Noninvasive diagnosis of peripheral arterial disease

Noninvasive diagnosis of peripheral arterial disease

Author
Emile R Mohler, III, MD
Section Editor
Denis L Clement, MD, PhD
Deputy Editor
Gordon M Saperia, MD, FACC



Last literature review version 16.2: May 2008 | This topic last updated: April 15, 2008 (More)


INTRODUCTION — In patients with suspected lower extremity peripheral arterial disease (PAD) based upon the history and physical examination (eg, symptoms of intermittent claudication) or in patients with risk factors for vascular disease (eg, older age, smoking, diabetes mellitus), noninvasive tests are performed to confirm the clinical diagnosis and to further define the level and extent of obstruction [1] . (See "Clinical features, diagnosis, and natural history of lower extremity peripheral arterial disease").

The noninvasive tests available to the clinician to diagnose lower extremity PAD will be reviewed here. The clinical manifestations and natural history of claudication and its management by medical therapy, angioplasty, or surgery are discussed separately. (See appropriate topic reviews).

GENERAL PRINCIPLES — The location of pain in patients with claudication varies with the vessels that are involved. The usual relationship between the site of pain and site of arterial disease can be summarized as follows:

• Buttock and hip — aortoiliac disease
• Thigh — common femoral artery or aortoiliac
• Upper two-thirds of the calf — superficial femoral artery
• Lower one-third of the calf — popliteal artery
• Foot claudication — tibial or peroneal artery


Despite these general relationships, the history and physical examination are not reliable for the detection of lower extremity PAD. It has been estimated that relying solely on the classic symptoms of claudication will miss up to 90 percent of cases [2,3] . This was best illustrated in a study of 6417 patients at risk for peripheral arterial disease (either age >70 or age 50 to 60 with a history of diabetes or more than 10 pack-years of cigarette smoking) in a primary care setting [2] . PAD, identified by an ankle-brachial index ≤0.9, was present in 1865 (29 percent), only 11 percent of whom presented with classic claudication symptoms. (See "Clinical features, diagnosis, and natural history of lower extremity peripheral arterial disease", section on Atypical symptoms and section on Asymptomatic disease).

The physical examination is also unreliable. As an example, an abnormal femoral pulse has a high specificity and positive predictive value but low sensitivity for large vessel disease [4] . The best single discriminator is an abnormal posterior tibial pulse.

Patients at risk — Given these limitations, the diagnosis of lower extremity PAD often begins with noninvasive testing. The 2005 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on PAD and the 2007 TASC II consensus document on the management of patients with PAD identified the following groups at risk for lower extremity PAD [5,6] :

• Age ≥70 years
• Age 50 to 69 years with a history of smoking and.or diabetes
• Age 40 to 49 with diabetes and at least one other risk factor for
• atherosclerosis

• Leg symptoms suggestive of claudication with exertion or ischemic pain at rest
• Abnormal lower extremity pulse examination
• Known atherosclerosis at other sites (eg, coronary, carotid, or renal arterial disease)
• All patients with a Framingham risk score of 10 to 20 percent (see "Estimation of cardiovascular risk in an individual patient without known cardiovascular disease", section on Framingham risk score).


In such patients, the standard review of symptoms should include questions related to a history of walking impairment, symptoms of claudication, ischemic rest pain, or nonhealing wounds [5,6] . Measurement of the resting ankle-brachial index should be performed in patients with one or more of these findings.

NONINVASIVE TESTS — A variety of noninvasive examinations are available to assess the presence and degree of peripheral arterial disease (show algorithm 1 and show algorithm 2). They include the ankle-brachial index (ABI), exercise treadmill test, segmental limb pressures, segmental volume plethysmography, and ultrasonography. Data suggest that magnetic resonance imaging may become an important noninvasive method for assessment [7] ; however, the cost and the time necessary for the study limit its use as a routine screening modality at this time. (See "Clinical utility of cardiovascular magnetic resonance imaging").

Ankle-brachial index — A relatively simple and inexpensive method to confirm the clinical suspicion of arterial occlusive disease is to measure the resting and post-exercise systolic blood pressures in the ankle and arm. This measurement is referred to as the ankle-brachial (or ankle-arm) index or ratio, and provides a measure of the severity of peripheral arterial disease [8] .

Calculation of the ankle-brachial index (ABI) is performed by measuring the systolic blood pressure (by Doppler probe) in the brachial, posterior tibial, and dorsalis pedis arteries (show figure 1) [9,10] . The highest of the four measurements in the ankles and feet is divided by the higher of the two brachial measurements:

• The normal ABI is 1.0 to as high as 1.3, since the pressure is higher in the ankle than in the arm. Values above 1.30 suggest a noncompressible calcified vessel.
• An ABI below 0.9 has 95 percent sensitivity (and 100 percent specificity) for detecting angiogram-positive peripheral arterial disease and is associated with ≥50 percent stenosis in one or more major vessels.
• An ABI of 0.40 to 0.90 suggests a degree of arterial obstruction often associated with claudication.
• An ABI below 0.4 represents advanced ischemia.

The ABI should be measured in both legs in all new patients with suspected PAD both to confirm the diagnosis and to establish a baseline [5] .

If ABIs are normal at rest but symptoms strongly suggest claudication, ABIs and segmental pressures should be obtained before and after exercise on a treadmill (see "Exercise treadmill testing" below) or using active pedal plantarflexion, which involves repeatedly standing up on the toes [11] .

The ABI correlates with clinical measures of lower extremity function such as walking distance, velocity, balance, and overall physical activity [12] . In addition, a low ABI has been associated with a higher risk of coronary heart disease, stroke, transient ischemic attack, progressive renal insufficiency, and all-cause mortality [13-17] .

• In a prospective study among nearly 1500 women, 82 (5.5 percent) had an ABI of less than 0.9, 65 of whom had no symptoms of peripheral arterial disease. Compared to the cohort with an index greater than 0.9, this group had markedly increased relative risks of 3.1 and 3.7 for death and coronary heart disease at four years [14] .
• In a report from the Framingham study of 251 men and 423 women (mean age 80 years), 141 (21 percent) had an ABI less than 0.9 [16] . Those with a low ABI had at four years a significantly increased risk of transient ischemic attack or stroke (13 versus 5 percent; adjusted hazard ratio 2.0).

There is a general but not absolute correlation between symptoms and the site and severity of PAD. In a report described in detail elsewhere, patients with unilateral PAD as determined from the ABI often had bilateral leg pain and 14 percent of those with unilateral pain had pain in the other leg [18] . (See "Clinical features, diagnosis, and natural history of lower extremity peripheral arterial disease", section on Correlation of ABI with symptoms and site of PAD).

High ABI — A potential source of error with the ABI is that calcified vessels may not compress normally, possibly resulting in falsely elevated Doppler signals. Thus, an ABI above 1.3 is suspicious for a calcified vessel. In some patients with arterial calcification, an accurate pressure may be obtained by measuring the toe pressure and calculating the toe-brachial index. In this setting, one must recognize that a pressure gradient of 20 to 30 mmHg normally exists between the ankle and the toe.

An abnormally high ABI (>1.4) is also associated with higher rates of leg pain [18] and of cardiovascular risk [15] . The increase in cardiovascular risk was suggested in a report of 4393 native American patients in the Strong Heart Study who had bilateral ABI measurements and were followed for a mean of eight years [15] . There were 1022 deaths (23 percent) of which 272 (27 percent of all deaths) were cardiovascular. Patients with an ABI ≤0.9 or >1.4 had an increased risk of all-cause mortality (adjusted hazard ratios 1.7 and 1.8) and cardiovascular mortality (adjusted hazard ratios 2.5 and 2.1).

Similarly, data from the National Health and Nutrition Survey (NHANES) estimated 1.4 percent of adults age >40 years in the United States have an ABI >1.4, accounting for approximately 20 percent of all adults with PAD [19] .

Exercise treadmill testing — The dynamics of blood flow across a stenotic lesion depend in part upon whether the individual is at rest or exercising and upon the severity of the obstruction. Exercise normally decreases vascular resistance and enhances blood flow to the exercising extremities. An arterial stenosis of less than 70 percent may not be of sufficient severity to significantly perturb blood flow at rest or to produce a systolic pressure gradient. Exercise in such patients can induce a systolic pressure gradient across the stenosis or, in patients with more severe disease, increase the systolic pressure gradient.

These changes may be detected clinically by a fall in the ABI followed by recovery. This pattern is detected by measurement of the ABI at one minute intervals for five minutes after exercise. As a result, exercise testing is a sensitive method for evaluating patients with typical symptoms of claudication in whom the resting ABI is normal.

Several protocols exist for treadmill testing and are generally divided into those using a fixed versus a graded routine [20] . The standard exercise test is a treadmill test for five minutes at 2 mph on a 12 percent incline. Severe claudication can be defined as an inability to complete the treadmill exercise due to leg symptoms and ankle systolic pressures below 50 mmHg.

Segmental limb pressures — Once the presence of arterial occlusive disease has been verified using ABI measurements at rest or during exercise, the level and extent of PAD is routinely assessed by segmental limb pressures. A 20 mmHg or greater reduction in pressure is considered significant if such a gradient is present either between segments along the same leg or when compared to the same level in the opposite leg.

As with ABI measurements, segmental pressure measurements may be artifactually increased or not interpretable in patients with noncompressible vessels [5] . (See "High ABI" above).

Several blood pressure cuff positions have been employed to detect the level of peripheral arterial disease [21] . As examples, a significant reduction in pressure [5] :

• Between the brachial artery and the upper thigh reflects aortoiliac disease
• Between the upper and lower thigh reflects superficial femoral artery disease
• Between the lower thigh and upper calf reflects distal superficial femoral artery or popliteal disease
• Between the upper and lower calf reflects infrapopliteal disease

In addition, a toe pressure of less than 60 percent of the ankle pressure indicates digital artery occlusive disease.


Use of two specially designed narrow blood pressure cuffs rather than one large cuff on the thigh permits the differentiation of aortoiliac and superficial femoral artery disease. This technique, which is performed in the vascular laboratory, involves placement of a narrow cuff on the upper and lower thigh. The upper (proximal) thigh cuff is inflated to a pressure above systolic and then gradually deflated to determine the systolic pressure as heard by Doppler at the foot. This process is then repeated for the lower (distal) thigh cuff.

If the upper thigh systolic pressure is reduced compared to the brachial pressure (thigh-brachial index [TBI] <1.1), then the patient has a lesion in the aortoiliac territory. If, on the other hand, the TBI is >1.1 in the upper thigh and less than 1.1 in the lower thigh, the lesion is in the superficial femoral artery. In one prospective study, the use of two narrow thigh cuffs correctly identified the location in 78 percent of extremities with peripheral arterial disease versus a rate of only 19 percent with the use of a large cuff [21] .

The localization of the lesion may also be suspected from the history in patients with intermittent claudication. Thus, one should ascertain whether the pain is in the buttock or hip (suggesting aortoiliac disease), thigh (common femoral disease), upper calf (superficial femoral disease), lower calf (popliteal disease), or foot (tibial or peroneal disease). (See "Clinical features, diagnosis, and natural history of lower extremity peripheral arterial disease").

In the patient with possible upper extremity peripheral arterial disease, a difference of ≥10 mmHg between brachial pressures suggests innominate, subclavian, axillary, or proximal brachial arterial occlusion.

Potential disadvantages in using Doppler ultrasound for segmental limb pressures are that the technique is insensitive at extremely low blood flow rates (<3 cm per second) and a venous signal can be confused with an arterial signal (especially if pulsatile venous flow is present as can occur with congestive heart failure).

Segmental volume plethysmography — Plethysmography, or the measurement of volume change in an organ or limb, is usually used in conjunction with segmental limb pressures to assess the level of arterial disease. This technique is performed by injecting a standard volume of air into pneumatic cuffs placed at various levels along the extremity. Volume changes in the limb segment below the cuff are translated into pulsatile pressure, which is detected by a transducer and then displayed as a pressure pulse contour.

The normal pulse volume recording is composed of a systolic upstroke with a sharp systolic peak followed by a downstroke that contains a prominent dicrotic notch. A change in the pulse volume contour indicates proximal arterial obstruction and is due to the dissipated energy that occurs due to arterial narrowing [22,23] .

Variations in the contours of the pulse volume recording reflect disease severity (show figure 2). As an example, mild disease is characterized by the absence of a dicrotic notch. With progressive obstruction, the upstroke and downstroke become equal, and with severe disease, the amplitude of the waveform is blunted. Pulse volume recordings are most useful in detecting disease in calcified vessels which tend to yield falsely elevated pressures.

Since the absolute amplitude of plethysmographic recordings is influenced by cardiac output and vasomotor tone, interpretation of these measurements should be limited to the comparison of one side of an extremity to the other in the same patient and not between patients. The clinician should also recognize that a dicrotic notch may be absent from the recording of a normal artery in the presence of low resistance, as may occur after exercise.

Duplex ultrasonography — Although ultrasonography is accurate in detecting peripheral arterial disease, resting segmental pulse volumes and systolic pressures are the initial screening tests in many laboratories. Ultrasonography is currently used to depict anatomy, hemodynamics, and lesion morphology; ultrasonographic equipment used for these tasks include B-mode imaging, pulse wave Doppler, continuous wave Doppler, and color Doppler display [8] .

Lower extremity examinations using the duplex Doppler begins at the common femoral artery and proceeds distally to the popliteal artery. An area of stenosis is localized with color Doppler and assessed by measuring Doppler velocities at several arterial sites.

The normal peripheral arterial velocity waveform is triphasic and consists of [24,25] :

• A forward flow systolic peak
• Reversal of flow in early diastole
• Forward flow in late diastole


With progressive peripheral arterial disease, there is elimination of the reverse flow, a decrease in systolic peak and an increase in flow in diastole (show figure 3).

It has been suggested that the main purpose of duplex Doppler ultrasonography is to avoid diagnostic angiography before intervention in patients with arterial disease proximal to the calf [26] . A meta-analysis of 14 studies found that sensitivity and specificity of this technique for ≥50 percent stenosis or occlusion were 86 and 97 percent for aortoiliac disease and 80 and 98 percent for femoropopliteal disease [26] .

Multidetector computed tomography — The development of multidetector computed tomographic (MDCT) scanners now allows rapid acquisition of high resolution, intravenous contrast enhanced images from patients with suspected peripheral arterial disease. A number of reports of small series of patients have noted excellent correlation between MDCT and digital subtraction angiography (DSA) in the detection of aortic and lower extremity arterial disease [27-29] , but these findings have not been universal [30] . In addition the total burden of radiation is relatively high.

A meta-analysis of 12 studies in which MDCT was used to evaluate 9541 lower extremity arterial segments in 436 symptomatic patients compared test performance to DSA [31] . The sensitivity and specificity for detecting a stenosis of a least 50 percent were 92 and 93 percent, respectively, compared to DSA. In the three studies that evaluated subdivisions of the arterial system, diagnostic performance in the infrapopliteal tract was lower than, but not statistically different from, that in the aortoiliac and femoropopliteal tracts.

A separate issue is the ability of MDCT to guide therapy. In an initial series of 58 patients with claudication, the findings on MDCT were used to determine whether or not an intervention was necessary [32] . Among the 29 patients in whom conservative management was indicated by MDCT, none required revascularization at a mean follow-up of 501 days.

INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. (See "Patient information: Claudication"). We encourage you to print or e-mail this topic review, or to refer patients to our public web site, www.uptodate.com/patients, which includes this and other topics.

RECOMMENDATIONS — We agree with the recommendations of the 2005 ACC/AHA guideline and the 2007 TASC II consensus document on the management of PAD with regard to the identification of asymptomatic PAD and for the evaluation of patients with intermittent claudication [5,6] .

Asymptomatic patients — The main value of identifying patients with asymptomatic lower extremity PAD is related to the association of these lesions with an increased risk of myocardial infarction, stroke, and cardiovascular mortality [5,33-35] . PAD is considered to be a coronary equivalent and such patients should be treated with risk factor reduction. (See "Medical management of claudication" and see "Secondary prevention of cardiovascular disease: Risk factor reduction").

The ACC/AHA guidelines made the following general recommendations for patients with no leg symptoms or atypical leg symptoms [5] . (See "Clinical features, diagnosis, and natural history of lower extremity peripheral arterial disease", section on Atypical symptoms and section on Asymptomatic patients).

• In patients ≥70 years of age or ≥50 years of age with a history of smoking and/or diabetes (ie, those at increased risk for PAD), the standard review of symptoms should include questions related to a history of walking impairment, symptoms of claudication, ischemic rest pain, or nonhealing wounds. Use of the Walking Impairment questionnaire can be considered. (See "Patients at risk" above).
• The resting ABI should be measured in patients with one or more of these findings. The ABI should be measured in both legs in all new patients with PAD to confirm the diagnosis and to establish a baseline.


These recommendations are consistent with those made in the 2007 TASC II consensus document on the management of PAD [6] .

Similar recommendations were made by the American Diabetes Association for monitoring asymptomatic patients with diabetes [36] . The guideline recommended that initial screening for PAD should include a history for claudication and an assessment of the pedal pulses and that consideration should be given to obtaining an ABI.

Further evaluation is dependent upon the ABI value [5] :

• An ABI ≤0.90 is diagnostic of PAD.
• An ABI of 0.91 to 1.30 is borderline or normal. Among patients with atypical symptoms, the ABI should be measured after exercise on a treadmill. An ABI that decreases by 20 percent following exercise is diagnostic of PAD, while a normal ABI following exercise eliminates the diagnosis and suggests the need to evaluate for other causes of the leg symptoms.
• An ABI >1.30 suggests the presence of calcified vessels and the need for additional vascular studies, such as pulse volume recording or measurement of the toe-brachial index. Abnormal results confirm the presence of PAD. (See "High ABI" above).


Symptomatic patients — The evaluation is similar in patients with classic claudication (cramping, pain, or muscle fatigue that is reproducibly induced by exercise and promptly resolves with rest). The history should document the degree of walking impairment and lifestyle limitation and the peripheral pulses should be examined.

Further evaluation is dependent upon the ABI value:

• An ABI ≤0.90 is diagnostic of PAD.
• An ABI of 0.91 to 1.30 should be followed by further testing, such as measurement of the ABI after exercise, segmental limb pressures, or duplex ultrasonography. An abnormal test is diagnostic of PAD, while a normal test excludes PAD although arterial entrapment syndromes may be considered.


Although considered the "gold standard" of diagnostic evaluation for peripheral atherosclerotic disease, the use of iodinated contrast agents involves exposure to the patient of risk from iodine allergy, contrast nephropathy and the risks inherent to percutaneous intervention. With the advent of rapid 3-D imaging sequences combined with existing extracellular gadolinium contrast agents, magnetic resonance angiography (MRA) has shown promise to become a time-efficient and cost-effective tool for the complete assessment of peripheral arterial disease [1-3] . Current available gadolinium compounds are typically used "off-label" and are not approved by FDA for MRA in the United States.

One potential complication with use of gadolinium in patients with chronic kidney disease is skin sclerosis and, therefore, should be used with caution in this population. (See "Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy in advanced renal failure", section on gadolinium).

MRA is usually performed if revascularization is being considered. (See "Clinical features, diagnosis, and natural history of lower extremity peripheral arterial disease" and see "Indications for surgery in the patient with claudication").