{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:13:03Z","timestamp":1792458783070,"version":"4.5.0"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"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: Non-traumatic lower-limb amputations are associated with high mortality and a dramatic loss of quality of life. Peripheral artery disease and diabetes are the most common causes of non-traumatic lower-limb amputations. The aim of the study was to assess temporal trends in mortality, comorbidities and sex differences in patients with non-traumatic lower-limb amputations. Methods: A total of 1107 patients who underwent lower-limb amputation for non-traumatic causes at the Medical University of Innsbruck between 2006 and 2022 were reviewed and analyzed. Temporal trends in mortality, sex-differences in outcomes and the comorbidity spectrum were assessed. Results: In hospitals, 30-day and 1-year mortality has remained high from 2006 to 2022 (4.14%; 16.2%; 23.2%) with chronic kidney disease, heart failure and major amputations as predictors of 1-year mortality. Diabetes, peripheral artery disease and cerebrovascular disease were the most common causes of death in females, and liver disease, renal disease and myocardial infarction in males, respectively. Overall comorbidity frequency was high, with there being even increasing rates of coronary heart disease, atrial fibrillation and chronic pulmonary disease during the study period. Age at first amputation was significantly higher in women than in men (78.9 vs. 68.1 years). Median age increased and median LDL-cholesterol decreased in males but not in females during the time period. Major amputations were performed more frequently in females than in males as the first surgical intervention. Conclusions: Mortality and morbidity are high in patients with non-traumatic limb amputation. Our data underline the need of intensified risk-factor management with lower limb amputation, especially in females.<\/jats:p>","DOI":"10.3390\/jcm14124030","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T11:08:31Z","timestamp":1749208111000},"page":"4030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Non-Traumatic Lower-Limb Amputations: Outcome, Sex-Differences, Comorbidity Patterns and Temporal Trends from 2006 to 2022"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2524-5218","authenticated-orcid":false,"given":"Susanne","family":"Kaser","sequence":"first","affiliation":[{"name":"Department for Internal Medicine I, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7034-8155","authenticated-orcid":false,"given":"Bernhard","family":"Radlinger","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine I, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Blasinger","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Koellenberger","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine I, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Streitberger","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine I, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8238-8297","authenticated-orcid":false,"given":"Lena","family":"Kopp","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8029-2456","authenticated-orcid":false,"given":"Elena","family":"Bifano","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Aziz","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3510-9594","authenticated-orcid":false,"given":"Harald","family":"Sourij","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Goebel","sequence":"additional","affiliation":[{"name":"Institute of Clinical Epidemiology, Public Health, Health Economics, Medical Statistics and Informatics, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Klocker","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e875","DOI":"10.1161\/CIR.0000000000000967","article-title":"Reducing Nontraumatic Lower-Extremity Amputations by 20% by 2030: Time to Get to Our Feet: A Policy Statement from the American Heart Association","volume":"143","author":"Creager","year":"2021","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1002\/bjs.10823","article-title":"Population-based study of mortality and major amputation following lower limb revascularization","volume":"105","author":"Heikkila","year":"2018","journal-title":"Br. J. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1161\/CIRCULATIONAHA.123.067687","article-title":"Illness Trajectories After Revascularization in Patients with Peripheral Artery Disease: A Unified Approach to Understanding the Risk of Major Amputation and Death","volume":"150","author":"Li","year":"2024","journal-title":"Circulation"},{"key":"ref_4","first-page":"e38944","article-title":"Life Expectancy and Mortality After Lower Extremity Amputation: Overview and Analysis of Literature","volume":"15","author":"Qaarie","year":"2023","journal-title":"Cureus"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"76","DOI":"10.2337\/dc24-1644","article-title":"Trends in Peripheral Artery Disease, Lower Extremity Revascularization, and Lower Extremity Amputation in Incident Type 2 Diabetes: A Danish Population-Based Cohort Study","volume":"48","author":"Gyldenkerne","year":"2025","journal-title":"Diabetes Care"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lopez-de-Andres, A., Jimenez-Garcia, R., Hernandez-Barrera, V., de Miguel-Diez, J., de Miguel-Yanes, J.M., Omana-Palanco, R., and Carabantes-Alarcon, D. (2022). Trends of Non-Traumatic Lower-Extremity Amputation and Type 2 Diabetes: Spain, 2001\u20132019. J. Clin. Med., 11.","DOI":"10.3390\/jcm11051246"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"108477","DOI":"10.1016\/j.diabres.2020.108477","article-title":"Epidemiology of major lower extremity amputations in individuals with diabetes in Austria, 2014\u20132017: A retrospective analysis of health insurance database","volume":"170","author":"Aziz","year":"2020","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1007\/s00125-023-05891-x","article-title":"Sex differences in type 2 diabetes","volume":"66","author":"Leutner","year":"2023","journal-title":"Diabetologia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1016\/S0140-6736(10)60484-9","article-title":"Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: A collaborative meta-analysis of 102 prospective studies","volume":"375","author":"Sarwar","year":"2010","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1136\/bmj.38678.389583.7C","article-title":"Excess risk of fatal coronary heart disease associated with diabetes in men and women: Meta-analysis of 37 prospective cohort studies","volume":"332","author":"Huxley","year":"2006","journal-title":"BMJ"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S2213-8587(18)30111-6","article-title":"Diabetes and cardiovascular mortality: The impact of sex","volume":"6","author":"Norhammar","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/S2213-8587(18)30079-2","article-title":"Sex-specific relevance of diabetes to occlusive vascular and other mortality: A collaborative meta-analysis of individual data from 980 793 adults from 68 prospective studies","volume":"6","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u20132019: Update from the GBD 2019 Study","volume":"76","author":"Roth","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1161\/CIRCRESAHA.121.320702","article-title":"Sex Differences in Peripheral Artery Disease","volume":"130","author":"Pabon","year":"2022","journal-title":"Circ. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sigvant, B., Lundin, F., Nilsson, B., Bergqvist, D., and Wahlberg, E. (2011). Differences in presentation of symptoms between women and men with intermittent claudication. BMC Cardiovasc. Disord., 11.","DOI":"10.1186\/1471-2261-11-39"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e000651","DOI":"10.1161\/JAHA.113.000651","article-title":"Gender-specific risk factors for peripheral artery disease in a voluntary screening population","volume":"3","author":"Hiramoto","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e005967","DOI":"10.1161\/JAHA.117.005967","article-title":"Twenty-Year Predictors of Peripheral Arterial Disease Compared with Coronary Heart Disease in the Scottish Heart Health Extended Cohort (SHHEC)","volume":"6","author":"Peters","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s12933-020-01130-4","article-title":"Diabetes as a risk factor for incident peripheral arterial disease in women compared to men: A systematic review and meta-analysis","volume":"19","author":"Chan","year":"2020","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1093\/eurheartj\/ehn018","article-title":"Risk factors for myocardial infarction in women and men: Insights from the INTERHEART study","volume":"29","author":"Anand","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1001\/jama.295.2.180","article-title":"International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis","volume":"295","author":"Bhatt","year":"2006","journal-title":"JAMA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1161\/HYPERTENSIONAHA.109.142240","article-title":"Outcomes Among hypertensive patients with concomitant peripheral and coronary artery disease: Findings from the INternational VErapamil-SR\/Trandolapril STudy","volume":"55","author":"Bavry","year":"2010","journal-title":"Hypertension"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S86","DOI":"10.1161\/CIRCOUTCOMES.115.002180","article-title":"Sex Differences in the Incidence of Peripheral Artery Disease in the Chronic Renal Insufficiency Cohort","volume":"9","author":"Wang","year":"2016","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1177\/2047487312452968","article-title":"Peripheral arterial disease, prevalence and cumulative risk factor profile analysis","volume":"21","author":"Eraso","year":"2014","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.jacc.2019.11.057","article-title":"Sex-Specific Risks of Major Cardiovascular and Limb Events in Patients with Symptomatic Peripheral Artery Disease","volume":"75","author":"Haine","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e877","DOI":"10.1161\/CIR.0000000000001310","article-title":"Sex Differences in Peripheral Vascular Disease: A Scientific Statement from the American Heart Association","volume":"151","author":"Kim","year":"2025","journal-title":"Circulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J. Chronic Dis."},{"key":"ref_27","unstructured":"R Core Team (2024). A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_28","unstructured":"R Core Team (2020). RStudio: Integrated Development Environment for R, RStudio, PBC."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16","DOI":"10.18637\/jss.v057.i12","article-title":"Building Bivariate Tables: The compareGroups Package for R","volume":"57","author":"Subirana","year":"2014","journal-title":"J. Stat. Softw."},{"key":"ref_30","unstructured":"TM, T. (2025, June 02). A Package for Survival Analysis in R. Available online: https:\/\/cran.r-project.org\/web\/packages\/survival\/vignettes\/survival.pdf."},{"key":"ref_31","unstructured":"Wasey, J.O.L.M. (2024). icd: Comorbidity Calculations and Tools for ICD-9 and ICD-10 Codes, R Core Team."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sarroca, N., Valero, J., Deus, J., Casanova, J., Luesma, M.J., and Lahoz, M. (2021). Quality of life, body image and self-esteem in patients with unilateral transtibial amputations. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-91954-1"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1553","DOI":"10.1016\/S2214-109X(23)00355-8","article-title":"Global burden of peripheral artery disease and its risk factors, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"11","author":"Collaborators","year":"2023","journal-title":"Lancet Glob. Health"},{"key":"ref_34","unstructured":"IDF (2021). IDF Diabetes Atlas."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101079","DOI":"10.1016\/j.lanepe.2024.101079","article-title":"Trends in avoidable mortality from cardiovascular diseases in the European Union, 1995\u20132020: A retrospective secondary data analysis","volume":"47","author":"Cherla","year":"2024","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41581-023-00784-z","article-title":"Differences in the epidemiology, management and outcomes of kidney disease in men and women","volume":"20","author":"Chesnaye","year":"2024","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1093\/ndt\/gfx042","article-title":"Performance of glomerular filtration rate estimating equations in a community-based sample of Blacks and Whites: The multiethnic study of atherosclerosis","volume":"33","author":"Inker","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/nrneph.2017.181","article-title":"Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease","volume":"14","author":"Carrero","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1016\/0735-1097(94)90141-4","article-title":"Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction","volume":"24","author":"Celermajer","year":"1994","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4692","DOI":"10.1210\/jc.2012-2244","article-title":"Endothelial function is impaired across the stages of the menopause transition in healthy women","volume":"97","author":"Moreau","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1161\/01.HYP.28.4.576","article-title":"Menopause is associated with endothelial dysfunction in women","volume":"28","author":"Taddei","year":"1996","journal-title":"Hypertension"},{"key":"ref_42","first-page":"342","article-title":"A hidden problem: Peripheral artery disease in women","volume":"9","author":"Kavurma","year":"2023","journal-title":"Eur. Heart J. Qual. Care Clin. Outcomes"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1024\/0301-1526\/a001137","article-title":"Peripheral arterial disease in women","volume":"53","author":"Kozak","year":"2024","journal-title":"Vasa"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1016\/j.jcin.2020.08.036","article-title":"Predictors of Underutilization of Medical Therapy in Patients Undergoing Endovascular Revascularization for Peripheral Artery Disease","volume":"13","author":"Altin","year":"2020","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/dom.15988","article-title":"Metabolic risk factor targets in relation to clinical characteristics and comorbidities among individuals with type 2 diabetes treated in primary care\u2014The countrywide cross-sectional AUSTRO-PROFIT study","volume":"27","author":"Sourij","year":"2025","journal-title":"Diabetes Obes. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ramirez-Morros, A., Franch-Nadal, J., Real, J., Miro-Catalina, Q., Bundo, M., Vlacho, B., and Mauricio, D. (2024). Clinical characteristics and degree of cardiovascular risk factor control in patients with newly-diagnosed type 2 diabetes in Catalonia. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1339879"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1161\/CIRCULATIONAHA.117.032235","article-title":"Low-Density Lipoprotein Cholesterol Lowering with Evolocumab and Outcomes in Patients with Peripheral Artery Disease: Insights from the FOURIER Trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk)","volume":"137","author":"Bonaca","year":"2018","journal-title":"Circulation"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"110799","DOI":"10.1016\/j.diabres.2023.110799","article-title":"Glucagon-like peptide-1 treatment reduces the risk of diabetes-type 2 related amputations: A cohort study in Denmark","volume":"202","author":"Schafer","year":"2023","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.ejvs.2012.01.006","article-title":"Young women with PAD are at high risk of cardiovascular complications","volume":"43","author":"Wisman","year":"2012","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.advms.2020.01.004","article-title":"Gender differences and long-term clinical outcomes in patients with chronic total occlusions of infrainguinal lower limb arteries treated from retrograde access with peripheral vascular interventions","volume":"65","author":"Pawlik","year":"2020","journal-title":"Adv. Med. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1097\/HJH.0b013e3281fc975a","article-title":"2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)","volume":"25","author":"Mancia","year":"2007","journal-title":"J. Hypertens."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/12\/4030\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:47:53Z","timestamp":1760032073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/12\/4030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,6]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["jcm14124030"],"URL":"https:\/\/doi.org\/10.3390\/jcm14124030","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,6]]}}}