Chronic limb ischaemia is the result of peripheral artery disease (PAD). This article will discuss the epidemiology, aetiology and pathophysiology of the disease, as well as critically evaluating the methods of assessment and surgical treatment used. A case study will be presented. Patient details have been anonymised to protect confidentiality, in line with the Nursing and Midwifery Council Code (2018).
Epidemiology
PAD affects more than 200 million people worldwide (Yang et al, 2017) and is the third most common clinical presentation of atherosclerosis after coronary artery disease (CAD) and stroke (Song et al, 2019). Previously an ailment of more affluent nations, the disease is now becoming more common in poorer countries (Coughlin, 2019a). The upward trend in international incidence has been attributed to a number of causative factors, with arguably the most important being a significant increase in life expectancy (Baubeta Fridh et al, 2017). This is a reasonable theory when considering there is a proven link between ageing and PAD presentation, with various studies identifying a sharp increase in prevalence from 3% to 10% among the general populace to 15% to 20% when focusing on those aged more than 70 years (Coughlin, 2019a).
True incidence and trends can be skewed owing to the fact that the majority of individuals with PAD are asymptomatic (Nickinson and Bown, 2019). For example, male gender is widely considered to carry a higher risk for PAD (De Nunzio and England, 2015; Cea-Soriano et al, 2018), whereas other studies that screened indiscriminately for PAD found that the incidence was higher than published and with little discernible difference between males and females (Coughlin, 2019a). It is reported that one in five people living in the UK aged over 60 have been diagnosed with PAD (Coughlin, 2019a), carrying an annual financial burden of more than £200 million to the NHS (Nickinson and Bown, 2019).
Aetiology
PAD is a chronic inflammatory process driven by lipids, whereby atherosclerotic plaques are formed within the arterial tree as a result of a complex chain of reactions (Mylankal and Fitridge, 2019). Although the exact mechanism of its origin is not fully understood, its development is thought to begin with naturally occurring vascular changes in the form of intimal thickening, consisting of layers of smooth muscle cells and extracellular matrix (Sakakura et al, 2013). These changes have been observed in around 35% of neonates and are more common in larger arteries at sites of bifurcation (Sakakura et al, 2013).
The accumulation of foam cells, combined with smooth muscle cells (SMC) and proteoglycan, form fatty streaks, considered to be the earliest atherosclerotic lesion (Sakakura et al, 2013). Over time, the build-up of fatty streaks creates a swelling within the lumen of the artery and restricts blood flow (Nair, 2018).
Risk factors
Owing to the systemic nature of atherosclerosis, the risk factors of PAD reflect those of coronary and carotid artery diseases, and PAD is considered an independent risk factor for cardiovascular morbidity and mortality (Olinic et al, 2018). Risk factors for PAD are often referred to as belonging to two sub-categories, namely non-modifiable and modifiable (Nickinson and Bown, 2019). Non-modifiable risk factors are listed as age, ethnicity and hereditary propensity for the disease, whereas those thought to be modifiable to some extent are smoking, obesity, hypertension, hyperlipidaemia and diabetes mellitus (Gould and Dyer, 2018).
Smoking
Tobacco smoking is recognised as a leading cause of PAD development (Nickinson and Bown, 2019). The presence of cigarette smoke and toxins within the vasculature act to stimulate endothelium dysfunction associated with PAD (Gimbrone and García-Cardeña, 2016). Individuals who smoke are four times more likely to develop PAD than non-smokers, a risk which is maintained for up to 20 years after cessation (Coughlin, 2019a). There is also a positive correlation between the number of cigarettes smoked and the severity of PAD (Olinic et al, 2018). However, smoking may become less significant in the future due its downward trend in prevalence, with the number of smokers in the UK falling by almost a quarter since 2013 (Selbie, 2018).
Obesity
Metabolic syndrome is a term used to describe the coexistence of risk factors for atherosclerosis within an individual (O'Neill and O'Driscoll, 2015). It is defined as the combined presence of hypertension, abdominal obesity, hyperlipidaemia, insulin resistance and inactivity and it is believed to double the risk of cardiovascular disease and increase the risk of developing type 2 diabetes fivefold (Grundy, 2016). Obesity has been identified as the driving force behind metabolic syndrome and is often the precursor to the appearance of the other risk factors (O'Neill and O'Driscoll, 2015). Obesity is now considered a global epidemic by the World Health Organization (WHO) (2021), having doubled in incidence over the past 30 years (Samson and Garber, 2014). Given its increasing prevalence and substantial adverse implications for health, it is the authors' opinion that obesity could reasonably be predicted to replace smoking in the near future as the leading cause of PAD.
Case study
A male in his 60s, John Jones (name and some details changed) (Table 1), presented to a surgical assessment unit in a secondary care setting with a 3-week history of paraesthesia to his left foot and toes. He described increasing intermittent claudication over the preceding few months, with his exercise tolerance having reduced to just 20 yards (18.2 metres). He reported suffering worsening pain in the 2 weeks leading up to admission, which had progressed to waking him at night. The pain was exacerbated by elevating his foot. He reported no high temperatures or shivering episodes. There had been no recent flights or long distance travel.
Table 1. Case study: patient history
| History | Details |
|---|---|
| Age | 60 |
| Sex | Male |
| History of presenting complaint and symptoms | 2–3 week history of paraesthesia to left foot and toes. Increasing intermittent claudication over past few months—exercise tolerance now reduced to 20 yards (around 18 metres)Noticed increasing pain to left foot over past 2 weeks—has been woken at night by pain. Pain is worse on elevation. Struggling to wiggle toes on left foot. No fevers/chills/sweats. No recent flights or long distance travel. No swelling to calves |
| Past medical/surgical/psychiatric history | Chronic obstructive pulmonary diseaseHypertensionCancer with metastases |
| Drug history (include OTC and herbal) | Ventolin: 100 mcg/dose inhaler: 2 puffs (PRN) Amlodipine: 5 mg (OD) |
| Allergies | No known drug allergies |
| Family history | No significant |
| Social history | Lives with wife and is currently caring for two grandchildren. Smoking: 40 pack-year history. Drinks 4 cans of lager daily. Independent with care needs, does own shopping and housework |
| Risk factors | SmokingHypertensionCancer |
| Differential diagnoses | Chronic lower limb ischaemiaCritical lower limb ischaemiaDeep vein thrombosis |
Key: OD=once a day; OTC=over the counter (non prescription) medicines; PRN=as needed
Mr Jones had a past medical history of hypertension and chronic obstructive pulmonary disorder (COPD), and he had recently been diagnosed with metastases from a previous cancer diagnosis. He had a 40 pack-year history of smoking and his alcohol intake was around 8 units daily. He was lightly active, with a WHO performance status of 1 (Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Cancer Research Group, 2020).
On clinical examination (see Table 2), Mr Jones's left foot was warm and perfused but became pale on elevation. The dorsalis pedis pulse was palpable bilaterally, but the posterior tibial pulse was absent to the left foot. Femoral and popliteal pulses were also present bilaterally. There was reduced movement and sensation to the left foot compared with the right. The skin on the left toes was blanching with a prolonged capillary refill time of 5 seconds. Following assessment by the vascular consultant surgeon, the foot was deemed to be viable. A diagnosis of chronic lower limb ischaemia was made against differentials of critical limb ischaemia or deep vein thrombosis.
Table 2. Case study: patient investigations and management
| Investigations/management | Details |
|---|---|
| Investigations and examination findings | Left foot warm and perfused, became pale on elevation. Palpable DP pulse but not PT. Femoral and popliteal pulses present. All pulses present to right foot and legReduced movement to left toes and reduced sensation to left foot compared with right. Left toes blanching, reduced capillary refill time to 5 seconds. No other abnormal findings at systemic review. Vascular consultant surgeon deemed foot to be viableMRA both lower limbs (radiological report):Right leg: there is a tight stenotic segment of the right external iliac artery proximally and a moderate stenosis of internal iliac artery origin. There is a tiny proximal stump of SFA above a 35 cm long SFA occlusion. The profunda remains widely patent and well collateralisedThe above-knee popliteal artery reconstitutes via collaterals and there are at least 2 moderate stenoses above the knee joint. There is 2 vessel run off with a dominate anterior tibial. The peroneal artery is stenosed proximallyLeft: There is a linear filling defect within the left common iliac artery that may represent an infected flap. There are a couple of at least moderate stenoses of the proximal and distal left external iliac artery, the latter being web-like. There is a good calibre common femoral artery. There is a short SFA stump above a 35 cm long occlusion. The profunda is patent with some distal stenoses. The above knee popliteal artery reconstitutes via collateral. There are moderate stenoses of the popliteal artery at the level of the knee joint. There is severe tibial disease. The anterior tibial is patent from its origin but tightly stenosed with a collateral. There is an occlusion of the TP trunk but collateral filling of a good peroneal artery beyond this |
| Potential management/referrals/communication | Discussed in multidisciplinary team meetingReferred for angioplasty and stenting to left iliac arteryGraft surveillance follow upMay need to consider femoral-popliteal bypass surgery if angioplasty failsReferred to smoking-cessation serviceTreated medically with dual antiplatelet therapy |
Key: DP=dorsalis pedis; PT=posterior tibial; MRA=magnetic resonance angiogram; SFA=superficial femoral artery; TP=tibioperoneal
A magnetic resonance angiogram (MRA) was performed and showed multiple areas of advanced atherosclerotic disease and stenoses to the left leg. The most significant findings included a 35 cm long occlusion originating in the superior femoral artery and extending distally along the vessel, and severe tibial disease with collateral circulation. There was occlusion of the tibioperoneal trunk but collateral filling of a patent peroneal artery beyond this.
The case was discussed at the vascular multidisciplinary team (MDT) meeting for consideration of a management plan. A diagnosis of COPD put the patient at a higher anaesthetic risk, and the active presence of malignant metastases would mean any bypass grafting would be likely to fail. It was therefore decided that the patient should undergo an angioplasty with stenting to the left iliac artery and subsequent surveillance to be arranged. He was started on long-term dual oral antiplatelet and statin therapy for further disease prevention.
Discussion
This case study has been presented as an example of the complexities surrounding the management of chronic limb ischaemia in secondary care settings and aims to provide some insight into the factors taken into consideration during the decision-making process. Invariably, the issues surrounding treatment options are multifactorial owing to the presence of multiple comorbidities as a result of PAD and the prevalence of other diseases associated with the aforementioned risk factors (Coughlin, 2019b). Typically, PAD is diagnosed and managed in primary healthcare settings, and so admission to hospital heralds the advanced progression of the disease to the point where a limb is threatened (Golledge et al, 2018).
The patient described in the case study initially presented with intermittent claudication (IC) that had progressed to experiencing pain at rest. IC is the result of reduced blood flow and tissue perfusion that cannot meet the metabolic demands of the exercising muscle groups (Mylankal and Fitridge, 2019). This is characterised as severe cramping pain at a predictable time interval after starting exercise and is quickly relieved by rest (Nickinson and Bown, 2019). Normal arterial physiology dictates that laminar blood flow in combination with vasodilation allows for increased oxygen to be delivered to the exercising muscle. Arterial plaques cause turbulence to blood flow and restrict the expansion of arterioles, resulting in local tissue hypoxia and pain (Hiatt et al, 2015). On review of any patient with IC, the specific site of claudication pain should be documented during assessment, as it can be used to identify the point of atherosclerotic occlusion, with pain in the calf muscle indicating femoropopliteal disease (Mylankal and Fitridge, 2019).
History taking
Methodical history taking in conjunction with effective communication skills are vital when identifying a diagnosis of chronic leg ischaemia from the potential differentials. Pain at rest is indicative of multilevel atherosclerotic disease that has progressed to the point where blood flow can no longer meet the basal metabolic needs (Nickinson and Bown, 2018) and is a red flag symptom for potential critical limb ischaemia, a vascular emergency (Mylankal and Fitridge, 2019). Mr Jones reported being woken by severe pain at night, for which he found some relief in allowing his left leg to hang out of the bed. This was likely caused by the reduction in gravitational influence on perfusion of the lower extremities that is encountered when the limb is elevated (Nickinson and Bown, 2018).
Arteriogenesis
The preserved perfusion could have been due to the formation of collateral circulation formed as a product of macrovascular compensation (Krishna et al, 2015). Shear stress caused by turbulent blood flow through the area of stenosis increases the production of nitric oxide (NO), which in turn promotes the enlargement of existing collateral arteries, termed arteriogenesis (Krishna et al, 2015). As the disease process progresses, additional compensatory mechanisms are required to maintain tissue perfusion by angiogenesis. Increasing levels of hypoxia stimulates the release of specific growth factors, namely vascular endothelial growth factor (VEGF) and hypoxia inducible factor (HIF)-1a. These promote the synthesis of new vessels from the surrounding capillary beds, (Krishna et al, 2015).
As a consequence of continued exposure to risk factors and disease progression, these compensatory measures fail, resulting in inadequate tissue perfusion and rest pain. In the advanced stage, tissue hypoxia can extend to the skin and subcutaneous layers, affecting the blood and nerve supply and resulting in critical limb ischaemia. This is characterised by a lower limb that is cold, pale and painful with severe paralysis and possible gangrene (Hiatt et al, 2015). It was considered that this patient presented at a time when the macrovascular compensation was beginning to fail, resulting in pain at rest, but was still able to maintain a degree of tissue perfusion.
Assessment and monitoring
When nursing this cohort of patients, frequent assessment of the affected limb is vital when monitoring on the ward in order to facilitate the early detection of critical limb ischaemia. Regular documentation should be made of the appearance of the limb, including colour, warmth and whether pulses are present or absent (Atkin et al, 2015). Consideration should also be given to the increased risk of tissue breakdown and ulceration to the affected limb as a result of poor perfusion (Hall, 2010). Frequent interventions for the same patient during a shift affords opportunities for regular assessment of the affected limb that is unique to the nursing team. Nurses are therefore vital to the early detection and escalation of any skin changes that may signal a deterioration in condition.
In Mr Jones's case, chronic limb ischaemia was confirmed by MRA, which showed extensive multilevel disease with collateral circulation. Discussion at the MDT meeting led to the decision to perform left iliac artery stenting via angioplasty.
Health promotion
The emphasis of modern health care is moving away from treatment and more towards health promotion, to prevent development of disease or its further deterioration (Bright and Burdett, 2019). This is evidenced in the NHS Long Term Plan (NHS England/NHS Improvement, 2019), which focuses heavily on preventive care, claiming that this could save up to 500 000 lives per year (NHS England/NHS Improvement, 2019). Health promotion and lifestyle advice is paramount in ensuring the best outcomes for patients with PAD (Donnelly, 2015) and is endorsed by the National Institute for Health and Care Excellence (NICE) guidelines for PAD (NICE, 2020). Nurses are ideally placed for encouraging lifestyle changes and signposting to support services. Active participation from the patient is imperative for any potential modifications, which should be individualised as part of a holistic care plan, to ensure patient engagement and compliance (Hall, 2010).
This is supported by the nature of nursing education and training, which is heavily focused on patient-centred care as being the primary objective in order to provide high-quality care (Fix et al, 2017). The nursing Fundamentals of Care (FOC) framework addresses the provision of essential care, such as hydration, nutrition and elimination, while incorporating three core elements. These are the development of a meaningful nurse-patient relationship, integrating FOC into the care plan and ensuring the care environment is favourable to FOC (Kitson, 2018). The common denominator within these elements has been identified as communication (Avallin et al, 2020), and provides nurses with a sound foundation for skills in health promotion (Bright and Burdett, 2019).
The working patterns of nursing staff compared with their medical colleagues also provide a more advantageous platform for health promotion and assessment. Repeated encounters with the same patient throughout the shift give opportunities to build rapport, and offer the chance of more meaningful conversations that can help make the patient feel more included and respected (Avallin et al, 2020).
In the case of Mr Jones, effective communication skills were vital to educate the patient on the detrimental influence his smoking was having on the progression of PAD within his lower limbs. Smoking cessation should be promoted as a dual modality of behavioural therapy as well as nicotine replacement for maximum chance of success (Atkin et al, 2015). On discussion with the patient, he had come to the conclusion that smoking was now having a significant impact on his health and was keen to use the services offered to him.
Treatment of PAD
Treatment of PAD can be problematic, with repeated attempts at revascularisation ultimately resulting in amputation (Krishna et al, 2015). Controversy surrounds the initial treatment for revascularisation, namely intravascular bypass surgery or endovascular angioplasty. Limited evidence is available as to which method should be employed as the primary intervention.
The largest and only randomised controlled trial (RCT) undertaken in the UK to date is the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial. For this research, 452 patients were randomly assigned either vascular bypass surgery or angioplasty as first-line treatment for severe lower limb ischaemia (Bradbury et al, 2010). Outcomes were measured by overall survival after 2 years, as well as limb salvage and the need for further intervention. Results significantly favoured bypass surgery, with patients having undergone angioplasty being associated with early failure rate and further progression to bypass surgery (Bradbury et al, 2010). However, there were a number of influencing variables, such as the site of vascular disease and whether surgical grafts were prosthetic or taken from a vein, with vein grafts proving to give superior amputation free and overall survival rates (Bradbury et al, 2010).
The BASIL trial results are disputed by some clinicians who argue that current endovascular practices far surpass the results reflected in BASIL (Meecham et al, 2019). This view is supported by the Belgian-Italian trial, BRAVISSIMO (de Donato et al, 2015), investigating Abbott vascular iliac stents in the treatment of Trans-Atlantic Inter-Society Consensus (TASC) A, B, C and D iliac lesions (Hardman et al, 2014). The trial recommended endovascular intervention as first-line treatment (de Donato et al, 2015). However, it is worth noting that the BRAVISSIMO trial was not randomised, raising the possibility of bias.
The Claudication: Exercise Versus Endoluminal Revascularisation (CLEVER) trial was a randomised controlled trial investigating the effect of supervised exercise therapy (SET) in combination with best medical treatment on the symptoms of IC (Murphy et al, 2015). The aim of the programme was to gradually increase exercise tolerance in participants with symptoms of IC and compare these participants with those treated with endovascular intervention. They found no discernible differences in the improvement of symptoms and quality of life between the two groups, and both groups were significantly superior to the control group receiving best medical treatment only (Murphy et al, 2015). These findings have been since corroborated by other studies (Varcoe, 2019). Despite this evidence and the added benefits SET would bring to the reduction of other risk factors such as hypertension and obesity, SET is not commonly employed as a first-line treatment strategy in practice. This could be due to the high labour intensity of SET and delay in tangible improvement in symptoms (Varcoe, 2019).
There remains a worldwide propensity for endovascular stenting as initial therapy (Meecham et al, 2019). Several factors may contribute to this decision making. Patients with vascular disease are often advanced in age, with multiple comorbidities, and consequently have increased anaesthetic risks (Telford, 2019). Endovascular revascularisation can negate the need for general anaesthesia and is associated with a more instantaneous relief of symptoms, coupled with reduced length of stay in hospital (Varcoe, 2019), and so could be the treatment of choice for many patients.
Treatment decision making
The overriding factor in the decision-making process was the fact that the Mr Jones had advanced metastatic disease. This scenario has been found to have a significantly high failure rate following revascularisation due to malignancy-induced hypercoagulopathy, principally due to the aptitude of tumour cells to activate the clotting cascade (Mitrugno et al, 2016). For this reason, it was agreed at the MDT meeting that bypass grafting was almost certainly going to fail as a result of restenosis. Although this was also true for the stent, the angioplasty offered a less invasive option to relieve his symptoms and improve his quality of life for the immediate future. In view of the patient's uncertain prognosis, more invasive treatment was deemed not to be in his best interests.
Further research
To better rationalise treatment options, research is currently under way looking into the role of biomarkers to diagnose PAD, its severity and likely outcomes of certain therapies (Krishna et al, 2015). Although relationships have been established between various biomarkers and the severity of PAD, study samples have tended to be small and the quality of evidence low (Krishna et al, 2015). However, the potential impact of this research is substantial, as it raises the possibility of calculating the probable outcomes of certain therapies in an individual, thereby significantly assisting in the selection of individualised intervention (Paquissi, 2016).
Conclusion
PAD is an increasingly prevalent disease with a wide spectrum of severity. Diagnosis is often not detected until symptoms manifest themselves, as with the case of chronic limb ischaemia as described above. The existence of comorbidities and longstanding risk factors are a common theme among this patient group and consequently treatment is usually problematic. Although advances in radiological technology and biochemical screening offer the potential for earlier intervention and improved survival rates, a review of the evidence presented above adds weight to the argument that commitment to more conservative approaches, such as exercise therapy and health promotion, could have more sustainable, longer-term benefits for patients with chronic limb ischaemia. Therefore, emphasis should remain on the management and prevention of modifiable risk factors, for which the nurse's role is an integral part to ensure success.
KEY POINTS
- Chronic limb ischaemia is a consequence of peripheral artery disease (PAD)
- PAD is a chronic inflammatory process causing the formation of atheromatous plaques
- There are modifiable and non-modifiable causes of PAD
- Diagnosis is often not made until chronic limb ischaemia occurs
- Surgical intervention for PAD can be problematic
CPD reflective questions
- Why are the risk factors for peripheral artery disease (PAD) similar to coronary artery disease?
- Why is it important to take a comprehensive history of patients with PAD and what signs or symptoms would you consider to be ‘red flags’?
- When assessing limbs of patients with PAD, what should you consider documenting and why is this important?
- Nurses are well placed to offer health promotion and lifestyle advice. What advice would you consider offering to someone newly diagnosed with PAD?