Philip J Walker
As a manifestation of systemic atherosclerosis, peripheral arterial disease (PAD) signifies an increased risk of cardiovascular events. Peripheral arterial disease has received less attention than other atherosclerotic diseases, leading to under-diagnosis and under-treatment. Peripheral arterial disease affects approximately 10–15% of the general population, and approximately 50% of PAD patients are asymptomatic.
This article aims to review the literature on the rationale for screening for lower extremity PAD in the general practice setting, and to identify the barriers to screening for PAD experienced by general practitioners, with a focus on the Australian context.
Screening for asymptomatic PAD among high risk groups has been recommended by major PAD authorities to increase early diagnosis. Screening for PAD using the ankle-brachial index can detect asymptomatic patients. Research into the effect of cardiovascular risk reduction therapies for asymptomatic patients is lacking, and available evidence is inconclusive. The prevalence of screening and barriers to screening experienced by Australian GPs has not yet been studied. Available data on the benefits of PAD screening is inconclusive, and further research is required to determine a survival benefit with treatment of asymptomatic PAD.
Cardiovascular disease is the leading cause of morbidity and mortality in the Western world, and is becoming increasingly common in developing nations.1 A large body of data demonstrates that secondary prevention can reduce future cardiovascular morbidity and mortality indicating the potential value of early disease detection.2 Atherosclerosis affects both coronary and peripheral arterial beds, typically developing in multiple vascular beds and remaining subclinical for many years before manifesting with clinical symptoms.1 The risk factors for peripheral arterial disease (PAD) are similar to those for atherosclerosis in other beds with the strongest risk factors for PAD being increased age, smoking and diabetes.3
Approximately 20% of people over the age of 65 years have symptomatic or asymptomatic PAD.4 The age standardised population prevalence in men aged 65–83 years of PAD in Australia is 15.6%.5 A diagnosis of PAD holds important prognostic value as a marker of increased mortality and vascular event risk, but methods to identify PAD at an early stage are not widely used.6
A diagnosis of PAD presents the opportunity to initiate secondary prevention by instituting atherosclerosis risk factor modification, and thus reducing the risk of cardiovascular complications. A failure to diagnose PAD misses this opportunity.4 Factors postulated to be responsible for the current under-diagnosis of PAD include the asymptomatic nature of most PAD, the inappropriate use of recommended screening and diagnostic tools, and poor awareness of the prevalence, natural history and prognostic significance of PAD among public and medical communities.7
This article aims to review the literature on the rationale for screening for lower extremity PAD in the general practice setting, and identify the barriers to screening for PAD experienced by general practitioners, with focus on the Australian context.
Databases searched included PubMed, Cochrane, EMBASE, Scopus, Web of Science and Informit Health Collection. The search was carried out in May 2012. The following search terms were used: ‘peripheral arterial disease’, ‘screen’, ‘asymptomatic’, ‘detection’, ‘ankle brachial index’, ‘examination’ and ‘general practice’.
Rationale for screening
Asymptomatic PAD affects up to 12% of primary care patients aged 65 years and over.4 Symptomatic PAD has been found in 8% of primary care patients aged more than 65 years, defined by an ankle-brachial index (ABI) of <0.9 in addition to intermittent claudication (IC), ischaemic rest pain, ischaemic ulcers, or gangrene.2,4 Typical characteristics of IC include exertional cramping or aching muscle discomfort, typically located in the calf, but may also include the buttock or thigh, that is not positional, has a reproducible onset, and is relieved within 10 minutes of rest. In addition to patients presenting with typical symptoms, it is increasingly recognised that a large portion of PAD patients have atypical leg symptoms and thus, many patients with PAD are easily missed in routine GP consultations.8 Guidelines relating to PAD screening are presented in Table 1. Of note, there is no current Australian guideline relating to PAD screening. The World Health Organization criteria for an appropriate screening program are presented in Table 2 and discussed below in the context of screening for PAD with the ABI.9
Table 1. Guidelines relating to screening for PAD
|Guidelines||Year of publication||Recommendation and rationale|
|American College of Cardiologists and the American Heart Association (ACC/AHA)
- Screen high risk patients with ABI
- Symptoms: exertional leg pain, non-healing ulcers
- Age >65 years
- Age >50 years PLUS either smoking or diabetes
|TransAtlantic InterSociety Consensus
- Screen high risk patients with ABI
- Symptoms: exertional leg pain
- Age 50–69 years with cardiovascular risk factors
- Age >70 years
|United States Preventive Services Task Force10
||Recommend against screening
||Benefits of screening are outweighed by the harms; based on the outcome of PAD related morbidity, not cardiovascular risk
|National Health and Medical Research Council23 [rescinded 2004]
||Recommend against screening
||Additional sensitivity and specificity data for detection tools required
Table 2. WHO principles of screening21
||Important health problem
|Recognisable asymptomatic stage
|Known natural history of disease
||Suitable and acceptable test
||Treatment must be available
Asymptomatic PAD has long been disregarded because of the erroneous belief that it is benign. Contrary to this, asymptomatic and symptomatic PAD patients have a similarly increased cardiovascular mortality risk.3,4 Compared to patients without PAD, asymptomatic patients without known cardiovascular disease in other arterial sites have a two-fold increased risk of premature death.10
Detection of PAD relying on history alone, or using a symptom based questionnaire, must necessarily miss all patients with asymptomatic PAD.8 General practitioners commonly diagnose symptomatic and asymptomatic PAD using physical examination findings, such as absence of pulses, femoral bruit and trophic skin changes.8 While specific for PAD, these findings have low sensitivity (Table 3).11–13 The ABI is a simple test to effectively detect asymptomatic lower limb PAD.
Table 3. Sensitivities and specificities of PAD detection methods11–13
|Edinburgh Claudication Questionnaire
|Examination: absence of both pedal pulses
|Examination: femoral bruit
|Duplex arterial ultrasound
ABI measurement as a screening test
The ABI is sensitive, symptom independent, non-invasive and cost effective, and has proven efficacy for community screening of high risk patients.6 The ABI is calculated as the quotient of the higher of the posterior tibial or dorsalis pedis artery systolic pressures in the one leg, and the higher of the right and left brachial artery systolic pressures.8
The ACC/AHA 2011 guidelines define values between 1.0–1.4 as normal, 0.9–0.99 as borderline PAD, <0.9 as diagnostic of PAD, and >1.4 indicates non-compressible arteries.2
The diagnostic value of ABI is limited in diseases that cause arterial calcification and non-compressibility (eg. advanced diabetes, renal insufficiency and in the very elderly).8
Measurement of the ABI and arterial waveform analysis using a hand-held Doppler ultrasound device currently attracts a Medicare fee of $63.75 (MBS Item Number 11610) provided a hard copy trace and report are supplied.14
Treatment of asymptomatic PAD
The desired outcome of early detection of PAD is to identify patients at increased risk of cardiovascular events and mortality and to take action to reduce their risk. As many PAD patients have involvement of multiple arterial sites and are likely to already be receiving secondary prevention therapies, it has been questioned whether detection of early PAD will significantly alter management. However, half of those patients with undiagnosed, asymptomatic PAD have no known cardiovascular disease in other vascular beds.1
Secondary prevention of cardiovascular disease is detailed in Table 4. Despite the known benefit of these therapies in reducing cardiovascular risk in symptomatic coronary artery disease and stroke patients, limited data exists on the impact of early intervention on asymptomatic PAD patients.
Table 4. National Heart Foundation recommendations for secondary prevention of cardiovascular disease22
|Secondary prevention of cardiovascular disease|
||Moderate level activity (brisk walking) 30 min/day at least 5 days per week
||Mediterranean diet: emphasis on fruits, vegetables, healthy oils, nuts/seeds and fish; limit sugar, saturated fats and salt
||Target BMI <25 kg/m2; waist measurement <94 cm for men and <80 cm for women; recommend weight loss 5–10% of starting weight or 1–4 kg/month
||No more than two standard drinks per day for men and women, and no more than four standard drinks on a single occasion
||Lifestyle modification ± drug therapy to achieve BP <140/90 mmHg
||Dietary modification and statin therapy is recommended for all people with clinical evidence of vascular disease. Targets:
- LDL-C <2.5 mmol/L
- HDL-C >1 mmol/L
- TC <4 mmol/L
- Triglycerides <1.5 mmol/L
||HbA1c <7%; fasting blood glucose 4–8 mmol/L
||75–162 mg/day aspirin is advised for all patients with symptomatic cardiovascular disease
There is little data supporting the use of aspirin for cardiovascular risk reduction amongst PAD patients.2,8 Available evidence from two studies suggests that 100 mg of aspirin daily has no benefit in preventing fatal or non-fatal cardiovascular events among asymptomatic PAD patients (Table 5).15,16 The Heart Outcomes Prevention Evaluation (HOPE) trial evaluated the impact of ramipril, an angiotensin converting enzyme inhibitor (ACEI), on the prevention of fatal or non-fatal myocardial infarction (MI) or stroke among patients with PAD, including those described as having subclinical PAD. The investigators demonstrated a reduction in vascular events amongst subjects with subclinical PAD randomised to ACEI.17 The effect of lipid lowering therapy for PAD patients with asymptomatic disease has not been studied.
Table 5. Summary of evidence for early intervention
|Treatment||Study title||Year||Study type||Study size||Study population (inclusion)||Intervention<||Finding/results|
||Aspirin for Asymptomatic Atherosclerosis (AAA) Trialists15
||Randomised controlled trial
||Age 50–75 years + ABI ≤0.95 + no history of CVD
||100 mg vs placebo
||HR=1.03 (0.84–1.27) for fatal or non-fatal MI or stroke or revascularisation
|Prevention Of Progression of Arterial Disease And Diabetes
||Randomised controlled trial
||Age >40 years + type 1 or 2 diabetes + ABI ≤0.99 + no symptomatic CVD
||100 mg aspirin ± antioxidants vs placebo
||HR=0.98 (0.76–1.26) for fatal or non-fatal MI or stroke or amputation
||Randomised controlled trial
||2118 with asymptomatic PAD
||Age ≥55 years + existing CVD or other CV risk factors + ABI <0.9 + no clinical symptoms
||10 mg ramipril vs placebo + vitamin E vs placebo
||RR: 0.72 (0.56–0.92) for patients with asymptomatic PAD (ABI 0.6–0.9) for fatal or non-fatal MI or stroke
|Multiple preventive therapies
||General population aged ≥40 years included in NHANES without previously established CVD
||Two or more preventive therapies (aspirin, ACEI, and/or statin) were associated with 65% reduced risk of all-cause mortality HR=0.35, 95% CI: 0.20–0.86, p=0.02
Data from the National Health and Nutrition Evaluation Survey (NHANES) suggested that secondary prevention in asymptomatic PAD patients without known atherosclerotic disease carries a survival benefit, with a 65% reduction in the risk of all cause mortality in the patients treated with multiple preventive therapies compared to no prevention.10
No studies have been published to date regarding the cost effectiveness of PAD screening with an ABI or whether widespread implementation of a PAD screening program and appropriate treatment results in survival benefit.
Barriers to screening
In view of their position in the community as primary carers, GPs are best positioned to detect patients at high risk of PAD.2 However, international studies indicate that screening is rarely practiced.2 There is no literature concerning the prevalence of PAD screening in Australia. European and American reports suggest that this may be due to poor community and physician awareness of PAD, lack of familiarity with guidelines, and underutilisation of screening tools contribute.7
Studies have revealed suboptimal awareness of PAD and its consequences amongst both the public and medical community, with only half of GPs aware of their patient’s PAD diagnosis.18 Education interventions can effectively improve physician awareness of PAD and have resulted in significant changes to the number of GPs regularly measuring ABI.18
The ABI is underutilised, and research into the barriers to ABI use is lacking. A study of 886 American primary care physicians found that time constraints, lack of reimbursement and staff availability were identified as major barriers to ABI use.19 Most GPs measure ABI within 15 minutes, however, over half regarded this as prohibitively too long.19 The automated oscillometric measurement of ABI is a novel technology that is quick and easy to perform in the office setting and demonstrates high accuracy for detecting PAD.23
Cardiovascular disease remains the major cause of mortality in the developed world. Despite the attendant cardiovascular risk associated with even asymptomatic disease, PAD is under-diagnosed and under-treated. Early detection offers the advantage of early intervention to reduce the risk of future cardiovascular events.
While there are guidelines for screening for PAD in high risk groups in the United States and Europe, there are currently no Australian guidelines relating to PAD screening. Screening is rarely performed in general practice and there is a deficit in research on this subject in the Australian context. Data on the benefits of screening are inconclusive and more evidence of a survival benefit associated with treatment of asymptomatic PAD is needed in order to confidently recommend PAD screening. There is a clear need for further research and Australian guidelines in this area. At this time, in the absence of Australian guidelines, it may be reasonable to recommend screening for PAD with ABI measurement in Australia in high risk groups as outlined by the ACC/AHA; ie. in patients with symptoms of lower extremity PAD, age 65 years and over, or 50 years and over with a history of smoking or diabetes.2
Competing interests: None.
Funding: National Health and Medical Research Council (Project Grants and Centre of Research Excellence) and the Queensland government. John Golledge holds fellowships from the NHMRC and Queensland Government.
Provenance and peer review: Not commissioned; externally peer reviewed.
- Sabouret P, Cacoub P, Dallongeville J, et al. REACH: international prospective observational registry in patients at risk of atherothrombotic events. Results for the French arm at baseline and one year. Arch Cardiovasc Dis 2008;101:81–8.
- Rooke TW, Hirsch AT, Misra S, et al. 2011 ACCF/AHA Focused Update of the Guideline for the Management of Patients With Peripheral Artery Disease (updating the 2005 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2011;58:2020–45.
- Hooi JD, Kester AD, Stoffers HE, Overdijk MM, van Ree JW, Knottnerus JA. Incidence of and risk factors for asymptomatic peripheral arterial occlusive disease: a longitudinal study. Am J Epidemiol 2001;153:666–72.
- Diehm C, Allenberg JR, Pittrow D, et al. Mortality and vascular morbidity in older adults with asymptomatic versus symptomatic peripheral artery disease. Circulation 2009;120:2053–61.
- Fowler B, Jamrozik K, Norman P, Allen Y. Prevalence of peripheral arterial disease: persistence of excess risk in former smokers. Aust N Z J Public Health 2002;26:219–24.
- Hayoz D, Bounameaux H, Canova CR. Swiss Atherothrombosis Survey: a field report on the occurrence of symptomatic and asymptomatic peripheral arterial disease. J Intern Med 2005;258:238–43.
- Cimminiello C, Kownator S, Wautrecht JC, et al. The PANDORA study: peripheral arterial disease in patients with non-high cardiovascular risk. Intern Emerg Med 2011;6:509–19.
- Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007;45(Suppl S):S5–67.
- Australian Population Health Development Principal Committee – Screening Subcommittee. Population Based Screening Framework. Canberra: Commonwealth of Australia, 2008.
- Pande RL, Perlstein TS, Beckman JA, Creager MA. Secondary prevention and mortality in peripheral artery disease: National Health and Nutrition Examination Study, 1999 to 2004. Circulation 2011;124:17–23.
- Dachun X, Jue L, Liling Z, et al. Sensitivity and specificity of the ankle-brachial index to diagnose peripheral artery disease: a structured review. Vasc Med 2010;15:361–9.
- Khan NA, Rahim SA, Anand SS, Simel DL, Panju A. Does the clinical examination predict lower extremity peripheral arterial disease? JAMA 2006;295:536–46.
- Collins R, Burch J, Cranny G, et al. Duplex ultrasonography, magnetic resonance angiography, and computed tomography angiography for diagnosis and assessment of symptomatic, lower limb peripheral arterial disease: systematic review. BMJ 2007;334:1257.
- Australian Government Department of Health and Aging. Measurement of ankle brachial indices and arterial waveform analysis. Commonwealth of Australia, 2013. Available at www.mbsonline.gov.au/internet/mbsonline [Accessed 12 April 2013].
- Fowkes FG, Price JF, Stewart MC, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA 2010;303:841–8.
- Belch J, MacCuish A, Campbell I, et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ 2008;337:a1840.
- Ostergren J, Sleight P, Dagenais G, et al. Impact of ramipril in patients with evidence of clinical or subclinical peripheral arterial disease. Eur Heart J 2004;25:17–24.
- McDermott MM, Mandapat AL, Moates A, et al. Knowledge and attitudes regarding cardiovascular disease risk and prevention in patients with coronary or peripheral arterial disease. Arch Intern Med 2003;163:2157–62.
- Mohler ER 3rd, Treat-Jacobson D, Reilly MP, et al. Utility and barriers to performance of the ankle-brachial index in primary care practice. Vasc Med 2004;9:253–60.
- Beckman JA, Higgins CO, Gerhard-Herman M. Automated oscillometric determination of the ankle-brachial index provides accuracy necessary for office practice. Hypertension 2006;47:35–8.
- U.S. Preventive Services Task Force. Screening for peripheral arterial disease: recommendation statement. Am Fam Physician 2006;73:497–500.
- Heart Foundation of Australia. Information for professionals. 2011. Available at www.heartfoundation.org.au/information-for-professionals/Pages/information-professionals.aspx [Accessed 15 June 2011].
- National Health and Medical Research Council. Guidelines for preventive interventions in primary health care. Canberra: Commonwealth of Australia,1996; pp. 52–5.