By: Richard Ni
Peer Reviewed
Peripheral artery disease (PAD) is a common manifestation of atherosclerotic cardiovascular disease that remains underrecognized compared to coronary artery disease (CAD) and cerebrovascular disease (CVD). While myocardial infarction and stroke are widely known consequences of atherosclerosis, PAD—despite its high prevalence and associated morbidity and mortality—receives less clinical and public attention.[1]
PAD is caused by buildup of atherosclerotic plaque in peripheral arteries, most commonly the femoral and popliteal arteries of the legs. It is estimated to affect around 8.5 million people in the US.1 Despite its high prevalence, cross-sectional surveys of Americans show that only around 30% of respondents are aware of PAD and its associated risks.[2] PAD classically presents with exertional calf pain (claudication) but may present with atypical lower extremity symptoms, such as a sensation of leg heaviness or fatigue. PAD contributes to around 150,000 non-traumatic lower extremity amputations performed in the US annually, many of which may be preventable with earlier diagnosis and preventive treatment.[3] Outcomes after advanced PAD are poor; one study among Medicare patients with PAD undergoing lower-extremity amputation from 2000 to 2008 reported nearly 50% mortality within one year after amputation.[4]
A timely diagnosis of PAD is crucial not only to prevent amputations, but also to identify patients who are at high risk of major adverse cardiovascular events (MACE), including myocardial infarction and stroke. Studies have found that patients with PAD are at markedly elevated risk for MACE compared to the general population.[5] Notably, patients with PAD experience MACE at equal or even higher rates than patients with prior myocardial infarction or stroke, underscoring just how high-risk this patient population is.[6,7] Accordingly, all patients with symptomatic PAD are recommended to take a high-intensity statin and antiplatelet therapy, usually aspirin or clopidogrel (with evidence for superiority of clopidogrel over aspirin in these patients),[8] for prevention of cardiovascular events.[9]
Given the need for improved detection for PAD, why not screen for PAD? After all, the ankle-brachial index (ABI)–the most common screening diagnostic test for PAD–is noninvasive, low-cost, and low-risk. Ankle systolic BP less than 90% of brachial systolic BP (the cutoff for diagnosing PAD) is independently associated with increased risk for cardiovascular events and death, including patients without symptoms.[10,11] ABI testing is recommended for patients with symptoms or physical exam findings suggestive of PAD.[9] However, the role of routine ABI screening in asymptomatic individuals remains controversial. In 2018, the U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to make a recommendation regarding ABI screening for asymptomatic patients.[12] One reason for this recommendation is a lack of high-quality evidence demonstrating improved clinical outcomes when utilizing ABI screening in asymptomatic individuals. While antiplatelet therapy decreases cardiovascular events in patients with symptomatic PAD, studies have yet to show consistent evidence that antiplatelet therapy yields benefit in asymptomatic individuals with abnormal ABI.[12]
In contrast, there is evidence that statins improve outcomes for patients with asymptomatic PAD, notably including patients who are considered at low cardiovascular risk and who may not receive statins otherwise.13 These findings raise the possibility that earlier identification of asymptomatic PAD could allow for initiation of preventive therapies (including statin therapy to attain an LDL-cholesterol level <70 mg/dL) to improve long-term outcomes, although additional studies are needed to clarify the benefits of screening.
The USPSTF recommendation leaves potential for patients to fall through the cracks. Reserving ABI testing for patients with concerning clinical history and exam findings seems reasonable, but the caveat is that pain from PAD may be misattributed to or confounded by hip or knee arthritis or neuropathic pain, especially among older patients, among whom PAD is most prevalent.[1] Furthermore, a significant proportion of patients with PAD do not exhibit classical symptoms. In fact, most patients report either no symptoms (20%-50%) or atypical symptoms (40-50%), with classic claudication occurring in a minority of patients (10-35%).[14,15] To make matters more complicated, the designation of “asymptomatic PAD” is not straightforward. Patients who are “asymptomatic” may self-limit their walking or lead sedentary lifestyles so that they never develop or notice symptoms of PAD. In a study of 460 patients with PAD, 40% of patients who self-reported no exertional leg pain developed leg pain on the 6-minute walk test.[14] These factors make it challenging to identify high-risk patients from clinical history who would benefit from testing and treatment for PAD.
Because of these obstacles, major society guidelines for management of PAD take a more proactive approach than the USPSTF. The 2024 ACC/AHA guidelines provide a Class 2a recommendation (moderate benefit over risk) for ABI screening of asymptomatic patients with risk factors for PAD such as age over 65 or age 50-64 with risk factors for atherosclerosis.[9] Despite the lack of evidence of a benefit of antiplatelet therapy in patients with asymptomatic PAD, major societies acknowledge that the line between asymptomatic and symptomatic PAD is blurry and give a Class 2a recommendation–based on expert opinion–to initiate single antiplatelet therapy among patients with asymptomatic PAD. The guidelines conclude with the identification of an evidence gap: more high-quality studies are needed specifically focused on patients with asymptomatic PAD to evaluate the benefits and risks of screening and treatment.[9]
In the effort to improve management of PAD, timely diagnosis is only half the battle. Another critical issue is that PAD is undertreated compared to other atherosclerotic diseases. Multiple studies have shown that guideline-directed medical therapy for PAD, including statins and antiplatelet therapy, is underprescribed in PAD despite clear evidence of their benefit in this patient population.[16,17]This is especially pronounced when comparing rates of preventive therapy across atherosclerotic diseases. A study examining statin prescription rates found that in 2016 only 37.5% of patients with isolated PAD were prescribed statins, compared to 80.9% of patients with coronary artery disease and 65.8% of patients with ischemic stroke or transient ischemic attack.[18] Notable disparities exist in treatment, with women and Black patients less likely to receive appropriate medications.[19,20] This pattern of undertreatment may be due to physician unawareness of appropriate guidelines or a perception that PAD is less clinically consequential than CAD or CVD. PAD substantially increases the risk of heart attack and stroke and should elicit the same level of concern.
Recognizing the need for an improved approach to PAD, over 25 major organizations including the American Heart Association, American College of Cardiology, and Society of Vascular Surgery created a PAD National Action Plan in 2021 dedicated to improving outcomes for patients with PAD.[21] The action plan targets six areas: public awareness, professional education, detection and treatment, public health, research, and advocacy. It will be interesting to see how future clinical research may change our paradigm towards screening and treatment of asymptomatic PAD. Lack of clear-cut evidence regarding management of asymptomatic PAD is likely a driver for the underdiagnosis and undertreatment of patients. If successful, the efforts of these major organizations will result in positive changes on both the patient and physician ends of PAD management, with more discussions in the clinic about PAD, its associated risks, and strategies for management.
Richard Ni is a Class of 2026 Medical Student at NYU Grossman School of Medicine
Peer Reviewed by Michael Tanner, MD Executive Editor, Clinical Correlations
Image Courtesy of Patho, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
References
1. Criqui MH, Matsushita K, Aboyans V, et al. Lower Extremity Peripheral Artery Disease: Contemporary Epidemiology, Management Gaps, and Future Directions: A Scientific Statement from the American Heart Association. Circulation. 2021;144(9):e171-e191. doi:10.1161/CIR.0000000000001005
2. Hirsch AT, Murphy TP, Lovell MB, et al. Gaps in public knowledge of peripheral arterial disease. Circulation. 2007;116(18):2086-2094. doi:10.1161/CIRCULATIONAHA.107.725101
3. Creager MA, Matsushita K, Arya S, et al. Reducing Nontraumatic Lower-Extremity Amputations by 20% by 2030: Time to Get to Our Feet: A Policy Statement From the American Heart Association. Circulation. 2021;143(17):e875-e891. doi:10.1161/CIR.0000000000000967
4. Jones WS, Patel MR, Dai D, et al. High mortality risks after major lower extremity amputation in Medicare patients with peripheral artery disease. Am Heart J. 2013;165(5):809-815.e1. doi:10.1016/j.ahj.2012.12.002
5. Agnelli G, Belch JJF, Baumgartner I, Giovas P, Hoffmann U. Morbidity and mortality associated with atherosclerotic peripheral artery disease: A systematic review. Atherosclerosis. 2020;293:94-100. doi:10.1016/j.atherosclerosis.2019.09.012
6. Subherwal S, Patel MR, Kober L, et al. Peripheral artery disease is a coronary heart disease risk equivalent among both men and women: results from a nationwide study. Eur J Prev Cardiol. 2015;22(3):317-325. doi:10.1177/2047487313519344
7. Bonaca MP, Nault P, Giugliano RP, et al. Low-Density Lipoprotein Cholesterol Lowering With Evolocumab and Outcomes in Patients With Peripheral Artery Disease. Circulation. 2018;137(4):338-350. doi:10.1161/CIRCULATIONAHA.117.032235
8. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). The Lancet. 1996;348(9038):1329-1339. doi:10.1016/S0140-6736(96)09457-3
9. Gornik HL, Aronow HD, Goodney PP, et al. 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024;149(24):e1313-e1410. doi:10.1161/CIR.0000000000001251
10. Diehm C, Allenberg JR, Pittrow D, et al. Mortality and vascular morbidity in older adults with asymptomatic versus symptomatic peripheral artery disease. Circulation. 2009;120(21):2053-2061. doi:10.1161/CIRCULATIONAHA.109.865600
11. Messeder SJ, Salt E, Pepper C, et al. Is the Ankle Brachial Pressure Index an Independent Predictor for Cardiovascular Morbidity and Mortality in the Asymptomatic Population?: A Systematic Review and Meta-analysis. Eur J Vasc Endovasc Surg. Published online September 23, 2025:S1078-5884(25)00927-X. doi:10.1016/j.ejvs.2025.09.040
12. Guirguis-Blake JM, Evans CV, Redmond N, Lin JS. Screening for Peripheral Artery Disease Using the Ankle-Brachial Index: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2018;320(2):184-196. doi:10.1001/jama.2018.4250
13. Ramos R, García-Gil M, Comas-Cufí M, et al. Statins for Prevention of Cardiovascular Events in a Low-Risk Population With Low Ankle Brachial Index. JACC. 2016;67(6):630-640. doi:10.1016/j.jacc.2015.11.052
14. McDermott MM, Greenland P, Liu K, et al. Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. JAMA. 2001;286(13):1599-1606. doi:10.1001/jama.286.13.1599
15. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286(11):1317-1324. doi:10.1001/jama.286.11.1317
16. Kirkham AM, Paquet M, Fergusson DA, et al. Clinician underprescription of and patient nonadherence to clinical practice guideline-recommended medications for peripheral artery disease: a systematic review and meta-analysis. eClinicalMedicine. 2025;86:103391. doi:10.1016/j.eclinm.2025.103391
17. Berger JS, Ladapo JA. Underuse of Prevention and Lifestyle Counseling in Patients with Peripheral Artery Disease. J Am Coll Cardiol. 2017;69(18):2293-2300. doi:10.1016/j.jacc.2017.02.064
18. Yao X, Shah ND, Gersh BJ, Lopez-Jimenez F, Noseworthy PA. Assessment of Trends in Statin Therapy for Secondary Prevention of Atherosclerotic Cardiovascular Disease in US Adults From 2007 to 2016. JAMA Netw Open. 2020;3(11):e2025505. doi:10.1001/jamanetworkopen.2020.25505
19. Menard MT, Jaff MR, Farber A, et al. Baseline modern medical management in the BEST-CLI trial. J Vasc Surg. 2023;78(3):711-718.e5. doi:10.1016/j.jvs.2023.05.006
20. Singh N, Ding L, Devera J, Magee GA, Garg PK. Prescribing of Statins After Lower Extremity Revascularization Procedures in the US. JAMA Netw Open. 2021;4(12):e2136014. doi:10.1001/jamanetworkopen.2021.36014
21. McDermott MM, Ho KJ, Alabi O, et al. Disparities in Diagnosis, Treatment, and Outcomes of Peripheral Artery Disease. JACC. 2023;82(24):2312-2328. doi:10.1016/j.jacc.2023.09.830