Peripheral Arterial Disease(PAD)

Peripheral Arterial Disease(PAD)

M. Saifur Rohman, dr SpJP. PhD. FICADept of Cardiology and Vascular Medicine

Faculty of Medicine, Brawijaya University

M. Saifur Rohman, dr SpJP. PhD. FICADept of Cardiology and Vascular Medicine

Faculty of Medicine, Brawijaya University

OverviewOverview

PAD (peripheral arterial disease) – a marker for MI and ISEpidemiological data on PAD

Risk factors Prevalence Atherothrombosis – coexistence of PAD, coronary and

cerebrovascular disease Natural history Low ABPI as an independent predictor of ischaemic risk

Symptomatology of PAD Diagnosis and management of PADClopidogrel – a new standard of treatment for atherothrombosis

PAD – a marker for MI and IS

Cerebrovascular disease(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 existing atherosclerosis

Occurs in multiple arterial beds

Risk factors for PADRisk factors for PAD

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.

Gender (male) Age Smoking Hypertension Diabetes Hyperlipidaemia Fibrinogen Homocysteinaemia

PAD

Ischaemicstroke

Myocardialinfarction

Atherosclerosis Atherothrombosis

PAD

Atherogenesis

Progression of Plaque toward ruptureProgression of Plaque toward rupture

Prevalence of PAD – variation according to diagnostic criterionPrevalence of PAD – variation according to diagnostic criterion

6.3 million individuals with symptomatic, established PAD are diagnosed in the USA and EU1

Epidemiological studies imply that real* prevalence may be approx. 20 million (= 9.5% of the population > 50 years old)

In 613 men and women (mean age 66 years), real prevalencewas found to be underestimated by two- to seven-fold2

ABPI (ankle:brachial pressure index) correlates with angiographically determined disease3

ABPI < 0.9 is a marker of diffuse atherothrombosis4

1 17 Western European countries. Statistical Supplement; WHO Yearbooks, Annual Statistics, 1997;2 Criqui MH et al. Vasc Med 1997;2:221–226; 3Shinozaki T et al. J Clin Epidemiol 1998;15:1263–1269; 4Kornitzer M et al. Angiology 1995;46:211–219.*ABPI < 0.9, symptomatic or not, diagnosed or not.

Epidemiology of PAD – effect of age and genderEpidemiology of PAD – effect of age and gender

Epidemiological data on PAD vary according to:Population studiedMethod of diagnosing PAD

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 yearsSimilar trend in women, increase with age

More common in men than in womenTwice as many men as women aged > 50 years have intermittent

claudication (3.5% and 2%, respectively)

Predominance in males disappears after age of 70Weitz JI et al. Circulation 1996;94:3026–3049. * Rose questionnaire criteria Bull. Wld Hlth Org. 1962;27:645-658

Atherothrombosis – coexistence of symptomatic PAD and coronary or cerebrovascular diseaseAtherothrombosis – coexistence of symptomatic PAD and coronary or cerebrovascular disease

Per

cen

tag

e o

f g

rou

p

Concurrentcardiovascular disease(MI, CABG, stroke orstroke surgery)

PADNo

0

10

20

30

40

50

Men Women

Yes YesNo

Criqui MH et al. Vasc Med 1997;2:221–226.

Atherothrombosis – symptomatic atherosclerosisin CAPRIE (overlap between PAD, CAD and CVD)Atherothrombosis – symptomatic atherosclerosisin CAPRIE (overlap between PAD, CAD and CVD)

1CAPRIE Steering Committee. Lancet 1996;348:1329–1339.

CAPRIE1 (n = 19 185)

Cerebrovascular disease (CVD)

Peripheral Arterial Disease (PAD)

Coronary artery disease (CAD)

24.6% 29.9%

19.2%

3.3%3.8%

7.3%

11.9%

5-year natural history of PAD5-year natural history of PAD

100 patients with asymptomatic PAD

100 patientswith claudication who do notseek medical advice

Local Events 100 patients diagnosed

with claudicationSystemic Events

• CHD 15• Other cardiovascular

and cerebrovascular 5• Non-cardiovascular 10

PLUS

Major amputation 2 patients

10 to 20 non-fatal MIs or strokes

Dormandy JA. Hosp Update 1991;April:314–318.

30 deaths:Surgical revascularization

10 patients

Worsening claudication25 patients

PAD mortality – 10-year survival rates of subjects in the San Diego Artery StudyPAD mortality – 10-year survival rates of subjects in the San Diego Artery Study

Criqui MH et al. N Engl J Med 1992;326:381–386.

Time (years)0 2 4 6 8 10 12

0.00

0.25

0.50

0.75

1.00

Surv

ival

Severe symptomatic

Symptomatic

Asymptomatic

Normal

Intermittent claudication – an independent risk factor for increased mortality ratesIntermittent claudication – an independent risk factor for increased mortality rates

Smith GD et al. Circulation 1990;82:1925–1931.

In the Whitehall study (n = 18 388), mortality rates in individuals with intermittent claudication were twiceas high as those in healthy controls (17 years’ follow-up study)

Increased mortality even after adjustment for coronary risk factors

Cardiac ischaemia at baseline Systolic blood pressure Plasma cholesterol concentration Smoking behaviour Employment grade Degree of glucose intolerance

Low ABPI is a strong predictor ofcardiovascular mortalityLow ABPI is a strong predictor ofcardiovascular mortality

Reduced ABPI is a significant independent predictor of cardiovascular and coronary mortality

Age-adjusted relative risks for 10-year cardiovascular and coronary mortality are higher in those with ABPI < 0.9

The risk of cardiovascular death increases with decreasing ABPI

ABPI measurement is underutilized and can be usefully incorporated in risk assessment and screening programmes

ABPI measurements are inexpensive, simple and non-invasive

Kornitzer M et al. Angiology 1995;46:211–219. McKenna M et al. Atherosclerosis 1991;87:119–128.

Dormandy JA et al. J Cardiovasc Surg 1989;30:50–57.

ABPI – inverse relationship with 5-year risk of cardiovascular events and deathABPI – inverse relationship with 5-year risk of cardiovascular events and death

Dormandy JA, Creager MA. Cerebrovasc Dis 1999;9(Suppl 1):1–128 (Abstr 4).

10.2% relative risk increaseper 0.1 decrease in ABPI

(p = 0.041)

1.00.80.60.40.20.0

1.0

1.5

2.0

2.5

ABPI

Ris

k re

lativ

e to

AB

PI

Symptomatology of PAD Symptomatology of PAD

Intermittent claudication Exercise-induced ischaemic calf-muscle pain while walking

and/or weakness, relieved by rest

Mortality rate from stroke and MI two to three times greaterthan in age-matched controls1

Prognosis varies with multiple risk factors and/or severityof disease

Critical limb ischaemia Pain at rest, eventually resulting in gangrene and amputation2

1Dormandy JA et al. J Cardiovasc Surg 1989;30:50–57.2European Working Group on Critical Leg Ischemia. Circulation 1991;84(Suppl IV):IV1–IV26.

Diagnosis of PAD Diagnosis of PAD

Evaluation of pulses and auscultation of bruits

Ankle:arm blood pressure index (ABPI) Ratio of ankle:brachial systolic blood pressure Simple, non-invasive, suitable for routine screening

Exercise testing Pain-free and maximal walking distance Size and duration of drop in ankle systolic BP upon

claudication

Weitz JI et al. Circulation 1996;94:3026–3049.

Progression of Plaque toward rupture

Thrombus forms and extends into the lumen

Adventitia

Lipid core

Thrombus

Weissberg, 1999

Thrombus formation Acute Limb IschemiaThrombus formation Acute Limb Ischemia

Definition of Acute Limb IschemiaDefinition of Acute Limb Ischemia

SuddenSudden decrease of arterial limb perfusion causing threat to limb

viability

Etiology of acute limb ischemiaEtiology of acute limb ischemia

Acute arterial embolism:

Acute traumatic ischemia:

Of a relatively Of a relatively health arterial health arterial treetree

Acute arterial thrombosis: Of a previously Of a previously diseased arterial diseased arterial treetree

PathophysiologyPathophysiologyAcute Embolic Ischemia

Acute Thrombotic

Ischemia

An embolus suddenly

occludes a relatively healthy

arterial tree

AtherosclerosiAtherosclerosiss causes

progressive narrowing of the arterial

treeStimulates

development of collaterals

Sluggish flow & rough

surface will favor acute thrombosis

It usually arrest at arterial

bifurcation

Aortic bifurcation

Iliac bifurcation

Femoral bifurcation

Popliteal trifurcation

An embolus can originate from the heart (MS with atrial fibrillation, MI with mural

thrombus) or dilated diseased arteries (aortic aneurism)

It is important to differentiate between embolic & thrombotic ischemia: It is important to differentiate between embolic & thrombotic ischemia:

Because the Because the management is management is

differentdifferent

Clinical Features Suggestive of acute EmbolismEmbolism::

Sudden onset of symptomsSudden onset of symptoms

Known embolic sourceKnown embolic source

Absence of previous claudicationAbsence of previous claudication

Normal pulse in the other limbNormal pulse in the other limb

The severity of acute ischemia depends on:The severity of acute ischemia depends on:

a)a) Capability of existing collaterals to carry blood around the acute obstruction (collaterals are more developed in

patients with preexisting chronic ischemia) Accordingly, arterial embolism is more likely to produce sudden symptoms & severe ischemia then arterial thrombosis

b) b) The location of obstruction in relation to the number of axial arteries

Aorta & common iliac One axial a. with limited collateral pathways

Internal & external iliac Two axial aa. With better collateral potentials

Two axial aa. With better collateral potentialsSuperficial & deep femoral

Popliteal artery One axial a. with limited collateral pathways

Three axial aa. with better collateral potentialsTibial arteries

c)c) The extent of obstructionThe larger the obstruction, the more collaterals are lostd)d) The duration

Flow distal to the obstruction is sluggish. If collaterals cannot increase the flow above a critical point, a stagnation clot will develop in the distal arterial tee. This the reason why heparin should be given as early as possible

For Example:

Popliteal a occlusion (a single axial a.) results in severe ischemia, while posterior tibial occlusion may be asymptomatic if other leg arteries are patent

Clinical Evaluation of Acute Ischemia (Clinical Picture)Clinical Evaluation of Acute Ischemia (Clinical Picture)

Symptoms of acute ischemia:Symptoms of acute ischemia:

Pain: Diffuse foot & leg severe aching pain of acute onset (more acute in embolic ischemia)

Pain may diminish in intensity by time if collaterals open improving circulation, or if ischemia progresses causing ischemic sensory loss

Coldness is an early symptom

Numbness followed by sensory loss (late)

Muscle weakness (heavy limb) followed by paralysis (late)

Clinical Evaluation of Acute Ischemia Clinical Evaluation of Acute Ischemia (Clinical Picture)(Clinical Picture)

Signs of acute ischemia

5P5PsPain: symptom

++

Pulseless

Pale

Parathesia

Paralysis

InspectionInspection

COLOR:

EarlyEarly: pale

LaterLater: cyanosed mottling fixed mottling & cyanosis

Pallor

Reversible mottling

An area of fixed

cyanosis surrounded

by reversible mottling

Empty veins: compare the Rt. (ischemic) & Lt. (normal)

Fixed mottling & cyanosis

Clinical Evaluation of Acute Ischemia (Clinical Picture)

Signs of acute ischemia

5P5PsPainPain: : symptomsymptom

++

PulselessPulseless

PalePale

ParathesiaParathesia

ParalysisParalysis

PalpationPalpation

Loss of sensory function

Numbness will progress to anesthesia

Progress of Sensory loss

Light touch

Vibration sense

Proprioreception

Deep pain

Pressure sense

LateLate

Clinical Evaluation of Acute Ischemia (Clinical Picture)

Signs of acute ischemia

5P5PsPainPain: : symptomsymptom

++

PulselessPulseless

PalePale

ParathesiaParathesia

ParalysisParalysis

PalpationPalpation

Loss of motor function:Loss of motor function:

Indicates advancedadvanced limb threatening ischemia

Late irreversible ischemia: Muscle turgidity

Intrinsic foot muscles are affected first, followed by the leg muscles

Detecting early muscle weakness is difficult because toes movements are produced mainly by leg muscles

Classes of Acute IschemiaClasses of Acute Ischemia

Clinical FindingsClinical Findings DopplerDoppler PrognosisPrognosis

ClassClass Sensory Sensory lossloss

Motor Motor weaknessweakness

Arterial Arterial signalssignals

Venous Venous SignalsSignals

I.I. ViableViable -ve-ve -ve-ve audibleaudible audibleaudible Not immediately Not immediately threatenedthreatened

II.aII.a Marginal Marginal threatthreat

Minimal Minimal sensory losssensory loss

No muscle No muscle weaknessweakness

Often not Often not audibleaudible

audibleaudible Salvageable if prompt ttt Salvageable if prompt ttt (there is time for (there is time for

angiography)angiography)

II.bII.b Immediate Immediate threatthreat

Rest pain w Rest pain w sensory loss sensory loss more than toesmore than toes

Mild to Mild to moderatemoderate

Usually Usually not audiblenot audible

audibleaudible Salvageable with Salvageable with immediate ttt immediate ttt (no time for (no time for

angiography)angiography)

III.III.IrreversibleIrreversible Severe Severe anesthesiaanesthesia

Paralysis Paralysis w w muscle rigormuscle rigor

InaudibleInaudible InaudibleInaudible Not salvageable, Not salvageable, permanent N. & muscle damage ,permanent N. & muscle damage ,

needs amputationneeds amputation

Summary Summary

PAD is a marker of atherosclerosis in the coronary and cerebral arteries

PAD is often underestimated and underdiagnosed, and requires proper diagnosis:

Risk factors need to be managed: smoking cessation, regular exercise training

Atherogenesis=CAD

Plaque rupture=Limb Ischemix