European Journal of Clinical Investigation最新文献

{"title":"The impact of clinical phenotypes of coronary artery disease on outcomes in patients with atrial fibrillation: A post-hoc analysis of GLORIA-AF registry.","authors":"Bi Huang, Yang Liu, Ho Man Lam, Hironori Ishiguchi, Tze-Fan Chao, Menno V Huisman, Gregory Y H Lip","doi":"10.1111/eci.14378","DOIUrl":"https://doi.org/10.1111/eci.14378","url":null,"abstract":"<p><strong>Background: </strong>Coronary artery disease (CAD) and atrial fibrillation (AF) often coexist, but the impact of clinical phenotypes of CAD on outcomes in AF patients in the non-vitamin K antagonist oral anticoagulant drugs (NOACs) era is less well understood.</p><p><strong>Methods: </strong>This was a post-hoc of the GLORIA-AF registry, a global, multicenter, prospective AF registry study. Patients were divided into three groups: prior history of myocardial infarction (MI)/unstable angina group (Group 1); stable angina group (Group 2); and a control group without stable angina or history of MI/unstable angina. The primary endpoint was the composite of all-cause death or stroke, and the safety endpoint was major bleeding.</p><p><strong>Results: </strong>A total of 24,827 patients were included in this analysis (median age was 71 (IQR, 64-78) years; 55% male) and 5394 (21.7%) had CAD. During a follow-up of 2 years, the incidence of the primary endpoint was 5.99 (95% CI, 5.33, 6.71) per 100 patient-years in Group 1, 4.04 (95% CI, 3.55, 4.70) per 100 patient-years in Group 2, and 2.79 (95% CI, 2.62, 2.96) per 100 patient-years in the control group (p < .001). Compared the control group, the adjusted hazard ratio of the primary composite endpoint in Groups 1 and 2 were 1.58 (95% CI, 1.37, 1.83, p < .001) and 1.22 (95% CI, 1.04, 1.43, p = .012), respectively. Among anticoagulated patients with AF and CAD, NOACs were associated with a reduced risk of the primary composite endpoint and major bleeding, compared with vitamin K antagonists (VKA).</p><p><strong>Conclusions: </strong>CAD was prevalent in patients with AF, and clinical phenotypes of CAD influenced outcomes in patients with AF, with a history of MI/unstable angina being associated with a significantly increased risk of CV events, compared to stable angina. NOACs were superior to VKA in terms of the effectiveness and safety outcomes in patients with AF and concomitant CAD.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14378"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term fasting induces a remodelling of fatty acid composition in erythrocyte membranes.","authors":"Katharina Gewecke, Franziska Grundler, Massimiliano Ruscica, Clemens von Schacky, Robin Mesnage, Françoise Wilhelmi de Toledo","doi":"10.1111/eci.14382","DOIUrl":"https://doi.org/10.1111/eci.14382","url":null,"abstract":"<p><strong>Introduction: </strong>Long-term fasting (LF) activates an adaptative response to switch metabolic fuels from food glucose to lipids stored in adipose tissues. The increase in free fatty acid (FFA) oxidation during fasting triggers health benefits. We questioned if the changes in lipid metabolism during LF could affect lipids in cell membranes in humans. We thus analysed the FA composition in erythrocyte membranes (EM) during 12.6 ± 3.5 days of LF and 1 month after food reintroduction.</p><p><strong>Methods: </strong>A total of 98 subjects out of three single-arm interventional studies underwent a medical supervised long-term fasting (12.6 ± 3.5 days) programme. The distribution pattern of 26 FA as well as the HS-Omega-3 Index were assessed in the EM using gas chromatography.</p><p><strong>Results: </strong>Eighteen of 26 FA showed significant changes. Within the group of saturated FA, myristic (14:0) and stearic acid (18:0) decreased while palmitic (16:0) and arachid acid (20:0) increased. While most monounsaturated FA increased, trans fatty acids decreased or remained unchanged. Within the polyunsaturated FA, arachidonic (20:4n6) and docosahexaenoic (22:6n3) acid increased, while linoleic (18:2n6), alpha-linolenic (18:3n3) and eicosapentaenoic acid (20:5n3) decreased. Consequently, the HS-Omega-3 Index increased. 11 out of the 18 FA with significant changes returned to baseline levels 1 month afterwards. Levels of linoleic and alpha-linolenic acid increased over baseline levels.</p><p><strong>Conclusions: </strong>Long-term fasting triggers changes in the FA composition of EM.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14382"},"PeriodicalIF":4.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic scores in patients with severe tricuspid regurgitation: An external validation study.","authors":"Consuelo Fernández-Avilés, Martín Ruiz Ortiz, Ana Fernández Ruiz, Gloria Heredia Campos, Adriana Resúa Collazo, Rafael González-Manzanares, Mónica Delgado Ortega, Ana Rodríguez Almodóvar, Fátima Esteban Martínez, Luis Carlos Maestre Luque, Alberto Morán Salinas, Alberto Torres Zamudio, Javier Herrera Flores, Manuel Díaz Andrade, José López Aguilera, Manuel Anguita Sánchez, Manuel Pan Álvarez-Osorio, Dolores Mesa Rubio","doi":"10.1111/eci.14379","DOIUrl":"https://doi.org/10.1111/eci.14379","url":null,"abstract":"<p><strong>Background: </strong>Four scores have been published in 2022 for assessing mortality risk of patients with tricuspid regurgitation (TR): the TRI-SCORE, those reported by Hochstadt and Wang and the TRIO score. Our objective was to perform an external validation of available scores for predicting mortality and the combined endpoint of mortality and heart failure (HF) admission, in an independent cohort of patients with severe TR and to compare their discriminative ability.</p><p><strong>Methods: </strong>Discriminative ability of the scores for predicting events was assessed by means of receiver operating characteristics (ROC) curves.</p><p><strong>Results: </strong>The validation cohort retrospectively included 614 consecutive patients (69 ± 13 years, 72% women) with severe TR studied with echocardiography in a tertiary care hospital and followed for up to 14 years (median 5 years, p25-75 2-7 years), with 358 deaths and 620 HF admissions on follow-up. Discriminative abilities for predicting death (C-statistic .72 [95% CI .68-.76] for the TRI-SCORE; .75 [.71-.78] for the Hochstadt score; .72 [.68-.76] for the Wang score; and .74 [.70-.78] for the TRIO score, p < .0005 for all) or the combined endpoint (C-statistic .74 [.70-.78]; .74 [.70-.78], .73 [.69-.77] and .76 [.72-.80], respectively, p < .0005 for all) on follow-up were statistically significant for all of them. Paired comparisons among them for predicting both endpoints were all non-significant.</p><p><strong>Conclusions: </strong>All tested scores showed significant and similar discriminative ability for predicting the combined endpoint of mortality or HF admission in this independent validation study of patients with severe TR.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14379"},"PeriodicalIF":4.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A scoping review evaluating the current state of gut microbiota and its metabolites in valvular heart disease physiopathology.","authors":"Caroline Chong-Nguyen, Bahtiyar Yilmaz, Bernadette Coles, Harry Sokol, Andrew MacPherson, Matthias Siepe, David Reineke, Selim Mosbahi, Daijiro Tomii, Masaaki Nakase, Sarah Atighetchi, Cyril Ferro, Christoph Wingert, Christoph Gräni, Thomas Pilgrim, Stephan Windecker, Hélène Blasco, Camille Dupuy, Patrick Emond, Yara Banz, Tereza Losmanovà, Yvonne Döring, George C M Siontis","doi":"10.1111/eci.14381","DOIUrl":"https://doi.org/10.1111/eci.14381","url":null,"abstract":"<p><strong>Background: </strong>The human microbiome is crucial in regulating intestinal and systemic functions. While its role in cardiovascular disease is better understood, the link between intestinal microbiota and valvular heart diseases (VHD) remains largely unexplored.</p><p><strong>Methods: </strong>Peer-reviewed studies on human, animal or cell models analysing gut microbiota profiles published up to April 2024 were included. Eligible studies used 16S rRNA or shotgun sequencing, metabolite profiling by mass spectrometry, and examined osteogenesis or fibrosis signalling in valve cells. Methods and findings were qualitatively analysed, with data charted to summarize study design, materials and outcomes.</p><p><strong>Results: </strong>Thirteen studies were included in the review: five human, three animal and five in vitro. Of the nine studies on calcific aortic stenosis (CAS), elevated trimethylamine N-oxide (TMAO) levels were linked to an increased risk of cardiovascular events in cohort studies, with CAS patients showing higher levels of Bacteroides plebeius, Enterobacteriaceae, Veillonella dispar and Prevotella copri. In vivo, TMAO promoted aortic valve fibrosis, while tryptophan derivatives stimulated osteogenic differentiation and interleukin-6 secretion in valvular interstitial cells. Two studies on rheumatic mitral valve disease found altered microbiota profiles and lower short-chain fatty acid levels, suggesting potential impacts on immune regulation. Two studies on Barlow's mitral valve disease in animal models revealed elevated TMAO levels in dogs with congestive heart failure, reduced Paraprevotellaceae, increased Actinomycetaceae and dysbiosis involving Turicibacter and E. coli.</p><p><strong>Conclusions: </strong>TMAO has been mainly identified as a prognostic marker in VHD. Gut microbiota dysbiosis has been observed in various forms of VHD and deserve further study.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14381"},"PeriodicalIF":4.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial dysfunction in adults with congenital heart disease: A systematic review and meta-analysis.","authors":"Amalia Baroutidou, Theodoros Dimitroulas, Alexandra Arvanitaki, Triantafyllia Grantza, Nikolaos Otountzidis, Ioannis T Farmakis, Artemios G Karagiannidis, Vasileios Kamperidis, Antonios Ziakas, Pantelis Sarafidis, George Giannakoulas","doi":"10.1111/eci.14376","DOIUrl":"https://doi.org/10.1111/eci.14376","url":null,"abstract":"<p><strong>Background: </strong>Adults with congenital heart disease (ACHD) can face a lifelong risk of premature cardiovascular events. Endothelial dysfunction and arterial stiffness may be some of the key mechanisms involved. Early identification of endothelial damage in ACHD could be crucial to mitigate the adverse events. This systematic review and meta-analysis aims to investigate micro- and macroangiopathy in ACHD.</p><p><strong>Methods: </strong>We systematically searched four major electronic databases (PubMed, CENTRAL, Scopus and Web of Science), ClinicalTrials.gov and grey literature according to PRISMA guidelines. We included studies evaluating endothelial function with any semi- or non-invasive method in ACHD and healthy controls. Studies exploring arterial stiffness indices and carotid intima-media thickness were also investigated.</p><p><strong>Results: </strong>In total, 31 studies (1118 ACHD, 794 controls) were included in this systematic review. Brachial artery endothelium-dependent (assessed via flow-mediated dilatation, FMD) and -independent vasodilation (assessed via nitroglycerine-mediated dilatation, NMD) were attenuated in ACHD versus controls (mean difference [MD] -2.5, 95% confidence intervals [CI] -3.7; -1.3 and MD -3.9, 95% CI -6.8; -1.0, respectively). ACHD also demonstrated impaired microvascular function, evaluated via peripheral arterial tonometry (PAT), with significantly lower reactive hyperemia index and PAT ratio compared to controls (MD -.26, 95% CI -.48; -.04 and MD -.4, 95% CI -.5; -.4, respectively). Regarding arterial stiffness, pooled analysis revealed non-significant differences in pulse wave velocity between the study groups (standardized MD .2, 95% CI -.2; .6). However, the augmentation index was significantly higher in ACHD (standardized MD 1.6, 95% CI .8; 2.4).</p><p><strong>Conclusions: </strong>ACHD exhibit impaired macro- and microvascular function and elevated arterial stiffness, factors that may be responsible for the increased adverse cardiovascular events in this population.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14376"},"PeriodicalIF":4.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-arrest atrial fibrillation and neurological recovery after cardiac arrest among hospitalized patients: A retrospective cohort study.","authors":"Chih-Hung Wang, Yan-Yu Chen, Meng-Che Wu, Li-Ting Ho, Cheng-Yi Wu, Joyce Tay, Wei-Han Lin, Jr-Jiun Lin, Huang-Fu Yeh, Yen-Wen Wu, Chien-Hua Huang, Wen-Jone Chen","doi":"10.1111/eci.14375","DOIUrl":"https://doi.org/10.1111/eci.14375","url":null,"abstract":"<p><strong>Background: </strong>New-onset atrial fibrillation (AF) is associated with an increased risk of stroke in hospitalized patients with severe sepsis. Post-cardiac arrest patients experience conditions similar to sepsis. This study investigated whether pre-arrest AF is associated with poor neurological recovery following in-hospital cardiac arrest (IHCA).</p><p><strong>Methods: </strong>This single-centre retrospective study included patients experiencing IHCA between 2005 and 2020. Pre-arrest electrocardiograms (ECGs) were reviewed, including twelve-lead ECGs and ECG strips. New-onset AF was defined as AF absent on electronic health records (EHRs, including admission diagnosis, past medical history and hospitalization notes) but present on pre-arrest ECG. Without considering EHRs, AF-presence was defined as AF present on pre-arrest ECG.</p><p><strong>Results: </strong>A total of 2466 patients were included, including 93 (3.8%) with new-onset AF and 131 (5.3%) with evidence of AF on pre-arrest ECG. The median age was 67.6 (interquartile range [IQR]: 22.3) years and the median CHA₂DS₂-VASc score was 3.0 (IQR: 3.0). A total of 405 (16.4%) patients survived to hospital discharge, with 228 (9.2%) patients achieving favourable neurological recovery. Multivariable logistic regression analysis indicated that both new-onset AF (odds ratio [OR]: .34, 95% confidence interval [CI]: .12-.94, p-value: .04) and AF-presence (OR: .35, 95% CI: .15-.85, p-value: .02) were inversely associated with favourable neurological recovery in the primary and sensitivity analyses, respectively.</p><p><strong>Conclusions: </strong>Pre-arrest AF is a significant risk factor for poor neurological recovery following IHCA. Further research is needed to understand the underlying mechanisms, which could inform the development of strategies to improve outcomes in this patient subgroup.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14375"},"PeriodicalIF":4.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 diabetes and chronic kidney disease as long-term predictors of cardiovascular events in patients with coronary artery disease.","authors":"Laura Schnetzer, Andreas Leiherer, Andreas Festa, Axel Mündlein, Thomas Plattner, Gert Mayer, Christoph Saely, Heinz Drexel","doi":"10.1111/eci.14374","DOIUrl":"https://doi.org/10.1111/eci.14374","url":null,"abstract":"<p><strong>Background: </strong>Both chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) confer a high risk of cardiovascular disease and mortality. These entities frequently coincide. The separate and joint impact of CKD and T2DM on the risk of major cardiovascular events (MACE) and survival is unclear.</p><p><strong>Methods: </strong>In this prospective cohort study, patients with angiographically proven coronary artery disease were investigated according to their CKD and T2DM status (T2DM-/CKD-, T2DM+/CKD-, T2DM-/CKD+, T2DM+/CKD+) and followed for up to 18 years.</p><p><strong>Results: </strong>A total of 1441 patients were included in the study of whom 39% experienced MACE (T2DM-/CKD-: 31%, T2DM+/CKD-: 43%, T2DM-/CKD+: 53%, T2DM+/CKD+: 61%) and 53% died. A log-rank test revealed significant differences between the event-free time period of the four groups (χ² (3) = 112.57, p < 0.001). The presence of T2DM and CKD was associated with a 2.72-fold increase [1.98-3.73] in MACE compared to patients who suffered from neither condition (p < 0.001). T2DM alone led to a 1.37-fold increase [1.1-1.7], (p = 0.004), CKD alone to a 1.71-fold increase [1.31-2.25], (p < 0.001).</p><p><strong>Conclusion: </strong>T2DM and CKD in patients with coronary artery disease are mutually independent predictors of cardiovascular events. Patients with both CKD and T2DM are at an extremely high risk for cardiovascular events.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14374"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation, lipids and cardiovascular risk: The quest for improving risk stratification and prognosis in ischemic heart disease.","authors":"Giulio Francesco Romiti, Giovanni Buoninfante, Stefania Basili","doi":"10.1111/eci.14373","DOIUrl":"https://doi.org/10.1111/eci.14373","url":null,"abstract":"<p><p>Lp(a): Lipoprotein (a). Created in BioRender. Romiti, G. (2024) BioRender.com/g02a734.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14373"},"PeriodicalIF":4.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Residual risk prediction in anticoagulated patients with atrial fibrillation using machine learning: A report from the GLORIA-AF registry phase II/III.","authors":"Yang Liu, Yang Chen, Ivan Olier, Sandra Ortega-Martorell, Bi Huang, Hironori Ishiguchi, Ho Man Lam, Kui Hong, Menno V Huisman, Gregory Y H Lip","doi":"10.1111/eci.14371","DOIUrl":"https://doi.org/10.1111/eci.14371","url":null,"abstract":"<p><strong>Background: </strong>Although oral anticoagulation decreases the risk of thromboembolism in patients with atrial fibrillation (AF), a residual risk of thrombotic events still exists. This study aimed to construct machine learning (ML) models to predict the residual risk in these patients.</p><p><strong>Methods: </strong>Patients with newly diagnosed non-valvular AF were collected from the Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry. To predict the residual risk of the composite outcome of thrombotic events (defined as ischemic stroke, systemic embolism, transient ischemic attack and myocardial infarction), we constructed four prediction models using the logistic regression (LR), random forest, light gradient boosting machine and extreme gradient boosting machine ML algorithms. Performance was mainly evaluated by area under the receiver-operating characteristic curve (AUC), g-means and F1 scores. Feature importance was evaluated by SHapley Additive exPlanations.</p><p><strong>Results: </strong>15,829 AF patients (70.33 ± 9.94 years old, 55% male) taking oral anticoagulation were included in our study, and 641 (4.0%) had residual risk, sustaining thrombotic events. In the test set, LR had the best performance with higher AUC trend of 0.712. RF has highest g-means of 0.295 and F1 score of 0.249. This was superior when compared with the CHA₂DS₂-VA score (AUC 0.698) and 2MACE score (AUC 0.696). Age, history of TE or MI, OAC discontinuation, eGFR and sex were identified as the top five factors associated with residual risk.</p><p><strong>Conclusion: </strong>ML algorithms can improve the prediction of residual risk of anticoagulated AF patients compared to clinical risk factor-based scores.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14371"},"PeriodicalIF":4.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subtyping strokes using blood-based protein biomarkers: A high-throughput proteomics and machine learning approach.","authors":"Shubham Misra, Praveen Singh, Shantanu Sengupta, Manoj Kushwaha, Zuhaibur Rahman, Divya Bhalla, Pumanshi Talwar, Manabesh Nath, Rahul Chakraborty, Pradeep Kumar, Amit Kumar, Praveen Aggarwal, Achal K Srivastava, Awadh K Pandit, Dheeraj Mohania, Kameshwar Prasad, Nishant K Mishra, Deepti Vibha","doi":"10.1111/eci.14372","DOIUrl":"https://doi.org/10.1111/eci.14372","url":null,"abstract":"<p><strong>Background: </strong>Rapid diagnosis of stroke and its subtypes is critical in early stages. We aimed to discover and validate blood-based protein biomarkers to differentiate ischemic stroke (IS) from intracerebral haemorrhage (ICH) using high-throughput proteomics.</p><p><strong>Methods: </strong>We collected serum samples within 24 h from acute stroke (IS & ICH) and mimics patients. In the discovery phase, SWATH-MS proteomics identified differentially expressed proteins, which were validated using targeted proteomics in the validation phase. We conducted interaction network and pathway analyses using Cytoscape 3.10.0. We determined cut-off points using the Youden Index. We developed three prediction models using multivariable logistic regression analyses. We assessed the model performance using statistical tests.</p><p><strong>Results: </strong>We included 20 IS and 20 ICH in the discovery phase and 150 IS, 150 ICH, and six stroke mimics in the validation phase. We quantified 375 proteins using SWATH-MS. Between IS and ICH, we discovered 20 differentially expressed proteins. In the validation phase, the combined prediction model including three biomarkers: GFAP (aOR 0.04; 95%CI .02-.11), MMP-9 (aOR .09; .03-.28), APO-C1 (aOR 5.76; 2.66-12.47) and clinical variables independently differentiated IS from ICH (accuracy: 92%, negative predictive value: 94%). Adding biomarkers to clinical variables improved discrimination by 26% (p < .001). Additionally, nine biomarkers differentiated IS from ICH within 6 h, while three biomarkers differentiated IS from mimics.</p><p><strong>Conclusions: </strong>Our study demonstrated that GFAP, MMP-9 and APO-C1 biomarkers independently differentiated IS from ICH within 24 h and significantly improved the discrimination ability of prediction models. Temporal profiling of these biomarkers in the acute phase of stroke is warranted.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14372"},"PeriodicalIF":4.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}