Abstract
Approximately 6% of adults worldwide have atherosclerosis and thrombosis of the lower limb arteries (peripheral artery disease (PAD)) and the prevalence is rising. PAD causes leg pain, impaired health-related quality of life, immobility, tissue loss and a high risk of major adverse events, including myocardial infarction, stroke, revascularization, amputation and death. In this Review, I describe the pathophysiology, presentation, outcome, preclinical research and medical management of PAD. Established treatments for PAD include antithrombotic drugs, such as aspirin and clopidogrel, and medications to treat dyslipidaemia, hypertension and diabetes mellitus. Randomized controlled trials have demonstrated that these treatments reduce the risk of major adverse events. The drug cilostazol, exercise therapy and revascularization are the current treatment options for the limb symptoms of PAD, but each has limitations. Novel therapies to promote collateral and new capillary growth and treat PAD-related myopathy are under investigation. Methods to improve the implementation of evidence-based medical management, novel drug therapies and rehabilitation programmes for PAD-related pain, functional impairment and ischaemic foot disease are important areas for future research.
Key points
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Peripheral artery disease (PAD) is present in 6% of adults and is associated with leg pain, walking impairment and high risk of major adverse cardiovascular events, including amputation and death.
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PAD usually presents with leg pain, ischaemic ulceration or gangrene and is usually caused by atherosclerosis and thrombosis, although all current animal models use surgically created hindlimb ischaemia.
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Treatment options for the leg symptoms of PAD include cilostazol, exercise therapy and revascularization, with novel therapies under investigation including autologous cell therapy, organic nitrates and antioxidants.
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Antithrombotic and LDL-cholesterol-lowering medications, smoking cessation and treatment of hypertension and diabetes mellitus reduce the risk of major adverse events, but programmes to improve uptake of these measures are needed.
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Acknowledgements
J.G. received grants from the National Health and Medical Research Council (1180736), Heart Foundation, Tropical Australian Academic Health Centre, Townsville Hospital and Health Service Study, Education and Research Trust Fund and Queensland Government. J.G. holds a Practitioner Fellowship from the National Health and Medical Research Council (1117601) and a Senior Clinical Research Fellowship from the Queensland Government. The author thanks S. Thangaimani, J. Phie and C. Burrows (James Cook University, Australia) for help with production of the figures for initial submission and A. Golledge for help with proof reading. He thanks all the past and current researchers from the Queensland Research Centre for Peripheral Vascular Disease and collaborators for their ongoing research on peripheral artery disease, which has contributed towards the insights included in this Review. Finally, the author apologizes to scientists whose research could not be included in this Review owing to space limitations.
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The author has received honoraria from Amgen and Bayer for giving lectures on PAD.
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Nature Reviews Cardiology thanks Brian H. Annex; Iris Baumgartner, who co-reviewed with Dario Häberli; Mary Kavurma; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Glossary
- Revascularization
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Minimally invasive interventional (such as stenting) or open surgical (such as endarterectomy) procedures to improve distal blood supply.
- Myopathy
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Muscle damage with various causes, including impaired muscle blood supply owing to peripheral artery disease.
- Arteriogenesis
-
The expansion of existing collateral arteries to improve distal blood supply.
- Angiogenesis
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The sprouting of new capillaries and formation of new networks of small vessels to improve distal blood supply.
- Cell therapy
-
Administering stem or progenitor cells to encourage angiogenesis.
- Gene therapy
-
Administering harmless viruses that have been modified to carry a gene of interest into the local tissue.
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Golledge, J. Update on the pathophysiology and medical treatment of peripheral artery disease. Nat Rev Cardiol 19, 456–474 (2022). https://doi.org/10.1038/s41569-021-00663-9
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DOI: https://doi.org/10.1038/s41569-021-00663-9
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