{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:35:29Z","timestamp":1781526929353,"version":"3.54.1"},"reference-count":24,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Atrial fibrillation (AF) and chronic kidney disease (CKD) often overlap and may amplify cardiovascular risk. Whether renal dysfunction should be incorporated into composite cardiovascular endpoints in AF remains uncertain. We aimed to quantify AF-associated risk of MACE and evaluate the incremental prognostic value of kidney measures (eGFR and albuminuria) to inform composite outcomes and clinical management. Methods: We performed a retrospective, community-based cohort study of 40,297 adults aged 65\u201395 years. Individuals with incident AF (n = 2574) were followed for 5 years. MACE and components were ascertained from linked health records; only events after AF diagnosis were analyzed. Cox models estimated adjusted hazard ratios (HRs). Risk was further stratified by eGFR stages and urine albumin-to-creatinine ratio (UACR) categories. Exploratory machine learning (ML) was developed to predict MACE in patients with AF and CKD, with model interpretability assessed by feature importance analysis. Results: Incident AF was associated with higher risk of MACE (HR 3.52), CKD (HR 1.97) and all-cause mortality (HR 1.14). CKD was nearly twice more frequent in AF than in non-AF (30.9% vs. 14.5%; p &lt; 0.001). Among patients with AF, a graded eGFR\u2013risk relationship was observed: compared with higher eGFR, MACE risk increased across G3a\u2013G5, peaking in G5 (HR 2.08). Albuminuria showed a parallel gradient: versus UACR &lt;30 mg\/g, UACR 30\u2013299 mg\/g and \u2265300 mg\/g were associated with an increased risk of MACE (HR 1.51 and 1.76, respectively). Conclusions: Newly diagnosed AF confers a substantial excess risk of MACE and its components. The consistent eGFR and albuminuria in AF support considering clinically meaningful renal endpoints within composite outcomes and prioritizing integrated cardiorenal management. These findings provide actionable evidence to refine risk stratification and endpoint selection in AF research and care.<\/jats:p>","DOI":"10.3390\/medsci13040289","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T10:25:16Z","timestamp":1764239116000},"page":"289","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Risk of Chronic Kidney Disease and Implications in Patients with Atrial Fibrillation for the Development of Major Adverse Cardiovascular Events with Machine Learning"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2703-0408","authenticated-orcid":false,"given":"Pedro","family":"Molt\u00f3-Balado","sequence":"first","affiliation":[{"name":"CSI Ll\u00edria, Departament de Salut de Arnau de Vilanova, Conselleria de Sanitat, 46160 Valencia, Spain"},{"name":"Cl\u00ednica Equilibria, 46160 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6508-5741","authenticated-orcid":false,"given":"Josep-Llu\u00eds","family":"Clua-Espuny","sequence":"additional","affiliation":[{"name":"Ebrictus Research Group, Research Support Unit Terres de l\u2019Ebre, Institut Universitari d\u2019Investigaci\u00f3 en Atenci\u00f3 Prim\u00e0ria Jordi Gol (IDIAP Jordi Gol), 43500 Tortosa, Spain"},{"name":"Primary Health-Care Center Tortosa Est, Institut Catal\u00e0 de la Salut, Primary Care Service (SAP) Terres de l\u2019Ebre, 43500 Tortosa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Tarongi-Vidal","sequence":"additional","affiliation":[{"name":"Nephrology Department at D\u00e9nia Hospital, Conselleria de Sanitat, 03700 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Barrios-Carmona","sequence":"additional","affiliation":[{"name":"Nephrology Department at D\u00e9nia Hospital, Conselleria de Sanitat, 03700 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Alonso-Barber\u00e1n","sequence":"additional","affiliation":[{"name":"Institut d\u2019Educaci\u00f3 Secund\u00e0ria El Camin\u00e0s, Conselleria d\u2019Educaci\u00f3, 12003 Castell\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Teresa","family":"Balado-Albiol","sequence":"additional","affiliation":[{"name":"CS Rafalafena, Departament del General de Castell\u00f3, Conselleria de Sanitat, 12003 Castell\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7842-2374","authenticated-orcid":false,"given":"Andrea","family":"Sime\u00f3-Monz\u00f3","sequence":"additional","affiliation":[{"name":"Cl\u00ednica Equilibria, 46160 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3297-6078","authenticated-orcid":false,"given":"Jorge","family":"Canela-Royo","sequence":"additional","affiliation":[{"name":"CS Delicias Norte (Zaragoza), Servicio Aragon\u00e9s de Salud, 50010 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1842-0977","authenticated-orcid":false,"given":"Alba","family":"del Barrio-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"CSI Ll\u00edria, Departament de Salut de Arnau de Vilanova, Conselleria de Sanitat, 46160 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.cjco.2024.11.017","article-title":"Trends in Global Burden and Socioeconomic Profiles of Atrial Fibrillation and Atrial Flutter: Insights from the Global Burden of Disease Study 2021","volume":"7","author":"Tan","year":"2025","journal-title":"CJC Open"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Daoudi, S., John, K., Chalhoub, F., Chee, J., Infeld, M., Elbaz-Greener, G., Homoud, M., Ruskin, J.N., Heist, E.K., and Madias, C. (2024). Nationwide Trends in Hospitalizations for Atrial Fibrillation and Flutter in the United States before and during the Outbreak of the COVID-19 Pandemic. J. Clin. Med., 13.","DOI":"10.3390\/jcm13164883"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100786","DOI":"10.1016\/j.lanepe.2023.100786","article-title":"Atrial fibrillation: Epidemiology, screening and digital health","volume":"37","author":"Linz","year":"2024","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Molt\u00f3-Balado, P., Revert\u00e9-Villarroya, S., Moncl\u00fas-Arasa, C., Balado-Albiol, M.T., Baset-Mart\u00ednez, S., Carot-Domenech, J., and Clua-Espuny, J.L. (2023). Heart Failure and Major Adverse Cardiovascular Events in Atrial Fibrillation Patients: A Retrospective Primary Care Cohort Study. Biomedicines, 11.","DOI":"10.3390\/biomedicines11071825"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1161\/CIRCRESAHA.120.316340","article-title":"Epidemiology of Atrial Fibrillation in the 21st Century: Novel Methods and New Insights","volume":"127","author":"Kornej","year":"2020","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Molt\u00f3-Balado, P., Revert\u00e9-Villarroya, S., Alonso-Barber\u00e1n, V., Moncl\u00fas-Arasa, C., Balado-Albiol, M.T., Clua-Queralt, J., and Clua-Espuny, J.-L. (2024). Machine Learning Approaches to Predict Major Adverse Cardiovascular Events in Atrial Fibrillation. Technologies, 12.","DOI":"10.3390\/technologies12020013"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2024). KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int., 105, S117\u2013S314.","DOI":"10.1016\/j.kint.2023.10.018"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"825","DOI":"10.7326\/0003-4819-158-11-201306040-00007","article-title":"Evaluation and management of chronic kidney disease: Synopsis of the kidney disease: Improving global outcomes 2012 clinical practice guideline","volume":"158","author":"Stevens","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.kint.2023.10.016","article-title":"Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: Known knowns and known unknowns","volume":"105","author":"Levin","year":"2024","journal-title":"Kidney Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1001\/jamacardio.2022.2825","article-title":"Sex differences in atrial fibrillation risk: The VITAL Rhythm Study","volume":"7","author":"Siddiqi","year":"2022","journal-title":"JAMA Cardiol."},{"key":"ref_11","unstructured":"Vaidya, S.R., and Aeddula, N.R. (2025, October 03). Chronic Kidney Disease, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK535404\/."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e028496","DOI":"10.1161\/JAHA.122.028496","article-title":"Association of Chronic Kidney Disease With Atrial Fibrillation in the General Adult Population: A Nationwide Population-Based Study","volume":"12","author":"Kim","year":"2023","journal-title":"J. Am. Heart Assoc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"103","DOI":"10.23876\/j.krcp.2018.37.2.103","article-title":"Atrial fibrillation and chronic kidney disease: A bad combination","volume":"37","author":"Kiuchi","year":"2018","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1053\/j.ajkd.2023.07.023","article-title":"Kidney Function, Albuminuria, and Risk of Incident Atrial Fibrillation: A Systematic Review and Meta-Analysis","volume":"83","author":"Ha","year":"2024","journal-title":"Am. J. Kidney Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1681\/ASN.2018050514","article-title":"Cardiovascular Events After New-Onset Atrial Fibrillation in Adults With CKD (CRIC)","volume":"29","author":"Bansal","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"i4482","DOI":"10.1136\/bmj.i4482","article-title":"Atrial Fibrillation and Risks of Cardiovascular Disease, Renal Disease, and Death: Systematic Review and Meta-analysis","volume":"354","author":"Odutayo","year":"2016","journal-title":"BMJ"},{"key":"ref_17","first-page":"191","article-title":"Incident AF and Risk of CHF, MI, ESKD, and Mortality in Decreased eGFR","volume":"71","author":"Kuwornu","year":"2018","journal-title":"Am. J. Kidney Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1016\/j.jacc.2016.06.057","article-title":"Atrial Fibrillation and Thromboembolism in CKD","volume":"68","author":"Lau","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1093\/cvr\/cvaa258","article-title":"Pathophysiology of Atrial Fibrillation and Chronic Kidney Disease","volume":"117","author":"Ding","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.amjcard.2020.07.004","article-title":"Effects of AF and CKD on Major Adverse Cardiovascular Events","volume":"132","author":"Ding","year":"2020","journal-title":"Am. J. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ocak, G., Khairoun, M., Khairoun, O., Bos, W.J.W., Fu, E.L., Cramer, M.J., Westerink, J., Verhaar, M.C., Visseren, F.L., and UCC-SMART study group (2022). Chronic Kidney Disease and Atrial Fibrillation: A Dangerous Combination. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0266046"},{"key":"ref_22","first-page":"e1","article-title":"2023 ACC\/AHA\/ACCP\/HRS Guideline for the Diagnosis and Management of AF","volume":"149","author":"Joglar","year":"2024","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102458","DOI":"10.1016\/j.semerg.2025.102458","article-title":"Estado de malnutrici\u00f3n como factor pron\u00f3stico de eventos cardiovasculares adversos mayores (MACE) en los pacientes con fibrilaci\u00f3n auricular [Poor nutrition status as a predictor of major adverse cardiovascular events (MACE) in patients with atrial fibrillation]","volume":"51","year":"2025","journal-title":"Semergen"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cersosimo, A., Zito, E., Pierucci, N., Matteucci, A., and La Fazia, V.M. (2025). A Talk with ChatGPT: The Role of Artificial Intelligence in Shaping the Future of Cardiology and Electrophysiology. J. Pers. Med., 15.","DOI":"10.3390\/jpm15050205"}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/13\/4\/289\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T10:58:50Z","timestamp":1764241130000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/13\/4\/289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":24,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["medsci13040289"],"URL":"https:\/\/doi.org\/10.3390\/medsci13040289","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,27]]}}}