Methods of symptom evaluation and their impact on peripheral artery disease (PAD) symptom prevalence: A review

Symptom definitions

A relatively strict definition of claudication (the ‘typical’ PAD symptom) has persisted over time. As previously described, in its original form, ¹⁶ classic claudication is exertional pain restricted to one or both calves that causes a patient to slow down or stop walking, resolves within 10 minutes of standing still, does not resolve while the patient is walking, and does not begin at rest. While the introduction of the ECQ allowed for the presence of symptoms elsewhere in the lower extremities, pain still had to be present in one or both calves to be classified as definite claudication.^17,28,29

The creation of the SDCQ allowed for the presence of more specific symptom categories beyond classic claudication, and the assessment of leg-specific symptoms (right versus left). ¹⁸ The SDCQ consists of five possible symptom categories per leg: Rose claudication, non-Rose exercise calf pain, previously referred to as ‘possible IC’ ²⁸ and ‘probable IC’, ²⁹ non-calf exercise leg pain, pain at rest, and no pain. ¹⁸ Table 2 summarizes the evolution of claudication questionnaires, including symptom categories and their associated characteristics that most frequently appear in the literature.

OPEN IN VIEWER

Table 2.

Evolution of claudication questionnaires.

Questionnaire	Year created / revised	Symptom category	Symptom characteristics
Rose 16 WHO/Rose 25	1962	• Intermittent claudication (Rose IC)  Grade 1  Grade 2	• Exertional calf pain Walking uphill or hurrying Walking at ordinary pace on the level • Never starts at rest (standing/sitting) • Never disappears while walking • Causes patient to slow down or stop • Usually disappears in 10 minutes or less
	1985	• Possible IC 28	• Exertional calf pain• Never starts at rest• Otherwise not fully concordant with the Rose IC criteria
	1991	• Probable IC 29	• Exertional calf pain• One WHO/Rose criteria not fulfilled
ECQ 17	1992	• Definite IC (Rose IC) Grade 1 Grade 2• Atypical IC	• Fully concordant with Rose IC criteriaWalking uphill or hurryingWalking at ordinary pace on the level• Pain in thigh or buttock in the absence of calf pain, otherwise concordant with Rose IC criteria
SDCQ 18	1996	• Rose IC• Non-Rose exercise calf pain• Non-calf exercise leg pain• Leg pain on exertion and at rest• No pain	• Fully concordant with Rose IC criteria• Exertional calf pain; at least one Rose IC criteria not fulfilled• Pain in either leg excluding calf (can be thigh or buttock), does not begin at rest• Exertional leg pain starts at rest• Reports no pain in calf, thigh, or buttock

IC, intermittent claudication; ECQ, Edinburgh Claudication Questionnaire; SDCQ, San Diego Claudication Questionnaire.

Despite the evolution of these questionnaires, patients reporting pain in the hamstrings, feet, shins, joints, or radiating pain in the absence of calf pain would still not classify as ‘symptomatic’, and subsequently would not be suspected of having PAD. Furthermore, although the number of symptom categories has increased on questionnaires, none allow for the reporting of symptom descriptors such as tingling, numbness, burning, throbbing, or shooting that have been reported by patients with PAD as being part of the symptom experience.^23,24

Typical symptoms

The symptom most frequently recognized as the hallmark sign of arterial insufficiency is claudication. Claudication comes from the Latin word claudicare, meaning to limp. But, the use of this term is misleading, as patients who experience symptoms other than classic claudication are still shown to be functionally limited^30,31 and report a decreased quality of life. ³² Aside from confusion about the meaning of claudication, using classic claudication as the gold standard for PAD symptom recognition results in significant under-diagnosis of disease. Over the last 10–15 years, the reported prevalence of classic claudication in patients with symptomatic PAD has been highly variable, ranging from 7.5% ²⁰ to 33%.^18,21,22 Higher prevalence has been reported in smaller populations (43.8%) ³³ and specific populations including only individuals complaining of leg pain (78.8%), ³⁴ or excluding individuals who have non-compressible arteries, CLI, or a history of revascularization (43.6%). ³⁵ Overall, study results indicate that there are specific characteristics of individuals who are more likely to report classic claudication. Reporting appears to increase as age increases,^{21,28,29,36,37} and be more prevalent among men,^21,36,37 and in individuals with diabetes, ²¹ hypertension, ³⁸ a previous diagnosis of PAD,^2,18 or a more severe form of the disease.^18,21,37 Disease location may also influence the reporting of classic claudication, with a higher prevalence among those with distal lesions ³⁵ or large vessel PAD. ²⁸

The highest reported prevalence of classic claudication is 100%.^39–41 The most recent study conducted by Gardner and colleagues ⁴⁰ included 114 participants with symptomatic PAD recruited from vascular and primary care clinic referrals. Prior to exercise testing, participants fell into the following three symptom categories: leg pain on exertion and rest (40.3%), atypical leg pain (27.2%), and classic claudication (32.5%). However, during a graded treadmill test, all of the participants reported symptoms consistent with classic claudication. In 2007, Gardner and colleagues ³⁹ reported similar findings. The study included 715 participants self-reporting exertional leg pain consistent with one of the first four categories on the SDCQ. Initial classic claudication prevalence was 56.8%. As with the 2012 study, during treadmill testing, all of the study participants experienced exertional leg pain that was consistent with classic claudication (i.e. participants stopped walking due to calf pain that resolved with subsequent rest). McDermott and colleagues ⁴¹ reported similar findings with a group of 57 patients who initially self-reported no symptoms, but over half became symptomatic during a 6-minute walking test. These results raise important questions that have not been previously explored: Are the patients classified in the literature as ‘asymptomatic’ truly not experiencing symptoms, or are they slowing their walking pace or limiting ambulation to prevent the onset and/or progression of leg symptoms which could be revealed under controlled exercise testing? The issue of under-reporting versus true symptom prevalence deserves further attention.

Atypical symptoms

When Rose ¹⁶ developed the first claudication questionnaire in 1962, the characteristics of PAD were thought to be well-delineated, which made it suitable for diagnosis in epidemiologic surveys. However, over the last five decades, researchers have discovered a more diverse presentation of PAD symptoms. With classic claudication consistently being reported by less than one-third of patients with PAD, claudication questionnaires have been forced to evolve in order to capture the broad array of symptom experiences.^17,18 But, revised claudication questionnaires are still not sufficient, as patients are reporting symptoms and symptom experiences that are not detected by these questionnaires. Until a more comprehensive tool exists, it is essential for clinicians to recognize that patients with underlying PAD are reporting ‘atypical’ symptoms more frequently than classic claudication,^{2,20,22,27,42–45} and adapt their assessment techniques accordingly.

In the literature reviewed, the prevalence of atypical symptoms was difficult to ascertain compared to classic claudication, despite its increased frequency. The main reasons were the use of a variety of definitions for atypical symptoms and inconsistent use of symptom categories from study to study. In its simplest form, atypical symptoms included any lower-extremity symptom that was not consistent with classic claudication^2,18 and increased in complexity to include all lower-extremity symptoms not located in the calf, ¹⁷ exercise calf pain not present at rest, but otherwise not fully concordant with the Rose criteria (‘possible IC’),^28,46 calf pain, but one Rose criteria not fulfilled (‘probable IC’), ²⁹ atypical pain on exertion (non-Rose walk-through pain and non-Rose stop because of pain), and pain on exertion and rest.^39,41 Atypical pain was used to refer to ‘walk-through pain’ and/or pain that was not consistently relieved within 10 minutes of rest. ³⁸ However, prolonged symptom recovery was also grouped together with pain at rest into a ‘no pain’ category. ⁴⁷ Pain that presented at rest and on exertion was often referred to as ‘leg pain on exertion and rest’,^{21,39–41,45} but was also referred to as ‘pain at rest’,^18,22,42,48 ‘rest pain’,^43,49 or ‘symptoms at rest’. ³⁵ Some studies subdivided the ‘no symptoms with exertion’ category into active and inactive participants, resulting in a total of six leg categories,^41,50 whereas Collins and colleagues ²⁰ condensed the five symptom categories of the SDCQ into three: no pain, atypical leg pain (pain at rest, non-calf exercise pain, and non-Rose exercise calf pain), and Rose claudication. Others followed the original five symptom categories established by the SDCQ ²¹ or used a general category of ‘leg symptoms’ ⁴⁴ or ‘symptomatic’ that included lower-extremity revascularization, amputation secondary to PAD, or report of claudication regardless of ABI. ⁵¹ The use of either category – ‘leg symptoms’ or ‘symptomatic’ – limits the understanding of symptom presentation by classifying symptomatic patients as asymptomatic and vice versa.

Discovering a wider variety of PAD symptoms has not been entirely without challenge, particularly since responses to some symptom categories can be difficult to interpret. For example, the rest pain category on the SDCQ could represent an individual experiencing ischemic rest pain or pain at rest not associated with PAD, but attributable to a comorbid condition such as arthritis. Additionally, it is imperative that symptoms consistent with ischemia are differentiated from those not consistent with ischemia in order to identify atypical PAD symptoms versus manifestations of comorbid conditions unrelated to PAD (i.e. symptom confounders). Figure 2 illustrates how a symptom can be classified as ischemic or non-ischemic in three phases: at rest, during exercise, and during recovery.

OPEN IN VIEWER

Figure 2.

Conceptual model of symptom differentiation.

Potential symptom confounders

It has been demonstrated that older adults are more likely to become afflicted with PAD.^52,53 Older age also makes it more likely that patients with PAD are afflicted with other age-related conditions that could cause or contribute to lower-extremity symptoms. Consideration should also be given to PAD severity and its influence on the symptom experience. While several researchers have recognized the potential influence of comorbid conditions on symptom presentation,^{24,27,41,42,53–56} the topic has not been thoroughly researched or reported in the literature. Findings from McDermott and colleagues ⁴¹ revealed an increased prevalence of diabetes, neuropathy, and spinal stenosis in patients who reported pain on exertion and rest. Similarly, Newman and colleagues ²⁷ discovered a higher prevalence of arthritis and depression in patients reporting exertional leg pain other than classic claudication. Findings from Bernstein and colleagues ⁵⁷ revealed a low prevalence of classic claudication (2%) among patients with PAD, half of whom were also diagnosed with degenerative joint disease. Insulin resistance without a diagnosis of diabetes has also been identified as a factor influencing claudication prevalence. ⁵⁸ Further support for the effect of comorbid conditions came from a study conducted by Weinberg and colleagues, ⁵⁴ indicating that regional neuropathy is commonly associated with chronic ischemia and CLI.

The neuropathic component of ischemic pain has been examined more closely by researchers and the current understanding is that the character of ischemic pain changes from nociceptive pain in patients with classic claudication to predominately neuropathic pain in patients with CLI. ²⁴ Despite the large numbers of patients diagnosed with PAD and reporting neuropathy, the knowledge of the role of ischemia in neuropathic pain remains limited. Overall, these preliminary results suggest that there are differences in the symptoms reported and/or differences in the character of the symptom in the presence of certain comorbid conditions or in those with severe PAD (i.e. CLI). This provides additional evidence that using classic claudication as the defining symptom of PAD is insufficient to capture the breadth of symptoms experienced, particularly in this patient population.

Similarly, differential diagnoses have been described in PAD literature in an attempt to clear the blurring of symptom reporting that occurs in the presence of multiple comorbidities, but it has not been extensively studied.^59–65 An understanding of physiology can allow a clinician to locate the site of arterial occlusion based on the location of the symptom(s). For example, pain or discomfort in the calf, ankle, or foot could indicate an obstruction/occlusion in the popliteal or superficial femoral arteries. ⁶⁰ Symptoms located primarily in the calf or thigh could indicate involvement of the femoral arteries or their branches, whereas symptoms in the buttock, hip, and thigh indicate higher disease in the aorta or iliac artery.

The location of symptoms can serve as a guide, but they do not guarantee the presence or location of a lesion with 100% certainty. Symptoms of a patient with claudication may overlap with the symptomatology of other conditions, particularly neurological and musculoskeletal diseases. ⁶³ Take, for instance, a patient reporting calf pain. The pain could indicate claudication secondary to a femoral artery occlusion or it could indicate a venous occlusion, chronic compartment syndrome, nerve root compression, or a Baker’s cyst (a tight bursting pain/dull ache that worsens on standing and resolves with leg elevation).^59,61,63,66 The presence of any of these conditions could lead a provider to suspect claudication, which could be ruled out if the symptom is relieved by a change in position. Symptoms in the hip, thigh, or buttock could be related to hip arthritis.^59,63 However, arthritis is usually a more persistent pain compared to the intermittent nature of claudication and typically associated with symptoms in other joints.^63,67 Spinal cord compression should also be considered, particularly when a patient is reporting a history of back pain, with symptoms that worsen upon standing, but are relieved by positional changes. ⁵⁹ Patients reporting foot symptoms could have an inflammatory condition such as arthritis or Buerger’s disease.^63,64 Current clinician recommendations are to conduct a thorough physical exam and symptom assessment that includes the location, duration, and intensity. ⁶² If PAD is suspected based on patient symptom report or a patient’s risk factor profile, a confirmatory ABI should be performed.