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CVI and PAD: A review of venous and arterial disease

Chronic venous insufficiency and peripheral arterial disease have similar symptoms. Here’s what to look for to make the correct diagnosis.

Carie Bahr, PA-C, MPAS

Carie Bahr is a physician assistant with Cardiovascular Associates of Northern Wisconsin in Wausau. She has indicated no relationships to disclose relating to the content of this article.

Two prevalent vascular conditions affecting many Americans are chronic venous insufficiency (CVI) and peripheral arterial disease (PAD). These diseases are associated with significant morbidity and mortality, and they may indicate the presence of other serious vascular conditions. People with CVI and PAD experience a decreased quality of life due to pain and disability. These conditions often result in a loss of the ability to perform activities of daily living.

CVI and PAD have different mechanisms of action. Clinicians should understand this and be familiar with the signs and symptoms of each condition. A thorough history and physical examination will give clues as to whether the patient’s problem is of venous or arterial nature. For each condition, both medical and surgical treatment options are available. Patients also can make important lifestyle modifications that will slow disease progression. Underdiagnosis in primary care can be a barrier to secondary prevention, which is known to decrease morbidity and mortality; clinicians need to be aware of these conditions and be able to identify those patients at risk.

CHRONIC VENOUS INSUFFICIENCY

CVI affects approximately 2.5 million people in the United States.¹ It is caused by venous hypertension and incompetent valves leading to dilated veins, discoloration, swelling, pain, skin changes, and ulceration. CVI involves both superficial and deep venous systems. A serious complication of CVI is venous ulcer. Only 50% of ulcers heal within 4 months, and venous ulcers have a 6% to 15% chance of recurring.^1,2 An estimated 2 million workdays are lost per year because of complications of venous ulcers.

Pathophysiology A healthy venous system is comprised of two parts, superficial circulation and deep circulation, which are connected by perforating veins. The two circuits work in unison to store blood and return blood to the heart. In order for the venous system to work adequately, a series of valves and muscle pumps must function properly. Bicuspid valves within the veins keep blood flowing toward the heart. Muscle pumps in the foot, calf, and thigh aid the valves in preventing backflow towards the feet.^1,3

CVI is the result of an interruption of blood flow within the venous system (see Figure 1). The interruption is caused by valvular reflux, thrombotic obstruction of the valves, or a combination of the two (see “Table. Causes of chronic venous insufficiency”). A disturbance in calf muscle pump function exacerbates the reflux and obstruction.^1,3-5

An immune-mediated response to severe CVI is an increase in inflammatory cells such as macrophages and T-lymphocytes, which can cause endothelial damage.² As CVI progresses, increased microvascular blood flow causes the capillaries to become dilated and tortuous.⁶ Increasing hydrostatic forces lead to the accumulation of perivascular and lymph fluids causing edema; decreased oxygenation to surrounding tissues; and skin changes, particularly stasis dermatitis.⁷ Hyperpigmentation, an irreversible red-purple hue, is the result of RBCs leaking from the blood vessels and becoming trapped under the skin.¹ Complications of severe CVI result in the formation of thromboses, reducing blood flow and depriving the skin of nutrients and oxygen. The result is ulceration and microedema and, ultimately, the development of venous ulcers.

History and examination Key findings in the physical examination of patients with CVI are edema, pain, and skin changes. Completely expose the patient’s legs from the thigh to the foot and carefully inspect the skin for color changes, edema, stasis dermatitis, varices, and ulcers. Have the patient stand up to allow for maximum dilation of the venous vasculature, and palpate for tenderness and assess pulses. Pulses are generally palpable but may be lost due to severe edema or PAD.¹ Table 1 shows a side-by-side comparison of the signs and symptoms of CVI and PAD versus limb threatening ischemia.^3,5,8

Risk factors for CVI include increased time standing, pregnancy, prior deep venous thrombosis (DVT), obesity, age, sex, and previous leg injury.^1,3,5 CVI is three times more prevalent in females than in males; this higher incidence is related to pregnancy prior to onset of CVI. Differential diagnoses of lower extremity pain and edema are heart failure, nephritic syndrome, endocrine disorders, liver disease, Baker’s cyst, hematoma, Achilles’ tendon tear, DVT, or the side effects of medications (eg, calcium channel blockers, NSAIDs, oral hypoglycemic agents, and statins).¹

Testing The tourniquet test, an easy-to-use office test, distinguishes superficial reflux from deep reflux. While the patient is lying down, a tourniquet is placed on the leg to empty the lower extremity veins. The patient is then asked to stand up. If the varicosities are superficial and the tourniquet is proximal to the site of reflux, the vein will remain collapsed. If reflux is due to deep insufficiency, varicose veins will appear.¹

Continuous-wave Doppler scanning detects reflux at the saphenofemoral and saphenopopliteal junctions. The probe is placed on the area in question while the patient performs the Valsalva maneuver. A detectable signal of more than 0.5 seconds indicates reflux.^1,2 Because crossing vessels in the area can give false results, follow-up with duplex scanning is needed to confirm the diagnosis.²

Duplex scanning is the test of choice because it is easy to use, noninvasive, and cost-effective. It demonstrates venous anatomy along with venous flow pattern. This test shows the presence of reflux and the anatomic extent of disease, but cannot indicate disease severity. Operator skill, patient obesity, and edema can inhibit adequate imaging.^2,9,10

Ascending phlebography, the gold standard for venous testing, displays reflux and anatomic extent and distinguishes valvular dysfunction due to valve-cusp nonunion from postphlebitic syndrome. Descending phlebography identifies points of leakage from the pelvis into the lower limbs. Phlebography is an invasive procedure and cannot show severity of reflux.^2,10

The International Consensus Committee on CVI recommends using the CEAP (Clinical, Etiologic, Anatomic, Pathophysiologic) classification scale,¹⁰ along with the history, physical examination, and venous scans to determine the extent of disease.^2,10 The CEAP classification scale, developed during the 1994 American Venous Forum, classifies venous disorders according to clinical presentation, etiology, anatomic location, and pathophysiology. The scale is used to identify disease state, mark disease progression, and aid in therapeutic decision making.^2,10

Treatment Compression is the first-line therapy for CVI. The mechanism of action is utilized to oppose hydrostatic forces; it reduces venous reflux and improves venous pumping. The preferred method is graded elastic compression stockings.^1,2,7 The stockings exert greater compression near the ankle, gradually becoming looser fitting towards the thigh. The increased pressure at the ankle prevents backflow without causing a tourniquet effect.⁷ Patients should wear stockings with 20 to 50 mm Hg of compression.^1,2,7 Contraindications are the presence of PAD and an ankle-brachial index (ABI) of less than 0.8.^5,9

For patients with venous ulcers, pneumatic compression is used until the ulcer begins to heal, and then elastic stockings are used. The exact mechanism of action is unknown, but lowering the venous pressure appears to allow ulcers to heal. Basic principles of wound care are applied to enhance healing, including assessing for signs of infection.^5,11 Patients who have stasis dermatitis should be treated with a topical corticosteroid and moisturizer.¹

Severe symptoms and recurrent nonhealing ulcers are indications for surgical intervention. Surgical options for symptomatic CVI include bypass, stent placement, and valvuloplasty. Patients with venous outflow obstruction are usually treated with cross-femoral venous bypass or iliac vein reconstruction. Recently, iliac stents have become more widely used for venous obstruction. Varicose veins are treated with various medical and surgical treatments. Sclerotherapy involves injecting sodium tetradecyl sulfate or sodium morrhuate to obliterate the vein.⁷ Complications include hyperpigmentation and medication-caused necrosis. Surgical treatments include high ligation of the saphenofemoral junction, saphenous vein stripping, endoscopic perforator vein ligation, stab-avulsion phlebectomies, endovenous obliteration, and ablative endovenous radiofrequency therapy.^1,12,13

No pharmacologic treatments are currently approved for CVI in the United States. In Europe, CVI is treated with several agents (ie, coumarins, flavonoids, saponins, and plant extracts) believed to improve venous tone and capillary permeability.⁷

Nicotine is a strong vasoconstrictor that can impede perfusion of lower extremities. Carbon monoxide inhaled while smoking binds tightly with hemoglobin and can decrease oxygen delivery to tissues, slowing wound healing.⁵ Patients who smoke should be urged to quit.

PERIPHERAL ARTERIAL DISEASE

PAD has been diagnosed in approximately 8 to 12 million people in the United States.¹⁴ However, a national survey called PAD Awareness Risk and Treatment: New Resources for Survival found that only 49% of primary care physicians recognized the signs of PAD in their patients and aggressively managed the risk factors.^14,15 PAD refers to chronic occlusive arterial vessel disease due to atherosclerotic plaque obstructing and decreasing blood flow (see Figure 2). Although PAD can affect all blood vessels, this discussion focuses on PAD in the lower extremities. The condition is a strong marker for future cardiovascular events.^16,17

Pathophysiology PAD is caused by atherosclerotic changes identical to the process of atherosclerotic coronary artery disease (CAD)^16,18 (see “Figure. Pathogenesis of peripheral arterial disease”). The degree and length of the stenosis, the flow velocity, and the blood viscosity propagate resistance in the vascular system. As resistance increases with exercise and walking, blood flow cannot overcome these forces. Patients have decreased blood flow to their lower extremities accompanied with symptoms of claudication. This process is not clinically relevant until a thrombus reduces the diameter of a blood vessel by more than 80%.¹⁶ Left untreated, PAD can lead to serious physical limitations, occlusion of the affected vessel, ulceration, and eventual loss of the limb that receives its blood supply from the obstructed vessel.

Chronic PAD also affects the lower extremity musculature. Ischemia of the musculature results in a buildup of lactate and acylcarnitines, which is inversely related to exercise performance. Patients with PAD have skeletal muscle deterioration, specifically of the type 2 fibers, and muscle fiber denervation. Loss of these fibers is permanent and leads to decreased muscle strength and atrophy.¹⁸

History and examination Patients with PAD are generally seeking pain relief.^7,16,19,20 Pain associated with PAD is defined as claudication, which is brought on by a consistent amount of walking or exercising. Relief is achieved with rest; however, the patient will continue to have a predictable pain-rest cycle. Strenuous efforts, such as walking uphill, will further shorten the distance the patient is able to walk before pain develops.

In addition to a careful inspection of the lower extremities for discoloration and ulcers, palpation of the pulses is essential. An absent or diminished pulse along with a history of claudication symptoms increases the suspicion of PAD. The location of PAD can be determined by the presence or absence of pulses and by where the patient feels pain^8,15,16 (see Table 2). Patients should receive a thorough cardiac and neurologic examination as well because of the strong link between PAD, CAD, and cerebrovascular complications.

As the disease progresses, so does the amount and type of pain. Ischemic rest pain occurs when arterial blood flow is insufficient to match tissue metabolic needs and manifests as muscle cramps in the extremity while at rest.¹⁹ Acute limb ischemia, a blockage of blood flow to the limb, is an emergent, limb-threatening condition. Other signs of acute limb ischemia include lack of a pulse, pain, pallor, paresthesia, and paralysis.²⁰

Risk factors for PAD include increasing age, sex (PAD is more prevalent in males), diabetes mellitus, smoking, hypertension, hyperlipidemia, hypertriglyceridemia, and hyperhomocystinemia.^15,21,22 The differential diagnosis for arterial disease includes nerve impingement, spinal stenosis, diabetic neuropathy, muscle aches, reflex sympathetic dystrophy, and arthritis. Generally these conditions are not position independent, relieved with rest, or as diffusely distributed as PAD.^8,16

Testing ABI is used to objectively diagnose PAD¹⁹ (see Table 3). ABI is calculated by dividing the ankle systolic pressure (measured with a BP cuff placed at the malleoleus) and the higher of the two systolic brachial pressures.¹⁶ In patients with mild PAD or iliac disease, measuring the ABI before and after treadmill exercise increases the sensitivity of the measurement. A large difference between the two values indicates the presence of PAD.⁸ In patients with calcific lower arterial disease, diabetes, or renal failure, the toe-brachial pressure index is more accurate since these patients’ vessels are not compressible in the extremities and produce falsely elevated ABI measurements.⁴ ABI has a sensitivity of 90% and specificity of 98% for an angiographically identified stenosis of greater than 80%.²³

Waveforms on Doppler ultrasonography should be triphasic, indicating forward blood flow during systole, reverse direction of flow during early diastole, and a return back to forward flow during mid to late diastole. If disease is present, the patient will have a biphasic or monophasic waveform, even though the ABI may be normal.^8,23 The limitations of ABI include an underestimate of mild or moderate disease, especially in patients with good collateral support; poor evaluation if calcific arteries are present; and operator errors, including improper cuff placement and using an improper cuff size.^9,18

Contrast arteriography is the gold standard test for PAD. A small amount of contrast material is injected into the vessels to determine arterial patency. This procedure is invasive and generally performed only before surgical intervention.¹⁶

Transcutaneous oximetry helps determine whether an ulcer will heal, where revascularization should take place, or to predict where an amputation should be done. A reading of 30 mm Hg or less indicates a high risk of severe ischemia, development of nonhealing wounds, or the need for minor amputation.^16,20

Several serum tests aid in the diagnosis of PAD. C-reactive protein levels, plasma creatinine levels, and plasma urate levels can be increased in patients with PAD, which can also indicate renal dysfunction and parallel coronary heart disease.

A thorough cardiovascular workup is recommended because these patients are at risk for cardiovascular disease. The Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events trial showed that 41.1% of patients with PAD also had CAD or cerebrovascular disease.¹⁶

Treatment Exercise is an effective treatment for PAD. An exercise ECG should be done to ensure that there is no underlying cardiac ischemia before a patient begins an exercise program. Ideally, patients should be enrolled in a cardiac rehabilitation program with a structured, monitored environment. Exercise is most beneficial when performed three to five times a week for at least 50 minutes. The routine should include treadmill walking with periods of rest interspersed throughout, for a total of 30 minutes of physical activity and 20 minutes of rest. Other treatment options are listed in “Table. Treatment options for peripheral arterial disease.”

Pharmacotherapy options for claudication symptoms are cilostazol and pentoxifylline, which are less beneficial than exercise.¹⁹ Aggressive risk factor management includes medication for hyperlipidemia, hypertension, and platelet aggregation, as well as smoking cessation and a healthy diet.^14,24

Patients who have mild intermittent claudication rarely are candidates for elective lower extremity vascular repair surgery.^16,22 The 2005 American College of Cardiology/American Heart Association guidelines indicate when revascularization is appropriate and the risk stratification for vascular surgical procedures.²⁵ Patients with PAD should be considered for surgical intervention if claudication interferes with their activities of daily living, if limb salvage is necessary, or if vasculogenic impotence is present. Surgical options include endarterectomy, bypass grafting, percutaneous transluminal angioplasty, and intra-arterial stent with angioplasty. Immediate revascularization and thrombolysis is required for acute limb ischemia.

The rate of major amputation for patients with PAD over a 5-year period is 1% to 3%. One third of patients with severe PAD who develop gangrene will lose their limb. Patients who smoke have an 11% risk of major limb amputation. Patients with diabetes have a 10-fold higher risk for major limb amputation over patients who do not have diabetes.²⁰

PREVENTION AND PATIENT EDUCATION

In closing, CVI and PAD have serious implications, including ulceration and amputation. Patients have a 50% chance of experiencing a cardiovascular event within 5 years of receiving a diagnosis of PAD.¹⁸ Patients should have a complete physical examination, including annual inspection and palpation of the lower extremities. Patients also should be asked about symptoms of claudication or lower extremity discomfort. If a clinician suspects CVI or PAD, the patient should be sent for appropriate testing to confirm the clinical diagnosis and to begin treatment. Patients should be educated about healthy, active lifestyles that can prevent disease progression and reduce symptom severity. Most importantly, clinicians must be aware of CVI and PAD and know the best tools to use to make a diagnosis and treat the patient.

DRUGS MENTIONED

Aspirin
Cilostazol (Pletal)
Clopidogrel (Plavix)
Pentoxifylline (Pentoxil, Trental)
Sodium morrhuate (Morrhuate Sod)
Sodium tetradecyl sulfate (Sotradecol)

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