The Ankle-Brachial Pressure Index and a Standardized Questionnaire Are Easy and Useful Tools to Detect Peripheral Arterial Disease in Non-Claudicating Patients at High Risk

By Sprynger, M Fassotte, C; Verhaeghe, R

Aim. This observational study (Survey of Peripheral Arterial Disease Epidemiology, SPADE) evaluated the prevalence of asymptomatic peripheral arterial disease (PAD) in general practice. Methods. PAD was determined as an ankle-brachial pressure index (ABI) <0.9 measured with Doppler ultrasound. Included patients had a history of ischemic events and/or risk factors for PAD, but no spontaneous complaints of intermittent claudication. Patients with an ABI <0.9 filled in a standardized questionnaire and their drug use was registered. A total of 4 536 patients was included.

Results. The prevalence of PAD was 18.7% for the total population, 26.5% for those with a history of ischemic events and 15.2% for those without such history. The prevalence increased with age, but was independent of gender. A standard questionnaire revealed leg pain when walking uphill or when hurrying in 2/3 of patients with an ABI <0.9 and in 45% criteria for claudication were met.

Conclusion. ABI detects PAD in a considerable number of asymptomatic patients at increased risk and followed in general practice. When properly questioned almost half of these patients appear to have intermittent claudication.

[Int Angiol 2007;26:239-44]

Key words: Blood pressure monitors – Questionnaires – Peripheral arterial disease.

Peripheral arterial disease (PAD) is a progressive disease caused by atherothrombotic (sub-) occlusion of the arteries of the lower limb, leading to inadequate blood perfusion. Patients with PAD have a 3-4 fold increased risk of myocardial infarction (MI) and ischemic stroke (IS).1,2 As MI and IS are among the most important causes of death in the western world, it is of the utmost importance to identify these patients.

Many patients with PAD go undetected as long as they remain asymptomatic. Nevertheless most patients at augmented risk of PAD regularly consult their family doctor. This repeated contact creates an opportunity for PAD screening and detection.

The ankle-brachial index (ABI) is a non-invasive inexpensive procedure to accurately identify patients with PAD. Patients with an ABI <0.9 are considered to have PAD associated with an increased risk of cardiovascular ischemic events.3 A systematic screening for PAD using ABI in asymptomatic high-risk patients may be the basis for an adapted management to prevent future ischemic complications.

This Survey of Peripheral Arterial Disease Epidemiology (SPADE) was performed in general practice to determine the prevalence of PAD under real life conditions in an asymptomatic Belgian population at high risk.

Materials and methods

This study is an observational study in 430 general practitioners’ (GP) offices in Belgium. The GP were asked to screen 20 consecutive patients with a previous ischemic event (MI, stroke- transient ischemic attack, TIA) or with PAD risk factors (arterial hypertension, diabetes mellitus, hypercholesterolemia, smoking, family history of PAD). A history of percutaneous transluminal coronary angioplasty (PTCA) or of coronary artery bypass graft (CABG) in the absence of an ischemic event was also counted as a risk factor. Patients >55 years needed at least one risk factor, those <55 years needed at least two.

Prior to the start of the study, all participating GP attended a workshop to explain the aim and design of the study and to learn appropriate use of the Doppler instrument.

Ankle-brachial index measurement

Measurement of ABI was performed with the patient supine; systolic blood pressure was recorded at both arms and both ankles with a hand-held Doppler ultrasound device (HADECO BIDOP ES-100V3 Doppler) using an 8 MHz probe. ABI was calculated for each leg by dividing the highest ankle pressure by the highest pressure of both arms. Patients with an ABI <0.9 were diagnosed as having PAD.3

Drug treatment

Drug treatments related to atherothrombotic ischemic events and to risk factors were registered.

Questionnaire

The Edinburgh Claudication Questionnaire of Leng and Fowkes, an improved version of the WHO/Rose Questionnaire, was filled in for every patient with an ABI <0.9 to evaluate possible intermittent claudication.4

Sample size considerations

A positive diagnosis of PAD (ABI <0.9) in 8 600 patients with a prevalence of 20% was estimated with a precision (standard deviation) of 0.44%, resulting in a 95% confidence interval around this estimate of 19.1-20.9%, with a length of 1.8%.

Statistical analysis

Descriptive statistics were used for continuous variables, and included the mean, median, standard deviation, minimum, maximum, 95% confidence interval on the mean, number of available observations, and number of missing observations. Frequency distributions are used for ordinal and nominal variables and include numbers and percentages of each of the scores or categories. For key variables, 95% confidence interval on the percentage was calculated. The statistical analysis was performed on the basis of all patients for whom a case report form was completed (total population).

Ethical aspects

The study protocol received approval of two Ethical Committees: for the French speaking GP from the University Center for General Practice (Centre Universitaire des Medecins Generalistes, CUMG, Universite Libre de Bruxelles) and for the Flemish speaking GP from the Institute for General Practice (Vlaams Huisartsen Instituut, VHI, Vrije Universiteit Brussels). Informed consent was obtained from all participating patients.

Results

Baseline characteristics

In total, data on 4 582 patients were collected. Forty-six patients did not fulfill the inclusion criteria and were excluded from the analysis, resulting in 4 536 patients or 52.7% of the number projected.

The mean age of the total population was 67 years (range 18-98 years); 60% was male and 40% female. The age and sex distribution is shown in Table I. Mean systolic and diastolic blood pressure values were 142.1 mmHg (90-220 mmHg) and 81.7 mmHg (50-157 mmHg), respectively. A total of 1 440 patients (31.8%) had a history of at least one ischemic event, 102 (7.1%) of them had at least two events. The number and type of previous ischemic events is shown in Table II.

About 75% of the MI patients were male and 25% were female. No gender differences were observed for stroke and TIA. Relatively more patients with previous atherothrombotic ischemic events were observed in the highest age groups.

Table III shows the distribution of risk factors for PAD in patients with a history of MI, stroke or TIA. Sixteen percent of these patients had 2 risk factors for PAD and 26% of the patients had either 3 or 4 risk factors. Of the patients with previous MI 34.1% had a PTCA and 36.4% a CABG (for patients with stroke and with TIA, the numbers were 10.7/7.6% and 14.8/8.1%, respectively)

Risk factors

Of the total population, 70.5% (n=3 096) was included on the basis of risk factors only. Most patients were older than 55 years (87.8%). The distribution of risk factors in this group is presented in Table IV. Arterial hypertension (75.5%) and/or hypercholesterolemia (60.2%) were the most common risk factors; 12.2% had an history of PTCA and 11.3% of CABG.

Gender differences were not observed, except for smoking (54.4% for males versus 22.3% for females); 38% of the patients had 3 risk factors and 31.5% had at least 4. The most frequently observed combinations of risk factors were age >55 and hypertension, or age hypertension and hypercholesterolemia (both in 10.6%).

Ankle-brachial index

For 4 491 out of the 4 536 included patients, an ABI could be calculated. The mean ABI was 1.02+-0.19. An ABI <0.9 (PAD diagnosis) was observed in 862 patients (18.7%). For 14.1%, the ABI was between 0.7 and 0.9 (mild PAD), but for 4.1% it was between 0.4 and 0.7 (moderate PAD) and for 0.5% <0.4 (severe PAD). The frequency of an abnormal ABI was similar for males and females, but increased with age. Half of the patients with an ABI <0.9 had an abnormal value at both ankles indicating bilateral disease.

Of the patients, 26.5% (376 of 1 421) with a history of atherothrombotic ischemic event(s) had an ABI <0.9 compared to 15.2% (466 of 3 070 patients) of those without such a history. Table V shows the percentage of patients with abnormal ABI according to type of event.

Individual risk factors had no influence on the prevalence of an abnormal ABI, except PTCA and CABG (Table VI).

Claudication questionnaire

The Edinburgh Claudication Questionnaire of Leng and Fowkes was filled out for 842 patients with an ABI <0.9. A total of 477 (66.6%) responded positively to the question, if they had pain when walking uphill or hurrying. When they felt pain, 61.4% stopped, 32% slowed down, and 6.6% continued at the same speed. The pain disappeared in less than 10 min in 81% upon stopping the effort. The criteria for typical claudication (beginning of pain in legs/calves while walking and rapid disappearance of this pain after stopping) were present in 45.6% (n=384) of the patients with an ABI <0.9, although none of them had spontaneous complaints of intermittent claudication.

Drug treatment

Table VII summarizes drug treatment to prevent ischemic atherothrombotic events and to control risk factors in patients with a previous event and in those with hypercholesterolemia.

Patients with a previous MI had on average 2 to 3 classes of drugs, those with stroke or TIA 0 to 2, and those with hypercholesterolemia 0 to 1. Only 7% of patients with a previous MI received no drugs versus 28% of those with a previous stroke or TIA and 51% of those with hypercholesterolemia. Aspirin was the most prescribed drug. In patients with a previous MI aspirin-beta- blocking agent and aspirin-beta-blocking agent-angiotensin converting enzyme inhibitor were the most popular combinations of drugs. Antithrombotic drugs were more commonly used in patients with an abnormal compared to a normal ABI. GP were also asked to evaluate whether hypertension, diabetes and hypercholesterolemia were adequately controlled by treatment. Results are shown in Table VIII. Estimated frequencies were similar for patients with a previous event and with risk factors only and for those with abnormal versus normal ABI.

Discussion

The aim of the present survey was to collect epidemiological data on the prevalence of PAD in asymptomatic patients at risk visiting regularly their family doctor and at the same time to augment the GP’s awareness of PAD. In a non-specialized medical practice, the presence of PAD is often recognized late, because the disease remains ‘silent’ for a long time and initial complaints are easily mistaken for symptoms of degenerative osteo-articular disorders ascribed to age. The design had to be simple and practical without interfering with normal functioning of a busy doctor’s office. Asymptomatic PAD can be estimated only by using non-invasive techniques. ABI is the most effective, accurate and practical screening method of PAD detection applicable in a large population. It is a simple, non-invasive and inexpensive test to assess the patency of the lower extremity arterial system and it requires only minimal experience and training.3 The sensitivity of an ABI reading is 90% and the specificity is 98% for an angiographically defined stenosis of 50% or more in a major leg artery.5-7

The target population was expected to have an increased risk of PAD. The prevalence largely varies from roughly 1% to over 20% and largely depends on the detection technique as well as on the population screened.8 An American survey which aimed to elaborate a community-based program measuring current rates of PAD awareness, physician recognition and treatment intensity, included 7 000 patients 9 and found PAD in 29% of them. The selection focused on patients older than 70 years, or between 59 and 70 years old with one additional risk factor (smoking or diabetes mellitus). Among patients with PAD, 44% had isolated peripheral disease, whereas the remaining 56% had associated cardiovascular disease (coronary disease, cerebrovascular disease or abdominal aortic aneurysm). Among those with isolated PAD, 8.7% had classical symptoms of claudication. The present survey used no lower age cut-off but requested the presence of two additional risk factors in those younger than 55. The difference in selection of the included patients may help to explain the clearly lower prevalence rate since age appears one of the main determinants of the presence of PAD. The German GETABI study conducted in unselected patients visiting their primary care physician yielded a similar 19% prevalence of PAD.10 An additional 22.5% of the current survey patients had an ABI between 0.9 and 1. Their index at rest thus remains above the preset cut- off point for PAD. However, it is conceivable that a treadmill exercise test may provoke a fall in index value and reveal the presence of obstructive arterial lesions in an proportion of them, thus augmenting further the prevalence of silent disease.

The present survey focused on patients with a high risk of PAD, but without spontaneous complaints of intermittent claudication. Still, a standardized questionnaire yielded answers suggestive of claudication in almost half of those with an ABI <0.9. Limited mobility in elderly patients and restricted reserve capacity in patients with cardiac or pulmonary disorders frequently hide the presence of overt claudication. However, it is more likely that a proportion of the patients included in the current survey pays little or no attention to their leg problem or accept a certain discomfort as inherent to their age or their condition. Questionnaires are designed for screening people in epidemiologic studies on large populations, but the present data suggest that a few specific questions directed at detecting walking problems can be useful in a doctor's office as well and may be helpful for earlier identification of PAD.

Cardiovascular morbidity and mortality are particularly high in population with PAD. The 10-year survival of asymptomatic PAD patients is not higher than 50%.’ The mortality rate in these patients approaches that of many common cancers and is mainly due to cardiac and cerebrovascular complications. Patients with an ABI <0.4 have a 5-year probability of survival of only 44%11 a rate lower than the survival of colon cancer (63%) and of non-Hodgkin's lymphoma (52%).12 Well-known risk factors for developing PAD are smoking habits, diabetes mellitus, arterial hypertension and hypercholesterolemia. However, the link between PAD and associated risk is relatively underestimated and patients rarely receive adapted medical care until symptoms of claudication or critical ischemia develop. Detection of silent disease is thus important in order to start appropriate treatment as early as possible in asymptomatic patients. Recognition of risk factors can be the initial step, but patients with a previous ischemic cardiac or cerebral event and those with a history of PTCA or CABG had a clearly higher chance of having an ABI <0.9 than those with classical risk factors alone.

Efforts to screen patients at risk for PAD start from the assumption that their current management is suboptimal and that a better adapted medical care may forestall disease progression both in the affected limb and in the whole cardiovascular system.7,13 An effective management program includes exercise rehabilitation, measures to promote and support smoking cessation, dietary modifications and pharmacological intervention to control lipid profile, blood sugar and arterial pressure. In addition, long-term antiplatelet drug therapy is expected to reduce the risk of vascular death and non-fatal vascular events.14 Aspirin is the most commonly prescribed antiplatelet agent in claudicating patients,15 although ticlopidine and clopidogrel are effective as well in patients with PAD.16 The data collected in the current survey indicate that prescription of antiplatelet therapy is indeed suboptimal at least in some subgroups of the patients at risk.

Conclusions

The present survey found PAD to be present in almost 1/5 of an asymptomatic population responding to a particular risk profile and regularly visiting a general practitioner and specific questioning detects claudication symptoms in almost half of these patients. ABI and a standardized questionnaire are easily applicable tools to help the GP to detect early stage PAD in patients at high risk and to potentially select more accurately patients who may benefit from cardiovascular preventive measures.

Acknowledgements.-We thank The Belgian Working Group of Angiology for their discussion on the data.

Received on March 13, 2007; acknowledged on march 16, 2007; accepted for publication on May 7, 2007.

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M. SPRYNGER1, C. FASSOTTE2, R. VERHAEGHE3

1 University Hospital Center of Liege, Liege, Belgium

2 Medical Department, Sanofi-Aventis, Diegem, Brabant, Belgium

3 Catholic University of Leuven (KUL), Leuven, Belgium

Address reprint requests to: Prof. R. Verhaeghe, Vascular Center, University of Leuven, Herestraat 49, 3000 Leuven, Belgium. E-mail: raymond.verhaeghe@uz.kuleuven.ac.be

Copyright Edizioni Minerva Medica Sep 2007

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