Treatment of lower-extremity chronic wounds doesn’t only entail preventing infections and mitigating any patient pain or discomfort, it also requires management of the underlying pathophysiology that caused them. That is often easier said than done since many patients may have several comorbid conditions, which can either be the cause of chronic wounds, hinder their treatment, or both. An example of the latter is Peripheral Artery Disease (PAD).

In 2015 there were 236.62 million individuals with PAD (or LEAD, Lower Extremity Artery Disease, as it is increasingly also referred to as today), up from 202 million in 2010 [1, 2]. This growing trend is likely to continue due to the general ageing of the population (particularly in economically developed countries) and an increase in several important risk factors [2].
One of the most important risk factors for PAD is diabetes mellitus (type 1 and type 2), which is also rapidly increasing in prevalence. It is estimated that there were 285 million adults with diabetes in 2010, 415 million in 2015, 451 million in 2017 and it is projected that number will increase to 693 million by 2045 [3, 4, 5].
Diabetes has numerous deleterious effects on the development, morbidity, severity of complications and the (un)timely diagnosis of PAD. It is estimated that at least 20 % of diabetic patients have PAD, but that number, although obtained by the Framingham Heart Study, represents only those with the symptomatic form of the disease (diagnosis of intermittent claudication) [6].
Ulcers and chronic wounds are also, not coincidentally, the topic of this blog post, or more specifically the contribution of PAD to their development, a reduction of healing rates and an increase in the incidence and severity of complications and the differentiation between wound types on the basis of their etiology. Naturally, any appropriate treatment regime is predicated on accurate and timely diagnosis of PAD and a comprehensive assessment of its severity.
This can usually be achieved only through the use of modern diagnostic devices, which can measure either the ABI, the Toe-Brachial Index (TBI) or both. However such tools might not be available in every wound care/compression therapy facility, despite their obvious usefulness, requiring instead the use of methods for identifying and stratifying at-risk patients. A comprehensive questionnaire is one such method.

What should a wound care provider ask every patient?
The majority (72 %) of all lower-extremity ulcers are caused by Chronic Venous Insufficiency (CVI), while PAD is responsible for 10 % to 30 % of all cases with diabetes, i.e. neuropathic ulcers are a distant third with prevalence in the ballpark of 15 % to 25 % [21]. Ulcers might also have a less common etiology, such as lymphatic or infectious, which represent only a very small number of cases, where the former (lymphatic ulcers) were found in only 2.5 % of patients enrolled in a comprehensive study of treatment of lower-extremity ulceration [22]. It should be noted that patients might have ulcers of mixed etiology.
Successful treatment is predicated on the timely diagnosis of PAD and the management of risk factors (primarily modifiable ones such as smoking) with possible surgery/endovascular intervention – lest it is too late – and those arterial ischemic wounds that progress into gangrene and Critical Limb Ischemia (CLI). Diagnosis of CLI is unfortunately associated with high amputation rates (ranging from 10 % to 40 % for a 6-month period after diagnosis) and significant mortality (from 20 % in the 6-month period to 50 % in 5 years after diagnosis) [25-29].
Venous ulcers are usually (conservatively) managed using compression therapy, but its utility is limited in patients with only arterial insufficiency ulcers or those with both types of ulcers (due to the possible use of lower compression levels) and may be even be entirely inappropriate for those with severe PAD [35, 36]. The only exception is intermittent pneumatic compression (IPC) systems, which are suitable for improving healing rates in patients with venous, arterial and neuropathic ulcers [37-39].
The questionnaire for assessing the relative risk of PAD in wound care patients/patients with chronic wounds takes into account well-known risk factors for the disease with an additional emphasis on information pertinent to wound care/compression therapy providers.
List of questions for assessing the relative risk of PAD in patients with chronic wounds:
1. Age. How old is the patient in question?
Older patients (generally over 50 years of age) are at an increased risk of PAD, which might be asymptomatic [40].
2. Ethnicity. In most cases self-evident.
There are statistically significant discrepancies in PAD prevalence and morbidity in individuals of different ethnic groups. Studies have shown that blacks (specifically African Americans) are at higher risk of developing PAD than whites [41].
3. Gender. Self-evident as well.
Some studies have indicated greater prevalence of PAD (particularly more severe forms) in women than in men [42].
4. Tobacco smoking. Does the patient smoke (current smoker) and how much or did s/he ever smoke (how long has the patient been a former smoker)?
Current smokers have a far greater risk of developing PAD [43]. Association between tobacco smoking and PAD is especially strong in female smokers who are at an up to 20-times greater risk for the disease than females who have never smoked [44]. Information about past smoking (former smokers) is also important: the health benefits of smoking cessation don’t translate well to PAD as even former smokers are at an increased risk with up to 2.6-times greater prevalence of PAD (in comparison with non-smokers) [45].
5. Diabetes. Does the patient have type 1 or 2 diabetes mellitus?
Diabetes-induced hyperglycaemia greatly increases the incidence and prevalence of PAD [14].
6. Previous diagnosis of Coronary Artery Disease (CAD). Does the patient have CAD?
Already present (diagnosed) CAD is indicative of possible atherosclerosis in other vascular beds – prevalence rates of PAD in CAD patients range from 22 % to 42 % [46-48].
7. History of Myocardial Infarction (MI), strokes or Transient Ischemic Attacks (TIA). Was the patient diagnosed with MI, a stroke or TIA?
History of MI and cerebrovascular events is associated with higher prevalence rates of PAD, often in its asymptomatic form (diagnosis on basis of the ABI score) [49-51].
8. Diagnosis of Chronic Kidney Disease CKD. Was the patient diagnosed with CKD or renal insufficiency in general (self-evident if the nephrologist is already treating such a patient)?
Individuals with renal insufficiency are 9-times more likely to have an abnormal ABI score (defined as ABI <0.9, which is an indication of PAD) [52].
9. Diagnosis of rheumatoid arthritis. Was the patient diagnosed with rheumatoid arthritis?
Patients with rheumatoid arthritis are more likely to have incompressible arteries, precluding the use of some diagnostic methods for PAD [19].
10. Diagnosis of incompressible arteries. Does the patient have incompressible arteries (this is not really a question for the patient, as incompressible arteries are rarely diagnosed on their own and it is unlikely s/he would have this information, but up to the examiner to determine on the basis of diagnosis of other conditions)?
Incompressible arteries are quite likely in those who have answered the 5th, 8th and 9th question with YES – a warning sign for the examiner that diagnostic methods other than ABI (i.e. TBI) will have to be used.
11. Diagnosis of chronic obstructive pulmonary disease (COPD). Was the patient diagnosed with COPD?
Patients with COPD are at double the risk of developing PAD [53].
12. Hyperlipidaemia. Does the patient suffer from abnormally elevated levels of lipids (lipoproteins)?
Abnormal levels of blood lipids and lipoproteins is associated with mild risk for development of large-vessel PAD [54].
13. Hypertension. Is the patient hypertensive or is receiving treatment for hypertension?
Hypertension is a known risk factor for PAD (and other CVDs) [55].
14. Weight. Is the patient over or underweight for her/his height and sex?
Weight is a risk factor for PAD (and many other medical conditions) as studies have shown that older individuals with greater BMI (body mass index) have a higher incidence of PAD [56].
15. Intermittent claudication. Does the patient report pain during any sort of physical exercise, even walking? Does the pain subside when s/he takes a rest? Where (part of the leg) is the pain located?
Accurately diagnosing intermittent claudication on the basis of physical sensations the patient feels during physical exertion and when still/resting is best done using the Edinburgh Claudication Questionnaire [57].
16. Cold feet/legs. Does the patient report cold feeling in his leg(s) or feet despite feeling otherwise (in other parts of the body) warm or otherwise comfortable at the current ambient temperature?
Reduced blood flow leads to disruption of normal thermoregulation.
17. Scaly skin/of pale or blueish hue/deformed toenails. Does the patient have abnormal skin texture and colour and/or suffers from deformed toenails?
Occlusion in the arteries of lower extremities reduces flow of nutrients to skin and toenails, leading to stunted growth and deformations. Pallor in the affected leg is possible when it is in an elevated position [58].
18. Open wounds and sores. Does the patient have any types of wounds or other tissue damage on her/his legs/feet that heals very slowly or doesn’t appear to heal at all or had ulcers that already healed?
This is another tell-tale sign of PAD, but one that is typical for the advanced form of the disease.
19. Compression therapy. Is the patient receiving compression therapy or was s/he a recipient of such treatment at any point in his medical history?
This is not directly connected to diagnosing PAD as it is possible that a patient with venous ulcers was a recipient of compression therapy without prior PAD assessment, but it is a cue for an evaluation of the suitability of such treatment for the patient in question.
20. Erectile dysfunction (men). Does the patient suffer from erectile dysfunction?
Diagnosis of erectile dysfunction carries a two-fold increase in the likelihood of PAD [59].
21. Family history. Does the patient have any relatives that have or have had PAD?
Patients with a family history of PAD are at twice the risk of the disease than those without such a familial medical history [60].
Comprehensive chronic wound assessment and treatment should include an ABI or TBI assessment to confirm or dismiss the presence of PAD. Where modern diagnostic tools are lacking, a comprehensive questionnaire may be used to identify at-risk patients who might benefit from further examination, but not in lieu of them.
[1] Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis > https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61249-0/fulltext
[2] Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis > https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(19)30255-4/fulltext
[3] Global estimates of the prevalence of diabetes for 2010 and 2030 > https://www.ncbi.nlm.nih.gov/pubmed/19896746
[4] IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040 > https://www.diabetesresearchclinicalpractice.com/article/s0168-8227(17)30375-3/fulltext
[5] IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045 > https://www.ncbi.nlm.nih.gov/pubmed/29496507
[6] Intermittent Claudication – A Risk Profile From The Framingham Heart Study > https://www.ahajournals.org/doi/full/10.1161/01.CIR.96.1.44
[7] Peripheral Arterial Disease Detection, Awareness, and Treatment in Primary Care > https://jamanetwork.com/journals/jama/fullarticle/194205
[8] Leg Symptoms in Peripheral Arterial Disease – Associated Clinical Characteristics and Functional Impairment > https://jamanetwork.com/journals/jama/fullarticle/194250
[9] Peripheral Arterial Disease in Patients With Diabetes > https://www.sciencedirect.com/science/article/pii/S0735109705028627
[10] The Pathophysiology of Cardiovascular Disease and Diabetes: Beyond Blood Pressure and Lipids > https://spectrum.diabetesjournals.org/content/21/3/160
[11] Inflammation and Diabetes-Accelerated Atherosclerosis: Myeloid Cell Mediators > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578033/
[12] Diabetic Autonomic Neuropathy > https://care.diabetesjournals.org/content/26/5/1553
[13] Updates in diabetic peripheral neuropathy > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847561/
[14] Peripheral Arterial Disease in People With Diabetes > https://care.diabetesjournals.org/content/26/12/3333
[15] Prevalence and Risk Factors for the Peripheral Neuropathy in Patients with Peripheral Arterial Occlusive Disease > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480317/
[16] Peripheral neuropathy associated with ischemic vascular disease of the lower limbs > https://www.ncbi.nlm.nih.gov/pubmed/8678331
[17] Medial arterial calcification in diabetes and its relationship to neuropathy > https://www.ncbi.nlm.nih.gov/pubmed/19756483/
[18] Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality > https://academic.oup.com/ndt/article/18/9/1731/1842064
[19] Lower limb arterial incompressibility and obstruction in rheumatoid arthritis > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1755423/
[20] Neuropathic diabetic foot ulcers – evidence-to-practice > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282596/
[21] The Evaluation of Lower-Extremity Ulcers > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036466/
[22] The diagnosis and management of 689 chronic leg ulcers in a single-visit assessment clinic > https://www.ejves.com/article/S1078-5884(02)91906-4/fulltext
[23] An Economic Evaluation of the Impact, Cost, and Medicare Policy Implications of Chronic Nonhealing Wounds > https://www.valueinhealthjournal.com/article/S1098-3015(17)30329-7/fulltext
[24] Psychosocial Aspects in Patients With Chronic Leg Ulcers > https://www.woundsresearch.com/article/psychosocial-aspects-patients-chronic-leg-ulcers
[25] Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial > https://www.ncbi.nlm.nih.gov/pubmed/16325694
[26] Medical treatment of peripheral arterial disease: a comprehensive review > https://www.ncbi.nlm.nih.gov/pubmed/15525738
[27] The natural history of untreated severe or critical limb ischemia > https://www.jvascsurg.org/article/S0741-5214(15)01625-0/fulltext
[28] Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) > https://www.jvascsurg.org/article/S0741-5214(06)02296-8/fulltext
[29] Chapter I: Definitions, Epidemiology, Clinical Presentation and Prognosis > https://www.ejves.com/article/S1078-5884(11)60009-9/fulltext
[30] Surgical or endovascular revascularization in patients with critical limb ischemia: influence of diabetes mellitus on clinical outcome > https://www.ncbi.nlm.nih.gov/pubmed/17306950/
[31] Surgical or endovascular revascularization in patients with critical limb ischemia: Influence of diabetes mellitus on clinical outcome > https://www.jvascsurg.org/article/S0741-5214(06)02258-0/fulltext
[32] Ethnic differences in peripheral arterial disease in the NHLBI Genetic Epidemiology Network of Arteriopathy (GENOA) study > https://journals.sagepub.com/doi/abs/10.1191/1358863x03vm511oa
[33] Association of elevated fasting glucose with lower patency and increased major adverse limb events among patients with diabetes undergoing infrapopliteal balloon angioplasty > https://journals.sagepub.com/doi/full/10.1177/1358863X14538330
[34] Diabetic Foot Ulcers and Vascular Insufficiency: Our Population Has Changed, but Our Methods Have Not > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262731/
[35] Clinical Review – Management of venous ulcer disease > https://www.bmj.com/content/341/bmj.c6045
[36] Compression therapy for venous leg ulcers > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144247/
[37] Effect of High-pressure, Intermittent Pneumatic Compression for the Treatment of Peripheral Arterial Disease and Critical Limb Ischemia in Patients Without a Surgical Option > https://www.ncbi.nlm.nih.gov/pubmed/26574751
[38] The case for intermittent pneumatic compression > https://www.woundsinternational.com/download/wint_article/7127
[39] Compression Therapy in Diabetic Foot Ulcer Management: A Review of Clinical Effectiveness, Cost-effectiveness and Guidelines [Internet] > https://www.ncbi.nlm.nih.gov/books/NBK253659/
[40] Journal of the American College of Cardiology (JACC) > http://www.onlinejacc.org/content/accj/61/16/1736.full.pdf
[41] Ethnicity and Peripheral Arterial Disease – The San Diego Population Study > https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.105.546507
[42] Sex differences in the prevalence of peripheral artery disease in patients undergoing coronary catheterization > https://journals.sagepub.com/doi/pdf/10.1177/1358863X10388345
[43] Meta-analysis of the association between cigarette smoking and peripheral arterial disease > https://heart.bmj.com/content/100/5/414
[44] Smoking, Smoking Cessation and Risk of Symptomatic Peripheral Artery Disease in Women: A Prospective Study > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111942/
[45] Influence of smoking on incidence and prevalence of peripheral arterial disease > https://www.sciencedirect.com/science/article/pii/S0741521404011413
[46] The prevalence of peripheral arterial disease in high risk subjects and coronary or cerebrovascular patients > https://www.ncbi.nlm.nih.gov/pubmed/17626985
[47] Lower extremity peripheral arterial disease in hospitalized patients with coronary artery disease > https://www.ncbi.nlm.nih.gov/pubmed/15125482
[48] Peripheral artery disease in patients with coronary artery disease > https://www.ncbi.nlm.nih.gov/pubmed/7658111
[49] Prevalence and risk factors associated with peripheral arterial disease in an adult population from Colombia > https://www.elsevier.es/es-revista-archivos-cardiologia-mexico-293-articulo-prevalence-risk-factors-associated-with-S1405994017300113
[50] Systemic risk score evaluation in ischemic stroke patients (SCALA): a prospective cross sectional study in 85 German stroke units > https://www.ncbi.nlm.nih.gov/pubmed/17668260
[51] Low ankle–brachial index predicts an adverse 1‐year outcome after acute coronary and cerebrovascular events > https://onlinelibrary.wiley.com/doi/full/10.1111/j.1538-7836.2006.02225.x
[52] High Prevalence of Peripheral Arterial Disease in Persons With Renal Insufficiency > https://www.ahajournals.org/doi/full/10.1161/01.CIR.0000114519.75433.DD
[53] COPD is associated with an increased risk of peripheral artery disease and mortality > https://openres.ersjournals.com/content/4/4/00086-2018
[54] The prevalence of peripheral arterial disease in a defined population > https://pdfs.semanticscholar.org/0594/15ad0ba1e52dc181e40468283e8513542cb9.pdf
[55] Hypertension in peripheral arterial disease > https://www.ncbi.nlm.nih.gov/pubmed/15579058
[56] Association of Body Mass Index With Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study > https://academic.oup.com/aje/article/174/9/1036/168550/
[57] Edinburgh Claudication Questionnaire > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2560464/?page=1
[58] Approach to the Patient With Peripheral Arterial Disease > https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.113.000502
[59] The association between erectile dysfunction and peripheral arterial disease as determined by screening ankle-brachial index testing > https://www.ncbi.nlm.nih.gov/pubmed/19501825
[60] Family History of Peripheral Artery Disease is associated with Prevalence and Severity of Peripheral Artery Disease: The San Diego Population Study (SDPS) > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215334/