PATHOPHYSIOLOGY AND NATURAL HISTORY
PERIPHERAL VASCULAR DISEASE
The prevalence of peripheral arterial disease in
defined population
a
MICHAEL H. CRIQUI, M.D., M.P.H., ARNOST FRONEK, M.D., PH.D.,
ELIZABETH BARRETT-CONNOR, M.D., MELVILLE R. KLAUBER, PH.D.,
SAM GABRIEL, B.S., AND DEBORAH GOODMAN, M.P.H.
ABSTRACT Because patients with peripheral arterial disease (PAD) may be asymptomatic or may
findings, the true population prevalence of PAD is essentially
unknown. We used four highly reliable, sophisticated noninvasive tests (segmental blood pressure,
flow velocity by Doppler ultrasound, postocclusive reactive hyperemia, and pulse reappearance halftime) to assess the prevalence of large-vessel PAD and small-vessel PAD in an older (average age 66
years) defined population of 613 men and women. A total of 11. 7% of the population had large-vessel
PAD on noninvasive testing, and nearly half of those with large-vessel PAD also had small-vessel PAD
(5.2%). An additional 16.0% of the population had isolated small-vessel PAD. Large-vessel PAD
increased dramatically with age and was slightly more common in men and in subjects with hyperlipidemia. Isolated small-vessel PAD, by contrast, was essentially unrelated to sex, hyperlipidemia, or
age, although it was somewhat less common before age 60. Intermittent claudication rates in this
population were 2.2% in men and 1.7% in women, and abnormalities in femoral or posterior tibial
pulse were present in 20.3 % of men and 22.1% of women compared with the noninvasively assessed
large-vessel PAD rate of 11.7%. Thus assessment of large-vessel PAD prevalence by intermittent
claudication dramatically underestimated the true large-vessel PAD prevalence and assessment by
peripheral pulse examination dramatically overestimated the true prevalence.
Circulation 71, No. 3, 510-515, 1985.
present with atypical symptoms or
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THE PREVALENCE of peripheral arterial disease
(PAD) in the general population is essentially unknown, primarily because of the lack of data on
asymptomatic PAD. Most studies have focused on
symptomatic or clinical populations, and previous reports in free-living populations are limited to assessment by symptoms, pulse palpation, or older noninvasive tests. 1-13 Recently, highly reliable and valid
noninvasive tests for PAD have been developed. These
newer methods permit accurate, risk-free evaluation of
PAD in subjects unselected for symptoms.' l9
We used such noninvasive tests in a defined, freeliving population to determine the true prevalence of
PAD and the degree of error resulting from assessment
From the School of Medicine, University of California, San Diego,
La Jolla.
Supported by National Institutes of Health grant HL 22255. Dr.
Criqui is the recipient of a Research Career Development Award (HL
00946) from the National Heart, Lung, and Blood Institute.
Address for correspondence: Michael H. Criqui, M.D., M.P.H.,
Division of Epidemiology, Department of Community and Family
Medicine, M-007, University of California, San Diego, La Jolla, CA
92093.
Received Aug. 31, 1984; revision accepted Dec. 13, 1984.
510
of PAD by the traditional methods, intermittent claudication and pulse palpation.
Methods
All 624 subjects were members of a geographically defined
population initially studied under a Lipid Research Clinics
(LRC) protocol.20 21 Subjects were recruited for the study with
an introductory letter, followed by a telephone call to schedule
an appointment. About half of the subjects (5 1.7%) were from a
random sample of the LRC cohort and-the others were selected
from the same earlier study for hyperlipidemia, defined as being
at or above age- and sex-specific 90th percentiles for cholesterol
concentration or 95th percentiles for triglyceride concentration
or use of lipid-lowering medications. Subjects were from a
predominantly white, upper-middle-class community in southern California, and informed consent was obtained after the
procedures had been fully explained.
Eleven subjects (1.8%) were excluded because of missing
data or unreliable results of noninvasive testing. Two hundred
seventy-five men and 338 women ranging in age from 38 to 82
years (mean 66) remained. One hundred fifty-eight subjects
were 38 to 59 years old, 161 were 60 to 69 years old, and 294
were 70 to 82 years old.
Criteria for PAD measurements
Intermittent claudiation. Claudication was assessed by the
standardized Rose questionnaire developed at the London
School of Hygiene and Tropical Medicine.22 Claudication was
defined by the Rose criteria: exercise calf pain not present at rest
CIRCULATION
PATHOPHYSIOLOGY AND NATURAL HISTORY-PERIPHERAL VASCULAR DISEASE
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relieved within 10 min by rest. We also defined as "possible"
claudication, exercise calf pain not present at rest but otherwise
not fully concordant with the Rose criteria. The remaining subjects, including subjects with leg pain at rest and subjects with
exercise pain not including the calf, were categorized as not
having claudication.
Pulse palpation. On 508 (82.9%) of the subjects, a single
examiner performed a standardized bilateral palpation of the
femoral, posterior tibial, and dorsalis pedis arteries, with pulses
subjectively graded from 0 to 4, and auscultation of the groin for
femoral bruits. Pulses lower than grade 3 or audible bruits were
considered abnormal. This examination was done before noninvasive testing, and the examiner was unaware of the subject's
responses to the claudication questionnaire.
Noninvasive testing. Four different noninvasive measurements of limb perfusion in the lower extremities were made:
segmental blood pressure, flow velocity, postocclusive reactive
hyperemia, and pulse reappearance half-time.
SEGMENTAL BLOOD PRESSURE. The ratio of arm systolic blood
pressure to pressure at five different levels of the lower extremity (upper thigh, above knee, below knee, above ankle, and toe)
was recorded by the sphygmomanometric technique and a mercury-in-Silastic gauge attached to the toe.l1l6
FLOW VELOCITY. The Doppler effect produced by backscattered ultrasound from red blood cells in motion was used
to measure flow velocity in the femoral and posterior tibial
arteries. '7
POSTOCCLUSIVE REACTIVE HYPEREMIA. This phenomenon
was used to mimic exercise blood flow requirements. Arterial
flow was halted by inflating a cuff below the knee to a suprasystolic value for 4 min. Upon release of the cuff, the Doppler flow
velocity response (reactive hyperemia) was recorded from
the femoral artery. The percentage increase above baseline as
well as the time for the response to fall to 50% of peak were
recorded. '8
PULSE REAPPEARANCE HALF-TIME. Simultaneously with the
postocclusive reactive hyperemia test, the pulse reappearance
half-time, or the time it took after releasing the cuff for the pulse
amplitude to reach one-half the baseline value, was recorded. 19
Large-vessel PAD. Large-vessel PAD was defined as either
an abnormal segment-to-arm blood pressure ratio (LVBP +) or
an abnormal large-vessel flow velocity (LVFV +).
LVBP + was defined as
(both an above ankle and below knee ratio c 0.8)
or
above ankle or below knee ratio ' 0.8, and
a toe ratio
0.7 or
an above knee ratio ' 0.8 or
an upper thigh ratio ' 0.8
an
LVFV + was defined as either a
( femoral peak forward flow of ' 20 cm/sec)
and
260 msec or
a femoral pulse decay of
100 cm/sec2 J
a femoral deceleration of
or
(
posterior tibial peak forward flow of 10 cm/sec)
and
a posterior tibial pulse decay of> 220 msec or
a posterior tibial deceleration of ' 70 cm/sec2'
a
<
Although these tests measure dynamic aspects of perfusion
rather than the degree of anatomic obstruction, they have been
demonstrated to have a good correlation with moderate or greater large-vessel-PAD determined angiographically.l*47
Small-vessel PAD. Small-vessel PAD was defined by an isolated toe pressure abnormality or a pulse reappearance half-time
Vol. 71, No. 3, March 1985
abnormality or a combination of abnormalities in pulse reappearance half-time, postocclusive reactive hyperemia, and time
for hyperemic response to fall to 50% of peak.
Specifically, the presence of small-vessel PAD was defined
as
(a T ratio . 0.7 with the above ankle ratio and the below
knee ratio normal)
or
(a pulse reappearance half-time ' 20 sec)
or
( a pulse reappearance half-time > 15 sec and a postocclusive reactive hyperemia < 75% and
time for hyperemic response to fall to 50% of peak > 40 sec
The cutpoints chosen represent extreme values from previous
studies of normal control subjects."18 19 Since small-vessel PAD
cannot be reliably assessed angiographically, anatomic correlation of these tests is impractical.
Surgeryfor PAD. Subjects were asked whether they had ever
had surgery for poor circulation to the extremities, other than for
varicose veins, and the nature and location of the surgery. Subjects with documented surgery for PAD underwent the noninvasive testing along with other subjects. For this analysis, subjects
who had had surgery were arbitrarily considered to be LVBP +
and LVFV +.
Statistical analysis. Tests for association in 2 x 2 tables were
performed with Pearson's chi square with Yates' correction.
The Mantel-Haenszel chi-square procedure corrected for continuity was used to test for association in ordered contingency
tables.23 The independent associations of age, sex, and selection
reason (random sample or hyperlipidemia) with PAD were assessed by multiple logistic regression.24
Results
Table 1 shows the prevalence of PAD in this population as assessed by the traditional methods of intermittent claudication by history and pulse palpation by
examination. For this and subsequent tables, numbers
of subjects vary slightly because of missing or incomplete data. The proportion reporting Rose claudication
was somewhat higher for men than women (2.2% vs
1.7%), and this difference was magnified when Rose
and possible claudication were combined. For both
Rose and Rose-plus-possible claudication, the prevalence increased steadily with age, reaching 2.7% for
Rose and 7.7% for Rose-plus-possible claudication in
the 70 years and older group. None of the trends noted
above were statistically significant, perhaps in part
because of the small number of subjects with claudication. However, the associations with age were suggestive (p < .09).
The prevalence of abnormal pulses was grouped into
femoral (including femoral bruit), posterior tibial, dorsalis pedis, and an "any pulse abnormality" group
defined as an abnormal femoral or posterior tibial pulse
or a femoral bruit. The dorsalis pedis pulse was excluded from the "any pulse abnormality" category
because it is unilaterally or bilaterally congenitally absent in 4% to 12% of subjects.25 26 The prevalence of
an abnormal femoral pulse or bruit was more common
511
CRIQUI et al.
TABLE 1
Prevalence of PAD by traditional assessment: intermittent claudication and pulse palpation
% Claudication
Sex
Men
Women
Age (yr)
<60
60-69
70+
% Pulse abnormalities
n
Rose
Rose
+ possible
Femoral
inc. bruit
Posterior
tibial
Dorsalis
pedis
AnyA
275
338
2.2
1.7
7.2
4.9
11.5
6.8
13.2
17.7
30.3
29.1
20.3
22.1
158
161
294
0.0
2.4
2.7
3.1
5.4
7.7
1.4
7.6
14.1
4.9
9.8
25.5
18.2
26.5
38.3
5.6
15.9
33.8
AExcludes dorsalis pedis.
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in men than women (11.5% vs 6.8%; p - .052),
whereas an abnormal posterior tibial pulse was slightly
more common in women (17.7% vs 13.2%; p = NS).
For the "any pulse abnormality" category, the prevalence was quite similar in men and women, 20.3% and
22.1%, respectively. Dorsalis pedis abnormalities
were highly prevalent, reflecting to some extent congenital absence, but the prevalence also increased with
age, reflecting true occlusion with age.
For the other pulse categories, the prevalence of
abnormalities rose sharply with age, with the prevalence in the "any pulse abnormality" group increasing
FIGURE 1. Distribution of large-vessel PAD (LVPAD) and small-vessel PAD (SV-PAD) in the study
population. LVBP + = large-vessel PAD present by
segmental blood pressure criteria; LVFV + = largevessel PAD present by flow velocity criteria.
512
from 5.6% at ages under 60 years to 15.9% at ages 60
to 69 and 33.8% at ages 70 and older (p < .001).
Figure 1 shows the overall prevalence results from
noninvasive testing. A total of 27.7% of the population
had large-vessel PAD or small-vessel PAD; 1 1. 7% had
large-vessel PAD as manifested by LVBP + or LVFV +.
Proportions of subjects with various combinations of
LVBP+ 5 LVFV+X and previous surgery for PAD are
shown. About 10% of the subjects with large-vessel
PAD were so categorized because of previous surgery,
half of whom still had large-vessel PAD on noninvasive testing.
PAD
72. 3%
NO
CIRCULATION
PATHOPHYSIOLOGY AND NATURAL HISTORY-PERIPHERAL VASCULAR DISEASE
multiple logistic regression, a technique that allows us
to evaluate the contribution of a given factor while
7
7
20
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
t
15
LV-PAD
7
10
/
7
7
5
S.1
65-69
<60 60-64
7
7
7
7
7
7
1
-sr-
*
70-74
75+
Age Groups, yrs.
FIGURE 2. Prevalence of large-vessel PAD (LV-PAD) by age and
sex.
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Sixteen percent of subjects had isolated small-vessel
PAD (small-vessel PAD only). However, of the
11.7% of subjects with large-vessel PAD, about half
(5.2%) also had small-vessel PAD for an overall smallvessel PAD prevalence of 21.2%.
Figure 2 shows the prevalence of large-vessel PAD
by age and sex. The prevalence of large-vessel PAD
rose sharply with age, from less than 3% at under 60
years to over 20% at age 75 and older. At most ages
large-vessel PAD was slightly more common in men.
Figure 3 shows the results for isolated small-vessel
PAD (small-vessel PAD accompanying large-vessel
PAD excluded). Isolated small-vessel PAD, in contrast to the results in figure 2, showed little difference
in prevalence between the sexes and little change in
prevalence with age after age 60. The prevalence appeared lower before age 60, but the result was of borderline statistical significance (p = .076).
To evaluate the independent associations of age,
sex, and subject selection criteria (random sample vs
hyperlipidemia) with large-vessel PAD and isolated
small-vessel PAD, we estimated relative risks using
tlen
E
WJomen
20
/
%
Isolated
SV-PAD
10
7
7
7
7
7
7
7
7
7
11 V
t
7
7
7
r-111
-111
<60
1
6
a ---1
1
b0-b64
-
1.
P1 -11
1-
70-74
1-
1.
75+
Age Groups, yrs.
FIGURE 3. Prevalence of isolated small-vessel PAD (SV-PAD) by
age and sex.
Vol. 71, No. 3, March 1985
Discussion
Our claudication rates of 2.2% in men and 1.7% in
women in a population with an average age of 66 years
tend to be lower than earlier results in men but comparable with those in women. Earlier studies have generally evaluated younger populations and most have used
the Rose questionnaire. In men 50 to 59 years old the
percent prevalence of claudication in six earlier studies
was 0.8%, 1.1%, 1.2%, 2.3%, 2.8%, and 3.1%±.4 1u
TABLE 2
Independent relative risksA of age, sex, and selection reason for
large-vessel PAD and isolated small-vessel PAD
Isolated
SV-PAD
LV-PAD
RR
Age (yr)
<60
60-64
65-69
70-74
75 +
Sex
Women
Men
Selection criteria
Random sample
Hyperlipidemic
p
value
RR
p
value
<.001
.O
1.85
1.92
1.60
1.59
.27
1lOOB
1.30
4.78
6.02
7.94
1.OOB
1.27
.34
1.OOB
1.29
.34
OOB
0.97
.87
1.00B
1.04
.82
E
65-59
1 1
simultaneously adjusting for other factors considered.
Table 2 shows the results. Age was strongly and significantly related to large-vessel PAD, with the risk
increasing stepwise. With subjects less than 60 years
of age as the reference value, subjects 75 years of age
or older had about an eightfold greater risk. There was
also 27% more large-vessel PAD in men than women
and a 29% excess in patients with hyperlipidemia, but
neither increment was statistically significant with our
sample size. However, in the small group of subjects
with large-vessel PAD with both LVBP + and LVFV +
(figure 1), the RR for men compared with women was
2.66 (p = .04).
Isolated small-vessel PAD was unrelated to sex or
hyperlipidemia. The overall association with age was
also nonsignificant, although there was a 60% to 90%
excess for each older age group compared with the
group less than 60 years old.
LV-PAD = large-vessel peripheral arterial disease; SV-PAD =
small-vessel peripheral arterial disease.
AFrom multiple logistic regression model.
BFixed reference value.
513
CRIQUI et al.
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A recent Finnish study also evaluating subjects 50 to
59 years old found high claudication rates in both men
(4.6%) and women (2.8%). 13 Previous reports concerning men 60 years old and older have indicated
claudication rates of 1. 3%8 and 2.7%.4 A Danish study
found Rose claudication prevalence rates of 5.8% in
men and 1.3% in women at age 60.12 A study in England found a 2.2% prevalence in men aged 45 to 69 and
1.2% in women aged 50 to 69.11 However, criteria in
that study included ankle blood pressure measurements, and the prevalence of claudication alone may
have been closer to 3% in men and 2% in women.
The claudication excess in men in our study was
thus less pronounced than that in earlier studies, but
the sex ratio in our study did increase when possible
claudication was included. The stepwise increase in
prevalence with age is concordant with earlier studies4' 68, 10, 13 and is concordant with reports of increasing incidence with age in the Framingham cohort.27
Previous reports of the population prevalence of
specific abnormal pulses have varied considerably. In
subjects 60 years old and older, the dorsalis pedis
pulses was reported to be absent in 22.7% of men but
only 9.8% of women in a British study' and 31.6% of
men and 19.5% of women in a Michigan study3 as
compared with diminished pulses in 30% of both men
and women in our study. The posterior tibial pulse was
absent in 12.8% of men and 20.6% of women in the
British study' and 23.7% of men and 37.5% of women
in the Michigan study3 compared with diminished
pulses in 13.2% of men and 17.7% of women in our
study. Our results are not directly comparable because
we included diminished as well as absent pulses, but
the studies do agree that a posterior tibial abnormality
may be more common in women despite their lesser
claudication prevalence. The Danish study that found a
high claudication rate in 60-year-old men of 5.8% reported the prevalence of either an absent dorsalis pedis
or posterior tibial pulse to be only 11.9% in men and
8.8% in women.'2
Our data suggest a steep rise in abnormal femoral or
posterior tibial pulses with age, from 5.6% at less than
age 60 to 33.8% at age 70 and greater, but no marked
sex differential. In addition, the dorsalis pedis pulse
was so frequently absent at younger ages in our study
that its clinical significance appears limited. The prevalence of "any pulse abnormality" was approximately
10 times the Rose claudication prevalence and about
three times the Rose-plus-possible claudication prevalence in men and four times that in women.
The true population prevalence of PAD in our study,
as assessed by noninvasive testing, indicated 11.7% of
514
subjects had large-vessel PAD, half of whom also had
small-vessel PAD, and an additional 16.0% prevalence of isolated small-vessel PAD. The category of
isolated small-vessel PAD was defined because of the
possibility that some of the small-vessel PAD accompanying large-vessel PAD might reflect reduced smallvessel flow primarily as a result of proximal stenoses
in larger vessels. There was a clear association of
large-vessel PAD with age and somewhat more largevessel PAD in men. In contrast, isolated small-vessel
PAD, while less prevalent before age 60, was unrelated to age after age 60 and did not show an excess in
men. The multivariable logistic analysis confirmed
these associations, although the excess in men for
large-vessel PAD was not statistically significant. The
logistic analysis also suggested some association with
hyperlipidemia, albeit not statistically significant, for
large-vessel PAD but not for isolated small-vessel
PAD. This suggests our prevalence estimates are only
slightly biased as a result of our population sample.
PAD has been previously reported to be much more
closely associated with cigarette smoking and diabetes
than with hyperlipidemia. An analysis of the association of PAD with cardiovascular risk factors in our
population will be reported separately.
The sharp difference in the association of age, sex,
and hyperlipidemia with large-vessel PAD as compared with isolated small-vessel PAD further suggests
that isolated small-vessel PAD is a distinct entity rather
than early or subcritical large-vessel PAD.
Our objective in this report was to define the true
amount of occlusive disease in our population, regardless of signs or symptoms. Only four previous studies
have had a comparable aim. Three studies were done
in unselected populations but used a limited noninvasive assessment. Eight percent of men 60 to 64 years
old in Basel, Switzerland, had a peripheral arterial
occlusion, with pulse oscillography used as a major
screening tool.2 Two studies in The Netherlands found
a 3% and 4% prevalence of an above-ankle ratio of
c. 9.10 A study in Denmark also used a criterion of an
above-ankle ratio c 0.9 and found a 14.3% prevalence
in 666 men and women aged 60.12 The fourth study
used extensive noninvasive testing in 458 diabetics
with an average age of 52.6 years and found an expectedly very high PAD prevalence of 36.0%.28 Thus our
study is the first to use extensive noninvasive testing in
a defined population unselected for disease status and
the first to report results separately for large-vessel
PAD and small-vessel PAD. We are unaware of other
studies of isolated small-vessel PAD prevalence.
In conclusion, the prevalence of intermittent claudiCIRCULATION
PATHOPHYSIOLOGY AND NATURAL HISTORY-PERIPHERAL VASCULAR DISEASE
cation was only about one-fifth the true prevalence of
large-vessel PAD in our population, whereas the prevalence by pulse abnormalities was nearly twice the true
rate. Thus population estimates of large-vessel PAD
determined only by symptoms or pulse evaluation result in a distorted view of the extent of occlusive disease.
Also of interest is the degree of association between
PAD assessed by traditional methods and large-vessel
PAD and isolated small-vessel PAD defined by noninvasive testing. This is the subject of the companion
11.
12.
13.
14.
15.
16.
report.29
17.
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The prevalence of peripheral arterial disease in a defined population.
M H Criqui, A Fronek, E Barrett-Connor, M R Klauber, S Gabriel and D Goodman
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Circulation. 1985;71:510-515
doi: 10.1161/01.CIR.71.3.510
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1985 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
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