{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:38:04Z","timestamp":1792103884164,"version":"4.4.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2019,8,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The mechanism of adverse limb events associated with peripheral artery disease remains incompletely understood. We investigated whether microvascular disease is associated with amputation in a large cohort of veterans to determine whether microvascular disease diagnosed in any location increases the risk of amputation alone and in concert with peripheral artery disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Participants in the Veterans Aging Cohort Study were recruited from April 1, 2003 through December 31, 2014. We excluded participants with known prior lower limb amputation. Using time-updated Cox proportional hazards regression, we analyzed the effect of prevalent microvascular disease (retinopathy, neuropathy, and nephropathy) and peripheral artery disease status on the risk of incident amputation events after adjusting for demographics and cardiovascular risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Among 125\u2009674 veterans without evidence of prior amputation at baseline, the rate of incident amputation over a median of 9.3 years of follow-up was 1.16 per 1000 person-years, yielding a total of 1185 amputations. In time-updated multivariable-adjusted analyses, compared with those without peripheral artery disease or microvascular disease, microvascular disease alone was associated with a 3.7-fold (95% CI, 3.0\u20134.6) increased risk of amputation; peripheral artery disease alone conferred a 13.9-fold (95% CI, 11.3\u201317.1) elevated risk of amputation; and the combination of peripheral artery disease and microvascular disease was associated with a 22.7-fold (95% CI, 18.3\u201328.1) increased risk of amputation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Independent of traditional risk factors, the presence of microvascular disease increases the risk of amputation alone and synergistically increases risk in patients with peripheral artery disease. Further research is needed to understand the mechanisms by which this occurs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.119.040672","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T05:00:16Z","timestamp":1562562016000},"page":"449-458","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":184,"title":["Microvascular Disease, Peripheral Artery Disease, and Amputation"],"prefix":"10.1161","volume":"140","author":[{"given":"Joshua A.","family":"Beckman","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine (J.A.B., M.S.D., Q.S.W., A.W.A., M.S.F.), Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith S.","family":"Duncan","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (J.A.B., M.S.D., Q.S.W., A.W.A., M.S.F.), Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Damrauer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania (S.M.D.), Philadelphia."},{"name":"Corporal Michael Crescenz VA Medical Center (S.M.D.), Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quinn S.","family":"Wells","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (J.A.B., M.S.D., Q.S.W., A.W.A., M.S.F.), Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joey V.","family":"Barnett","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (J.V.B.), Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Vanderbilt University, Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine (D.H.W.), Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger J.","family":"Bedimo","sequence":"additional","affiliation":[{"name":"Infectious Disease Section, VA North Texas Health Center and University of Texas Southwestern Medical Center, Dallas (R.J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeel A.","family":"Butt","sequence":"additional","affiliation":[{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY (A.A.B)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent C.","family":"Marconi","sequence":"additional","affiliation":[{"name":"Atlanta Veterans Affairs Medical Center and Emory University School of Medicine, GA (V.C.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason J.","family":"Sico","sequence":"additional","affiliation":[{"name":"VA Connecticut Healthcare System, West Haven (J.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary A.","family":"Tindle","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine and Public Health (H.A.T.), Nashville, TN."},{"name":"Yale School of Medicine, Departments of Neurology and Internal Medicine, New Haven, CT. 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