{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T18:13:49Z","timestamp":1778523229998,"version":"3.51.4"},"reference-count":23,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Frank\u2019s sign (FS), an acquired diagonal earlobe crease, has been associated with underlying cardiovascular (CV) disease. Pneumonia, a leading cause of hospitalization, may trigger CV events. FS may help identify patients at increased risk of CV complications following pneumonia. We aimed to evaluate the association between FS and CV events following pneumonia. Methods: We conducted a single-center prospective cohort study of internal medicine patients hospitalized with community-acquired pneumonia at a secondary hospital in Switzerland, followed for 18 months. FS was assessed at inclusion by trained investigators. Baseline characteristics were recorded. The primary outcome was a composite of CV endpoints: new-onset atrial fibrillation\/flutter, myocardial infarction, hospitalization for heart failure, peripheral arterial ischemic events, or stroke. Events were identified through hospital records and general practitioner data between 2020 and 2023. Results: Among 203 patients (median age 76.0 years [IQR 65.0 to 83.0]; 41.4% female), 71.2% had FS. During follow-up, 103 CV events occurred. In univariate Cox analysis, FS was associated with an increased hazard of CV events (p = 0.042). After adjustment for confounders, FS was not significantly associated with CV events (HR 0.97; 95% CI 0.59\u20131.59). Only a history of CV disease and CV risk factors were associated with an increased hazard of subsequent cardiovascular events following pneumonia. Conclusions: In this population of patients hospitalized with pneumonia, Frank\u2019s sign was not independently associated with cardiovascular events and appears to reflect underlying cardiovascular risk burden. It should not be interpreted as an independent prognostic marker.<\/jats:p>","DOI":"10.3390\/jcm15103656","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:17:42Z","timestamp":1778519862000},"page":"3656","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Frank\u2019s Sign and Risk of Cardiovascular Events in Patients Hospitalized for Pneumonia: A Prospective Single-Center Cohort Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6664-1734","authenticated-orcid":false,"given":"Laure","family":"Cochand","sequence":"first","affiliation":[{"name":"Division of General Internal Medicine, Department of Medicine, Biel Hospital, 2502 Biel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3375-1985","authenticated-orcid":false,"given":"Nils","family":"B\u00fcrgisser","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, Department of Medicine, Biel Hospital, 2502 Biel, Switzerland"},{"name":"Division of General Internal Medicine, Department of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland"},{"name":"Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clement P","family":"Buclin","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, Department of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland"},{"name":"Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline","family":"Habegger","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, Department of Medicine, Biel Hospital, 2502 Biel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy H.","family":"Martin","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, Department of Medicine, Biel Hospital, 2502 Biel, Switzerland"},{"name":"Division of General Internal Medicine, Department of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Hell","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, Department of Medicine, Biel Hospital, 2502 Biel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5086-5707","authenticated-orcid":false,"given":"Solenne","family":"Perrenoud","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, Department of Medicine, Biel Hospital, 2502 Biel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6314-0719","authenticated-orcid":false,"given":"Daniel","family":"Genn\u00e9","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, Department of Medicine, Biel Hospital, 2502 Biel, Switzerland"},{"name":"Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"ref_1","unstructured":"GBD 2021 Lower Respiratory Infections and Antimicrobial Resistance Collaborators (2024). Global, regional, and national incidence and mortality burden of non-COVID-19 lower respiratory infections and aetiologies, 1990\u20132021: A systematic analysis from the Global Burden of Disease Study 2021. Lancet Infect. Dis., 24, 974\u20131002."},{"key":"ref_2","unstructured":"Swiss Federal Statistical Office (2024, December 21). Hospitalisations Pour Maladies de L\u2019appareil Respiratoire 2012\u20132022\u2014GNP Diffusion. Hospitalisation Due to Disease of the Respiratory Tract-2012. Available online: https:\/\/www.bfs.admin.ch\/news\/fr\/2023-0178."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Desai, A., Aliberti, S., Amati, F., Stainer, A., and Voza, A. (2022). Cardiovascular Complications in Community-Acquired Pneumonia. Microorganisms, 10.","DOI":"10.3390\/microorganisms10112177"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1056\/NEJMra1808137","article-title":"Acute Infection and Myocardial Infarction","volume":"380","author":"Musher","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/S0140-6736(12)61266-5","article-title":"Acute pneumonia and the cardiovascular system","volume":"381","author":"Musher","year":"2013","journal-title":"Lancet Lond. Engl."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.amjmed.2021.11.021","article-title":"Relationship of Physical Examination Technique to Associated Clinical Skills: Results from a Direct Observation Assessment","volume":"135","author":"Clark","year":"2022","journal-title":"Am. J. Med."},{"key":"ref_7","first-page":"Doc58","article-title":"How well do final year undergraduate medical students master practical clinical skills?","volume":"33","author":"Stankiewicz","year":"2016","journal-title":"GMS J. Med. Educ."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1056\/NEJM197308092890622","article-title":"Aural sign of coronary-artery disease","volume":"289","author":"Frank","year":"1973","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s12024-022-00463-8","article-title":"The prognostic value of the Frank sign","volume":"18","author":"Prangenberg","year":"2022","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1324.e1","DOI":"10.1016\/j.amjmed.2017.03.059","article-title":"Diagonal Earlobe Crease (Frank\u2019s Sign): A Predictor of Cerebral Vascular Events","volume":"130","author":"Nazzal","year":"2017","journal-title":"Am. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.amjmed.2023.09.019","article-title":"Frank\u2019s Sign and Cardiovascular Risk: An Observational Descriptive Study","volume":"137","author":"Ascariz","year":"2024","journal-title":"Am. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1007\/s12105-020-01205-4","article-title":"The Histological Basis of Frank\u2019s Sign","volume":"15","author":"Stoyanov","year":"2021","journal-title":"Head. Neck Pathol."},{"key":"ref_13","unstructured":"R Core Team (2025, August 23). R: A Language and Environment for Statistical Computing, Available online: https:\/\/www.R-project.org\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e033792","DOI":"10.1136\/bmjopen-2019-033792","article-title":"Screening for Hypertension in the INpatient Environment(SHINE): A protocol for a prospective study of diagnostic accuracy among adult hospital patients","volume":"9","author":"Armitage","year":"2019","journal-title":"BMJ Open"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"72","DOI":"10.5114\/ait.2020.93219","article-title":"Frank\u2019s sign in anesthesia","volume":"52","author":"Elkoundi","year":"2020","journal-title":"Anaesthesiol. Intensive Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1001\/jama.2014.18229","article-title":"Association Between Hospitalization for Pneumonia and Subsequent Risk of Cardiovascular Disease","volume":"313","author":"Alvarez","year":"2015","journal-title":"JAMA"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wi\u0119ckowski, K., Gallina, T., Surdacki, A., and Chyrchel, B. (2021). Diagonal Earlobe Crease (Frank\u2019s Sign) for Diagnosis of Coronary Artery Disease: A Systematic Review of Diagnostic Test Accuracy Studies. J. Clin. Med., 10.","DOI":"10.3390\/jcm10132799"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13397","DOI":"10.1038\/s41598-017-13370-8","article-title":"Diagonal Earlobe Crease is a Visible Sign for Cerebral Small Vessel Disease and Amyloid-\u03b2","volume":"7","author":"Lee","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s10072-019-04080-2","article-title":"Diagonal earlobe crease (Frank\u2019s sign) and increased risk of cerebrovascular diseases: Review of the literature and implications for clinical practice","volume":"41","author":"Pacei","year":"2020","journal-title":"Neurol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1161\/ATVBAHA.124.321001","article-title":"COVID-19 Is a Coronary Artery Disease Risk Equivalent and Exhibits a Genetic Interaction With ABO Blood Type","volume":"44","author":"Hilser","year":"2024","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1007\/s12024-024-00868-7","article-title":"Prevalence of Frank\u2019s sign in healthy young individuals, morphological characteristics, and its association with family history of chronic disease","volume":"20","author":"Aksu","year":"2024","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5598134","DOI":"10.1155\/2024\/5598134","article-title":"Traditional Cardiovascular Risk Factors Associated with Diagonal Earlobe Crease (Frank Sign) in Mexican Adults: Aging, Obesity, Arterial Hypertension, and Being Male Are the Most Important","volume":"2024","year":"2024","journal-title":"Int. J. Hypertens."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1136\/thoraxjnl-2016-209405","article-title":"Adults miscoded and misdiagnosed as having pneumonia: Results from the British Thoracic Society pneumonia audit","volume":"72","author":"Daniel","year":"2017","journal-title":"Thorax"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/10\/3656\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:40:45Z","timestamp":1778521245000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/10\/3656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,9]]},"references-count":23,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["jcm15103656"],"URL":"https:\/\/doi.org\/10.3390\/jcm15103656","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,9]]}}}