Review
Patterns of Disease Distribution of Lower Extremity Peripheral Arterial Disease
Angiology 2015, Vol. 66(3) 211-218 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714525831 ang.sagepub.com
Qian Chen, MD1, Yang Shi, MD1, Yutang Wang, MD1, and Xiaoying Li, MD1
Abstract Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis that is associated with an increased risk of mortality and cardiovascular (CV) events. Peripheral arterial disease involves the arteries distal to the aortic bifurcation in a nonuniform manner. Studies have shown that symptoms and prognosis of patients with PAD vary according to the location and size of the affected artery. Several modalities have been used to identify the location of PAD, including noninvasive evaluations and invasive procedures. Peripheral arterial disease has a risk factor profile similar to that associated with coronary artery disease (ie, age, gender, diabetes, smoking, hypertension, and hyperlipidemia). Many studies have shown that the distribution, extent, and progression of PAD are influenced by CV risk factors but the findings are not consistent. Management strategies for PAD are different for proximal and distal PAD. The objective of this review is to discuss the patterns of diseases distribution in patients with PAD. Keywords atherosclerosis, peripheral artery disease, lower extremity, disease distribution
Introduction
Classification of Disease Location in PAD
Lower extremity peripheral arterial disease (PAD) refers to a partial or complete obstruction of lower limb arteries. The common cause is atherosclerosis.1 Atherosclerotic PAD affects nearly 10% of men aged 65 years, increasing to 20% of men and women 75 years.2-4 Despite the high prevalence of PAD, it is still underdiagnosed and undertreated.5 Peripheral arterial disease decreases functional capacity, which may eventually lead to disability and poor quality of life. Furthermore, patients with PAD are at increased risk of myocardial infarction (MI), stroke, and death. In fact, patients with PAD are 3 to 6 times more likely to have a MI or stroke than patients without PAD.1 Peripheral arterial disease involves all localizations, from large proximal arteries such as the terminal abdominal aorta to distal vessels such as small as foot arteries. Arterial geometry and anatomic, cellular, or biochemical properties of the arterial wall vary with location and may influence disease location.6 Within the lower limb arteries, the distribution of atherosclerotic disease tends to be segmental and the vessels show marked differences in the prevalence of occlusion.7 Evidence demonstrated that risk factor profile, prognosis, and management strategies for PAD differ according to disease location. We review the published data regarding the patterns of diseases distribution in patients with PAD and compare the similarities and differences of atherosclerosis in large (proximal) and small (distal) arteries.
Peripheral arterial disease involves the arteries distal to the aortic bifurcation but in a nonuniform manner. Lower limb atherosclerosis usually develops at several levels but may also be restricted to a single region. Hypotheses explaining site selectivity of atherosclerotic lesions include hemodynamic stress related to arterial geometry and anatomic, cellular, or biochemical variations in the arterial wall.8 Iliac arteries are characterized by elastic properties, whereas femoral and infragenicular arteries contain progressively more muscular elements.6 Moreover, the relation of the arterial lumen to wall thickness decreases from proximal to distal, both generating an alteration in arterial flow and shear stress associated with endothelial dysfunction.9 Peripheral arterial disease location is often classified as ‘‘proximal’’ or ‘‘distal’’ but the definition varies. In angiographic studies, proximal arteries usually referred to aortoiliac arteries.7,10 Other studies categorized the distribution of PAD
1
Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, 100853, China
Corresponding Author: Yutang Wang, Department of Geriatric Cardiology, Chinese PLA General Hospital, 28 FuXing Road, Beijing, 100853, China. Email: [email protected]
Downloaded from ang.sagepub.com at SETON HALL UNIV on March 31, 2015
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disease as ‘‘proximal’’ (lesions involving only the aortoiliac segment), ‘‘distal’’ (lesions involving only the femoropopliteal and/or tibial vessels), or ‘‘multilevel’’ (lesions involving both levels).11-13 Criqui et al and Aboyans et al defined PAD as large-vessel (above-ankle arteries) and small-vessel (belowankle arteries) PAD.6,14,15 In another study, Aboyans et al classified the localizations of PAD as follows: proximal lesions affecting the abdominal aorta bifurcation and the iliac arteries and distal lesions for any localization from the femoral arteries down to and including the infragenicular arteries.16
Modalities to Localize the Lesions in PAD The ankle-brachial index (ABI) is a simple and inexpensive test that can identify patients with PAD; an ABI of 50% and for correctly identifying occlusions.31 Because of the need for large volumes of iodinated contrast media, CTA cannot be performed in patients with borderline renal function, renal insufficiency, or acute renal failure.18 Another disadvantage is radiation exposure. Contrast-enhanced MRA. The ACC/AHA guidelines on PAD suggest that MRA may be useful in determining the location and severity of stenosis and may aid in decisions between endovascular and surgical revascularization.29 Magnetic resonance angiography may identify runoff vessels not visualized by conventional angiography.32 Magnetic resonance angiography has been demonstrated to have a high sensitivity and specificity for detecting acute occlusive disease when compared with digital subtraction angiography (DSA).33 With current technology, contrast-enhanced 3D MRA has a sensitivity of approximately 90% and a specificity of approximately
Downloaded from ang.sagepub.com at SETON HALL UNIV on March 31, 2015
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97% in the detection of stenoses as compared with DSA.34 A meta-analysis compared MRA with DSA and demonstrated that the sensitivity and specificity of MRA were both in the range of 90% to 100% for the detection of stenoses >50%, with the greatest accuracy occurring when gadolinium enhancement was used.35 Another systematic review suggested that contrastenhanced MRA has a better overall diagnostic accuracy than CTA or DUS and that MRA is generally preferred by patients over DSA.36 Magnetic resonance angiography has some limitations. Patients with implantable defibrillators and permanent pacemakers may not undergo magnetic resonance studies for fear of causing these devices to malfunction. In addition, MRA cannot reliably detect arterial calcification, which is a potential limitation when revascularization options are being considered.18 Digital subtraction angiography. Digital subtraction angiography is the reference method for diagnosing PAD.29 Digital subtraction angiography is usually indicated for mapping of the extent and location of arterial pathology prior to a revascularization procedure. Digital subtraction angiography assessment of stenoses provides a better overall visualization of the arterial tree and allows simultaneous execution of any therapeutic measures that may be required. The major advantage of DSA is the ability to selectively evaluate individual vessels, to obtain physiologic information such as pressure gradients, and to serve as a platform for percutaneous intervention. The drawbacks are those associated with arterial puncture, ionizing radiation, potential nephrotoxicity of iodinated contrast agents, and cost.37,38 Digital subtraction angiography shows only the patent vessel lumen. The morphology of vessel plaques and the surroundings of the vessels cannot be evaluated.39
The Frequency of PAD Location Diehm et al, in 2659 patients undergoing endovascular intervention for PAD, classified disease location of the 4205 atherosclerotic lesions as iliac, femoropopliteal, and infragenicular. The femoropopliteal location was the most common (51.2%).9 Haltmayer et al reported the distribution of PAD in 106 patients to be 77% with femoropopliteal disease.40 Similarly, among 575 patients with PAD having only singlesegment disease ascertained by noninvasive segmental blood pressure gradients involved in study of Vogt et al study, femoropopliteal disease was present in 47.3% of patients.41 However, a few studies reported different results. A study focused on early-onset PAD (50%. In fact, asymptomatic disease may be present in up to 50% of patients with PAD.10,29 With progression of disease, the symptoms typically intensify to intermittent claudication, rest pain, ulceration, and gangrene.10,63 A significant association was found between severity of limb ischemia and distribution of PAD. Intermittent claudication was significantly associated with aortoiliac disease, whereas critical limb ischemia was associated with crural disease.50 With proximal aortoiliac disease, thigh, hip, or buttock claudication or low back pain may develop while walking, usually preceded by calf pain. Distal tibial or peroneal arterial obstruction may cause ankle or foot pain while walking.30 Patients with more severe, limb-threatening ischemia typically have multisegmental disease. The ABI usually correlates with symptoms and functional status. Ischemic rest pain typically appears when the ABI is
Patterns of Disease Distribution of Lower Extremity Peripheral Arterial Disease
Angiology 2015, Vol. 66(3) 211-218 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714525831 ang.sagepub.com
Qian Chen, MD1, Yang Shi, MD1, Yutang Wang, MD1, and Xiaoying Li, MD1
Abstract Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis that is associated with an increased risk of mortality and cardiovascular (CV) events. Peripheral arterial disease involves the arteries distal to the aortic bifurcation in a nonuniform manner. Studies have shown that symptoms and prognosis of patients with PAD vary according to the location and size of the affected artery. Several modalities have been used to identify the location of PAD, including noninvasive evaluations and invasive procedures. Peripheral arterial disease has a risk factor profile similar to that associated with coronary artery disease (ie, age, gender, diabetes, smoking, hypertension, and hyperlipidemia). Many studies have shown that the distribution, extent, and progression of PAD are influenced by CV risk factors but the findings are not consistent. Management strategies for PAD are different for proximal and distal PAD. The objective of this review is to discuss the patterns of diseases distribution in patients with PAD. Keywords atherosclerosis, peripheral artery disease, lower extremity, disease distribution
Introduction
Classification of Disease Location in PAD
Lower extremity peripheral arterial disease (PAD) refers to a partial or complete obstruction of lower limb arteries. The common cause is atherosclerosis.1 Atherosclerotic PAD affects nearly 10% of men aged 65 years, increasing to 20% of men and women 75 years.2-4 Despite the high prevalence of PAD, it is still underdiagnosed and undertreated.5 Peripheral arterial disease decreases functional capacity, which may eventually lead to disability and poor quality of life. Furthermore, patients with PAD are at increased risk of myocardial infarction (MI), stroke, and death. In fact, patients with PAD are 3 to 6 times more likely to have a MI or stroke than patients without PAD.1 Peripheral arterial disease involves all localizations, from large proximal arteries such as the terminal abdominal aorta to distal vessels such as small as foot arteries. Arterial geometry and anatomic, cellular, or biochemical properties of the arterial wall vary with location and may influence disease location.6 Within the lower limb arteries, the distribution of atherosclerotic disease tends to be segmental and the vessels show marked differences in the prevalence of occlusion.7 Evidence demonstrated that risk factor profile, prognosis, and management strategies for PAD differ according to disease location. We review the published data regarding the patterns of diseases distribution in patients with PAD and compare the similarities and differences of atherosclerosis in large (proximal) and small (distal) arteries.
Peripheral arterial disease involves the arteries distal to the aortic bifurcation but in a nonuniform manner. Lower limb atherosclerosis usually develops at several levels but may also be restricted to a single region. Hypotheses explaining site selectivity of atherosclerotic lesions include hemodynamic stress related to arterial geometry and anatomic, cellular, or biochemical variations in the arterial wall.8 Iliac arteries are characterized by elastic properties, whereas femoral and infragenicular arteries contain progressively more muscular elements.6 Moreover, the relation of the arterial lumen to wall thickness decreases from proximal to distal, both generating an alteration in arterial flow and shear stress associated with endothelial dysfunction.9 Peripheral arterial disease location is often classified as ‘‘proximal’’ or ‘‘distal’’ but the definition varies. In angiographic studies, proximal arteries usually referred to aortoiliac arteries.7,10 Other studies categorized the distribution of PAD
1
Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, 100853, China
Corresponding Author: Yutang Wang, Department of Geriatric Cardiology, Chinese PLA General Hospital, 28 FuXing Road, Beijing, 100853, China. Email: [email protected]
Downloaded from ang.sagepub.com at SETON HALL UNIV on March 31, 2015
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Angiology 66(3)
disease as ‘‘proximal’’ (lesions involving only the aortoiliac segment), ‘‘distal’’ (lesions involving only the femoropopliteal and/or tibial vessels), or ‘‘multilevel’’ (lesions involving both levels).11-13 Criqui et al and Aboyans et al defined PAD as large-vessel (above-ankle arteries) and small-vessel (belowankle arteries) PAD.6,14,15 In another study, Aboyans et al classified the localizations of PAD as follows: proximal lesions affecting the abdominal aorta bifurcation and the iliac arteries and distal lesions for any localization from the femoral arteries down to and including the infragenicular arteries.16
Modalities to Localize the Lesions in PAD The ankle-brachial index (ABI) is a simple and inexpensive test that can identify patients with PAD; an ABI of 50% and for correctly identifying occlusions.31 Because of the need for large volumes of iodinated contrast media, CTA cannot be performed in patients with borderline renal function, renal insufficiency, or acute renal failure.18 Another disadvantage is radiation exposure. Contrast-enhanced MRA. The ACC/AHA guidelines on PAD suggest that MRA may be useful in determining the location and severity of stenosis and may aid in decisions between endovascular and surgical revascularization.29 Magnetic resonance angiography may identify runoff vessels not visualized by conventional angiography.32 Magnetic resonance angiography has been demonstrated to have a high sensitivity and specificity for detecting acute occlusive disease when compared with digital subtraction angiography (DSA).33 With current technology, contrast-enhanced 3D MRA has a sensitivity of approximately 90% and a specificity of approximately
Downloaded from ang.sagepub.com at SETON HALL UNIV on March 31, 2015
Chen et al
213
97% in the detection of stenoses as compared with DSA.34 A meta-analysis compared MRA with DSA and demonstrated that the sensitivity and specificity of MRA were both in the range of 90% to 100% for the detection of stenoses >50%, with the greatest accuracy occurring when gadolinium enhancement was used.35 Another systematic review suggested that contrastenhanced MRA has a better overall diagnostic accuracy than CTA or DUS and that MRA is generally preferred by patients over DSA.36 Magnetic resonance angiography has some limitations. Patients with implantable defibrillators and permanent pacemakers may not undergo magnetic resonance studies for fear of causing these devices to malfunction. In addition, MRA cannot reliably detect arterial calcification, which is a potential limitation when revascularization options are being considered.18 Digital subtraction angiography. Digital subtraction angiography is the reference method for diagnosing PAD.29 Digital subtraction angiography is usually indicated for mapping of the extent and location of arterial pathology prior to a revascularization procedure. Digital subtraction angiography assessment of stenoses provides a better overall visualization of the arterial tree and allows simultaneous execution of any therapeutic measures that may be required. The major advantage of DSA is the ability to selectively evaluate individual vessels, to obtain physiologic information such as pressure gradients, and to serve as a platform for percutaneous intervention. The drawbacks are those associated with arterial puncture, ionizing radiation, potential nephrotoxicity of iodinated contrast agents, and cost.37,38 Digital subtraction angiography shows only the patent vessel lumen. The morphology of vessel plaques and the surroundings of the vessels cannot be evaluated.39
The Frequency of PAD Location Diehm et al, in 2659 patients undergoing endovascular intervention for PAD, classified disease location of the 4205 atherosclerotic lesions as iliac, femoropopliteal, and infragenicular. The femoropopliteal location was the most common (51.2%).9 Haltmayer et al reported the distribution of PAD in 106 patients to be 77% with femoropopliteal disease.40 Similarly, among 575 patients with PAD having only singlesegment disease ascertained by noninvasive segmental blood pressure gradients involved in study of Vogt et al study, femoropopliteal disease was present in 47.3% of patients.41 However, a few studies reported different results. A study focused on early-onset PAD (50%. In fact, asymptomatic disease may be present in up to 50% of patients with PAD.10,29 With progression of disease, the symptoms typically intensify to intermittent claudication, rest pain, ulceration, and gangrene.10,63 A significant association was found between severity of limb ischemia and distribution of PAD. Intermittent claudication was significantly associated with aortoiliac disease, whereas critical limb ischemia was associated with crural disease.50 With proximal aortoiliac disease, thigh, hip, or buttock claudication or low back pain may develop while walking, usually preceded by calf pain. Distal tibial or peroneal arterial obstruction may cause ankle or foot pain while walking.30 Patients with more severe, limb-threatening ischemia typically have multisegmental disease. The ABI usually correlates with symptoms and functional status. Ischemic rest pain typically appears when the ABI is
