Peripheral Arterial Disease Case File

Peripheral Arterial Disease Case File

Eugene C. Toy, Md, Michael d . Faulx, Md

Case 5

A 67- year -old Caucasian man presents to his primary care physician complaining of bilateral lower extremity pain. The pain has been present for a few months, but he has noticed an increase within the last 3 weeks. He describes it as a sharp pain, 8/10 in severity that is equal in both legs and localizes to the calves and feet. The pain worsens when he walks long distances and subsides within a few minutes after he stops physical activity and rests. He denies any similar upper extremity pain or weakness. He denies any history of lower extremity trauma, or any associated neurologic dysfunction. The patient reports a history of hypertension for nearly 15 years for which he takes metoprolol. He also has hyperlipidemia,

and his most recent checkup demonstrated an LDL of 193 mg/dL, for which he was prescribed simvastatin. He has a 50-pack/year smoking history and currently smokes one pack per day . His remaining review of systems is normal. On physical examination his vital signs are temperature 98°F, pulse 81 bpm, blood pressure 137/83 mmHg , and respirations 16 breaths/min. Lungs are clear to auscultation bilaterally , and heart sounds are regular and normal with no associated murmurs, rubs, or gallops. Abdominal exam is within normal limits. Lower extremity exam reveals hairless legs with mildly glossy skin and no evidence of ulcers, discoloration, or erythema. No appreciable bruits are auscultated. Palpated pulses are 2+ femoral with 1+ dorsalis pedis and posterior tibial bilaterally .

c What is the most likely diagnosis?

c What is the best next diagnostic step?

c What is the best next step in therapy ?

Answer to Case 5:

Peripheral Arterial Disease

Summary: A 67-year-old Caucasian man with a medical history significant for hypertension and dyslipidemia along with an extensive smoking history presents with a one-month history of activity-associated lower extremity pain. He reports that the pain is exacerbated by exercise and relieved by rest. Physical exam is normal except for mildly decreased bilateral pedal pulses and skin changes consistent with reduced arterial flow to the legs.

• Most likely diagnosis: Peripheral arterial disease with claudication
• Next diagnostic step: Ankle-brachial index (ABI)
• Next step in therapy: Risk factor modification, antiplatelet medications

ANALYSIS

Objectives

1. Learn the pathophysiologic mechanism behind peripheral arterial disease.
2. Understand the appropriate use of imaging modalities used to make a diagnosis.
3. Be able to differentiate between claudication and pseudoclaudication based on a thorough medical history and physical exam.
4. Be familiar with the treatment algorithm for peripheral arterial disease.

Considerations

This 67-year-old man with multiple medical comorbidities presents with activity related lower extremity pain that is completely relieved by rest. Because of his age and medical issues, we must thoroughly consider multiple diagnoses. His history of hypertension, dyslipidemia, and smoking certainly places him at risk for atherosclerosis. The fact that he has thus far not suffered any cardiac consequences should not deter us from further peripheral vascular investigation. Because of his age and activity- related lower extremity pain, we must also consider osteoarthritis as a potential etiology. Bilateral x-rays of the knees may be warranted to determine the cause of his pain if other tests are equivocal. At this time, however, on the basis of his medical history and physical exam findings, the most likely diagnosis is peripheral arterial disease, and ABI measurements via Doppler should be ordered.

Approach To:

Noncoronary Arterial Disease

DEFINITIONS

PERIPHERAL ARTERIAL DISEASE: A disorder that obstructs the blood supply

to lower or upper extremities.

CLAUDICATION: Pain or fatigue that occurs in a particular muscle region. Typically resolves with cessation of activity.

ANKLE-BRACHIAL INDEX (ABI): The ratio of ankle systolic blood pressure to brachial systolic blood pressure. Value can indicate presence and/or severity of disease.

CLINICAL APPROACH

Epidemiology

Peripheral arterial disease tends to exclusively affect individuals over 40, and incidence tends to increase in the more elderly age groups. The National Health and Nutrition Examination Survey (NHANES), which utilized data collected from 2174 participants during 1999–2000, calculated prevalence based on an ABI of <0.90, indicating disease. The study demonstrated an associated increase in the incidence of PAD as age increased. PAD tends to occur with relatively equal frequency between genders, with women demonstrating increased incidence as compared to men after age 70 years. Among ethnic groups, PAD tends to occur more in African Americans than non-Hispanic whites. As the proportion of the US population that is elderly continues to grow, physicians can anticipate that the prevalence of PAD will continue to increase as well.

It is traditionally accepted that the risk factors for peripheral arterial disease are similar to those associated with the development of coronary atherosclerosis. Specifically, hypertension, dyslipidemia, diabetes mellitus, and smoking have been strongly associated with PAD. Table 5-1 demonstrates the positive correlation between these risk factors and the incidence of PAD.

Clinical Presentation

The classic symptom of PAD is that of claudication. As mentioned earlier, claudication refers to pain and/or fatigue occurring in a particular muscle region that resolves with rest. Pain results from an imbalance of oxygen supply and demand. The atherosclerotic factors mentioned earlier result in progressive stenosis of blood vessels, and while compensation is sufficient during the resting state, blood flow tends to be inadequate during exercise. This results in the accumulation of lactate and other metabolites that activate local pain receptors. The location of pain is directly related to the vascular distribution that is affected by stenosis. Obstruction of the aortoiliac trunk results in hip and thigh claudication, whereas femoral and popliteal artery involvement classically results in calf claudication. If the severity of

(Reproduced, with permission from, Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. Robert O. Bonow and Eugene Braunwald, editors. 9th ed. Philadelphia, PA: Elsevier, Saunders; 2012.)

PAD progresses to extreme levels, patients may demonstrate resting pain and/or the development of skin ulcers, which is indicative of critical limb ischemia warranting immediate intervention.

While PAD-associated claudication is typically due to atherosclerosis, the clinician must also recognize that arterial thromboembolism, aneurysm, and direct vascular injury may produce similar physical findings. As one might imagine, these etiologies will result in a more immediate onset of lower extremity pain, as compared to the more insidious nature due to atherosclerosis. In the elderly population, another diagnosis to consider for activity-related pain is osteoarthritis. While osteoarthritis can certainly present with bilateral pain in an elderly individual, it is more often associated with the hip and/or knee joints, instead of the very specific calf pain found in PAD. Furthermore, PAD is typically relieved by cessation of activity, whereas the discomfort of osteoarthritis may persist, and progressively worsen throughout the day even with minimal activity.

The final differential diagnosis to consider is neuro- or pseudogenic claudication. This condition is due to spinal stenosis, and while it may mimic PAD, there are subtle differences that elucidate the difference between etiologies. Spinal stenosis often results in nerve root impingement, and this will cause patients to complain of a radiculopathic pain shooting down buttocks or legs. Furthermore, this pain is more position-related instead of activity-related, and most often occurs when the spine is in extension. As such, an individual can be standing still and have severe neurogenic claudication, whereas a patient with PAD will not experience such pain with simple standing. Patients with neurogenic claudication can perform extended duration of physical activity while sitting in flexion on a stationary bicycle, whereas a patient with PAD will be unable to tolerate prolonged physical activity due to the vascular imbalances alluded to earlier.

Diagnosis

As with any cardiovascular illness, the initial diagnostic approach should include a thorough history and physical exam. Relevant medical history should be queried, focusing on a history of hypertension, diabetes, dyslipidemia, and smoking and a previous history of cardiovascular events. A complete cardiovascular exam should be performed, including an auscultation for bruits and decreased distal pulses. The presence of both of these increases the likelihood of PAD, and specific anatomic location may correlate with the location of patient pain. Furthermore, the finding of glossy, hairless shins and muscle atrophy corroborate PAD and a vascular etiology

If a physician is suspicious for PAD, the next step in diagnosis would be to calculate the ankle-brachial index (ABI). The ABI is a fairly simple and cost-efficient method that can be used for determining disease severity and to guide treatment. As stated earlier, it is the ratio of the systolic blood pressure measured at the ankle to that of the systolic blood pressure measured in the arm (brachial artery). A standard pneumatic cuff is placed around the ankle and inflated to suprasystolic pressures. Concomitantly, a Doppler ultrasound probe is placed over the dorsalis pedis and posterior tibial arteries, and is used to determine recurrence of flow (systolic pressure) during cuff deflation. Similarly, the brachial systolic pressure can be measured by traditional methods using a stethoscope to auscultate for the first Korotkoff sound. It is important to remember to measure both ankle and brachial values bilaterally, to avoid the possibility of any unilateral anomalies skewing results. In healthy individuals, ankle SBP is higher than brachial SBP. Keeping this in mind, the range of values that are considered normal ABI are between 0.9 and 1.3. Values of <0.9 are considered diagnostic for PAD, and may warrant duplex ultrasound, CT, or magnetic resonance angiography (MRA) to elucidate specific vascular pathology.

Management

As stated earlier, PAD is secondary to several risk factors that also cause significant cardiovascular morbidity and mortality. As such, initial treatment is lifestyle modification of these risk factors, which will decrease not only PAD symptoms but also the overall risk of fatal cardiovascular events. Smoking cessation can have significantly positive effects on reducing symptoms and overall survival; patients with PAD who discontinue smoking have nearly twice the 5-year survival rate of those who continue to smoke. While current literature demonstrates that intensive insulin control has no change in the risk of PAD, physicians agree that appropriate management should still aim for a HbA1c <7.0% to reduce both microvascular complications and overall derangements. Similarly, while hypertension is a risk factor for developing PAD, there currently is no definitive study demonstrating that blood pressure management can decrease progression of PAD. However, aggressive management of hypertension can significantly reduce risk of myocardial infarction and overall cardiac complication, and thus use of beta-blockers and ACE inhibitors is still justified.

Multiple studies have demonstrated that the use of statins for dyslipidemia can have profound benefits on PAD symptoms. A randomized, double-blind trial that included 354 patients with claudication attributable to PAD examined difference between atorvastatin (10 or 80 mg/day) and placebo. At 12 months, there was a significant improvement in pain-free walking time with high-dose atorvastatin [63% vs. 38% with placebo (81 vs. 39 seconds)] and in community-based physical activity with both doses of atorvastatin. Current consensus among physicians is that ideal LDL cholesterol in patients with PAD should be <100 mg/dL.

While these methods focus around lifestyle modification, pharmacotherapy in PAD usually involves antiplatelet agents and/or cilostazol. Current data suggest minimal improvement of PAD symptoms with antiplatelet agents; however, their use is still encouraged as a means of reducing risk of common cardiac events such as MI and stroke. Cilostazol is a phosphodiesterase inhibitor that inhibits platelet aggregation while also serving as an arterial vasodilator and has been shown to significantly provide symptomatic relief of PAD. A meta-analysis of 2491 patients demonstrated a significant increase in maximal and pain-free walking distances when compared to placebo.

In summary, aggressive management of diabetes, hypertension, and dyslipidemia, and encouragement of smoking cessation along with pharmacotherapy, can have beneficial effects on PAD and also overall reduction in cardiovascular events. If further complications arise and/or these methods are not efficacious, therapeutic intervention in the form of angioplasty and stenting should be considered.

Complications

Aside from the previously mentioned cardiovascular events (MI, stroke, CHF) that may be due to overlapping PAD risk factors, a serious cause for concern is the development of PAD toward critical limb ischemia. Critical limb ischemia affects 1–2% of patients with PAD older than 50 years and can be defined as a condition where “arterial blood flow is insufficient to meet metabolic demands of resting muscle or tissue.” Symptoms include rest pain, gangrene, and the development of nonhealing lower extremity ulcers (Figure 5-1). These patients should be immediately referred to a vascular intervention specialist for consideration of surgical or percutaneous revascularization to prevent further complications such as limb amputation.

CASE CORRELATION

• See also Case 1 (acute coronary syndrome/STEMI), Case 2 (acute coronary syndrome/NSTEMI), and Case 4 (chronic coronary artery disease).

Figure 5-1. Dry gangrene of the foot in a patient with peripheral arterial disease. (Reproduced, with

permission, from Mehdi Shishehbor, DO.)

COMPREHENSION QUESTIONS

5.1 In a patient who presents to a primary care physician with signs and symptoms of claudication secondary to peripheral arterial disease, which of the following would be an ideal initial diagnostic modality?

A. Angiography

B. Treadmill walk test

C. Cardiac ultrasound

D. Ankle-brachial index

5.2 What is the pathophysiologic mechanism by which pain occurs during classic claudication of the calf muscles?

A. Imbalance between oxygen supply and demand due to inadequate blood flow, resulting in buildup of toxic metabolites

B. Hypertrophy of anterior and posterior compartment leg muscles that results in hyperactivation of nocireceptors

C. Arteriovenous fistulas

D. Microangiopathy secondary to diabetes

5.3 In a patient with PAD, what should be the ideal LDL goal for preventing further disease progression?

A. < 170 mg/dL

B. < 200 mg/dL

C. < 140 mg/dL

D. < 100 mg/dL

5.4 Which of the following symptoms would categorically suggest a diagnosis of pseudoclaudication over traditional claudication?

A. Pain in thighs and calves

B. Knee pain that increases with activity

C. Severe back and leg pain while walking downhill but not uphill

D. Chest pain during rest

5.5 A 67-year-old man is diagnosed with peripheral arterial disease. Modification of which of the following risk factors would be advisable for this patient?

A. Smoking cessation

B. Diabetes

C. Dyslipidemia

D. Hypertension

E. All of the above

ANSWERS

5.1 D. The ankle-brachial index serves as a convenient and cost-effective tool to determine the presence and/or severity in PAD. Arteriography is the gold standard, and may be warranted depending on results of the ankle-brachial index (it is very invasive, however); a treadmill walk test could be used if the results are equivocal. A cardiac ultrasound has no utility in the direct diagnosis of PAD.

5.2 A. As a result of atherosclerosis and vessel narrowing, inadequate blood flow occurs during periods of high physical activity, and thus oxygen supply is less than oxygen demand, resulting in vascular congestion and buildup of lactate and other metabolites that result in pain. While pain in the gastrocnemius (calf) is, indeed, a common complaint, it is not due to hypertrophy of the muscle, but instead lack of blood flow. While diabetes certainly worsens the microcirculation within muscle vasculature, it is not the reason for pain perception. Similarly, AV fistulas and microangiopathy secondary to diabetes are not pain generators in PAD.

5.3 D. The American College of Cardiology and STAHC II suggest that patients with PAD should be managed aggressively in regard to hyperlipidemia, as PAD is a cardiovascular risk factor.

5.4 C. Neurogenic or pseudoclaudication is due to spinal stenosis. As such, changes in position, namely, forward flexion that occurs during uphill walking, increase the diameter of the spinal column and relieve pain. Spinal extension, which occurs when walking downhill, narrows the vertebral canal and causes subsequent pain. Pain secondary to PAD, on the other hand, is not positional, and correlated only with quantity of physical activity. Patients with pseudoclaudication commonly complain of pain in back and buttocks, whereas PAD is more classically located in the thigh and calves. Knee pain that worsens with activity is a hallmark of osteoarthritis. Rest pain is highly suggestive of terminal PAD.

5.5 E. All of the factors listed significantly increase the risk for developing PAD, and both physicians and patients should be aggressive in their efforts to limit exposure to them.

CLINICAL PEARLS

C Peripheral arterial disease can have significant morbidity and mortality on patients. and every effort should be made to address the underlying risk factors.

C Peripheral arterial disease indicates significant systemic atherosclerosis, and as such patients are at higher risk for stroke, myocardial infarction. and angina.

C After a thorough history and physical exam, the ankle-brachial index is best initial diagnostic test of choice to guide further management.

C Aggressive management of diabetes, hypertension, and dyslipidemia, and encouragement of smoking cessation along with pharmacotherapy. can have beneficial effects on PAD and also overall reduction in cardiovascular events.

References

Creager MA, Libby P. Peripheral artery disease. In: Bonow O, Braunwald E, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, PA: Elsevier, Saunders; 2012: 1338–1356. 

Criqui MH, Vargas V, Denenberg JO, et al. Ethnicity and peripheral artery disease: The San Diego Population Study. Circulation. 2005;112:2703. 

Hiatt WR, Goldstein J, Smith SC Jr, et al. Atherosclerotic Peripheral Vascular Disease Symposium II: nomenclature for vascular diseases. Circulation. 2008;118:2826. 

Hirsch AT, Allison MA, Gomes AS, et al. American Heart Association Council on Peripheral Vascular Disease; Council on Cardiovascular Nursing; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology; Council on Epidemiology and Prevention. A call to action: women and peripheral artery disease: a scientific statement from the American Heart Association. Circulation. 2012;125(11):1449–1472. 

Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577. 

Lu JT, Creager MA. The relationship of cigarette smoking to peripheral artery disease. Rev Cardiovasc Med. 2004;5:189. 

Mohler ER 3rd, Hiatt WR, Creager MA. Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral artery disease. Circulation 2003;108(12):1481–1486. 

Pande RL, Hiatt WR, Zhang P, Hittel N, Creager MA. A pooled analysis of the durability and predictors of treatment response of cholesterol in patients with intermittent claudication. Vasc Med. 2010;15(3):181–188. 

Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999–2000. Circulation. 2004;110(6):738–743. 

Skyler JS, Bergenstal R, Bonow RO, et al. Intensive glycemic control and the prevention of cardiovascular events: Implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association. Circulation. 2009;119:351.

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