Microvascular disease increases the risk of lower limb amputation – A Western Danish cohort study
Abstract
Background 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. Methods We included every resident without previous lower limb amputation in Western Denmark aged 50-75 years on 1 January 2012 and followed them for 7 years. 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-specific analysis and estimated the population attributable fraction of the male sex. Results 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 2.98-3.73) and PAD only (adjusted hazard ratio 7.32, 95% CI 6.62-8.08) 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 10.43-14.80). Men had an increased absolute risk of amputation. The population attributable fraction associated with the male sex was 31%. Conclusions 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-fold amputation risk. T…
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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 [240]
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 [229]
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- Authors
- Olesen, K. K. W., Anand, S., Thim, T., Gyldenkerne, C., & Maeng, M.
- Affiliations
- Aarhus University Hospital (DK)
- Population Health Research Institute (CA)
- Department of Cardiology Aarhus University Hospital Aarhus N Denmark
- Corresponding author
- Olesen, Kevin Kris Warnakula
- Venue
- European Journal of Clinical Investigation
- Publisher
- Wiley
- Published
- 2022-05-28
- Volume
- 52
- Issue
- 10
- Pages
- e13812-e13812
- ISSN
- 0014-2972 (ISSN-L)
- 1365-2362
- OpenAlex
- W4229458582
- Cited by
- 21
- References
- 37
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 4 · 2022: 1
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- Scopus (Elsevier) (submittedVersion)
- Funders
- Aarhus Universitetshospital
- 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, lower limb amputation, amputation risk, sex differences, population attributable fraction, Western Denmark
- MeSH terms
- Amputation, Surgical, Denmark, Female, Humans, Male, Risk Factors, Cohort Studies, Treatment Outcome, Lower Extremity, Peripheral Arterial Disease
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