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Therapy Insight: peripheral arterial disease and diabetes—from pathogenesis to treatment guidelines

Nature Clinical Practice Cardiovascular Medicine volume 4, pages 151–162 (2007)Cite this article

Abstract

The increased risk of atherothrombotic events present in all patients with peripheral arterial disease (PAD) is amplified with concomitant diabetes. Moreover, diabetes is associated with increased PAD severity. This Review summarizes atherothrombosis and PAD in patients with diabetes, and American College of Cardiology and American Heart Association guidelines for management of patients with PAD. Patients with PAD and diabetes require optimal limb care and aggressive cardiovascular risk reduction. An LDL cholesterol level of less than 1.8 mmol/l (<70 mg/dl) is the therapeutic goal in these patients, and this target should be pursued using an aggressive statin regimen. Fibrate therapy can also be indicated. β-blockers and angiotensin-converting-enzyme inhibitors reduce cardiovascular events in high-risk patient populations, and these agents are recommended for use in patients with both diabetes and PAD. Blood pressure of less than 130/80 mmHg should be achieved, and glycated hemoglobin should be reduced to below 7%. Patients should also receive indefinite antiplatelet therapy with aspirin or clopidogrel. For patients with claudication, a supervised exercise program and cilostazol therapy to improve PAD symptoms and walking distance form the main noninvasive components of therapy. Revascularization can also be indicated in carefully selected patients with claudication. For patients with critical limb ischemia, diagnostic testing by a vascular specialist will determine whether revascularization or amputation is feasible.

Key Points

  • Peripheral arterial disease is associated with an increased risk of atherothrombotic events in other vascular beds owing to common pathophysiology

  • PAD is more prevalent and is associated with a worse prognosis in patients with diabetes mellitus than in nondiabetic patients, and patients with diabetes require more-intensive treatment to reduce cardiovascular risk, as diabetes is an independent risk factor for atherothrombotic events

  • PAD often goes undetected and untreated as only the minority of patients have classic claudication, and patients with diabetes can present later with more-severe disease secondary to neuropathy

  • Evidence-based guidelines for PAD published by the American College of Cardiology (ACC) and the American Heart Association (AHA) state that patients with PAD should receive treatment for cardiovascular risk reduction, including antiplatelet agents, lipid-lowering therapy and antihypertensives, in addition to smoking cessation therapy and improved glycemic control

  • The ACC/AHA guidelines also recommend exercise therapy and pharmacological therapy (primarily with cilostazol) to treat PAD symptoms, but patients who develop critical limb ischemia might require revascularization, and in the case of disease progression, amputation

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Figure 1: Natural history of lower extremity peripheral arterial disease
Figure 2: Effects of hyperglycemia and lipid metabolism on endothelial function
Figure 3: Recommended management of lower extremity peripheral arterial disease
Figure 4: Factors that increase the risk of lower extremity peripheral arterial disease
Figure 5: Effects of clopidogrel and aspirin on cardiovascular risk in patients with and without diabetes

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Acknowledgements

Editorial assistance for the development of this manuscript was provided by Jackie Campbell and Raewyn Poole, with the financial support of the BMS/Sanofi-Aventis Pharmaceuticals Partnership.

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  1. Hospital of the University of Pennsylvania, 4th Floor Penn Tower Building, 3400 Spruce Street, Philadelphia, PA 19104, USA emile.mohler@uphs.upenn.edu

Authors and Affiliations

  1. ER Mohler III is Associate Professor of Medicine at the University of Pennsylvania School of Medicine, and Director of Vascular Medicine for the University of Pennsylvania Health System, Philadelphia, PA, USA.,

    Emile R Mohler III

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Competing interests

ER Mohler III has received grant support from BMS-Sanofi, GlaxoSmithKline and Pfizer. He is/has been on the speakers' bureau for AstraZeneca, BMS-Sanofi, Merck and Pfizer.

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Mohler, E. Therapy Insight: peripheral arterial disease and diabetes—from pathogenesis to treatment guidelines. Nat Rev Cardiol 4, 151–162 (2007). https://doi.org/10.1038/ncpcardio0823

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