Peripheral arterial disease (PAD), sometimes referred to as LEAD (lower extremity artery disease), is an insidious vascular condition that often becomes apparent only when the patient is already suffering from its complications. The same could be said for many other cardiovascular diseases (CVDs), but whereas many of them require a more radical approach to avert or at least mitigate serious complications, PAD can be successfully managed by conservative means if it is diagnosed in a timely manner. However, despite several accurate and reliable diagnostic methods, some of which are more appropriate for general practice use, that is unfortunately rarely the case in practice as many clinicians rely on questionnaires and the unlikely presence of typical symptoms.
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Rates of morbidity and mortality associated with CVDs are intimately connected to a complex interaction of the disease with its risk factors and any comorbid diseases, and PAD is no exception. There were an estimated 236.62 million adults with the disease in 2015, up from 202 million in 2010, and that number is expected to increase in the future due to the projected rise of several risk factors, notably the age of the adult population [1, 2i].
Untreated, PAD can progress to arterial insufficiency ulcers (extremely difficult to treat, particularly in the presence of risk factors such as smoking and diabetes) and gangrene . Both are components of critical limb ischaemia (CLI), an advanced stage of PAD, which is associated with a significantly higher risk of mortality (from 20% in the six-month period to 50% five years after diagnosis) and amputation (in the six-month period after diagnosis) [4, 5, 6, 7, 8].
Despite this and the fact that (the presence/absence of) PAD— more specifically the ABI (ankle-brachial index) value—is recognised as an important predictor of cardiovascular risk beyond the Framingham Risk Score, the disease is still largely under-diagnosed and under-treated [9, 10, 11]. There are several reasons for this, amongst them the reliance of many healthcare professionals on screening on the basis of the most typical symptom – intermittent claudication (IC). Also known as classic claudication, Rose intermittent claudication (Rose IC), and definite claudication, it is described as a painful, aching, cramping, or tired feeling in the calves that occurs during walking that is relieved within 10 minutes or less when the individual stops walking and rests .
However, IC is reported only in between 7.5% and 33% of patients with confirmed PAD diagnosis, meaning that most cases are asymptomatic/have atypical symptoms [13, 14, 15, 16]. And, again despite this, IC is the basis of several symptom questionnaires currently in general use (to varying extents), prompting a closer look at their sensitivity and specificity in understanding their shortcomings in diagnosing PAD.
The first PAD symptom questionnaire was the Rose questionnaire, developed in 1962 and named after its inventor, which attempted to standardise the only known symptom of PAD (IC), for use in epidemiological studies, leading to its adoption by the World Health Organization (WHO) in 1968 [17, 18]. Initially, the questionnaire boasted high sensitivity and specificity, but subsequent studies with larger sample sizes found lower and wildly variable specificity [18, 19. 20].
An attempt at rectifying those issues resulted in the development of the Edinburgh Claudication Questionnaire (ECQ) in 1992 . Amongst other features, it included a lower-extremity body diagram for patients to indicate leg symptoms in multiple locations, allowing claudication to be classified as definite claudication or atypical claudication. That is the main shortcoming of the WHO/Rose questionnaire, which fails to identify patients with symptoms in an atypical location or multiple locations. Supposedly more reliable than the WHO/Rose questionnaire, the ECQ was tested in a population of patients aged over 55 years at the peripheral vascular clinic and in general practice .
The list of questionnaires is rounded off by the San Diego Claudication Questionnaire (SDCQ), developed in 1996 . Intended as a revised and expanded version of the WHO/Rose, it includes questions about buttock and thigh pain, but with the addition of asking whether the pain was in the right or left leg or both. Together with the WHO/Rose and ECQ, however, it is still largely insensitive to PAD detection in comparison with ABI. Further refinement is still needed to correctly identify patients with PAD, but with symptoms that differ from those regarded as classic IC. Moreover, even IC might become apparent only under specific circumstances.
As already mentioned, IC is generally regarded as the most typical symptom of PAD with varying prevalence [22, 23, 24]. The patients most likely to report IC are older, male, and have diabetes mellitus, hypertension or a previous diagnosis of PAD or are suffering from its more severe form [13, 15, 25, 26, 27, 28, 29]. The location of the disease also influences report rates for IC with a higher prevalence in those with distal lesions or large vessel PAD [25, 30].
However, recent studies have demonstrated that IC prevalence may even reach 100% in selected groups of patients who complained of leg pain and had a diagnosis of symptomatic PAD. One study comprised of 114 participants (only about a third reported classic IC, the rest had atypical or unspecified leg pain upon exertion) found that all of them reported symptoms of IC during a graded treadmill test .
These findings were supported by other studies, leading researchers to question the previous epidemiological studies and viability of current questionnaires [24, 32]. Are the patients classified in the literature as “asymptomatic” not experiencing symptoms, or are they slowing their walking pace/limiting physical activity to prevent the onset and/or progression of leg symptoms that could be identified under supervised exercise testing? Atypical symptoms and confounding factors further inhibit accurate diagnosis.
Ever since the development of the WHO/Rose questionnaire, researchers have discovered that despite the evolution/development of questionnaires, they are insufficient in detecting a wide variety of symptoms and symptom experiences that could be categorised as atypical. Moreover, atypical symptoms are reported more frequently than IC, but even an estimate of prevalence remains elusive since some epidemiological studies used mutually exclusive terms for the same phenomenon, hindering analysis [10, 14, 16, 20, 33, 34, 35, 36].
Confounding factors make analysis even harder, but to what extent? Several studies have noted the potential influence of comorbid conditions on symptom presentation and particularly highlighted diabetes, neuropathy, and spinal stenosis [20, 24, 33, 37, 38, 39, 40, 41]. More succinctly, the symptoms of claudication may overlap with the symptomatology of other diseases, like those of neurological and musculoskeletal nature .
Given the overwhelming evidence presented, the questionnaires currently in use (WHO/Rose, ECQ, and SDCQ) are inappropriate for preventive screening and diagnosis of PAD. Furthermore, due to the differences between them, i.e., definitions of claudication and atypical symptomatology, epidemiologists are facing difficulties in making comparisons across studies, weakening the quality of research. Further development and refinements of questionnaires in the light of new findings about atypical symptoms and confounding conditions in the presentation of IC is needed to potentially improve their usefulness in screening for PAD.
Current PAD symptom questionnaires are an inadequate tool for accurate and reliable screening for the disease in comparison with already widely utilised diagnostic methods like ABI.