Transcript Atherosclerosis

Atherosclerosis
• is a progressive inflammatory disorder of the
arterial wall that is characterised by focal
lipid-rich deposits of atheroma that remain
clinically silent until they become large
enough to impair tissue perfusion, or until
ulceration and disruption of the lesion result
in
thrombotic
occlusion
or
distal
embolisation of the vessel.
Early atherosclerosis
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Fatty streaks tend to occur at sites of altered arterial
shear stress, such as bifurcations, and are associated
with abnormal endothelial function.
They develop when monocytes bind to receptors expressed by
endothelial cells, migrate into the intima, take up oxidised low-density
lipoprotein (LDL) particles and become lipid-laden macrophages or foam
cells.
• Extracellular lipid pools appear in the intimal space when these foam
cells die and release their contents.
• In response to cytokines and growth factors produced by the activated
macrophages, smooth muscle cells migrate from the media of the
arterial wall into the intima, to stabilise the atherosclerotic lesion.
• Then the lipid core will be covered by smooth muscle cells and matrix,
producing a stable atherosclerotic plaque that will remain asymptomatic
until it becomes large enough to obstruct arterial flow.
Advanced atherosclerosis
• In an established atherosclerotic plaque, macrophages mediate
inflammation, the plaque becomes active or unstable and may be
complicated by ulceration and thrombosis. Cytokines, such as
interleukin-1, tumour necrosis factor-alpha, interferon-gamma, plateletderived growth factors, and matrix metalloproteinases are released by
activated macrophages; they cause the intimal smooth muscle cells
overlying the plaque to become senescent and collagen cross-struts
within the plaque to degrade. This results in thinning of the protective
fibrous cap, making the lesion vulnerable to mechanical stress that
ultimately causes erosion, fissuring or rupture of the plaque surface .
• Any breach in the integrity of the plaque will expose its contents to
blood, and trigger platelet aggregation and thrombosis that extend into
the atheromatous plaque and the arterial lumen. This type of plaque
event may cause partial or complete obstruction at the site of the lesion
or distal embolisation resulting in infarction or ischaemia of the affected
organ.
• 'Vulnerable' plaques are characterised by a lipid-rich core, a thin
fibrocellular cap and an increase in inflammatory cells that release
specific enzymes to degrade matrix proteins.
Risk factors
• 1- Age and sex. : Premenopausal women have
lower rates of disease than men, although this
sex difference disappears after the menopause.
• 2- Family history: The most common inherited
risk characteristics (hypertension,
hyperlipidaemia, diabetes mellitus) are
polygenic. A 'positive' family history is present
when clinical problems in first-degree relatives
occur at relatively young age, such as < 50 years
for men and < 55 years for women.
• 3- Smoking. There is a strong consistent and doselinked relationship between cigarette smoking and
ischaemic heart disease, especially in younger (< 70
years) individuals.
• 4- Hypertension : The incidence of atherosclerosis
increases as BP rises, and this excess risk is related to
both systolic and diastolic BP as well as pulse
pressure.
• 5- Hypercholesterolaemia : Risk rises with increasing
serum cholesterol concentrations.
• 6- Diabetes mellitus. This is a potent risk factor for all
forms of atherosclerosis and is often associated with
diffuse disease that is difficult to treat.
• 7- Haemostatic factors. Platelet activation and high levels of
fibrinogen are associated with an increased risk of coronary
thrombosis..
• 8- Physical activity. Physical inactivity roughly doubles the risk of
coronary heart disease and is a major risk factor for stroke. Regular
exercise (brisk walking, cycling or swimming for 20 minutes two or
three times a week) has a protective effect which may be related to
increased serum HDL cholesterol concentrations, lower BP, and
collateral vessel development.
• 9- Obesity : Obesity, particularly if central or truncal, is an independent
risk factor,
• 10- Alcohol. Alcohol consumption is associated with reduced rates of
coronary artery disease. Excess alcohol consumption is associated with
hypertension and cerebrovascular disease.
• 10- Other dietary factors. Diets deficient in fresh fruit, vegetables and
polyunsaturated fatty acids are associated with an increased risk of
cardiovascular disease.
• 11- Personality. Certain personality traits are associated with an
increased risk of coronary disease.
• 12- Social deprivation.
Primary prevention
• 1-population strategies
• 2- targeted strategies
• **Population advice to prevent coronary disease •
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Do not smoke
-Take regular exercise (minimum of 20 mins, three
times a week)
-Maintain 'ideal' body weight
-Eat a mixed diet rich in fresh fruit and vegetables
-Aim to get no more than 10% of energy intake from
saturated fat
The targeted strategy aims to identify and treat
high-risk individuals who usually have a combination
of risk factors
Secondary prevention
• Patients who already have evidence of atheromatous
vascular disease are at high risk of future cardiovascular
events and should be offered treatments and measures to
improve their outlook. For ex:
• 1- All patients with coronary heart disease should be
given statin therapy irrespective of their serum
cholesterol concentration .
• 2- BP should be treated to a target of ≤ 140/85 mmHg.
• 3- Aspirin and ACE inhibitors are of benefit in patients
with evidence of vascular disease
• 4- Beta-blockers benefit patients with a history of MI or
heart failure.
CORONARY HEART DISEASE
• () CAD is almost always due to atheroma & its
complications, particularly thrombosis.
• () occasionally, the coronary arteries are
involved in other disorders such as aortitis,
polyarteritis & other CT disease.
Stable angina
• is severe chest pain due to
• ischemia (a lack of blood, hence a lack of
oxygen supply) of the heart muscle, generally
due to obstruction or spasm of the coronary
arteries (the heart's blood vessels).
• the main cause of angina, is due to
atherosclerosis of the cardiac arteries.
• It may occur whenever there is an imbalance
between myocardial oxygen supply & demand.
()oxygen demand:
• HR
• BP
• Myocardial contractility
• LVH
• AS
()oxygen supply:
• Duration of diastole
• Coronary perfusion pressure
• Coronary vasomotor tone
• oxygenation
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Major risk factors
Age (≥ 55 yo for men, ≥ 65 for women)
Cigarette smoking
Diabetes mellitus (DM)
Dyslipidemia
Family History of premature Cardiovascular Disease(men <55 yo, female <65)
Hypertension (HTN)
Kidney disease (microalbuminuria or GFR<60 mL/min)
Obesity (BMI ≥ 30 kg/m2)
Physical inactivity
excessive thyroid replacement
vasoconstrictors
polycythemia which thickens the blood causing it to slow its flow through the
heart muscle
Smoking
profound anemia
uncontrolled HTN
hyperthyroidism
hypoxemia
tachyarrhythmia
bradyarrhythmia
valvular heart disease
hypertrophic cardiomyopathy
Clinical features
• its characterised by central chest pain or
dyspnea that are precipated by exertion, cold
exposure, heavy meals, intense motion.
• Uncommon by lying flat (decubitus angina) &
vivid dreams (nocturnal angina) & when they
start walking (warm up angina)
• & releived by rest, radiated to lf arm or
shoulders, jaw & teeth.
• Duration(1-15 min) .
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Examination:
-unremarkable
-valvular HD (AS)
-Risk factors(hpt, DM), xanthoma
-LV dysfunction (cardiomegally, gallop rhythm)
-arterial diseases(carotid bruit, PVD)
-features of anemia, thyrotoxicosis
investigations
()resting ECG:
• -Often normal
• -T-wave flattening or inversion
• -ST segment depression or elevation
• - evidence of previous MI
()CXR: normal, cardiomegally, calcification of coronary
arteries
()Exercise ECG:
• - planner or down-sloping ST segment depression of ≥ 1
mm.
() myocardial perfusion scanning: during stress by using Tc 99
()stress ECHO:
()coronary arteriography
()Currently, electron-beam computed tomography (EBCT)
and multi-detector computed tomography (MDCT) are the
primary fast CT methods for CAC measurement.
Risk stratification in stable angina
() high risk:
• Post-infarct angina
• Poor effort tolerance
• Isch at low workload
• Left main or three-vessel disease
• Poor LV function
Management
()general measures:
• -Do not smoke
• - ideal body wt
• - regular excersice
• - avoid heavy excertion, heavy meal, very cold
wheather
• -take sublingual nitrate before undertaking
excertion that may induce angina
• -Treat risk factors, including hypertension,
diabetes mellitus, obesity, and hyperlipidemia.
() In high-risk patients, a serum LDL cholesterol level
of less than 100 mg/dL is the goal.
– () Patients with established coronary disease and
low HDL cholesterol levels are at high risk for
recurrent events .
• Cholesteryl ester transfer protein (CETP)
inhibitors have been shown to have the
effect of increasing HDL cholesterol levels by
blocking this CETP. (Torcetrapib)
() antiplatelet:
• Aspirin 75 mg daily, clopidogrel 75mg
• ()nitrate: vasodilator, lower preload& after load
& increase myocardial oxygen supply (coronary
vasodilatation)
• -sublingual glyceryl trinitrate tab 300-500Mg or
400Mg spray, will relieve attack within 2-3min,
transdermal, oral isosorbide dinitrate or
mononitrate.
• S.E: headache, hypotension & rarely syncope
()beta-blocker:
• -decrease myoc oxygen demand by reducing
HR, BP, & myocardial contractility.
• -metoprolol 50-200mg daily, bisprolol 5-15 mg
• -S.E: bronchospasm, etcccccc
• -should not be withdraw abruptly because this
may lead to rebound effect & precipitate
dangerous arrhythmias, worsening angina: the
B- blocker withdrawal syndrome.
() CCB: lower myoca oxygen demand by
reducing BP & myoca contractility.
• S.E: flushing, odema, headache, dizziness.
() potassium channel activators: arterial &
venous dilator. Nicorandil
() channal antagonist: Ivabradine, its ion
channals blocker in sinus node.
() ranolazine: Na channel blokers
Invasive treatment
() percutaneous coronary intervention(PCI):
• -single or two-vessels disease
() coronary artery bypass grafting(CABG):
• -for three vessels disease or lf main stem.
• -two vessel disease with involvment of
proximal LAD.
PCI
CABG
<0.5%
<1.5%
2%
10%
Hospital stay
12-36hr
5-8 days
Return to work
2-5 days
6-12 wks
15-20% at 6 months
10% at 1 yr
10-20 % at 2 year
2% at 2 yr
rare
Common
Emergemcy CABG,
Vascular damage related to
access site
Diffuse MI
Infection
Wound pain
death
MI
Recurrent angina
Repeat revascularisation
Neurological cx
Other cx
Acute coronary syndrome
() Acute coronary syndrome is a term that
encompasses both unstable angina and MI.
() Unstable angina is characterised by new-onset
or rapidly worsening angina (crescendo angina),
angina on minimal exertion or angina at rest in
the absence of myocardial damage.
() In contrast, MI occurs when symptoms occur at
rest and there is evidence of myocardial
necrosis, as demonstrated by an elevation in
cardiac troponin or creatine kinase-MB
isoenzyme .
Universal definition of myocardial
infarction
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The term 'myocardial infarction' should be used when there is evidence of
myocardial necrosis in a clinical setting consistent with myocardial ischaemia, in
which case any one of the following meets the diagnosis for MI:
() Detection of rise and/or fall of cardiac biomarkers (preferably troponin), together
with at least one of the following:
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Symptoms of ischaemia
ECG changes indicative of new ischaemia (new ST-T changes or new left bundle branch block)
Development of pathological Q waves
Imaging evidence of new loss of viable myocardium or new regional wall motion
abnormality
() Sudden unexpected cardiac death, involving cardiac arrest, often with symptoms
suggestive of myocardial ischaemia, and accompanied by presumably new ST
elevation or new left bundle branch block, and/or evidence of fresh thrombus by
coronary angiography and/or at autopsy, but death occurring before blood
samples could be obtained or before the appearance of cardiac biomarkers in the
blood
() Pathological findings of an acute MI
Pathophysiology
• The culprit lesion is usually a complex ulcerated or
fissured atheromatous plaque with adherent plateletrich thrombus and local coronary artery spasm .
• In acute MI, occlusive thrombus is almost always
present at the site of rupture or erosion of an
atheromatous plaque.
• The thrombus may undergo spontaneous lysis over
the course of the next few days, although by this time
irreversible myocardial damage has occurred.
• Without treatment, the infarct-related artery remains
permanently occluded in 20-30% of patients.
• The process of infarction progresses over several
hours and most patients present when it is still
possible to salvage myocardium and improve
outcome
Clinical features of acute coronary
syndromes
Symptoms :
• -Prolonged cardiac pain: chest, throat, arms, epigastrium or back
• -Anxiety and fear of impending death
• -Nausea and vomiting
• -Breathlessness
• -Collapse/syncope
Physical signs :
• -Signs of sympathetic activation: pallor, sweating, tachycardia
• -Signs of vagal activation: vomiting, bradycardia
• -Signs of impaired myocardial function
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Hypotension, oliguria, cold peripheries
Narrow pulse pressure
Raised JVP
Third heart sound
Quiet first heart sound
Diffuse apical impulse
Lung crepitations
-Signs of tissue damage: fever
-Signs of complications: e.g. mitral regurgitation, pericarditis
Diagnosis and risk stratification
() The assessment of acute chest pain depends heavily on an analysis
of the character of the pain and its associated features, evaluation
of the ECG, and serial measurements of biochemical markers of
cardiac damage, such as troponin I and T.
• 12% of patients will die within 1 month and a fifth within 6
months of the index event.
• The risk markers that are indicative of an adverse prognosis
include:
• *recurrent ischaemia, *extensive ECG changes at rest or during
pain,
• *the release of biochemical markers (creatine kinase or troponin),
*arrhythmias, *recurrent ischaemia and haemodynamic
complications (e.g. hypotension, mitral regurgitation) during
episodes of ischaemia.
investigations
The ECG
• is central to confirming the diagnosis but may be
difficult to interpret if there is bundle branch
block or previous MI.
• The initial ECG may be normal or non-diagnostic
in one-third of cases.
• Repeated ECGs are important, especially where
the diagnosis is uncertain or the patient has
recurrent or persistent symptoms.
• ()Infarction of the posterior wall of the LV
does not cause ST elevation or Q waves in the
standard leads, but can be diagnosed by the
presence of reciprocal changes (ST
depression and a tall R wave in leads V1-V4).
Some infarctions (especially inferior) also
involve the RV.
• This may be identified by recording from
additional leads placed over the right
precordium.
Plasma cardiac markers
• () In unstable angina, there is no detectable rise in cardiac markers
or enzymes, and the initial diagnosis is made from the clinical
history and ECG only.
• () In contrast, MI causes a rise in the plasma concentration of
enzymes and proteins that are normally concentrated within
cardiac cells.
• These biochemical markers are creatine kinase (CK), a more
sensitive and cardiospecific isoform of this enzyme (CK-MB), and
the cardiospecific proteins, troponins T and I .
• CK starts to rise at 4-6 hours, peaks at about 12 hours and falls to
normal within 48-72 hours.
• The most sensitive markers of myocardial cell damage are the
cardiac troponins T and I, which are released within 4-6 hours and
remain elevated for up to 2 weeks.
()Other blood tests : leucocytosis is usual, reaching a peak on
the first day. The erythrocyte sedimentation rate (ESR)
and C-reactive protein (CRP) are also elevated.
() Chest X-ray : This may demonstrate pulmonary oedema.
• The heart size is often normal but there may be
cardiomegaly due to pre-existing myocardial damage.
() Echocardiography :
• This is useful for assessing left and right ventricular
function and for detecting important complications such
as mural thrombus, cardiac rupture, ventricular septal
defect, mitral regurgitation and pericardial effusion.
Immediate management
() Patients should be admitted urgently to hospital because there is a
significant risk of death or recurrent myocardial ischaemia during the
early unstable phase, and appropriate medical therapy can reduce the
incidence of these by at least 60%.
• If there are no complications, the patient can be mobilised from the
second day and discharged from hospital after 3-5 days.
() Analgesia : is essential not only to relieve distress, but also to lower
adrenergic drive and thereby reduce vascular resistance, BP, infarct size
and susceptibility to ventricular arrhythmias. Intravenous opiates
(initially morphine sulphate 5-10 mg or diamorphine 2.5-5 mg) and
antiemetics (initially metoclopramide 10 mg) should be administered .
• Intramuscular injections should be avoided because the clinical effect
may be delayed by poor skeletal muscle perfusion, and a painful
haematoma may form following thrombolytic or anti-thrombotic
therapy.
() Antiplatelet therapy : In patients with acute coronary syndrome,
oral administration of 75-300 mg aspirin daily improves survival,
with a 25% relative risk reduction in mortality. The first tablet (300
mg) should be given orally within the first 12 hours and therapy
should be continued.
• In combination with aspirin, the early (within 12 hours) use of
clopidogrel 600 mg, followed by 150 mg daily for 1 week and 75
mg daily thereafter, confers a further reduction in ischaemic
events . In patients with an acute coronary syndrome with or
without ST-segment elevation, ticagrelor (180 mg followed by 90
mg 12-hourly) is more effective than clopidogrel in reducing
vascular death, MI or stroke, and all-cause death without affecting
overall major bleeding risk.
• Glycoprotein IIb/IIIa receptor antagonists, such as tirofiban and
abciximab, block the final common pathway of platelet
aggregation and are potent inhibitors of platelet-rich thrombus
formation. They are of particular benefit in patients with acute
coronary syndromes who undergo PCI ,those with recurrent
ischaemia and those at particularly high risk, such as patients with
diabetes mellitus or an elevated troponin concentration.
() Anticoagulation reduces the risk of thromboembolic complications,
and prevents reinfarction in the absence of reperfusion therapy or
after successful thrombolysis Anticoagulation can be achieved
using unfractionated heparin, fractioned (low molecular weight)
heparin or a pentasaccharide. Comparative clinical trials suggest
that the pentasaccharides (subcutaneous fondaparinux 2.5 mg
daily) have the best safety and efficacy profile, with low molecular
weight heparin Anticoagulation should be continued for 8 days or
until discharge from hospital or coronary revascularisation.
• period of treatment with warfarin should be considered if there is
persistent atrial fibrillation or evidence of extensive anterior
infarction, or if echocardiography shows mobile mural thrombus,
because these patients are at increased risk of systemic
thromboembolism.
() Anti-anginal therapy :
• Sublingual glyceryl trinitrate (300-500 μg) is a
valuable first-aid measure in unstable angina or
threatened infarction, and intravenous nitrates (GTN
0.6-1.2 mg/hour or isosorbide dinitrate 1-2 mg/hour)
are useful for the treatment of left ventricular failure
and the relief of recurrent or persistent ischaemic
pain.
• Intravenous β-blockers (e.g. atenolol 5-10 mg or
metoprolol 5-15 mg given over 5 mins) relieve pain,
reduce arrhythmias and improve short-term mortality
in patients who present within 12 hours of the onset
of symptoms . However, they should be avoided if
there is heart failure (pulmonary oedema),
hypotension (systolic BP < 105 mmHg) or bradycardia
(heart rate < 65/min).
() CCB
Reperfusion therapy
• Indicated for the ST segment
• elevation acute coronary syndrome:
1-Primary percutaneous coronary intervention
(PCI) :
• This is the treatment of choice for ST segment
elevation MI , Outcomes are best when it is used
in combination with glycoprotein IIb/IIIa
receptor antagonists and intracoronary stent
implantation.
• Should be achieved within 2 hours of diagnosis,
2- Thrombolysis The appropriate use of
thrombolytic therapy can reduce hospital
mortality by 25-50% and this survival
advantage is maintained for at least 10 years
The benefit is greatest in those patients who:
() receive rx within 12 hr (particularly 6hr)
()LBBB, ST > 1mm in limb leads or >2mm in
chest leads
()age?
• Alteplase (human tissue plasminogen activator or
tPA) is a genetically engineered drug that is given over
90 minutes (bolus dose of 15 mg, followed by 0.75
mg/kg body weight, but not exceeding 50 mg, over 30
mins and then 0.5 mg/kg body weight, but not
exceeding 35 mg, over 60 mins).
• Analogues of tPA, such as tenecteplase and reteplase,
have a longer plasma half-life than alteplase and can
be given as an intravenous bolus.
• The major hazard of thrombolytic therapy is bleeding.
Cerebral haemorrhage causes 4 extra strokes per 1000
patients
Relative contraindications to
thrombolytic therapy:
• potential candidates for primary angioplasty
*Active internal bleeding
• *Previous subarachnoid or intracerebral
haemorrhage
• *Uncontrolled hypertension
• *Recent surgery (within 1 mth)
• *Recent trauma (including traumatic resuscitation)
• *High probability of active peptic ulcer
• *Pregnancy
complications
1- arrhythmias:
• Common arrhythmias in acute coronary syndrome :
• Ventricular fibrillation
• Ventricular tachycardia
• Accelerated idioventricular rhythm
• Ventricular ectopics
• Atrial fibrillation
• Atrial tachycardia
• Sinus bradycardia (particularly after inferior MI)
• Atrioventricular block
2- Post-infarct angina occurs in up to 50% of
patients treated with thrombolysis.
Most patients have a residual stenosis in the
infarct-related vessel despite successful
thrombolysis,
3- Acute circulatory failure : Acute circulatory
failure usually reflects extensive myocardial
damage and indicates a bad prognosis.
4- Pericarditis : This only occurs following infarction and is
particularly common on the second and third days.
• A pericardial rub may be audible. Opiate-based analgesia
should be used. Non-steroidal and steroidal antiinflammatory drugs may increase the risk of aneurysm
formation and myocardial rupture in the early recovery
period, and so should be avoided.
• The post-MI syndrome (Dressler's syndrome) is
characterised by persistent fever, pericarditis and pleurisy,
and is probably due to autoimmunity. The symptoms tend
to occur a few weeks or even months after the infarct and
often subside after a few days; prolonged or severe
symptoms may require treatment with high-dose aspirin,
NSAIDs or even corticosteroids.
5- Mechanical complications :
• Rupture of the papillary muscle can cause acute
pulmonary oedema and shock due to the sudden
onset of severe mitral regurgitation, which presents
with a pansystolic murmur and third heart sound.
• Rupture of the interventricular septum causes left-toright shunting through a ventricular septal defect.
This usually presents with sudden haemodynamic
deterioration accompanied by a new loud pansystolic
murmur radiating to the right sternal border, but may
be difficult to distinguish from acute mitral
regurgitation. surgery, the condition is usually fatal.
• Rupture of the ventricle may lead to cardiac
tamponade and is usually fatal
6- Embolism : Thrombus often forms on the
endocardial surface of freshly infarcted
myocardium. This can lead to systemic
embolism and occasionally causes a stroke or
ischaemic limb.
7- Impaired ventricular function, remodelling
and ventricular aneurysm
• Acute transmural MI is often followed by thinning and stretching of the
infarcted segment (infarct expansion). This leads to an increase in wall
stress with progressive dilatation and hypertrophy of the remaining
ventricle (ventricular remodelling, ) As the ventricle dilates, it becomes
less efficient and heart failure may supervene.
• Infarct expansion occurs over a few days and weeks but ventricular
remodelling can take years. ACE inhibitor therapy reduces late
ventricular remodelling and can prevent the onset of heart failure .
• A left ventricular aneurysm develops in approximately 10% of patients
with MI and is particularly common when there is persistent occlusion of
the infarct-related vessel.
• Other clinical features include a paradoxical impulse on the chest wall,
persistent ST elevation on the ECG, and sometimes an unusual bulge
from the cardiac silhouette on the chest X-ray. Echocardiography is
usually diagnostic. Surgical removal of a left ventricular aneurysm carries
a high morbidity and mortality but is sometimes necessary.
Late management of MI
() Lifestyle modification
• Cessation of smoking
• Regular exercise
• Diet (weight control, lipid-lowering)
() Secondary prevention drug therapy
• Antiplatelet therapy (aspirin and/or clopidogrel)
• β-blocker
• ACE inhibitor/ARB
• Statin
• Additional therapy for control of diabetes and hypertension
• Aldosterone receptor antagonist
() Rehabilitation: mobilise at 2nd day, return home at 3-5days & return to
work after 4-6weeks
• Devices : Implantable cardiac defibrillator (high-risk patients) EF≤30
PROGNOSIS
• () In almost one-quarter of all cases of MI, death occurs within a
few minutes without medical care.
• () Half the deaths occur within 24 hours of the onset of symptoms
and about 40% of all affected patients die within the first month.
• () Early death is usually due to an arrhythmia and is independent of
the extent of MI. However, late outcomes are determined by the
extent of myocardial damage
• () poor px include :
• poor left ventricular function, AV block and persistent ventricular
arrhythmias, anterior than for inferior infarcts, Bundle branch block
and high cardiac marker levels, Old age, depression and social
isolation are also associated.
• () Of those who survive an acute attack, more than 80% live for a
further year, about 75% for 5 years, 50% for 10 years and 25% for 20
years.
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