Intermittent Claudication

This week's edition of NEJM has a sweet little review on Intermittent Claudication. Nice opportunity to discuss this progressively painful topic...

What are risk factors for peripheral artery disease?

Cigarette smoking
Diabetes mellitus
Hypertension
Hyperlipidemia
Hyperhomocysteinemia
Age greater than 50y
Male gender

Remember that peripheral vascular disease and coronary artery disease go hand in hand.

How do patients with intermittent claudication typically present?

leg muscle discomfort on exertion, relieved by rest
leg fatigue
difficulty walking

Pain may be in the calves, thighs, feet, and/or buttocks. It is helpful to document the number of blocks the patient can walk before symptoms arise.

What does claudico (L) mean?

To limp

What are findings commonly seen on physical exam?

abnormal pulses
vascular bruits
low ankle-brachial index

What is the ankle-brachial index (ABI)?

The ratio of systolic blood pressure taken in the arm over the systolic blood pressure taken at the ankle. This indicates severity of lower extremity peripheral vascular disease. Can be taken at rest and after exercise.
>0.9 Normal
0.7-0.9 Mild obstruction
0.4-0.7 Moderate obstruction
<0.4 Severe obstruction - critical ischemia

What are issues with ABI measurements in diabetics?

Diabetics have non-compressible vessels from medial calcification so ABI measurements may not be valid indicators of peripheral vascular disease. An alternative is measuring toe-brachial indices using photoplethysmography.

What is the natural history of intermittent claudication?

The risk of limb loss is low for patients without diabetes (<2%).
The risk of limb loss increases 3X with diabetics requiring drug therapy.
The risk of limb loss increases 20-25% for every 0.1 reduction in ABI.
The risk of cardiovascular events (MI, CVA) is about 5-7%/year.

Peripheral vascular disease is a continuum from intermittent claudication, to rest pain, to gangrene with tissue loss. Only 20-30% of patients with intermittent claudication progress to require some kind of intervention.

What is pseudoclaudication?

Leg pain from non-vascular causes (i.e., osteoarthritis, spinal stenosis, compartment syndrome, sciatica)

What are adjunctive non-invasive studies for further working-up peripheral artery disease?

Doppler probe survey
Duplex ultrasound
Segmental pressure recordings
Pulse-volume recordings

These may help assess the location, presence, and severity of a lesion.

What is a Doppler probe survey?

Using a hand-held continuous-wave Doppler probe unit, the femoral, popliteal, posterior tibial, and dorsalis pedis arterial signals are assessed. With severe stenosis or occlusion the Doppler pulse becomes monophasic and low-pitched.

What is a triphasic arterial signal?

1) High-pitched sound, representing forward systolic blood flow.
2) Low-pitched sound from reversed flow in early diastole
3) Medium-pitched sound, from resumed forward flow.

How does duplex ultrasound evaluate stenoses?

The doppler component allows measurement of blood flow velocity.
20-49% stenosis = increase of peak systolic velocity of 30-100% across lesion.
Critical (>50%) stenosis = increase in peak systolic velocity by greater than 100%
Total occlusion = no flow

Duplex has a 82% sensitivity and 92% specificity in detecting stenoses.

Why is a reduction of only half of the luminal diameter considered a "critical" stenosis?

Reduction in half the diameter represents a 75% reduction in the cross-sectional area of the vessel, leading to a 94% reduction in flow. Critical stenosis is when this reduction in cross-sectional area compromises blood flow leading to symptoms.

What are determinants of Resistance to flow?

By rearranging Poiseuille's Law, R = (8*viscosity*L)/(pi*r^4)
This means that a longer stenosis will increase vascular resistance linearly.
This also means that decreasing the vessel lumen radius will increase the resistance to the fourth power!

What is a pulse volume recording?

A segmental plethysmograph that records arterial pressure contours at various cuffs placed on an extremity. This allows for an indirect assessment of blood flow across the extremity. The distinct upstroke (anacrotic slope), pulse peak, downstroke (catacrotic slope), and wavelengths inform the interpreter, with flattening of the contour seen with severe stenosis.

What are segmental leg pressures?

Simply measuring thigh, calf, and ankle systolic pressures for assessment of extremity occlusion. All pressures are taken with reference to the dorsalis pedis doppler signal.

What is the gold-standard for evaluation of peripheral artery disease?

Angiography
Used if a surgical or endovascular intervention is planned. Alternatives to consider include MRA and CTA.

What are complications of angiography?

Contrast reactions (<4%)
Contrast nephropathy (<2%)
Bleeding (<2%)
Cholesterol embolization (<0.1%)

How do you treat peripheral vascular disease presenting as intermittent claudication?

You READ before you even think about operating!
1. Risk-factor modification
2. Exercise
3. Antiplatelet Therapy
4. Drugs

What are methods of risk-factor modification?

smoking cessation
regular exercise
dietary modification
control of hyperlipidemia (LDL <100, or <70 if high risk)
control of diabetes (HgA1c <7%)
control of blood pressure (<140/<90 or <130/<80 with DM)

What are the benefits of Exercise?

There is Level 1 evidence that exercise increases maximum walking distance by 150% over 3-12 months, with improvements greater than angioplasty and antiplatelet therapy (Cochrane Review).

The greatest benefit has been seen from continued walking until pain is maximal, at least 3 times per week, for at least 30min, for more than 6 months. Give the leg a chance to collateralize!

What are forms of antiplatelet therapy?

1. Aspirin - reduces cardiovascular death by 25%
2. Clopidogrel (Plavix) - use as an alternative to aspirin
3. Cilostazol (Pletal) - increases walking distance by 50% after 3-6mo

There is Class I, Level A evidence of benefit from cilostazol (Pletal) in patients with intermittent claudication.
There is Class IIb evidence (conflicting) of benefit from pentoxifylline (Trental).

What is the USPSTF recommendation for Aspirin use?

All patients at increased risk of coronary artery disease should consider aspirin chemoprevention. (Grade A)

How does Aspirin work?

It irreversible acetylates the enzyme cyclooxygenase. By blocking thromboxane A2 formation in platelets it decreases platelet aggregation and local vasoconstriction. Low-dose aspirin is thought to inhibit platelet thromboxane more than endothelial prostacyclin. Higher dose aspirins likely inhibit both.

What does thromboxane A2 do to blood vessels?

Causes vasoconstriction

What does prostacyclin (PGI2) do to blood vessels?

Causes vasodilation

How does clopidogrel (Plavix) work?

It blocks the ADP receptor on platelets, inhibiting platelet activation and the coupled activation of the glycoprotein IIb/IIIa complex (fibrinogen receptor).
This leads to inhibition of platelet aggregation and white clot (platelet/fibrinogen plug) formation.

How does cilostazol (Pletal) work?

It is a reversible PDE (phosphodiesterase) inhibitor that increases platelet cAMP, leading to vasodilatation and inhibition of platelet aggregation.

What is the mechanism of action of pentoxifylline (Trental)?

It is thought to improve the rheologic properties of blood by lowering blood viscosity and improving erythrocyte flexibility.

What are other drugs to consider?

Statins (HMG CoA Inhibitors)
Beta blockers
ACE Inhibitors
Nicotine replacement therapies

What is the most common vascular lesion associated with intermittent claudication?

Superficial femoral artery stenosis or occlusion

The region where the distal SFA enters Hunter's adductor canal is especially at risk.

What are indications for revascularization by angioplasty or surgery?

Claudication that limits lifestyle or ability to perform job
Claudication that is refractory to exercise and pharmacologic therapy
Claudication that progresses to rest pain

What are favorable lesion features for percutaneous transluminal angioplasty (PTA)?

Single stenosis less than 10cm long
Single occlusion less than 5cm long

What type of lesions is surgery preferred?

Occlusion greater than 20cm
Occlusion of the popliteal or tibial-peroneal vessels.

Surgery is also strongly considered for multiple lesions over 15cm and recurrent lesions after two endovascular interventions.

What are outcomes of femoropopliteal PTA?

Patency rates of 87% at 1y, 69% at 3y, and 55% at 5y.

We'll talk about surgical approaches to infrainguinal occlusive disease at a later time... SG

Sources:
White C. Intermittent Claudication. NEJM 2007; 356: 1241-1250.
Leng GC, Fowler B, Ernst E. Exercise for intermittent claudication. Cochrane Database of Systematic Reviews 2000; 2:CD000990.
Handbook of Patient Care in Vascular Diseases, 4th ed. Lippincott (2001).