Pathology of Peripheral Artery Disease in Patients With Critical Limb Ischemia
Open accessAbstract
BACKGROUND Critical limb ischemia (CLI) is the most serious complication of peripheral artery disease (PAD). OBJECTIVES The purpose of this study was to characterize pathology of PAD in below- and above-knee amputation specimens in patients presenting with CLI. METHODS Peripheral arteries from 95 patients (121 amputation specimens) were examined; 75 patients had presented with CLI, and the remaining 20 had amputations performed for other reasons. The pathological characteristics were separately recorded for femoral and popliteal arteries (FEM-POP), and infrapopliteal arteries (INFRA-POP). RESULTS A total of 299 arteries were examined. In the 239 arteries from CLI patients, atherosclerotic plaques were more frequent in FEM-POP (23 of 34, 67.6%) compared with INFRA-POP (79 of 205, 38.5%) arteries. Of these 239 arteries, 165 (69%) showed ≥70% stenosis, which was due to significant pathological intimal thickening, fibroatheroma, fibrocalcific lesions, or restenosis in 45 of 165 (27.3%), or was due to luminal thrombi with (39 of 165, 23.6%) or without (81 of 165, 49.1%) significant atherosclerotic lesions. Presence of chronic luminal thrombi was more frequently observed in arteries with insignificant atherosclerosis (OR: 16.7; p = 0.0002), more so in INFRA-POP compared with FEM-POP (OR: 2.14; p = 0.0041) arteries. Acute thrombotic occlusion was less frequently encountered in INFRA-POP than FEM-POP arteries (OR: 0.27; p = 0.0067). Medial calcification was present in 170 of 239 (71.1%) large arteries. CONCLUSIONS Thrombotic luminal occlusion associated with insignificant atherosclerosis is commonly observed in CLI and suggests the possibility of atherothromboembolic disease. The pathological characteristics of arteries in CLI suggest possible mechanisms of progression of PAD to CLI, especially in INFRA-POP arteries, and may support the preventive role of antithrombotic agents.
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- Authors
- Narula, N., Dannenberg, A. J., Olin, J. W., Bhatt, D. L., Johnson, K. W., Nadkarni, G., Min, J., Torii, S., Poojary, P., Anand, S. S., Bax, J. J., Yusuf, S., Virmani, R., & Narula, J.
- Affiliations
- NewYork–Presbyterian Hospital (US)
- Icahn School of Medicine at Mount Sinai (US)
- Brigham and Women's Hospital (US)
- Population Health Research Institute (CA)
- Leiden University Medical Center (NL)
- Corresponding author
- Narula, Navneet
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 72
- Issue
- 18
- Pages
- 2152-2163
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2889325201
- Semantic Scholar
- f99cf8b5fae34d8b32249ee26771479599668caa
- Cited by
- 326
- References
- 29
- Citations by year
- 2026: 23 · 2025: 60 · 2024: 58 · 2023: 36 · 2022: 38 · 2021: 43 · 2020: 43 · 2019: 21 · 2018: 4
- FWCI
- 28.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Funders
- American Heart Association
- Cleveland Clinic
- Boston VA Research Institute
- Regado Biosciences
- Belvoir Media Group
- St. Jude Medical
- Duke Clinical Research Institute
- Janssen Pharmaceuticals
- Topics
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Aortic Thrombus and Embolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- critical limb ischemia, peripheral arterial disease, atherosclerosis, medial calcification, restenosis, fibrocalcific plaque, infrapopliteal artery, arterial stenosis, antithrombotic therapy, intimal thickening, acute thrombotic occlusion
- MeSH terms
- Adult, Aged, Aged, 80 and over, Amputation, Surgical, Female, Humans, Ischemia, Male, Middle Aged, Retrospective Studies, Limb Salvage, Lower Extremity, Peripheral Arterial Disease, Vascular Calcification
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