Sunday, May 26, 2024

Peripheral Arterial Disease: Challenges in Diagnosis and Management in Low-Income Countries

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In resource-limited settings, peripheral arterial disease (PAD) remains an inadequately characterized and appreciated condition, despite its disease burden rivaling that of coronary artery disease. Indeed, there is considerable lack of awareness in many low-income countries, with afflicted patients often seeking treatment only after presenting with advanced limb threat. PAD also carries prognostic implications for proper risk stratification of coronary and cerebrovascular disease states, making its recognition and treatment increasingly relevant not only for improvement of limb-specific outcomes, but also for reduction of cardiovascular mortality in the entire spectrum of ischemic disease. The purpose of this article is to provide contemporary information on the diagnosis and management of PAD as it pertains to resource-limited environments. Though epidemiological aspects of disease will be covered to set a context for PAD in low-income countries, detailed global burden of disease discussions are beyond the scope of this review.

Challenges in Diagnosis

In conclusion, several complex factors contribute to the challenges of diagnosing PAD in low-income countries. Understanding these issues is essential for formulating a strategy to prevent and manage this morbid and mortal condition.

Lack of awareness and education is a challenge for the management of many chronic diseases in low-income countries. It is true that PAD is under-diagnosed and under-treated worldwide, but especially so in developing countries. The general public may be unaware of the medical and cardiovascular risks associated with PAD, so those with claudication may dismiss it as part of normal aging. Even patients with critical limb ischemia may not recognize the urgency of their symptoms and seek medical attention. Public awareness campaigns and health education programs have been shown to be effective in increasing disease recognition and understanding. An example of this has been the diabetes “clear your vision” campaign in urban India, which led to a significant increase in the number of patients seeking treatment for diabetic retinopathy. Unfortunately, because PAD has not been recognized as a significant problem in low-income countries, few public and patient-directed resources are available. Physicians must also be educated on how to diagnose and manage PAD. With the exception of cardiac and renal complications, there is little outcome data to inform physicians on the severity-based management of PAD. This makes it difficult for a disease with such a high prevalence to compete with other cardiovascular conditions for the attention of limited resources.

Lack of Awareness and Education

The diagnosis of PAD in low-income countries can be challenging. The “gold standard” for diagnosis of PAD is an angiogram, but even in developed countries, this test is often not used initially, usually reserved for cases of critical ischemia or impending limb loss. The ankle-brachial pressure index (ABPI) is a simple, non-invasive test widely used for diagnosing PAD in the developed world. It is a ratio of the systolic blood pressure at the ankle to the systolic blood pressure in the arm. ABPI has been shown to be an accurate and cost-effective diagnostic tool for PAD. The cost of a Doppler machine is about 15 times that of one ABI test. A Doppler machine requires maintenance, occasional repair and replacement, whereas an ABI test requires only a sphygmomanometer and a stethoscope, both relatively cheap and durable items. Unfortunately, Doppler machines are widely unavailable in many low-income countries, making the ABPI unavailable. This is a significant obstacle to the diagnosis of PAD. Other tests, such as Magnetic Resonance Angiography (MRA) and Computerized Tomography Angiography (CTA) are often not available in countries where even basic healthcare resources are not adequately funded. Treatment of the condition cannot occur until it has been properly diagnosed, so limited access to diagnostic tools is a barrier to the management of PAD.

Limited access to diagnostic tools

Limited Access to Diagnostic Tools

Furthermore, the expense of angiography (both catheter and more modern angiography tools) often means that this diagnostic tool is unavailable to those who need it most. This is especially unfortunate given that in many of these countries, angiography is the only means of assessing the severity of PAD, and can affect financial allocation for treatment. In the absence of specific PAD diagnostic tools, it is important to remember that a simple, yet comprehensive history and physical examination can often provide the same information that might be obtained from an expensive imaging study. However, such history taking and examination is a dying art in the Western world and training in this area is limited in low-income countries.

Although early diagnosis is a fundamental aspect of optimal PAD management, this is another area where many low-income patients are disadvantaged. While the Western world enjoys a variety of imaging tools available both in and out of hospital, these tools are often non-existent in many low-income countries. For example, most peripheral CTA machines and MRIs have not made it to these countries and many rural clinics do not even have x-ray facilities. Even when such tools are available in major hospitals, their high cost means that they are often inaccessible to the average citizen. Similarly, while ABI is a simple, cost-effective means of diagnosing PAD, the equipment itself can be too expensive to be widely available in low-income countries.

Lack of Awareness and Education

Several studies have shown that large numbers of patients remain undiagnosed and unaware that they are suffering from PAD. Some studies have shown that up to 75% of patients with PAD are not aware that they have a very serious health problem and perceive the leg pain on walking as a normal sign of aging. This is in striking contrast to patients with other cardiovascular diseases who are usually very well informed about their condition. This lack of awareness is not confined to patients, as other studies have shown that in primary care, PAD patients are less likely to have their cardiovascular risk factors and co-existing atherosclerotic diseases recognized than those with other cardiovascular conditions. This seriously hampers the efforts of prevention of further atherosclerotic complications in PAD patients and the education of patients about positive lifestyle changes and activities that they can pursue without experiencing painful symptoms. This lack of awareness among patients and primary care providers is in part due to the atypical symptoms of PAD and the lack of a clear attributable cause between leg symptoms and functional impairment. The symptom of lower limb pain on exertion can be interpreted and diagnosed as many other musculoskeletal and neurological conditions and it is often the case that the patient is referred to various medical specialists before the diagnosis of PAD is made. Due to the vast differences in healthcare systems around the world, in some countries the diagnosis of PAD is only made at a very late stage when the patient presents with critical limb ischemia or an acute limb threat. During a phase III trial comparing a new medication with placebo, a Russian investigator was said to be in a paradoxical position. He was required to recruit PAD patients into the trial but said “In Russia, we have almost no PAD, because we are saving amputation for the very end”. These late diagnoses are too late for providing effective treatment to prevent disability and are a huge burden on the patient and the healthcare system. The lack of awareness and education also affects the involvement of PAD patients in decision making about their treatment. Informed decision making is vital in a progressive disease such as PAD where the natural history of symptoms can fluctuate and there are a range of medical and invasive treatment options. Patients who are unaware of their condition and the cause of symptoms may have different treatment goals and expectations compared to those who have a good understanding. Medical and endovascular treatments for PAD have advanced and evolved considerably but it has been several years since there has been a new medication for intermittent claudication and still many trials of new medications or revascularization procedures continue to have negative results. This has made studies to measure quality of life and functional outcomes essential in determining the most appropriate treatment for individual patients. Studies have shown that PAD patients have lesser quality of life and functional impairment compared to patients with other cardiovascular conditions and measures of severity of PAD such as the ankle brachial index have been shown to be a strong predictor of all-cause and cardiovascular mortality. However, due to the lack of awareness about these issues, patients may not be given the opportunity to consider their symptoms in the context of systemic disease and the potential benefits of various treatments.

Challenges in Management

Limited availability of treatment options. Critical limb ischemia (CLI) is an advanced stage of PAD and is characterized by chronic ischemic rest pain, ulcers, or gangrene in one or both legs or feet. It is included under symptomatic PAD and has a high rate of morbidity and mortality. It is estimated that CLI affects 1-1.5% of the population in western nations with an increase in prevalence with age. Those with CLI have a poor prognosis with a 25% amputation rate and 25% mortality rate within 6 months of diagnosis. Amputation often leads to loss of independence, impaired quality of life, and decreased life expectancy. In many developing countries, there is a lack of awareness of CLI and its consequences, such that many cases are not recognized. This is a result of insufficient medical education of CLI and poor understanding of the natural history of the disease. This leads to a failure to identify CLI in its early stages and a high threshold to refer to a vascular specialist. It has been predicted that the global prevalence of CLI will increase by 29.3% in 2025, with the greatest increase in the poorest regions of the world. This will lead to an alarming increase in amputation and mortality rates in developing countries. CLI and PAD in general require a coordinated healthcare approach with interventions from primary care physicians, diabetologists, orthopedists, infectious disease service, cardiothoracic and vascular surgeons. Because of the large variety of healthcare providers involved in diagnosing and treating PAD, a multidisciplinary approach is often lacking in developing countries. This can result in poor continuity of care and a lack of consensus on the optimal approach for patient management. Overall, the lack of awareness and medical education of PAD in developing countries contributes to underdiagnosis and undertreatment of the disease. This results in a disproportionately high incidence of severe PAD in developing countries, which is associated with high morbidity, mortality, and economic burden.

Limited Availability of Treatment Options

Peripheral artery disease (PAD) is a common manifestation of atherosclerosis and results in significant morbidity and mortality, with impaired quality of life if not addressed properly. Although PAD can be managed medically or with an intervention, many patients, particularly those in low-income countries, are left untreated. Patients with intermittent claudication have a mortality rate at 5 years similar to those with colon cancer or non-Hodgkin’s lymphoma. Unfortunately, peripheral artery disease receives considerably less attention than these conditions, with roughly 5-10% of patients receiving percutaneous revascularization or surgical bypass. A recent analysis found that only 1 in 4 Medicare patients with claudication was referred to a cardiologist or cardiovascular specialist. High-risk patients who are often unaware they have a serious, life-threatening disease are the most undertreated. This analysis included Medicare patients, and these numbers are likely much worse among patients in lower socioeconomic classes. These patients are often undertreated because of their older age, multiple comorbidities, and the lack of availability of medical facilities in their particular area.

Financial Constraints and Affordability

Evidence for this is mostly extrapolated from major amputation rates in the Third World, which are the highest in the world at 40-60 per 100,000 population, at least 10 times higher than those reported in the Western world. The dramatic failure in preventative health care for PAD is best illustrated by the continued high rates of major limb amputation. If translated to similar statistics in the developed world, the 40-60 amputations per 100,000 people would be a disaster. Health economic evaluations estimate the cost of secondary prevention with statins, angiotensin converting enzyme inhibitors, antiplatelet therapy, supervised exercise, and revascularization at $20,000-25,000 per QALY. Even with the highest endovascular or surgical revascularization procedures for intermittent claudication, it is still cost-effective at $50,000 per QALY. High amputation rates reveal that such costs are currently unaffordable in poverty-stricken communities. With the cheapest yet effective revascularization procedures being at least 40 times more expensive than major limb amputation, basic health care priorities advocate that less limb and life-threatening treatment would be more beneficial. Control of infection, wound management, and relief of pain can be the most humane and cost-effective management in advanced PAD. Resulting in palliative care with a high quality of life can be achieved by a large proportion of patients. Unfortunately, many of these cheap and simple treatments can still remain unavailable in Third World communities due to a lack of resources and poor healthcare infrastructure. This ultimately leads to a continuing cycle of repeated amputation in PAD patients.

Lack of Healthcare Infrastructure

The Western world has seen the development of diagnosis and treatment guidelines such as the Edinburgh Claudication Questionnaire, the ankle brachial pressure index, and angiography. When deciding which therapy suits the patient best, a multidisciplinary discussion including intervention radiologists, vascular surgeons, and medical officers is needed. The availability of these tests and medical officers willing to specialize in vascular medicine is lacking in low-income countries. Primarily due to a lack of vascular services and community unawareness of the disease, what little past research there has been done shows that less than 10% of PAD patients are ever referred to a vascular specialist. Combined with an environment that breeds infectious diseases and promotes smoking, the need for amputation due to severe cases of PAD is much higher in these countries. Unfortunately, there is a lack of suitable amputation procedures causing the death rate following amputation to be as high as 50% within 12 months. Post-procedure care is also inadequate as it is shown that race is a factor in determining whether a patient will be referred to a physical medicine and rehabilitation service following an amputation. This is a disturbing revelation that suggests racial discrimination in the medical field.

Conclusion

A primary antiplatelet agent reduced the risk of major cardiovascular events in symptomatic PAD patients with no prior myocardial infarction or stroke. It can be reduced by a simple regimen of aspirin. However, several trials that have evaluated other treatments in PAD have provided inconclusive or disappointing results. Consideration of specific populations and clearer definition and increased awareness of the disease may aid more informative future research. It is important that future PAD patients are not denied participation in generic cardiovascular trials, provided the complication of their PAD makes them eligible for the trial inclusion criteria.

There is a significant burden of PAD in low-income countries. The lack of reliable diagnostic tools means that many are diagnosed when the disease is advanced and limb salvage is the only option. Key to reducing the burden of this disease will be primary prevention. This would require identification of high-risk groups and raising awareness. Smoking cessation is an absolute necessity. In a country such as India, where 50% of men smoke and there is a high rate of smokeless tobacco usage, this is a monumental task. Aggressive treatment of diabetes and hypertension would also likely reduce the incidence of PAD. The cost-effectiveness of such an approach has not been formally studied but it is likely to be so. If successful, a significant amount of suffering and loss of the useful capacity to work to millions may be prevented.

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