Background. Peripheral arterial disease measured noninvasively by the
ankle-arm index (AAI) is common in older adults, largely asymptomatic,
and associated with clinically manifest cardiovascular disease (CVD).
The criteria for an abnormal AAI have varied in previous studies. To
determine whether there is an inverse dose-response relation between t
he AAI and clinical CVD, subclinical disease, and risk factors, we exa
mined the relation of the AAI to cardiovascular risk factors, other no
ninvasive measures of subclinical atherosclerosis using carotid ultras
ound, echocardiography and electrocardiography, and clinical CVD. Meth
ods and Results. The AAI was measured in 5084 participants greater-tha
n-or-equal-to 65 years old at the baseline examination of the Cardiova
scular Health Study. All subjects had detailed assessment of prevalent
CVD, measures of cardiovascular risk factors, and noninvasive measure
s of disease. Participants were stratified by baseline clinical CVD st
atus and AAI (<0.8, greater-than-or-equal-to 0.8 to <0.9, greater-than
-or-equal-to 0.9 to <1.0, greater-than-or-equal-to 1.0 to <1.5). Analy
ses tested for a dose-response relation of the AAI with clinical CVD,
risk factors, and subclinical disease. The cumulative frequency of a l
ow AAI was 7.4% of participants <0.8, 12.4% <0.9, and 23.6% <1.0. Part
icipants with an AAI <0.8 were more than twice as likely as those with
in AAI of 1.0 to 1.5 to have a history of myocardial infarction, angin
a, congestive heart failure, stroke, or transient ischemic attack (all
P<.01). In participants free of clinical CVD at baseline, the AAI was
inversely related to history of hypertension, history of diabetes, an
d smoking, as well as systolic blood pressure, serum creatinine, fasti
ng glucose, fasting insulin, measures of pulmonary function, and fibri
nogen level (all P<.01). Risk factor associations with the AAI were si
milar in men and women free of CVD except for serum total and low-dens
ity lipoprotein cholesterol, which were inversely associated with AAI
level only in women. Risk factors associated with an AAI of <1.0 in mu
ltivariate analysis included smoking (odds ratio [OR], 2.55), history
of diabetes (OR, 3.84), increasing age (OR, 1.54), and nonwhite race (
OR, 2.36). In the 3372 participants free of clinical CVD, other noninv
asive measures of subclinical CVD, including carotid stenosis by duple
x scanning, segmental wall motion abnormalities by echocardiogram, and
major ECG abnormalities were inversely related to the AAI (all P<.01)
. Conclusions. There was an inverse dose-response relation of the AAI
with CVD risk factors and subclinical and clinical CVD among older adu
lts. The lower the AAI, the greater the increase in CVD risk; however,
even those with modest, asymptomatic reductions in the AAI (0.8 to 1.
0) appear to be at increased risk of CVD.