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Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral Arterial Disease Detection, Awareness, and Treatment in Primary Care. JAMA. 2001;286(11):1317–1324. doi:10.1001/jama.286.11.1317
Author Affiliations, PARTNERS Investigators, and Financial Disclosure: Vascular Medicine Program, University of Minnesota Medical School, Minneapolis (Drs Hirsch, Treat-Jacobson, Krook, and Hunninghake); Department of Family and Preventive Medicine, University of California, San Diego, School of Medicine, San Diego (Dr Criqui); University of Colorado Health Sciences Center (Dr Regensteiner) and Divisions of Geriatrics and Cardiology, University of Colorado Health Sciences Center (Dr Hiatt), Denver; Brigham and Women's Hospital, Boston, Mass (Dr Creager); Heart and Vascular Institute, Morristown, NJ (Dr Olin); Temple University Hospital, Philadelphia, Pa (Dr Comerota); Jobst Center, Toledo, Ohio (Ms Walsh); and Northwestern University Medical School, Chicago, Ill (Dr McDermott).
Context Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis
that is common and is associated with an increased risk of death and ischemic
events, yet may be underdiagnosed in primary care practice.
Objective To assess the feasibility of detecting PAD in primary care clinics,
patient and physician awareness of PAD, and intensity of risk factor treatment
and use of antiplatelet therapies in primary care clinics.
Design and Setting The PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS)
program, a multicenter, cross-sectional study conducted at 27 sites in 25
cities and 350 primary care practices throughout the United States in June-October
Patients A total of 6979 patients aged 70 years or older or aged 50 through 69
years with history of cigarette smoking or diabetes were evaluated by history
and by measurement of the ankle-brachial index (ABI). PAD was considered present
if the ABI was 0.90 or less, if it was documented in the medical record, or
if there was a history of limb revascularization. Cardiovascular disease (CVD)
was defined as a history of atherosclerotic coronary, cerebral, or abdominal
aortic aneurysmal disease.
Main Outcome Measures Frequency of detection of PAD; physician and patient awareness of PAD
diagnosis; treatment intensity in PAD patients compared with treatment of
other forms of CVD and with patients without clinical evidence of atherosclerosis.
Results PAD was detected in 1865 patients (29%); 825 of these (44%) had PAD
only, without evidence of CVD. Overall, 13% had PAD only, 16% had PAD and
CVD, 24% had CVD only, and 47% had neither PAD nor CVD (the reference group).
There were 457 patients (55%) with newly diagnosed PAD only and 366 (35%)
with PAD and CVD who were newly diagnosed during the survey. Eighty-three
percent of patients with prior PAD were aware of their diagnosis, but only
49% of physicians were aware of this diagnosis. Among patients with PAD, classic
claudication was distinctly uncommon (11%). Patients with PAD had similar
atherosclerosis risk factor profiles compared with those who had CVD. Smoking
behavior was more frequently treated in patients with new (53%) and prior
PAD (51%) only than in those with CVD only (35%; P
<.001). Hypertension was treated less frequently in new (84%) and prior
PAD (88%) only vs CVD only (95%; P <.001) and
hyperlipidemia was treated less frequently in new (44%) and prior PAD (56%)
only vs CVD only (73%, P<.001). Antiplatelet medications
were prescribed less often in patients with new (33%) and prior PAD (54%)
only vs CVD only (71%, P<.001). Treatment intensity
for diabetes and use of hormone replacement therapy in women were similar
across all groups.
Conclusions Prevalence of PAD in primary care practices is high, yet physician awareness
of the PAD diagnosis is relatively low. A simple ABI measurement identified
a large number of patients with previously unrecognized PAD. Atherosclerosis
risk factors were very prevalent in PAD patients, but these patients received
less intensive treatment for lipid disorders and hypertension and were prescribed
antiplatelet therapy less frequently than were patients with CVD. These results
demonstrate that underdiagnosis of PAD in primary care practice may be a barrier
to effective secondary prevention of the high ischemic cardiovascular risk
associated with PAD.
Peripheral arterial disease (PAD) is a highly prevalent atherosclerotic
syndrome that affects approximately 8 to 12 million individuals in the United
States and is associated with significant morbidity and mortality.1-4 Because
of its high prevalence, high rates of nonfatal cardiovascular ischemic events
(myocardial infarction [MI], stroke, and other thromboembolic events), increased
mortality, and diminution of quality of life, the consequences of PAD in US
communities are significant.1-5
A regional pilot study of community screening for PAD demonstrated that patient
awareness of the PAD diagnosis was low and associated with low atherosclerosis
risk factor, antiplatelet, and claudication treatment intensity.5
There have been no national efforts in the United States to detect PAD in
community-based office practice, to assess both physician and patient awareness
of the diagnosis, or to assess the intensity of medical treatments. PAD has
not emerged as a focus of public health efforts to improve quality of life
nor to decrease the associated cardiovascular ischemic risk.
The PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS)
program was designed as a national investigation to assess the feasibility
of detecting PAD using the ankle-brachial index (ABI) in office-based practices.
Additional goals were to assess both patient and physician awareness of PAD,
to evaluate the magnitude of the associated atherosclerosis risk factor burden,
and to assess the intensity of use of risk-reduction strategies in community
practice. The program evaluated the following hypotheses: (1) that PAD is
prevalent but underdiagnosed in primary care practices and (2) that PAD is
undertreated in terms of risk factor modification and use of antiplatelet
therapies compared with that in other cardiovascular diseases (CVDs).
The program was designed by an interdisciplinary steering committee
as a national, community-based PAD detection program. The program established
physician-nurse partnerships at 27 regional coordinating centers selected
for their expertise in PAD, which in turn identified a total of 350 local
primary care sites for patient screening. The local study physician and coordinator
identified their patients who met the study entry criteria. The local nurse
administered standardized questionnaires; recorded the medical history, height,
weight, blood pressure, and waist circumference; and measured each patient's
ABI. The program design is shown in Figure
1. The protocol was reviewed and approved by the institutional review
boards at all study sites, and all patients provided written informed consent
prior to participation.
The survey population was identified prospectively by a predefined subject
age and risk factor profile based on the known epidemiology of PAD.1-4,6,7
Patients were enrolled at each practice site if they were 70 years or older
or if they were aged 50 through 69 years and had a history of diabetes or
cigarette smoking (at least 10 pack-years), or both. We anticipated that these
enrollment criteria would yield a PAD detection rate of 15% and a CVD detection
rate of 15%. Therefore, we projected evaluating approximately 10 000
individuals to identify 1500 patients with PAD and 1500 patients with CVD.
This sample size was estimated to provide sufficient power to test the second
hypothesis of a difference in treatment intensity for risk factors and use
of antiplatelet therapy between patients with PAD who had no history of CVD
vs patients with CVD who had no evidence of PAD. Data collection was conducted
from June through October 1999. The survey was concluded after 6979 patients
had been screened, for this sample had identified 1865 patients with PAD (825
with PAD only and 1040 with PAD and CVD). A total of 1527 patients were identified
with CVD only.
The cohort was divided into 4 predefined, mutually exclusive clinical
subgroups: (1) those without clinically recognized atherosclerosis in any
vascular bed (reference group), (2) those with PAD only, (3) those with CVD
only, and (4) those with both PAD and CVD. Individuals were considered to
have previously established prior PAD if it was documented by chart review,
if they had prior abnormal vascular laboratory studies confirming PAD, or
they had prior limb arterial revascularization, regardless of their ABI value
at the survey office visit. Patients with no previous chart documentation
of PAD were considered to have new PAD if their ABI was 0.90 or less during
the survey screening office visit.
A CVD diagnosis required a documented history of coronary artery disease,
cerebrovascular disease, or abdominal aortic aneurysm repair. Coronary artery
disease was established on the basis of a history of angina (stable or unstable),
MI, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery
bypass graft surgery. Patients were considered to have cerebrovascular disease
if they had a history of transient ischemic attack, stroke (ischemic or hemorrhagic),
or carotid endarterectomy.
All local sites received instruction on the accurate use of the Doppler
technique and the ABI calculation prior to study initiation. A 5-mHz Doppler
device (Elite-100R, Nicolet Vascular Inc, Golden, Colo) was used at each site
to measure the ABI. This unit included a broad-beam ultrasound probe designed
to facilitate performance of the ABI measurement. With each subject in the
supine position, the systolic blood pressures were recorded in the upper extremities
at the brachial arteries and in the lower extremities at the dorsalis pedis
and posterior tibial arteries. The ABI for each leg was separately calculated
by dividing the higher of the 2 ankle systolic pressures in that leg by the
higher brachial systolic pressure. The subject was considered to have PAD
if either leg ABI was 0.90 or less. The index leg was defined as the leg with
the lower ABI. The sensitivity of the ABI is 90%, and the specificity is 98%
for an angiographically defined stenosis of 50% or more in a major leg artery.8-10
A smoking history (current or former) was established in patients who
had 1 pack-year or more of tobacco use based on patient interview or chart
documentation. Diabetes was determined from the clinical record (based on
a chart diagnosis or use of diabetes medications), regardless of whether it
was type 1 or type 2. Laboratory screening for new diabetes was not performed.
In a similar fashion, hyperlipidemia was defined from the medical record as
a total cholesterol concentration of 240 mg/dL (6.2 mmol/L) or more, low-density
lipoprotein (LDL) cholesterol concentration of 160 mg/dL (4.1 mmol/L) or more,
high-density lipoprotein (HDL) cholesterol concentration of 35 mg/dL (0.9
mmol/L) or less, triglyceride concentration of 200 mg/dL (2.26 mmol/L) or
more, total cholesterol/HDL ratio of 5.0 or more,11-13
or if the medical record included past or present use of lipid-lowering agents.11 A fasting lipid profile was not obtained as part
of this program and therefore not every patient could be evaluated for the
presence of hyperlipidemia. Patients were designated as hypertensive if they
had a systolic blood pressure of 140 mm Hg or more or a diastolic blood pressure
of 90 mm Hg or more at the time of the office screening. Hypertension was
also diagnosed from the chart by the use of calcium channel blockers, angiotensin-converting
enzyme inhibitors, β-blockers, or diuretics for the indication of treatment
of hypertension. Women were considered postmenopausal by self-report or the
use of hormone replacement therapy.
Smoking cessation therapy was defined as current participation in or
previous referral to a smoking cessation program. Diabetes treatment was defined
as current use of dietary interventions or use of diabetes medications, including
insulin and oral hypoglycemic agents. Lipid-lowering therapy was defined as
the prescription of agents used to treat lipid abnormalities (statins, niacin,
fibrates, and bile acid binding resin agents). Treatment for hypertension
was identified by the prescription of antihypertensive medications. In women,
the use of estrogen and/or progesterone hormone replacement therapy was defined
as treatment for menopause. The use of antiplatelet agents, including aspirin,
clopidogrel, ticlopidine, and dipyridamole, was recorded.
The PAD Awareness Questionnaire asked patients if any prior health care
provider had informed them of a diagnosis of PAD or other limitations to lower
extremity arterial blood flow. A positive response to any of 5 awareness questions
was considered PAD aware. Primary care physician awareness of the PAD diagnosis
was determined by his/her written response to a prior diagnosis question on
the day of screening. Each participant received educational information regarding
the impact of PAD as an atherosclerotic disease and the treatment of atherosclerosis
risk factors, as well as a written record detailing ABI and blood pressure
measurements. All participants received the Fact Sheet on
Heart Attack, Stroke and Risk Factors.14
Patients diagnosed with PAD also received a newly written educational brochure, Take Steps Against Peripheral Arterial Disease.15
The San Diego Claudication Questionnaire, a modification of the Rose
questionnaire, was used to identify the prevalence of claudication or other
exertional leg pain.10 The questionnaire allows
for lateralization of leg symptoms (right, left, or both) and categorizes
leg symptoms as either classic claudication (meeting all Rose criteria, listed
below), atypical leg pain that was exertional but did not meet all Rose criteria,
or no leg pain. Rose claudication was defined as exercise-induced calf pain,
not present at rest, which required stopping, and remitted in 10 minutes or
The primary statistical analysis focused on the following contrasts:
(1) comparisons between the reference group and the pooled clinical groups
with atherosclerosis (PAD, CVD, or both), (2) comparisons between the prior
PAD-only group and the CVD-only group, and (3) comparisons between the new
PAD-only group and the prior PAD-only group.
Statistical analyses were performed by SAS version 6.12 (SAS Institute
Inc, Cary, NC, 1990). Continuous variables were compared across the 4 clinical
groups using analysis of variance with 2-tailed tests. For selected categorical
variables, tests were conducted to see if proportions across clinical groups
differed. The Mantel-Haenszel χ2 test was used unless small
cell sizes necessitated use of the Fisher exact test. Statistical significance
was accepted at the .01 level given the multiple contrasts stated above.
The data set was complete for 6417 patients, or 92% of the 6979 patients
screened. PAD was detected in 1865 patients (29%). As shown in Table 1, 1527 patients (24%) had CVD only, 825 (13%) had PAD only,
and 1040 (16%) had both PAD and CVD. Sixty-two percent of those screened were
70 years or older, and 38% of those screened were aged 50 through 69 years
with a history of smoking, diabetes, or both.
The study cohort reflected a national database, comprising 18% of patients
from the Northeast, 27% from the Southeast, 25% from the Midwest, 16% from
the Southwest, and 14% from the West Coast. Within the total cohort, 20% of
the patients were employed, 73% were retired, and 7% were unemployed. The
mean (SD) age of the population was 70 (10) years. There were approximately
equal proportions of men (48%) and women (52%) overall, but more men were
in the CVD-only group than in the reference and PAD-only groups (P<.001 for both contrasts). Black participants were overrepresented
in the group with PAD only vs the reference and CVD-only groups (pooled reference
group, P<.005; CVD only, P<.001; Table 1).
Of patients who had PAD only, 55% were newly diagnosed, whereas of patients
who had PAD with CVD, 35% were newly diagnosed (Table 1). Thus, a diagnosis of new PAD at the time of this evaluation
was more likely in patients without other evidence of CVD vs patients who
had other evidence of CVD (P<.001). Congestive
heart failure was more frequent in the CVD-only group vs the PAD-only and
reference groups (P<.001 for both contrasts).
The mean (SD) ABI in patients with PAD only was 0.78 (0.19) (the same
in new or prior PAD groups), and in patients having PAD with CVD the mean
(SD) ABI was 0.78 (0.20) (P<.001 for all pooled
PAD groups compared with the reference group, [ABI, 1.09] Table 2). All patients without PAD, by definition, had an ABI of
more than 0.90.
In the PAD-only group, only 8.7% had classic Rose claudication. Although
classic claudication was more common in patients with prior PAD than in those
with newly diagnosed PAD (12.6% vs. 5.5%, P<.001)
or in patients without atherosclerosis (1.7%, P<.001),
it was distinctly uncommon overall (Table
2). Atypical leg symptoms were much more frequent in all groups.
Eighty-three percent of the patients with a prior diagnosis of PAD were
aware of the diagnosis, but only 49% of their physicians had recognized the
PAD diagnosis at the time of screening (P<.01).
This discrepancy between patient and physician PAD awareness was similar whether
CVD was present or absent.
Histories of smoking and diabetes were more common in all 3 clinical
groups with atherosclerosis than in the reference group (Table 3, pooled comparison, P<.001).
The prevalence of smoking was higher in the patients with prior PAD only than
in those with CVD only (P<.001). Smoking cessation
interventions were prescribed more frequently in the prior PAD-only group
and in the new PAD-only group compared with the CVD-only group and in the
reference group. The diagnosis of diabetes was documented in more patients
with prior PAD only vs CVD only (P = .03). Diabetes
was treated to a similar extent in all patient groups.
Low-density lipoprotein cholesterol values were available from 63% of
new PAD-only and 65% of prior PAD-only patients compared with 73% of patients
with CVD only (P<.01 for prior PAD-only compared
with CVD-only groups). The prevalence of hyperlipidemia (derived from available
data) was significantly greater in the 3 patient groups compared with the
reference group (P<.001). However, patients with
prior PAD only had a lower prevalence of hyperlipidemia (77%) compared with
patients in the CVD-only group (82%, P<.01). The
patients in the reference group were treated less frequently for their lipid
disorders than were the patients with atherosclerosis (P<.001). Patients with a new PAD diagnosis were less intensively
treated for hyperlipidemia than were patients with a prior PAD diagnosis (P<.006) and had a similar treatment intensity to the
reference group. Importantly, prior PAD-only patients were less intensively
treated for hyperlipidemia vs the CVD only group (P<.001).
Hypertension was more prevalent in the 3 pooled patient groups compared
with the reference group (P<.001). Patients in
the reference group were less frequently treated for their hypertension than
were patients in the pooled groups with atherosclerosis (P<.001), whereas hypertension was treated more intensively in the
patients with CVD than in those patients with new or prior PAD only (P<.001).
By definition all of the women in the study population were aged 50
years or older. Thus, most were postmenopausal and the postmenopausal state
was equally prevalent across all diagnostic groups. Use of postmenopausal
hormonal therapies was low overall, but it was higher in the reference group
than in patients with atherosclerosis (P<.001).
Despite lack of a consistent national recommendation favoring the use
of antiplatelet therapies as primary prevention,16
34% of patients in the reference group were taking an antiplatelet drug (Table 3). This rate was significantly lower
than in the patients with previously diagnosed atherosclerotic syndromes (P<.001). Among patients with PAD only, those with a
new diagnosis were less intensively treated with antiplatelet therapy than
were those with a prior diagnosis (P<.001). This
low rate of use of antiplatelet treatments in those with new PAD was similar
to the reference group. Overall, patients who had CVD only were more likely
to be receiving an antiplatelet agent than were patients with prior PAD only
(P<.001). Patients with CVD and PAD used antiplatelet
therapies at the highest level (>71%). Use of specific antiplatelet medications
within the total study population included aspirin (48%), clopidogrel bisulfate
(2%), ticlopidine hydrochloride (<1%), and dipyridamole (<1%). In the
survey population, 49% were not using any antiplatelet medication.
Epidemiologic and natural history studies have determined that PAD is
prevalent and confers a high risk of fatal and nonfatal cardiovascular ischemic
This national study demonstrates that PAD is highly prevalent in primary care
settings and is easily detected by the ABI examination during routine primary
care office visits. The high 29% PAD prevalence documented in this community
survey supported our hypothesized underdiagnosis, because a new PAD diagnosis
was established in approximately half of those with the disease. Despite the
prevailing notion that PAD is a disease with a predilection for men,2,18,19 PAD was as common
in women in our investigation, especially in those without CVD. Furthermore,
PAD was detected at high rates in all national regions and all races, although
these data indicate that isolated PAD is particularly common in black persons,
as has been previously observed.20-22
These data demonstrate that although more than half of the patients
with PAD have leg symptoms, relatively few reported classic Rose claudication.
The presence of typical leg symptoms was more common in those patients whose
PAD diagnosis was previously established, and asymptomatic patients were more
likely to have their PAD diagnosis established only by the survey's ABI measurement.
These data suggest that clinicians who utilize a classic history of claudication
alone to detect PAD are likely to miss 85% to 90% of the PAD diagnoses.
These data corroborate that the PAD population carries a high atherosclerosis
risk factor burden and ischemic risk. In the PAD-only cohort, patients had
the same ABI as patients having PAD with CVD. More strikingly, new PAD-only
patients had the same ABI as prior PAD-only patients. Even in patients without
CVD, an ABI value of 0.78 portends an approximate 30% 5-year risk of MI, ischemic
stroke, and vascular death.22-24
This increased mortality risk could presumably be reduced by appropriate lifestyle
and pharmacological interventions within a primary care setting. Such interventions
would preferably be initiated by each patient's primary care provider, who
is best able to establish the PAD diagnosis and to maintain a long-term therapeutic
A second study hypothesis was that patients with a prior diagnosis of
PAD only would be less intensively treated for their atherosclerosis risk
factors and less frequently prescribed antiplatelet therapies than patients
with a prior diagnosis of CVD.5,25
Recognition of the role of tobacco in the pathogenesis of PAD has been widespread,
and smoking cessation reduces disease progression and mortality risk in PAD
patients.26,27 While PAD patients
were referred to smoking cessation programs at a higher rate than patients
with CVD or in the reference group, even in PAD patients smoking cessation
therapies only were prescribed approximately 50% of the time.
Diabetes was a risk factor treated at a similar intensity in all of
the clinical groups, including the reference group. Thus, the diagnosis of
diabetes was adequate to initiate treatment in almost all patients with this
disorder, regardless of the presence or absence of clinically evident CVD.
A similar pattern of treatment was observed for the use of hormone replacement
therapy in women with atherosclerosis although the role of hormone replacement
therapy remains controversial.28
Patients with prior PAD only were less intensively managed for hyperlipidemia
and hypertension and were less often prescribed antiplatelet therapies than
were patients with CVD. Current lipid-lowering guidelines of the National
Cholesterol Education Program suggest that patients with PAD should achieve
an LDL cholesterol concentration of 100 mg/dL (2.59 mmol/L) and treatment
for elevated serum triglyceride levels.12 Despite
these recommendations, lipid measurements were obtained less often in PAD-only
patients. In addition, these patients were less intensively treated, findings
that support our undertreatment hypothesis.
Guidelines published for the detection and treatment of hypertension
recognize PAD as evidence of clinical CVD requiring drug therapy for all stages
of hypertension.29 In this survey, hypertension
was generally treated at high levels in all patients evaluated in office practice.
Nevertheless, patients with PAD only were less frequently treated than patients
with documented CVD.
In patients with atherosclerosis, antiplatelet agents have been shown
to reduce the risks of MI, ischemic stroke, and vascular death.30-32
Antiplatelet therapy is therefore recommended for secondary disease prevention
in patients with CVD.33 This survey also demonstrated
lower rates of administration of antiplatelet therapy in patients with both
new and prior PAD compared with CVD patients without PAD.
This national study was not designed to evaluate the epidemiology and
natural history of PAD because this has been performed in many previous studies.3,4,20,34-37
Rather, the primary goal was to determine the yield of routinely measuring
ABI in the primary care setting to detect previously undiagnosed PAD. Potential
biases could have occurred in that clinicians at the practice sites were aware
of the goals of the study and therefore may have preferentially over-enrolled
patients with known PAD. Also, patients with leg symptoms may have been more
willing to participate. Despite this possibility, 44% of the PAD patients
were newly diagnosed at the time of the study.
A critical goal of this research program was to identify the prevalence
of atherosclerosis risk factors in the clinical groups. Although standard
clinical criteria were used to define cigarette smoking, diabetes, and hyperlipidemia,
we did not validate the application of these criteria by using biochemical
markers for each condition. It was impractical to obtain plasma cotinine,
or fasting glucose or lipid panels from each survey participant. Consequently,
the true prevalence of these risk factors in PAD-only patients was therefore
likely underestimated, thus potentially magnifying the undertreatment findings.
PAD is a prevalent atherosclerotic syndrome and is associated with a
very high risk of MI, stroke, and death. In the absence of a national program
of PAD education and detection, many patients will not receive a diagnosis
of PAD prior to the occurrence of a morbid or mortal ischemic event. The PARTNERS
program demonstrated that PAD is easily detected with the ABI technique by
both nurses and physicians in the primary care setting. Despite the known
benefits of antiplatelet therapy and treatment of hypertension and hyperlipidemia
to reduce ischemic event rates, PAD patients were less intensively treated
than patients with CVD. The underdiagnosis of PAD and subsequent exposure
of this large cohort to ischemic risk would be expected to adversely affect
their clinical outcome, increasing rates of MI and stroke, cardiovascular
mortality, long-term costs, and diminishing quality of life. In as much as
PAD affects between 8 and 12 million US residents, effective long-term care
of patients with PAD will require increased diagnostic efforts and appropriate
medical interventions in community-based, primary care settings to decrease
limb-specific symptoms, improve quality of life, and decrease systemic cardiovascular