{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:25:16Z","timestamp":1790799916260,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T00:00:00Z","timestamp":1653696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007606","name":"Aarhus Universitetshospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Peripheral artery disease is the leading cause of nontraumatic lower limb amputation. Microvascular disease (MVD) increases the risk of lower limb amputation in patients with peripheral artery disease (PAD). We estimated the risk of lower limb amputation associated with MVD and PAD in a Danish cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included every resident without previous lower limb amputation in Western Denmark aged 50\u201375\u2009years on 1 January 2012 and followed them for 7\u2009years. Participants were stratified by MVD and PAD. We estimated adjusted hazard ratios of lower limb amputation using individuals with no MVD and no PAD as reference. We also provide a sex\u2010specific analysis and estimated the population attributable fraction of the male sex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 933,597 individuals, of whom 16,741 had MVD only, 18,217 had PAD only and 1,827 had MVD and PAD. Both MVD only (adjusted hazard ratio 3.36, 95% CI 2.98\u20133.73) and PAD only (adjusted hazard ratio 7.32, 95% CI 6.62\u20138.08) increased the risk of lower limb amputation separately. Individuals with MVD and PAD had the highest risk of amputation (adjusted hazard ratio 12.27, 95% CI 10.43\u201314.80). Men had an increased absolute risk of amputation. The population attributable fraction associated with the male sex was 31%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Microvascular disease and PAD are independently associated with a threefold and sevenfold increase of amputation risk, respectively. Combined, they had an additive effect constituting a 12\u2010fold amputation risk. The amputation risk was higher in men than women, and 3 in 10 amputations were attributed to the male sex<jats:italic>.<\/jats:italic><\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.13812","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T04:10:57Z","timestamp":1652155857000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Microvascular disease increases the risk of lower limb amputation \u2013 A Western Danish cohort study"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0560-3615","authenticated-orcid":false,"given":"Kevin Kris Warnakula","family":"Olesen","sequence":"first","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital  Aarhus N Denmark"},{"name":"Department of Cardiology G\u00f8dstrup Regional Hospital  Herning Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Medicine, Population Health Research Institute, Hamilton Health Sciences McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-5559","authenticated-orcid":false,"given":"Troels","family":"Thim","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital  Aarhus N Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Gyldenkerne","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital  Aarhus N Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Maeng","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital  Aarhus N Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.040672"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.03.008"},{"issue":"10","key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1161\/CIRCULATIONAHA.115.019355","article-title":"Acute limb ischemia and outcomes with vorapaxar in patients with peripheral artery disease: results from the trial to assess the effects of vorapaxar in preventing heart attack and stroke in patients with atherosclerosis\u2010thrombolysis in myocardial infarction 50 (TRA2\u00b0P\u2010TIMI 50)","volume":"133","author":"Bonaca MP","year":"2016","journal-title":"Circulation"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/1403494810387965"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-014-9930-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S91125"},{"issue":"3","key":"e_1_2_7_8_1","first-page":"798","article-title":"Data resource profile: the Danish National Prescription Registry","volume":"46","author":"Pottegard A","year":"2017","journal-title":"Int J Epidemiol"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.10.110"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1403494811399958"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k757"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2009.02234.x"},{"issue":"2","key":"e_1_2_7_13_1","first-page":"167","article-title":"Who joins the military? 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