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C H A P T E R 148

PERIPHERAL ARTERY DISEASE

Reena L. Pande and Mark A. Creager

Peripheral artery disease (PAD) is an important manifestation of ABI alone, the differences in incidence between men and women are
1–4
systemic atherosclerosis with significant morbidity and mortality. less evident. In the Cardiovascular Health Study, for example, there
PAD affects the lower extremities and is defined as a stenosis or are no gender differences in the incidence of PAD based on ABI after
occlusion in the aorta or in the arteries supplying blood to the legs, adjusting for cardiovascular risk factors. At the other end of the
including the iliac, femoral, popliteal, or infrapopliteal vessels (pero- spectrum, CLI represents only 1% to 2% of the patients with PAD.
neal, posterior tibial, and anterior tibial arteries). Stenosis is typically The incidence of CLI is estimated to be approximately 400 to 1000
caused by atherosclerosis. Nonatherosclerotic causes of vascular per million individuals per year. 2
disease also can obstruct the peripheral arteries (see later discussion).
There are two major clinical consequences of PAD. First, PAD can
cause leg symptoms that include intermittent claudication, which Risk Factors
impairs walking ability and diminishes quality of life, and rest pain,
which occurs when there is critical limb ischemia (CLI). Second, as Atherosclerotic risk factors, including smoking, diabetes, hyperten-
an atherosclerotic disorder, PAD is associated with as much as a sion, hyperlipidemia, renal insufficiency, and inflammation, contrib-
four- to sixfold increased risk of cardiovascular death, myocardial ute to the development of PAD.
infarction (MI), and stroke. This chapter reviews the epidemiology, In virtually all population-based studies, smoking has been one of
pathophysiology, and management of PAD. the strongest risk factors for PAD. The risk is highest for current
smokers compared with nonsmokers, with a two to four times
increased odds of PAD, and the risk of PAD increases in a dose-
EPIDEMIOLOGY dependent manner relative to the number of cigarettes smoked and
the duration of tobacco use. In the Women’s Health Study, smoking
Prevalence and Incidence more than 15 cigarettes per day increased the risk of incident PAD
approximately 17-fold, and the risk was lower in former smokers than
The prevalence of PAD has been determined from several epidemio- in active smokers. In the Edinburgh Artery Study, smoking was two
logic studies. Early studies determined the prevalence of PAD from to three times more likely to cause lower extremity PAD compared
the presence of symptoms, such as intermittent claudication, or with coronary artery disease (CAD).
history of peripheral revascularization. Many patients with PAD are Diabetes is also a potent risk factor for PAD and increases the risk
asymptomatic, and the use of noninvasive diagnostic testing, specifi- of PAD by two- to fourfold. Data from the Rotterdam study and the
cally measurement of the ankle–brachial index (ABI), has provided San Luis Valley Diabetes study reveal that upwards of 12% to 20%
further clarification of the overall prevalence of disease. In most of of individuals with PAD have coexisting diabetes. Moreover, the risk
these studies, an ABI of 0.90 or less was used to define PAD. Based of PAD increases depending on the duration and severity of diabetes.
on data from the National Health and Nutrition Examination Survey In the Strong Heart Study, individuals with PAD had a more than
(NHANES), the prevalence of PAD in adults 40 years of age or older twofold higher prevalence of diabetes compared with those without
is estimated to be 5.9%, accounting for approximately 7.1 million PAD, and the diabetes tended to be of longer duration (11.7 vs. 8.4
5
adults in the United States alone. In addition, PAD is estimated to years, p < .001) and associated with higher glycosylated hemoglobin
affect as many as 202 million individuals worldwide, with increasing levels. Patients with PAD who have concomitant diabetes are also
6
prevalence in both high and low-middle income countries. There is more likely to develop intermittent claudication and ischemic ulcer-
a sharp increase in the prevalence of PAD with increasing age, ation and to require major amputation compared with those without
approximating 16.8% of women and 19.8% of men older than age diabetes.
65 years in the German Epidemiological Trial on ABI (GetABI Hypertension is a more modest risk factor for the development of
study). In a US-based observational study that examined a selected PAD compared with its importance as a risk factor for coronary and
1
population of adults older than 70 years or adults ages 50 to 69 years cerebrovascular disease. Although evidence suggests that hyperten-
with a history of diabetes or smoking, the prevalence of PAD was sion increases the prevalence of PAD by 1.5- to 2.2-fold, the associa-
7
29%. Recent studies have also shown higher PAD prevalence in tion of hypertension with incident or symptomatic PAD is less clear.
populations of lower socioeconomic status, including lower educa- Among American Indians in the Strong Heart Study, those with PAD
8
tion and lower income levels, as well as a disproportionate burden had a higher mean systolic blood pressure, and the prevalence of PAD
among some race/ethnicity groups, particularly blacks, as compared was significantly higher in those with established hypertension. In the
with Hispanic or non-Hispanic white populations. Framingham Heart Study, hypertension increased the risk of develop-
The incidence of PAD, which is largely based on the development ing intermittent claudication. However, in the Whitehall study of
of symptomatic disease, is less well established. Data from the Fram- more than 18,000 men ages 40 to 64 years, there was no significant
ingham Heart Study show an incidence rate of intermittent claudica- association between elevated blood pressure and claudication symp-
tion of less than 0.4 per 1000 per year in younger men (35–45 years) toms. Similarly, in the ARIC (Atherosclerosis Risk in Communities)
and a rate as high as 6 per 1000 per year in older men (older than study, there was no association of hypertension with incident PAD
65 years). The incidence of symptomatic PAD is lower in women at in subjects with diabetes. In the Women’s Health Study, however, the
most age groups, although the estimates are more comparable in the risk of incident PAD increased by 43% with every 10-mmHg increase
oldest age group. Estimates of the incidence of PAD based on ABI in systolic blood pressure.
are less commonly reported. One such study reports an incidence of Dyslipidemia, specifically elevated total cholesterol, low-density
1.7 per 1000 person-years for ages 40 to 54 years, 1.5 per 1000 lipoprotein (LDL) cholesterol and triglycerides, and reduced high-
person-years for ages 55 to 64 years, and 17.8 per 1000 person-years density lipoprotein (HDL) cholesterol, is associated with PAD.
for ages 65 years and older. When the diagnosis of PAD is based on Epidemiologic studies, such as the Cardiovascular Health Study and

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