O.P.); (I.-I.C.); (O.M.)
| | - Antoniu Octavian Petriș
- Department of Internal Medicine I (Cardiology), Faculty of Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania; (R.-S.M.); (A.O.P.); (I.-I.C.); (O.M.)
| | - Viviana Onofrei Aursulesei
- Department of Internal Medicine I (Cardiology), Faculty of Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania; (R.-S.M.); (A.O.P.); (I.-I.C.); (O.M.)
- Correspondence:
| | - Corina Cianga
- Department of Immunology, Faculty of Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania;
| | - Irina-Iuliana Costache
- Department of Internal Medicine I (Cardiology), Faculty of Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania; (R.-S.M.); (A.O.P.); (I.-I.C.); (O.M.)
| | - Ovidiu Mitu
- Department of Internal Medicine I (Cardiology), Faculty of Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania; (R.-S.M.); (A.O.P.); (I.-I.C.); (O.M.)
| | - Ionela-Larisa Miftode
- Department of Infectious Diseases, Faculty of Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania;
| | - Ionela-Lăcrămioara Șerban
- Department of Morpho-Functional Sciences (II), Faculty of Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania;
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20
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Dimitropoulos S, Mystakidi VC, Oikonomou E, Siasos G, Tsigkou V, Athanasiou D, Gouliopoulos N, Bletsa E, Kalampogias A, Charalambous G, Tsioufis C, Vavuranakis M, Tousoulis D. Association of Soluble Suppression of Tumorigenesis-2 (ST2) with Endothelial Function in Patients with Ischemic Heart Failure. Int J Mol Sci 2020; 21:9385. [PMID: 33317161 PMCID: PMC7764062 DOI: 10.3390/ijms21249385] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 11/29/2020] [Accepted: 12/06/2020] [Indexed: 02/07/2023] Open
Abstract
Soluble suppression of tumorigenesis-2 (sST2) has been introduced as a marker associated with heart failure (HF) pathophysiology and status. Endothelial dysfunction is a component underlying HF pathophysiology. Therefore, we examined the association of arterial wall properties with sST2 levels in patients with HF of ischemic etiology. We enrolled 143 patients with stable HF of ischemic etiology and reduced left ventricular ejection fraction (LVEF) and 77 control subjects. Flow-mediated dilation (FMD) was used to evaluate endothelial function and pulse wave velocity (PWV) to assess arterial stiffness. Although there was no significant difference in baseline demographic characteristics, levels of sST2 were increased in HF compared to the control (15.8 (11.0, 21.8) ng/mL vs. 12.5 (10.4, 16.3) ng/mL; p < 0.001). In the HF group, there was a positive correlation of sST2 levels with age (rho = 0.22; p = 0.007) while there was no association of LVEF with sST2 (rho = -0.119; p = 0.17) nor with PWV (rho = 0.1; p = 0.23). Interestingly, sST2 was increased in NYHA III [20.0 (12.3, 25.7) ng/mL] compared to patients with NYHA II (15.0 (10.4, 18.2) ng/mL; p = 0.003) and inversely associated with FMD (rho = -0.44; p < 0.001) even after adjustment for possible confounders. In patients with chronic HF of ischemic etiology, sST2 levels are increased and are associated with functional capacity. There is an inverse association between FMD and sST2 levels, highlighting the interplay between the dysfunctional endothelium and HF pathophysiologic mechanisms.
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Affiliation(s)
- Stathis Dimitropoulos
- First Department of Cardiology, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (S.D.); (V.C.M.); (G.S.); (V.T.); (D.A.); (N.G.); (E.B.); (A.K.); (G.C.); (C.T.); (D.T.)
| | - Vasiliki Chara Mystakidi
- First Department of Cardiology, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (S.D.); (V.C.M.); (G.S.); (V.T.); (D.A.); (N.G.); (E.B.); (A.K.); (G.C.); (C.T.); (D.T.)
| | - Evangelos Oikonomou
- First Department of Cardiology, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (S.D.); (V.C.M.); (G.S.); (V.T.); (D.A.); (N.G.); (E.B.); (A.K.); (G.C.); (C.T.); (D.T.)
- Third Department of Cardiology, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece;
| | - Gerasimos Siasos
- First Department of Cardiology, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (S.D.); (V.C.M.); (G.S.); (V.T.); (D.A.); (N.G.); (E.B.); (A.K.); (G.C.); (C.T.); (D.T.)
- Third Department of Cardiology, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece;
| | - Vasiliki Tsigkou
- First Department of Cardiology, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (S.D.); (V.C.M.); (G.S.); (V.T.); (D.A.); (N.G.); (E.B.); (A.K.); (G.C.); (C.T.); (D.T.)
| | - Dimitris Athanasiou
- First Department of Cardiology, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (S.D.); (V.C.M.); (G.S.); (V.T.); (D.A.); (N.G.); (E.B.); (A.K.); (G.C.); (C.T.); (D.T.)
| | - Nikolaos Gouliopoulos
- First Department of Cardiology, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (S.D.); (V.C.M.); (G.S.); (V.T.); (D.A.); (N.G.); (E.B.); (A.K.); (G.C.); (C.T.); (D.T.)
| | - Evanthia Bletsa
- First Department of Cardiology, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (S.D.); (V.C.M.); (G.S.); (V.T.); (D.A.); (N.G.); (E.B.); (A.K.); (G.C.); (C.T.); (D.T.)
| | - Aimilios Kalampogias
- First Department of Cardiology, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (S.D.); (V.C.M.); (G.S.); (V.T.); (D.A.); (N.G.); (E.B.); (A.K.); (G.C.); (C.T.); (D.T.)
| | - Georgios Charalambous
- First Department of Cardiology, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (S.D.); (V.C.M.); (G.S.); (V.T.); (D.A.); (N.G.); (E.B.); (A.K.); (G.C.); (C.T.); (D.T.)
| | - Costas Tsioufis
- First Department of Cardiology, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (S.D.); (V.C.M.); (G.S.); (V.T.); (D.A.); (N.G.); (E.B.); (A.K.); (G.C.); (C.T.); (D.T.)
| | - Manolis Vavuranakis
- Third Department of Cardiology, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece;
| | - Dimitris Tousoulis
- First Department of Cardiology, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (S.D.); (V.C.M.); (G.S.); (V.T.); (D.A.); (N.G.); (E.B.); (A.K.); (G.C.); (C.T.); (D.T.)
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21
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Borovac JA, Glavas D, Susilovic Grabovac Z, Supe Domic D, Stanisic L, D'Amario D, Kwok CS, Bozic J. Circulating sST2 and catestatin levels in patients with acute worsening of heart failure: a report from the CATSTAT-HF study. ESC Heart Fail 2020; 7:2818-2828. [PMID: 32681700 PMCID: PMC7524138 DOI: 10.1002/ehf2.12882] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 06/07/2020] [Accepted: 06/17/2020] [Indexed: 02/06/2023] Open
Abstract
AIMS Soluble suppression of tumourigenicity 2 (sST2) and catestatin (CST) reflect myocardial fibrosis and sympathetic overactivity during the acute worsening of heart failure (AWHF). We aimed to determine serum levels and associations of sST2 and CST with in-hospital death as well as the association between sST2 and CST among AWHF patients. METHODS AND RESULTS A total of 96 AWHF patients were consecutively enrolled, while levels of sST2 and CST were determined and compared between non-survivors and survivors. Predictive values of sST2 and CST for in-hospital death were determined by the penalized multivariable Firth logistic regression. The diagnostic ability of sST2 and CST for in-hospital death was assessed by the receiver operating characteristic analysis and examined with respect to the N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I, and C-reactive protein. The in-hospital death rate was 6.25%. Serum sST2 and CST levels were significantly higher among non-survivors than survivors [146.6 (inter-quartile range, IQR 65.9-156.2) vs. 35.3 (IQR 20.6-64.4) ng/mL, P < 0.001, and 19.8 (IQR 9.9-28.0) vs. 5.6 (IQR 3.4-9.8) ng/mL, P < 0.001, respectively]. Both sST2 and CST were independent predictors of in-hospital death [Firth coefficient (FC) 6.00, 95% confidence interval (CI), 1.48-15.20, P = 0.005, and FC 6.58, 95% CI 1.66-21.78, P = 0.003, respectively], while NT-proBNP was not a significant predictor (FC 1.57, 95% CI 0.51-3.99, P = 0.142). In classifying non-survivors from survivors, sST2 provided area under the curve (AUC) of 0.917 (95% CI 0.819-1.000, P < 0.001) followed by CST (AUC 0.905, 95% CI 0.792-1.000, P < 0.001), while NT-proBNP yielded AUC of 0.735 (95% CI 0.516-0.954, P = 0.036). High-sensitivity cardiac troponin I and C-reactive protein were not found as significant classifiers of in-hospital death (AUC 0.719, 95% CI 0.509-0.930, P = 0.075, and AUC 0.682, 95% CI 0.541-0.822, P = 0.164, respectively). Among survivors, those with sST2 serum levels ≥35 ng/mL had significantly higher CST levels, compared with those with sST2 < 35 ng/mL (9.05 ± 5.17 vs. 5.06 ± 2.76 ng/mL, P < 0.001). Serum sST2 levels positively and independently correlated with CST levels in the whole patient cohort (β = 0.437, P < 0.001). CONCLUSIONS Elevated sST2 and CST levels, reflecting two distinct pathophysiological pathways in heart failure, might indicate impending clinical deterioration among AWHF patients during hospitalization and facilitate prognosis beyond traditional biomarkers regarding the risk of in-hospital death (CATSTAT-HF ClinicalTrials.gov Number NCT03389386).
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Affiliation(s)
- Josip A Borovac
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2, Split, 21000, Croatia.,Institute of Emergency Medicine of Split-Dalmatia County, Split, Croatia.,Clinic for Cardiovascular Diseases, University Hospital of Split, Split, Croatia
| | - Duska Glavas
- Clinic for Cardiovascular Diseases, University Hospital of Split, Split, Croatia.,Department of Internal Medicine, University of Split School of Medicine, Split, Croatia
| | | | - Daniela Supe Domic
- Department of Medical Laboratory Diagnostics, University Hospital of Split, Split, Croatia.,Department of Health Studies, University of Split, Split, Croatia
| | - Lada Stanisic
- Department of Medical Laboratory Diagnostics, University Hospital of Split, Split, Croatia
| | - Domenico D'Amario
- Department of Cardiovascular and Thoracic Sciences, IRCCS Fondazione Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Chun S Kwok
- University Hospitals of North Midlands Royal Stoke University Hospital, Stoke-on-Trent, UK
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2, Split, 21000, Croatia
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