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Which of the following statements is False:
1. PAD is a major risk factor for lower-extremity amputation.
2. Hypertension and hyperlipidemia are
the strongest risk factors for PAD.
3. Data from the Framingham Heart Study revealed that
20% of symptomatic patients with PAD had diabetes.
4. Of those with PAD, over one-half are asymptomatic
or have atypical symptoms.5. The most common symptom of PAD is intermittent
claudication
PAD is a manifestation of atherosclerosis characterized by atherosclerotic
occlusive disease of the lower extremities and is a marker for atherothrombotic
disease in other vascular beds. PAD affects ~12 million people in the
U.S.; it is uncertain how many of those have diabetes. Data from the
Framingham Heart Study[1] revealed that 20% of symptomatic patients
with PAD had diabetes, but this probably greatly underestimates the
prevalence, given that many more people with PAD are asymptomatic rather
than symptomatic. As well, it has been reported that of those with PAD,
over one-half are asymptomatic or have atypical symptoms, about one-third
have claudication, and the remainder have more severe forms of the disease.[2]
The most common symptom of PAD is intermittent claudication, defined
as pain, cramping, or aching in the calves, thighs, or buttocks that
appears reproducibly with walking exercise and is relieved by rest.
More extreme presentations of PAD include rest pain, tissue loss, or
gangrene; these limb-threatening manifestations of PAD are collectively
termed critical limb ischemia (CLI).
PAD is also a major risk factor for lower-extremity amputation, especially
in patients with diabetes. Moreover, even for the asymptomatic patient,
PAD is a marker for systemic vascular disease involving coronary, cerebral,
and renal vessels, leading to an elevated risk of events, such as myocardial
infarction (MI), stroke, and death.
Diabetes and smoking are the strongest risk factors for PAD. Other well-known
risk factors are advanced age, hypertension, and hyperlipidemia.[3]
Potential risk factors for PAD include elevated levels of C-reactive
protein (CRP), fibrinogen, homocysteine, apolipoprotein B, lipoprotein(a),
and plasma viscosity. An inverse relationship has been suggested between
PAD and alcohol consumption.
In people with diabetes, the risk of PAD is increased by age, duration
of diabetes, and presence of peripheral neuropathy. African Americans
and Hispanics with diabetes have a higher prevalence of PAD than non-Hispanic
whites, even after adjustment for other known risk factors and the excess
prevalence of diabetes. It is important to note that diabetes is most
strongly associated with femoral-popliteal and tibial (below the knee)
PAD, whereas other risk factors (e.g., smoking and hypertension) are
associated with more proximal disease in the aorto-ilio-femoral vessels.
The true prevalence of PAD in people with diabetes has been difficult
to determine, as most patients are asymptomatic, many do not report
their symptoms, screening modalities have not been uniformly agreed
upon, and pain perception may be blunted by the presence of peripheral
neuropathy. For these reasons, a patient with diabetes and PAD may be
more likely to present with an ischemic ulcer or gangrene than a patient
without diabetes. While amputation has been used by some as a measure
for PAD prevalence, medical care and local indications for amputation
versus revascularization of the patient with critical limb ischemia
widely vary. The nationwide age-adjusted amputation rate in diabetes
is ~8/1,000 patient years with a prevalence of ~3%. However, regional
patterns differ—there is nearly a ninefold variation of major
amputations in people with diabetes across the U.S. Therefore, the incidence
and prevalence of amputation may be an imprecise measure of PAD.
The reported prevalence of PAD is also affected by the methods by which
the diagnosis is sought. Two commonly used tests are the absence of
peripheral pulses and the presence of claudication. Both, however, suffer
from insensitivity. A more accurate estimation of the prevalence of
PAD in diabetes should rely upon a validated and reproducible test.
Such a test is the ankle-brachial index (ABI), which involves measuring
the systolic blood pressures in the ankles (dorsalis pedis and posterior
tibial arteries) and arms (brachial artery) using a hand-held Doppler
and then calculating a ratio. Simple to perform, it is a noninvasive,
quantitative measurement of the patency of the lower extremity arterial
system. Compared with an assessment of pulses or a medical history,
the ABI has been found to be more accurate. It has been validated against
angiographically confirmed disease and found to be 95% sensitive and
almost 100% specific.[4] There are some limitations, however, in using
the ABI. Calcified, poorly compressible vessels in the elderly and some
patients with diabetes may artificially elevate values. The ABI may
also be falsely negative in symptomatic patients with moderate aortoiliac
stenoses. These issues complicate the evaluation of an individual patient
but are not prevalent enough to detract from the usefulness of the ABI
as an effective test to screen for and to diagnose PAD in patients with
diabetes. Using the ABI, one recent survey[5] found a prevalence of
PAD in people with diabetes >40 years of age to be 20%, a prevalence
greater than anticipated using less reliable measures, such as symptoms
or absent pulses. Moreover, another survey of patients with diabetes
>50 years of age showed a prevalence of PAD of 29%.[6] Thus, the
prevalence of PAD in diabetes appears higher than previously estimated.
Impact of PAD
The impact of PAD can be assessed by its progression, the presence of
symptoms, and the excess cardiovascular events associated with systemic
atherosclerosis. Approximately 27% of patients with PAD demonstrate
progression of symptoms over a 5-year period, with limb loss occurring
in ~4%. While the majority of patients remain stable in their lower-limb
symptomatology, there is a striking excess cardiovascular event rate
over the same 5-year time period, with 20% sustaining nonfatal events
(MI and stroke) and a 30% mortality rate.[7] For those with CLI, the
outcomes are worse: 30% will have amputations and 20% will die within
6 months.[8] The natural history of PAD in patients with diabetes has
not specifically been studied longitudinally, but it is known from prospective
clinical trials of risk interventions that the cardiovascular event
rates in patients with PAD and diabetes are higher than those of their
nondiabetic counterparts.
Diagnosis of PAD
Diagnosing PAD is of clinical importance for two reasons. The first
is to identify a patient who has a high risk of subsequent MI or stroke
regardless of whether symptoms of PAD are present. The second is to
elicit and treat symptoms of PAD, which may be associated with functional
disability and limb loss. PAD is often more subtle in its presentation
in patients with diabetes than in those without diabetes. In contrast
to the focal and proximal atherosclerotic lesions of PAD found typically
in other high-risk patients, in diabetic patients the lesions are more
likely to be more diffuse and distal. Importantly, PAD in individuals
with diabetes is usually accompanied by peripheral neuropathy with impaired
sensory feedback. Thus, a classic history of claudication may be less
common. However, a patient may elicit more subtle symptoms, such as
leg fatigue and slow walking velocity, and simply attribute it to getting
older. It has been reported that patients with PAD and diabetes experience
worse lower-extremity function than those with PAD alone.[9] Also, diabetic
patients who have been identified with PAD are more prone to the sudden
ischemia of arterial thrombosis[10] or may have a pivotal event leading
to neuroischemic ulceration or infection that rapidly results in an
acute presentation with critical limb ischemia and risk of amputation.
By identifying a patient with subclinical disease and instituting preventative
measures, it may be possible to avoid acute, limb-threatening ischemia.
PAD in diabetes also adversely affects quality of life, contributing
to long-term disability and functional impairment that is often severe.
Patients with claudication have a slower walking speed (generally <2
mph) and a limited walking distance. This may result in a "cycle
of disability" with progressive deconditioning and loss of function.
Finally, there are significant economic costs of health care, reduced
productivity, and personal expenses associated with a chronic manifestation
of atherosclerotic disease such as PAD.
References for:
1. Murabito JM, D'Agostino RB, Silbershatz H, Wilson
WF: Intermittent claudication: a risk profile from the Framingham Heart
Study. Circulation 96:44 -49, 1997
2. Hiatt WR: Medical treatment of peripheral arterial disease and claudication.
N Engl J Med 344:1608-1621, 2001
3. Criqui MH: Peripheral arterial disease: epidemiological aspects.
Vascular Medicine 6 (Suppl. 1):3-7, 2001
4. Bernstein EF, Fronek A: Current status of non-invasive tests in the
diagnosis of peripheral arterial disease. Surg Clin North Am 62:473-
487, 1982
5. Elhadd TA, Robb R, Jung RT, Stonebridge PA, Belch JJF: Pilot study
of prevalence of asymptomatic peripheral arterial occlusive disease
in patients with diabetes attending a hospital clinic. Practical Diabetes
Int 16:163-166, 1999
6. Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager
MA, Olin JW, Krook SH, Hunninghake DB, Comerota AJ, Walsh ME, McDermott
MM, Hiatt WR: Peripheral arterial disease detection, awareness, and
treatment in primary care. JAMA 286:1317-1324, 2001
7. Weitz JI, Byrne J, Clagett GP, Farkouh ME, Porter JM, Sackett DL,
Strandness DE Jr, Taylor LM: Diagnosis and treatment of chronic arterial
insufficiency of the lower extremities: a critical review. Circulation
94:3026-3049, 1996
8. Dormandy JA, Rutherford RB: Management of peripheral arterial disease
(PAD): TASC Working Group: TransAtlantic Inter-Society Concensus (TASC).
J Vasc Surg 31:S1-S296, 2000
9. Dolan NC, Liu K, Criqui MH, Greenland P, Guralnik JM, Chan C, Schneider
JR, Mandapat AL, Martin G, McDermott MM: Peripheral artery disease,
diabetes, and reduced lower extremity functioning. Diabetes Care 25:113-120,
2002
10. McDaniel MD, Cronenwett JL: Basic data related to the natural history
of intermittent claudication. Ann Vasc Surg 3:273- 277, 1989
Diabetes Care 26(12):3333-3341, 2003
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