Peripheral artery disease in the lower extremities - prevalence and epidemiology

Keywords

ankle brachial index (ABI), lower extremity artery disease (LEAD), peripheral artery disease (PAD)

Introduction

The ankle-brachial index (ABI) is the ratio of the systolic blood pressure at the ankle divided by systolic pressure at the upper arm. The blood pressure measurement is taken after the patient has been at rest in the supine position for about 10 minutes. The normal range of ABI lies between 0.9 and 1.4. The measurement is non-invasive and simple. This is the easiest way to detect the presence or absence of atherosclerotic peripheral arterial disease (PAD). In this article, the discussions for all practical purposes will be on “lower extremity artery disease” (LEAD).

An ABI value of 1.1 to 1.4 is good evidence of normal arterial flow. The percentage of the population affected by PAD/LEAD is very significant; however, a lot of apathy still remains on the part of clinicians to determine ABI routinely, particularly in patients with the modifiable risk factors of tobacco smoking, hypertension, diabetes and dyslipidaemia. These are all (either singly or in combination) significant risk factors for PAD/LEAD. The determination of an ABI of less than 0.9 is a reliable indicator of the presence of lower extremity PAD, indicating athero-occlusive arterial disease. This applies to both symptomatic as well as asymptomatic PAD/LEAD patients.

Although the diagnostic accuracy of computed tomography (CT) angiography is the gold standard for the detection of PAD [1], adding other diagnostic tools after ABI such as treadmill tests, ultrasound imaging, MRI imaging and digital subtraction angiography, is also invaluable for detecting PAD/LEAD [2].

Prevalence and epidemiology

Among individuals aged 40 years and older, the prevalence of LEAD is 4.3%, ranging from 3.1% to 5.5%. However, the prevalence in individuals with diabetes ranges from 20% to 30% [3]. Here lies the enormous importance of promoting the use of the ABI in regular clinical practice for early detection.

It is crucial to know that “intermittent claudication” does not reliably indicate the presence of PAD/LEAD. Hence, depending on this symptom of the peripheral occlusive vascular disease is of low sensitivity. Both sensitivity and specificity improve dramatically with the help of the most useful non-invasive test – the ABI. This is very helpful in screening for PAD of the lower extremities. An ABI of 0.9 or lower is indicative of PAD. In high-risk patients such as smokers, hypertensives and diabetics, determination of ABI should be routine practice by primary healthcare professionals. This will not only detect PAD but also add quality of life to the patients with the institution of therapeutic measures. The most common reason for not checking the ABI is the lack of practice of using Doppler ultrasound for better and accurate measurement of both brachial and ankle systolic pressures. All clinics should have Doppler instruments, and all clinicians should be trained on how to use this device.

ABI - the technical aspects of daily practice  

In regular practice, ABI testing is not carried out routinely. It is very much needed for those with comorbidities which are known to cause atherosclerotic vascular diseases. It is vital to have an idea of PAD and to understand that this is related to increased cardiovascular morbidity and mortality. However, PAD/LEAD is grossly underdiagnosed, as an estimation of ABI is not part of regular practice. Ironically, most clinicians believe that the ABI is only useful in the diagnosis and management of symptomatic PAD.

The fundamental limitations of using the ABI include time constraints (average time per patient is 10-15 minutes) in dealing with patients in the outpatient departments, lack of reimbursement by the insurance companies, and lack of availability of skilled staff (paramedics). Overall, most clinicians believe that ABI is equal to, or more useful than other widely available and reimbursable screening tests [4].

The ABI determination procedure is straightforward compared to coronary artery calcium scoring, measurement of carotid intima-media thickness (IMT), high-sensitivity C-reactive protein (hs-CRP), etc. The procedure is simple and can be carried out by a suitably trained healthcare professional. Issues such as reimbursement and time duration for ABI are the primary barriers to its widespread use. In the Indian scenario, the issue of reimbursement is not as important as it is in the western world. In our setting, this is mainly related to inadequate knowledge about the significance of ABI. In particular, the enormous importance of the detection of PAD and its high predictability concerning total risk of cardiovascular (CV) mortality is grossly underestimated.

Possible causes of mistakes

The ABI is a non-invasive, simple, and inexpensive test with an excellent diagnostic performance if carried out and determined by well-trained professionals. The measurement of ABI is dependent on the training and experience of the observer, which may be difficult in primary care practice. Moreover, there are various ways to perform the measurement and to calculate the index. Arm pressures can be measured in one or both arms, and ankle pressures at the posterior tibial and at the dorsal pedal artery.

In situations where the systolic pressures of two arms or two ankle arteries are measured, the highest, average, or lowest pressure can be used for calculating the index. Theoretically, this results in at least 25 different possible combinations to calculate the ABI [5]. Moreover, comparing ABI measurements in primary care practice with those in the vascular laboratory, with attention to the method used for blood pressure measurement and calculation of the index, the results are highly variable. Also, the techniques and ways to measure and calculate the ABI need to be well defined to avoid possible mistakes. To obtain error-free results, guidelines for determining the ABI with a hand-held Doppler instrument and a training programme are necessary.

False-negative results are seen in patients with non-compressible vessels. Hardening of vessels can cause a false high pressure and even be the cause of missing a real low pressure. It is also a strong marker of generalised atherosclerosis and CV risk. An ABI ≤0.90 is associated on average with a twofold to threefold increased risk of total and CV death. An ABI >1.40 represents arterial stiffening (medial arterial calcification) and is also associated with a higher risk of CV events and mortality. It is highly prevalent in elderly patients, mostly in those with diabetes or chronic kidney disease (CKD). When added to a risk score, ABI enables the risk estimation to be upgraded in one third and one fifth of “low-risk” women and men, respectively. It is a valid method of CV risk assessment in diverse ethnic groups, independent of risk factors. In contrast to the coronary calcium score and carotid intima-media thickness, ABI is inexpensive, and minimally time-consuming [2]. The combination of ABI, percentage of mean arterial pressure (%MAP) and upstroke time (UT) achieves higher sensitivity and accuracy than ABI alone for early PAD/LEAD lesions, compared to CT angiography [1].

ABI - specificity and sensitivity

In diagnosing PAD, low ankle pressure ABI has better sensitivity and overall accuracy than high ankle pressure ABI [6]. An ABI less than 0.9 has a 75% sensitivity and 86% specificity to diagnose LEAD. Its sensitivity is poorer in patients with diabetes or end-stage CKD because of medial calcification [2]. Also, an ABI of 0.9 or less is believed to be associated with 50% or higher vessel stenosis.

The leading symptom of PAD/LEAD is intermittent claudication (IC) which is the cardinal feature of peripheral arterial (occlusive) disease. As this is a subjective finding, there is an immense limitation in diagnosing PAD based only on IC and it is difficult to measure reliably. Both the WHO/Rose Questionnaire and the Edinburgh Questionnaire have shown responses with low sensitivity and therefore they underestimate the actual prevalence of PAD. Although it is essential to examine the patient's peripheral pulses, which is a more sensitive measure, it is less specific than the questionnaires. The most useful non-invasive test is ABI determination. The prevalence of IC is 3% to 6% in men of 60 years of age, and the prevalence increases with further increases in age. The prevalence of asymptomatic PAD may be as high as 20% in the adult population using non-invasive testing. This is important because PAD, whether symptomatic or asymptomatic, is a serious risk factor for cardiovascular morbidity and mortality [7].

Correlation of ABI to total risk

Life-threatening CV events such as myocardial infarction (MI) and cerebrovascular accidents (CVA, stroke) may afflict a person without a pre-existing CV disorder. Traditionally, primary emphasis is given to assessing the Framingham Risk Score (FRS) for those who are diabetic, hypertensive, those with dyslipidaemia and smokers. The FRS has limited accuracy, either overestimating the risk in low-risk populations or underestimating the risk in high-risk populations. Subsequently, the inclusion of high sensitivity C-reactive protein
(hs-CRP), coronary artery calcium scoring (CAC), carotid IMT and the ABI have improved the predictability of CV events in asymptomatic atherosclerotic patients. Of all these, the ABI is quickest and easiest to measure.

Although ABI indicates a diagnosis of PAD in the legs, it is also an indicator of generalised atherosclerosis. Lower levels (<0.9) have been associated with higher rates of concomitant coronary and cerebrovascular disease. The presence of other CV risk factors and a low ABI have been related to an increased incidence of total mortality, myocardial infarction and stroke. These increased relative risks have been shown to be independent of baseline cardiovascular disease and risk factors, suggesting that the ABI might have an independent role in predicting cardiovascular events.

When combined with the FRS, a low ABI (≤0.9) approximately doubled the risk of total mortality, cardiovascular mortality and major coronary events across all Framingham risk categories [8]. The association between high ABI and mortality was similar to that of low ABI and mortality, highlighting a U-shaped association between this non-invasive measure of PAD and mortality risk. The upper limit of normal ABI should not exceed 1.40 [9]. High values of ABI (greater than 1.40) are also indicative of increased risk of total CV morbidity and mortality. This could be related to poor arterial compressibility, resulting from stiffness and calcification which may occur more commonly in those with diabetes, hypertension, ageing, etc. (the prevalence of a low ABI is known to increase substantially with age). So, the high-risk group broadly remains between less than 0.9 and more than 1.4, which is widely accepted. Findings of the Strong Heart Study [9], Cardiovascular Health Study [10] and Multi-Ethnic Study of Atherosclerosis [11] are that the relationship between ABI and cardiovascular disease is non-linear and varies across the range of ABI. More than 95% of patients with PAD/LEAD have at least one CV risk factor, and most have multiple risk factors. More than one third of patients have significant coronary artery disease, and 25% have carotid artery disease. As a result, the risk of heart attack, stroke and death is increased severalfold in patients with PAD/LEAD.

A role for recording velocity and separating forward and backward flow

Although the ABI measurement is much easier and has better sensitivity and specificity for detecting LEAD, there are also other methods such as measuring the velocity of blood flow, namely the peak systolic velocity (PSV), for diagnosing LEAD, particularly to get information for detecting stenotic lesions without too much calcification. This is done with the help of Doppler ultrasound. The normal values of PSV are 80-100 cm/sec in femoral arteries, 60-80 cm/sec in popliteal arteries and 40-60 cm/sec in tibial arteries. Interpretation related to recording velocity are as follows:

• Less than 30% increase in PSV and forward flow with normal arterial triphasic waveform is related to mild disease of <20% arterial stenosis.
• 30% to 100% increase in PSV and a backward or reverse flow component indicates moderate disease of 20-50% arterial stenosis.
• More than 100% increase in PSV and loss of backward or reverse flow and the monophasic arterial waveform is the most severe category with 50 to 99% arterial stenosis [12]. Measuring forward and backward flow may have some importance from the surgical viewpoint in acute ischaemic settings. It is particularly useful to know the backward flow as it gives information about the status of collateral circulation, related to the success of surgical intervention of the arterial stenosis and postoperative outcomes. It is pertinent to mention here that in PAD/LEAD, factors such as vascular calcium depositions and increased inflammatory changes result in stiffening and loss of elastic recoil. The measurement of velocity and forward and backward flow does not have any practical importance as far as the diagnosis and management of LEAD is concerned.

Conclusion

Given its excellent predictability concerning future cardiovascular risks, the ABI, if carried out correctly, is very useful in clinical practice. It is essential to make clinicians aware of the importance of ABI determination during the physical examination. This is because ABI measurement is simple and convenient, with a high sensitivity and specificity for PAD/LEAD. The authors’ experience in cardiology practice over three decades or more shows that ABI is very much undervalued by all, both in individual clinics and in tertiary hospitals. In almost all cases, the ABI measurement is performed after development of symptoms such as intermittent claudication in the lower limbs.

ABI should be made mandatory for any patients who have at least one of the four risk factors – smoking addiction, hypertension, diabetes or dyslipidaemia. It is of immense importance as a significant number of patients with PAD have associated coronary artery disease. However, the opposite is not true. There is a need to motivate healthcare professionals for training and education in this matter. The only gadget that is required is a handheld pocket Doppler device. As ABI is a non-invasive test and involves minimal discomfort, the patient’s acceptability will always be very high. This will be beneficial both for doctors and patients. A low ABI of less than 0.9 should motivate the medical team to adopt adequate preventive measures. Thus, it will help the high-risk group of people by preventing untimely CV events.