Microvascular disease, peripheral artery disease, and amputation
Open accessAbstract
Background: 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. Methods: 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. Results: Among 125 674 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, 3.0–4.6) increased risk of amputation; peripheral artery disease alone conferred a 13.9-fold (95% CI, 11.3–17.1) elevated risk of amputation; and the combination of peripheral artery disease and microvascular disease was associated with a 22.7-fold (95% CI, 18.3–28.1) increased risk of amputation. Conclusions: 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.
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The presence of microvascular disease is associated with adverse outcomes in people with PAD, including an increased risk for future limb amputation.
“In addition, the presence of microvascular disease is associated with adverse outcomes in people with PAD, including an increased risk for future limb amputation (239,240).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [239]
The presence of microvascular disease is associated with adverse outcomes in people with PAD, including an increased risk for future limb amputation.
“In addition, the presence of microvascular disease is associated with adverse outcomes in people with PAD, including an increased risk for future limb amputation (228,229).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [228]
For patients with a diabetic foot ulcer, the risk of death at 5 years is 2.5 times higher than for patients with diabetes but no foot ulcer.
“For patients with a diabetic foot ulcer (diabetic foot disease), the risk of death at 5 years is 2.5 times higher than for patients with diabetes but no foot ulcer.752,756”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [756]
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Fowkes, F. G. R., Murray, G. D., Butcher, I., Heald, C. L., Lee, R. J., Chambless, L. E., Folsom, A. R., Hirsch, A. T., Dramaix, M., DeBacker, G., et al. (2008) · JAMA · doi:10.1001/jama.300.2.197 · Cited by 1,870 · see citing works
Hillege, H. L., Janssen, W. M. T., Bak, A. A. A., Diercks, G. F. H., Grobbee, D. E., Crijns, H. J. G. M., van Gilst, W. H., de Zeeuw, D., de Jong, P. E., & FOR THE PREVEND STUDY GROUP (2001) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.2001.00833.x · Cited by 628 · see citing works
Taqueti, V. R., Hachamovitch, R., Murthy, V. L., Naya, M., Foster, C. R., Hainer, J. M., Dorbala, S., Blankstein, R., & Carli, M. F. D. (2014) · Circulation · doi:10.1161/circulationaha.114.011939 · Cited by 498 · see citing works
Vascular Complications of Diabetes
Beckman, J. A., & Creager, M. A. (2016) · Circulation Research · doi:10.1161/circresaha.115.306884 · Cited by 416 · see citing works
Self-citationDiabetes Prevention Program Research Group (2007) · Diabetic Medicine · doi:10.1111/j.1464-5491.2007.02043.x · Cited by 363 · see citing works
Systemic nature of endothelial dysfunction in atherosclerosis
Anderson, T. J., Gerhard, M. D., Meredith, I. T., Charbonneau, F., Delagrange, D. M., Creager, M. A., Selwyn, A. P., & Ganz, P. (1995) · The American Journal of Cardiology · doi:10.1016/0002-9149(95)80017-m · Cited by 360 · see citing works
Risk of Major Adverse Cardiac Events Following Noncardiac Surgery in Patients With Coronary Stents
Hawn, M. T., Graham, L. A., Richman, J., Itani, K. M. F., Henderson, W. G., & Maddox, T. M. (2013) · JAMA · doi:10.1001/jama.2013.278787 · Cited by 339 · see citing works
Lieberman, E. H., Gerhard, M. D., Uehata, A., Selwyn, A. P., Ganz, P., Yeung, A. C., & Creager, M. A. (1996) · The American Journal of Cardiology · doi:10.1016/s0002-9149(96)00597-8 · Cited by 318 · see citing works
Development and Verification of a “Virtual” Cohort Using the National VA Health Information System
Fultz, S. L., Skanderson, M., Mole, L. A., Gandhi, N. R., BRYANT, K. J., Crystal, S., & Justice, A. C. (2006) · Medical Care · doi:10.1097/01.mlr.0000223670.00890.74 · Cited by 257 · see citing works
Moss, S. E., Klein, R., & Klein, R. (1999) · Diabetes Care · doi:10.2337/diacare.22.6.951 · Cited by 197 · see citing works
Retinal Vessel Caliber and Microvascular and Macrovascular Disease in Type 2 Diabetes
Klein, R., Klein, B. E. K., Moss, S. E., & Wong, T. Y. (2007) · Ophthalmology · doi:10.1016/j.ophtha.2007.02.023 · Cited by 183 · see citing works
Natural history of claudication: Long-term serial follow-up study of 1244 claudicants
Aquino, R. V., Johnnides, C., Makaroun, M. S., Whittle, J., Muluk, V. S., Kelley, M. E., & Muluk, S. C. (2001) · Journal of Vascular Surgery · doi:10.1067/mva.2001.119749 · Cited by 162 · see citing works
Chronic Limb-Threatening Ischemia
Farber, A. M. (2018) · New England Journal of Medicine · doi:10.1056/nejmcp1709326 · Cited by 162 · see citing works
Akasaka, T., Yoshida, K., Hozumi, T., Takagi, T., Kaji, S., Kawamoto, T., Morioka, S., & Yoshikawa, J. (1997) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(97)00242-8 · Cited by 140 · see citing works
Risk of diabetes in HIV infected veterans pre- and post-HAART and the role of HCV coinfection†
Butt, A. A., Fultz, S. L., Kwoh, K. C., Kelley, D. E., Skanderson, M., & Justice, A. C. (2004) · Hepatology · doi:10.1002/hep.20289 · Cited by 125 · see citing works
Self-citationMohammedi, K., Woodward, M., Hirakawa, Y., Zoungas, S., Williams, B., Lisheng, L., Rodgers, A., Mancia, G., Neal, B. C., Harrap, S. B., et al. (2016) · Diabetes Care · doi:10.2337/dc16-0588 · Cited by 120 · see citing works
Endothelial reactivity and cardiac risk factors in older patients with peripheral arterial disease
Yataco, A. R., Corretti, M. C., Gardner, A. W., Womack, C. J., & Katzel, L. I. (1999) · The American Journal of Cardiology · doi:10.1016/s0002-9149(98)00984-9 · Cited by 107 · see citing works
Association of Human Immunodeficiency Virus Infection and Risk of Peripheral Artery Disease
Beckman, J. A., Duncan, M. S., Alcorn, C., So‐Armah, K., Butt, A. A., Goetz, M. B., Tindle, H. A., Sico, J. J., Tracy, R. P., Justice, A. C., et al. (2018) · Circulation · doi:10.1161/circulationaha.117.032647 · Cited by 106 · see citing works
Self-citationLamparter, J., Raum, P., Pfeiffer, N., Pető, T., Höhn, R., Elflein, H. M., Wild, P. S., Schulz, A., Schneider, A., & Mirshahi, A. (2014) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2014.02.008 · Cited by 81 · see citing works
Microvascular endothelial dysfunction is associated with albuminuria
Martens, R. J. H., Houben, A. J. H. M., Kooman, J. P., Berendschot, T. T. J. M., Dagnelie, P. C., Kallen, C., Kroon, A. A., Leunissen, K. M. L., SANDE, F. M. V. D., Schaper, N. C., et al. (2018) · Journal of Hypertension · doi:10.1097/hjh.0000000000001674 · Cited by 75 · see citing works
Nguyen, T. T., Shaw, J. E., Robinson, C. V., Kawasaki, R., Wang, J. J., Kreis, A., & Wong, T. Y. (2011) · Diabetes Care · doi:10.2337/dc10-1985 · Cited by 54 · see citing works
Microalbuminuria in Type 2 diabetes indicates impaired microvascular vasomotion and perfusion
Schmiedel, O., Schroeter, M. L., & Harvey, J. N. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00558.2007 · Cited by 54 · see citing works
Peripheral Neuropathy Defined by Monofilament Insensitivity and Diabetes Status
Katon, J. G., Reiber, G. E., & Nelson, K. M. (2012) · Diabetes Care · doi:10.2337/dc12-1102 · Cited by 53 · see citing works
de Jong, P. E., Gansevoort, R. T., & Bakker, S. J. L. (2007) · Journal of Nephrology · doi:10.1093/joneph/20.4.375 · Cited by 48 · see citing works
Sukul, D., Grey, S. F., Henke, P. K., Gurm, H. S., & Grossman, P. M. (2017) · JACC: Cardiovascular Interventions · doi:10.1016/j.jcin.2017.08.026 · Cited by 45 · see citing works
Potier, L., Chequer, R. D. P., Roussel, R., Mohammedi, K., Sismail, S., Hartemann, A., Amouyal, C., Marre, M., Guludec, D. L., & Hyafil, F. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-017-0652-1 · Cited by 45 · see citing works
Schulman, D. S., Lasorda, D., Farah, T. G., et al. (1997) · American Heart Journal · doi:10.1016/s0002-8703(97)70112-1 · Cited by 34 · see citing works
Keenan, J. D., Fan, A. Z., & Klein, R. (2009) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2008.12.009 · Cited by 26 · see citing works
Personalized Approach to Revascularization of Critical Limb Ischemia
Shishehbor, M. H., & Reed, G. W. (2014) · Circulation Cardiovascular Interventions · doi:10.1161/circinterventions.114.001923 · Cited by 25 · see citing works
Coronary flow reserve as a link between exercise capacity, cardiac systolic and diastolic function
Blomster, J., Svedlund, S., Westergren, H. U., & Gan, L. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.04.179 · Cited by 21 · see citing works
Lin, C., Zhang, P., Xue, Y., Huang, Y., & Ji, K. (2017) · Cardiology Journal · doi:10.5603/cj.a2017.0074 · Cited by 17 · see citing works
Kim, D., Grodstein, F., Newman, A. B., Chaves, P. H. M., Odden, M. C., Klein, R., Sarnak, M. J., Patel, K. V., & Lipsitz, L. A. (2014) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu074 · Cited by 16 · see citing works
Youn, H., Park, C., Moon, K., et al. (2004) · International Journal of Cardiology · doi:10.1016/j.ijcard.2003.11.045 · Cited by 14 · see citing works
Bali, V., Yermilov, I., Coutts, K., & Legorreta, A. P. (2015) · Vascular Medicine · doi:10.1177/1358863x15616687 · Cited by 12 · see citing works
Association between coronary flow reserve and exercise capacity.
Eroğlu, S., Sade, L. E., Polat, E., et al. (2016) · PubMed · Cited by 6 · see citing works
Kalaycı, S., Kalaycı, B., Şahan, E., et al. (2017) · Kardiologia Polska · doi:10.5603/kp.a2017.0089 · Cited by 3 · see citing works
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Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Anderson, C. A. M., Arora, P., Avery, C. L., Baker-Smith, C. M., Beaton, A. Z., Boehme, A. K., Buxton, A. E., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001123 · Cited by 8,300 · see citing works
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Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Alonso, A., Beaton, A. Z., Bittencourt, M. S., Boehme, A. K., Buxton, A. E., Carson, A. P., Commodore-Mensah, Y., et al. (2022) · Circulation · doi:10.1161/cir.0000000000001052 · Cited by 5,987 · see citing works
Self-citation2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes.
Marx, N., Federici, M., Schütt, K., Müller-Wieland, D., Ajjan, R. A., Antunes, M. J., Christodorescu, R. M., Crawford, C., Di Angelantonio, E., Eliasson, B., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad192 · Cited by 1,642 · see citing works
10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Das, S. R., Echouffo-Tcheugui, J. B., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s010 · Cited by 339 · see citing works
Gornik, H. L., Aronow, H. D., Goodney, P. P., Arya, S., Brewster, L. P., Byrd, L., Chandra, V., Drachman, D. E., Eaves, J. M., Ehrman, J. K., et al. (2024) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2024.02.013 · Cited by 294 · see citing works
Creager, M. A., Matsushita, K., Arya, S., Beckman, J. A., Duval, S., Goodney, P. P., Gutierrez, J. A. T., Kaufman, J. A., Joynt Maddox, K. E., Pollak, A. W., et al. (2021) · Circulation · doi:10.1161/cir.0000000000000967 · Cited by 164 · see citing works
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American Diabetes Association Professional Practice Committee for Diabetes*, Bajaj, M., McCoy, R. G., Balapattabi, K., Bannuru, R. R., Bellini, N. J., Bennett, A. K., Beverly, E. A., Briggs Early, K., ChallaSivaKanaka, S., et al. (2026) · Diabetes Care · doi:10.2337/dc26-s010 · Cited by 107 · see citing works
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Behroozian, A., & Beckman, J. A. (2020) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.119.312859 · Cited by 94 · see citing works
Self-citation
- Authors
- Beckman, J. A., Duncan, M. S., Damrauer, S. M., Wells, Q. S., Barnett, J. V., Wasserman, D. H., Bedimo, R. J., Butt, A. A., Marconi, V. C., Sico, J. J., Tindle, H. A., Bonaca, M. P., Aday, A. W., & Freiberg, M. S.
- Affiliations
- Division of Cardiovascular Medicine (J.A.B., M.S.D., Q.S.W., A.W.A., M.S.F.), Nashville, TN.
- Philadelphia VA Medical Center (US)
- Department of Pharmacology (J.V.B.), Nashville, TN.
- Vanderbilt University (US)
- VA North Texas Health Care System (US)
- Weill Cornell Medicine (US)
- Emory University (US)
- VA Connecticut Healthcare System (US)
- Yale University (US)
- University of Colorado Anschutz (US)
- ORCID
- Venue
- Circulation
- Published
- 2019-08-06
- Volume
- 140
- Issue
- 6
- Pages
- 449-458
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC6682431
- OpenAlex
- W2961925837
- Cited by
- 196
- References
- 36
- Citations by year
- 2026: 20 · 2025: 28 · 2024: 30 · 2023: 27 · 2022: 35 · 2021: 28 · 2020: 26 · 2019: 1 · 2012: 1
- FWCI
- 21.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (IK2-CX001780)
- National Institutes of Health (UL1TR001863)
- National Institute on Alcohol Abuse and Alcoholism (U01AA020790)
- National Heart, Lung, and Blood Institute (R01HL125032, R01HL131977, T32HL007575)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vascular Procedures and Complications
- Keywords
- microangiopathy, peripheral arterial disease, amputation, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, veterans, synergistic risk
- MeSH terms
- Procedures and Techniques Utilization, Adult, Aged, Amputation, Surgical, Disease Susceptibility, Extremities, Female, Follow-Up Studies, Humans, Ischemia, Kidney Diseases, Male, Microcirculation, Middle Aged, Peripheral Nervous System Diseases, Prospective Studies, Retinal Diseases, Risk Factors, Veterans, Comorbidity, Prevalence, Proportional Hazards Models, Diabetes Complications, Peripheral Arterial Disease
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