PAD – a marker for MI and IS Atherothrombosis is a generalized process that occurs throughout the arterial tree. Peripheral arterial disease (PAD) is one of several manifestations of atherothrombosis. This process occurs when a platelet-rich clot (thrombus) forms at the site of an unstable or disrupted atherosclerotic plaque. In the brain, atherothrombosis may result in transient ischaemic attack or ischaemic stroke. In the coronary arteries it can lead to stable or unstable angina, and in the peripheral arteries atherothrombosis causes leg-muscle ischaemia (varying from asymptomatic to severe symptomatic disease). PAD can be asymptomatic (pre-existing atherosclerosis as a diffuse marker of the disease, placing patients at risk of an ischaemic event elsewhere in the vasculature) or symptomatic (intermittent claudication, critical leg ischaemia).
Risk factors for PAD As would be expected, the risk factors for PAD are similar to those for atherosclerosis affecting the heart and brain. These risk factors include those related to lifestyle, such as smoking, diet and physical inactivity. 1 Common conditions such as diabetes 1 and hypertension 1 are also associated with increased risk of PAD. The role of infection in the development of atherosclerosis is currently the focus of much interest. 2 Homocysteinaemia, 3 hypercholesterolaemia 1 and hypercoagulable states 4 also increase the risk of vascular disease. Thus, factors that can be controlled, such as diet and smoking, and factors that cannot be altered, such as genetic traits, gender, 1 and age, 1 are all known to be associated with increased risk of PAD. 1,2 Although there are similarities in risk factors for atherosclerosis throughout the vasculature, the degree of risk associated with a given risk factor may differ for each arterial bed. For example, smoking and diabetes are widely held to be the strongest risk factors for PAD. PAD patients are at high risk of ischaemic events, as PAD is a risk marker for MI and stroke. 1 Murabito JM, D’Agostino RB, Silbershatz H et al . Intermittent claudication. A risk profile from the Framingham Heart Study. Circulation 1997;96:44–49. 2 Laurila A, Bloigu A, Nayha S et al . Chronic Chlamydia pneumoniae infection is associated with a serum lipid profile known to be a risk factor for atherosclerosis. Arterioscler Thromb Vasc Biol 1997;17:2910–2913. 3 Malinow MR, Kang SS, Taylor LM et al . Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease. Circulation 1989;79:1180–1188. 4 Brigden ML. The hypercoagulable state: who, how, and when to test and treat. Postgrad Med 1997;101(5):249–262.
Epidemiology of PAD – effect of age and gender There are fewer epidemiological data on PAD than there are on myocardial infarction and stroke. Existing data show variations depending on the populations being studied and the diagnostic methods employed. However, general features of the epidemiology of PAD can be summarized as follows:(i) the increase and prevalence of PAD increase with age; (ii) PAD is more common in men than it is in women; (iii) the predominance of PAD in males diminishes in those aged > 70 years. 1 1 Weitz JI, Byrne J, Clagett GP et al . Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation 1996;94:3026–3049.
Atherothrombosis – coexistence of PAD and symptomatic coronary or cerebrovascular disease The findings of a number of epidemiological studies support the concept that PAD reflects more widespread atheromatous disease. The San Diego Artery Study, 1 in which an ankle-brachial pressure ratio (ABPR) of < 0.8 was used as a marker for PAD, assessed how often PAD occurred in association with other manifestations of atherosclerosis. Among men with PAD, 29.4% had cardiovascular disease (CVD; either CHD, defined as previous MI or bypass surgery, or cerebrovascular disease, indicated by a previous stroke or stroke-related surgery). Among women with PAD, 21.2% had CVD. In comparison, 11.5% of men and 9.3% of women without PAD had a history of CVD. Thus, in this study, other CVD occurred two to three times more frequently among persons with PAD. 1 Criqui MH, Denenberg JO, Langer RD et al . The epidemiology of peripheral arterial disease: importance of identifying the population at risk. Vasc Med 1997;2:221–226.
Symptomatology of PAD Intermittent claudication, the most common manifestation of PAD, consists of severe pain while walking and/or weakness of the calf muscles during exercise that is relieved by rest. A small percentage of patients with intermittent claudication (1.5–5%) 1 develop critical leg ischaemia, which causes pain at rest and may result in gangrene and amputation of the affected limb. According to the Fontaine classification, the common interpretation of the various stages involving severe ischaemia is as follows: stage 1, asymptomatic with no functional signs; stage 2, intermittent claudication; stage 3, rest pain caused by arterial disease; and stage 4, ulceration and/or gangrene caused by arterial disease. 2 1 Dormandy JA, Mahir M, Ascady G et al . Fate of the patient with chronic limb ischaemia. J Cardiovasc Surg 1989;30:50–57. 2 European Working Group on Critical Leg Ischemia. Second European Consensus Document on Chronic Critical Leg Ischemia. Circulation 1991;84(Suppl IV):IV1–IV26.
Management of PAD patients A key element of the management of PAD is risk-factor modification. In patients with PAD, morbidity and mortality can be significantly decreased by stopping smoking, taking regular exercise (three times a day), and reducing dietary fat intake. Importantly, pharmacological treatment should include secondary prevention of ischaemic events of atherothrombotic origin by an antiplatelet agent. Pharmacological treatment to reduce cholesterol, and to control diabetes and hypertension, where present, is also important. These risk-factor modification strategies also apply to reduction of ischaemic risk in patients with symptomatic atherosclerosis affecting the coronary and cerebral arterial beds. Cilostazol, a phosphodiesterase inhibitor, has recently been approved by the FDA for the reduction of symptoms, as measured by pain-free and maximal walking distance, for patients with intermittent claudication. 1,2 Pentoxifylline is an earlier therapy for intermittent claudication; however, a critical review of placebo-controlled trials has concluded that the improvement in walking distance obtained with pentoxifylline is often unpredictable and may not be clinically significant. 3 It is important to note that although symptomatic benefit may be obtained from vasodilator therapy, there is still a need to prescribe an antiplatelet agent that effectively reduces the risk of vascular ischaemic events such as ischaemic stroke, MI and vascular death. PAD also has considerable consequences upon patients’ community-based quality of life, and this can be significantly improved by exercise programmes. Additionally, a recent study highlighted the repercussions of PAD upon professional activities, with nearly half of patients stating that PAD had caused either a change in their activities, or partial suspension or cessation of work. 4 However, following treatment with naftidrofuryl, less than 10% of patients were on sick leave or required external assistance as a result of the disease (6-month follow-up), leading to improved quality of life (rather than positive outcomes). 1 Dawson DL, Cutler BS, Meissner MH et al . Cilostazol has beneficial effects in treatment of intermittent claudication. Results from a multicenter, randomized, prospective, double-blind trial. Circulation 1998;98:678–686. 2 Money SR, Herd JA, Isaacsohn JL et al . Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease. J Vasc Surg 1998;27:267–275. 3 Radack K, Wyderski RJ. Conservative management of intermittent claudication. Ann Intern Med 1990;113:135–146. 4 Rolland N, Lebrun T, Comte S et al . Conséquences de l'artériopathie oblitérante des membres inférieurs (AOMI) sur l'activité professionnelle des patients et sur les aides extérieures. J Mal Vasc 1999;24:208–139 (in French).
Management of PAD – intervention Intervention, either by direct reconstruction of diseased leg arteries by angioplasty (with or without subsequent stent placement), endarterectomy or by replacement by peripheral bypass grafting, can relieve symptoms caused by inadequate blood flow. The decision to operate should be based on symptom severity, degree of disability and perceived surgical risk. When performed by an experienced surgeon, vascular surgical procedures are associated with a lower mortality rate than amputation. 1 Obviously, interventions affecting the peripheral arteries do not reduce ischaemic risk in the cerebral or coronary arteries thus, chronic antiplatelet therapy and risk factor modification are still needed. 1 Kampozinski RF, Bernhard VM. Introduction and general considerations. In: Vascular Surgery (Rutherford RB, ed) Philadelphia, PA: WB Saunders: 1989;chap 53.
A marker for myocardial
infarction and ischemic stroke
Methas Arunnart MD.
PAD – a marker for MI and IS
(ischaemic stroke, transient ischaemic attack)
Coronary artery disease
(stable/unstable angina, myocardial infarction)
PAD (intermittent claudication, critical leg ischaemia,
amputation, gangrene, necrosis)
• Atherothrombosis = thrombus formation on top of
• Occurs in multiple arterial beds
Murabito JM et al. Circulation 1997;96:44–49; Laurila A et al. Arterioscler Throm Vasc Biol 1997;17:2910–2913;
Malinow MR et al. Circulation 1989;79:1180–1188; Brigden ML. Postgrad Med 1997;101:249–262.
• Incidence and prevalence of intermittent claudication*
increase with age
• Prevalence in men aged 45–50 years is 1%
• Prevalence is 3–3.5% in men aged > 50 years
• Similar trend in women, increase with age
• More common in men than in women
• Twice as many men as women aged > 50 years have
intermittent claudication (3.5% and 2%, respectively)
• Predominance in males disappears after age of 70
Weitz JI et al. Circulation 1996;94:3026–3049. * Rose questionnaire criteria Bull. Wld Hlth Org. 1962;27:645-658
(MI, CABG, stroke or
Criqui MH et al. Vasc Med 1997;2:221–226.
IIa Mild claudication
IIb Moderate to severe claudication
III Ischemic rest pain
IV Ulceration or gangreneCritical limb ischemia
• Detection of asymptomatic PAD has value
because it identifies patients at increased risk of
atherosclerosis at other sites.
• Patients with asymptomatic PAD, most often
detected by ABI, should be treated to reduce
• The normal ABI is 0.9-1.3 If symptoms strongly suggest
claudication, exercise testing should be performed.
• ABI >1.3 suggests the presence of calcified vessels and need
for additional vascular studies
• ABI ≤0.9 is diagnostic of PAD, has Sens.95% Spec.100%,
• ABI 0.4 - 0.9 often associated with claudication.
• ABI < 0.4 represents multilevel disease and may be
associated with Critical limb ischemia
• Intermittent claudication
• Exercise-induced ischemic calf-muscle pain relieved by rest
• Increased mortality rate from stroke and MI 2-3 times
• Atypical symptoms
•Pain similar to classic claudication, but does not cause the
patient to stop walking
•Pain similar to classic claudication, but does not involve calves
or not resolve within 10 min. of rest
•Leg pain on both exertion and rest
• Buttock and hip – aortoiliac disease
*Leriche syndrome triad - claudication,
absent femoral pulses and erectile dysfunction.
• Thigh – aortoiliac or common femoral artery
• Upper two-thirds of the calf – superficial femoral artery
• Lower one-third of the calf – popliteal artery
• Foot claudication – tibial or peroneal artery
• Ischemic rest pain - severe pain which is not
readily controlled by analgesics
• Ischemic ulcer - typically form at sites of
increased focal pressure such as the lateral
malleolus, tips of toes, metatarsal heads, and
bunion area. They are usually dry and
• Gangrene - can be described as either dry or wet.
• Segmental Doppler measurements involve placement of cuffs at
the levels of the proximal and distal thigh, calf, and ankle.
• At the thigh - aortoiliac or superficial femoral artery disease
• At the calf - distal superficial femoral artery, popliteal disease
• At the ankle - infrapopliteal disease.
• In addition, a toe pressure of less than 60% of the ankle pressure
indicates digital artery occlusive disease
• This technique is performed by injecting a standard volume of air
into pneumatic cuffs placed at various levels along the extremity.
Volume changes in the limb segment below the cuff are
translated into pulsatile pressure.
• in experienced hands, provide accurate localization and
quantification of lesions; it can also help differentiate stenosis
from occlusions, an advantage over segmental Doppler
pressures or plethysmography.
• However, a great deal of time and expertise are required,
this modality is not the first choice for screening.
• useful tool in following known lesions for evidence of progression
and for monitoring vascular reconstructions
• The development of multidetector computed tomographic
(MDCT) scanners now allows rapid acquisition of high resolution,
intravenous contrast enhanced images from patients with
suspected PAD and is increasingly being used in the evaluation
of critical limb ischemia
• Becoming increasingly popular, particularly in patients who have
a contraindication to standard contrast angiography.
• Requires careful evaluation and significant experience with MRA,
and cooperation between the radiologist and vascular surgeon.
• remains the gold standard
• It should be performed in patients without a contraindication
who are expected to undergo revascularization.
• A complete study of the aorta, iliac, femoral, popliteal, and
run-off vessels is usually done on both sides since
atherosclerotic disease is usually bilateral and occurs at
sudden decrease in limb perfusion that causes a potential threat
to limb viability in patients who present within 2weeks of the
manifested by ischemic rest pain
Pain Mild Severe Severe Variable
Capillary refill Intact Delayed Delayed Absent
Motor deficit None None Partial Complete
None Minimal Partial Complete
Audible Inaudible Inaudible Inaudible
Audible Audible Audible Inaudible
Treatment Urgent work-
• — Angiography is the diagnostic procedure that
provides the most useful information; demonstrating
detailed arterial anatomy, distinguish between
thrombosis and embolism.
• it is not possible to perform this test in every case.
Patient with threatened extremity should have
immediate surgical revascularization with intraoperative
• Heparin - Once the diagnosis of acute arterial occlusion
has been made the patient should immediately receive
an intravenous heparin bolus followed by a continuous
• Refer to speccialist
• should undergo urgent arteriography to plan surgical or
• Thrombolytic therapy VS surgical revascularization
thrombolytic therapy is a safe and effective alternative to surgery
in appropriately selected patients. Although many patients
treated with thrombolytic therapy will subsequently require
surgical or percutaneous revascularization
• Clinical features are useful to help determine
(embolus versus thrombus)
• The location and length of the lesion
• The duration of symptoms
• The availability of autologous vein for bypass grafting
• The suitability of the patient for surgery
• As an example, a proximal embolus at the bifurcation of the
common femoral artery is an ideal lesion for embolectomy. On
the other hand, embolus to a distal vessel (eg, to the tibial artery)
may be best treated with a thrombolytic agent. The major use of
PTA is in the treatment of an underlying lesion after the clot has
been lysed with thrombolytic therapy.
• Should undergo emergent surgical revascularization.
• irreversible changes can occur within 4-6 hours of ischemia.
• Embolectomy is often all that is required to relieve the occlusion
and provide adequate blood flow to the extremity.
• intraoperative completion arteriogram after the embolectomy to
evaluate the adequacy of distal blood flow.
• Intraoperative thrombolytic therapy may also be used if there are
small emboli in the distal runoff vessels.
• Fasciotomy may be required to prevent the development of a
• should undergo prompt amputation.
• Arteriography is usually not necessary.
• Delays in amputation of a nonviable extremity can
result in infection, myoglobinuria, acute renal failure,
• Definition: decrease in limb perfusion that causes a potential
threat to limb viability in patients who present > 2weeks
• most often seen when two or more levels of the arterial tree
• The ACC/AHA practice guidelines suggested the following
distribution of outcomes at one year in these patients:
• Alive with two limbs – 50%
• Amputation – 25%
• Cardiovascular mortality – 25%
• Risk factor reduction
• Wound care – conservative management
• Prostaglandin E1?? - there was no long-term clinical benefit and
at six months
• Imaging – duplex imaging,CTA,MRA,contrast angiographyt
• Revascularization: Angioplasty VS Bypass surgery
Catheter-based intraarterial thrombolytic therapy
ACC/AHA guidelines for PAD recommend the following:
•For patients with an estimated life expectancy < 2 years or those
who do not have autogenous vein available as a conduit, balloon
angioplasty is reasonable as the initial procedure
•For patients with an estimated life expectancy of ≥ 2 years, and
who have available autogenous vein conduit, a bypass surgery is
reasonable to perform as the initial treatment
• — Catheter-based intraarterial thrombolytic therapy is an
alternative to surgery or percutaneous intervention in the
management of acute thrombosis superimposed on chronic
stenosis or occlusion in patients with critical limb ischemia