ATHEROSCLEROSIS Seminar Prepared by :- Ali Abdulazeem Shilan Adnan Abdulrahman Alaa Shamil Guldan Hameed Internal Medicine College of Medicine - University of Kirkuk

1. ATHEROSCLEROSIS
Supervised by: Dr. sabah Zangana
Presented by:
1. Alaa Shamel
2. Guldan hameed
3. Shilan Adnan
4. Ali Abdulazeem

2. • Arteriosclerosis: is a general term
describing any hardening (and loss of
elasticity) of medium or large arteries
• Arteriolosclerosis: is any hardening (and
loss of elasticity) of arterioles (small
arteries)
• Atherosclerosis: is a hardening of an artery
specifically due to an atheromatous plaque.
2

3. Atherosclerosis can affect any artery in the
body. When it occurs in the heart, it may
cause angina, MI and sudden death; in the
brain, stroke and transient ischaemic attack
(TIA); and in the limbs, claudication and
critical limb ischaemia. Occult coronary
artery disease is common in those who
present with other forms of atherosclerotic
vascular disease, such as intermittent
claudication or stroke, and is an important
cause of morbidity and mortality in these
patients.3

4. 4
Atherosclerosis is a progressive inflammatory
disorder of the arterial wall that is
characterised by focal lipidrich 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.
Pathophysiology

5. 5

6. 6
Stages of
atheroscleros

7. 7
Type I (initial) lesion Isolated macrophage foam
cells, From first decade, Clinically silent.

8. 8
Type III (intermediate) lesion Type II changes and
small extracellular lipid pools, From third decade,
Clinically silent.

9. 9
Type IV (atheroma) lesion Type II changes and core
of extracellular lipid, From third decade, Clinically
silent or overt.

10. 10
Type V (fibroatheroma) lesion Lipid core and fibrotic layer, or
multiple lipid cores and fibrotic layers, or mainly calcific, or
mainly fibrotic, Accelerated smooth muscle and collagen
increase, From fourth decade, Clinically silent or overt.

11. 11
In an established atherosclerotic plaque,
macro-phages mediate inflammation and
smooth muscle cells promote repair. If
inflammation predominates, the plaque
becomes active or unstable and may be
complicated by ulceration and thrombosis.
Advanced atherosclerosis

12. 12
Type VI (complicated) lesion Surface defect, haematoma-
haemorrhage, thrombus, From fourth decade, Clinically silent
or overt.

13. 13

14. 14
Vulnerable plaques are characterised by a lipid-rich
core, a thin fibrocellular cap, speckled calcification
and an increase in inflammatory cells that release
specific enzymes to degrade matrix proteins.
In contrast, stable plaques are typified by a small
lipid pool, a thick fibrous cap, heavy calcification
and plentiful collagenous crossstruts.

15. 15

16. 16
Fissuring or rupture tends to occur at sites of
maximal mechanical stress, particularly the margins
of an eccentric plaque, and may be triggered by a
surge in BP, such as during exercise or emotional
stress.

17. 17
Atherosclerosis may induce complex changes in the
media that lead to arterial remodelling:
Negative remodelling: some arterial segments may
slowly constrict.
Positive remodelling: some arterial segments may
gradually enlarge.

18. 18

19. Risk factors

20. “
⊷Key factors have emerged but do not
explain all the risk, and unknown
factors may account for up to 40% of
the variation in risk from one person
to the next.
⊷A monozygotic twin of an affected
individual has an eightfold increased
risk and a dizygotic twin a fourfold
increased risk of dying from coronary
artery disease, compared to the
general population.
⊷The effect of risk factors is multiplic-
ative rather than additive.
20

21. “
It is important to distinguish between
relative risk (the proportional increase in
risk) and absolute risk (the actual chance
of an event). Thus, a man of 35 years
with a plasma cholesterol of 170 mg/dL,
who smokes 40 cigarettes a day, is
relatively much more likely to die from
coronary disease within the next decade
than a non-smoking woman of the same
age with a normal cholesterol, but the
absolute likelihood of his dying during
this time is still small (high relative risk,
low absolute risk).
21

22. Age and sex:
Age is the most powerful independent risk factor for
atherosclerosis. Pre-menopausal women have lower
rates of disease than men, although this sex difference
disappears after the menopause. However, HRT has no
role in the primary or secondary prevention of coronary
artery disease, and isolated oestrogen therapy may
cause an increased cardiovascular event rate.
22

23. Family history:
Atherosclerotic vascular disease often runs in families,
due to a combination of shared genetic, environmental
and lifestyle factors. 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 below 50 years
for men and below 55 years for women.
23

24. Smoking:
This is probably the most important avoidable cause of
atherosclerotic vascular disease. There is a strong,
consistent and dose-linked relationship between
cigarette smoking and coronary artery disease,
especially in younger (< 70 years) individuals.
24

25. Hypertension:
The incidence of atherosclero-sis increases as BP rises,
and this excess risk is related to both systolic and
diastolic BP, as well as pulse pressure.
Antihypertensive therapy reduces cardiovascular
mortality, stroke and heart failure.
25

26. 26
Hypercholesterolaemia:
Risk rises with increasing serum cholesterol
concentrat-ions.Lowering serum total and LDL
cholesterol concentrations reduces the risk of
cardiovascular events, including death, MI,
stroke and coronary revascularisation.

27. 27
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. Insulin resistance
(normal glucose homeostasis with high levels of
insulin) is associated with obesity and physical
inactivity, and is a risk factor for coronary artery
disease (p. 805). Glucose intolerance accounts for a
major part of the high incidence of ischaemic heart
disease in certain ethnic groups, e.g. South Asians.

28. 28

29. 29
Haemostatic factors:
Platelet activation and high plasma fibrinogen
concentrations are associated with an increased risk
of coronary thrombosis. Antiphospholipid
antibodies are associated with recurrent arterial
thromboses

30. 30
Physical activity:
Physical inactivity roughly doubles the risk of coronary
artery 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 that may be related to increased serum
high-density lipoprotein (HDL) cholesterol
concentrations, lower BP, and collateral vessel
development.

31. 31
Obesity:
Obesity, particularly if central or truncal, is an
independent risk factor, although it is often associated
with other adverse factors, such as hypertension, diabetes
mellitus and physical inactivity.

32. 32
Alcohol:
Alcohol consumption is associated with reduced rates of
coronary artery disease. Excess alcohol consumption is
associated with hypertension and cerebrovascular
disease.

33. 33
Other dietary factors:
Diets deficient in fresh fruit, vegetables
and polyunsaturated fatty acids are
associated with an increased risk of CVD.
The introduction of a Mediterranean style
diet reduces CV events. However, dietary
supplements, such as vit C and E, beta-
carotene, folate and fish oils, do not reduce
cardiovascular events and, in some cases,
have been associated with harm.

34. 34
Personality:
Certain personality traits are associated
with an increased risk of coronary disease.
Nevertheless, there is little or no evidence
to support the popular belief that stress is a
major cause of coronary artery disease.

35. 35
Social deprivation:
Health inequalities have a major influence
on cardiovas-cular disease. The impact of
established risk factors is amplified in
patients who are socially deprived and
current guidelines recommend that
treatment thresholds should be lowered for
them.

36. 36

37. Clinical presentation and diseases of atheroscrelosis
37

38. CORONARY ARTERY DISEASE
38
It is the most common form of heart disease. By
2020, it is estimated that it will be the major cause
of death in all of the world. In the UK, 1 in 3 men
and 1 in 4 women die from CAD, an estimated 330
000 people have a myocardial infarct each year,
and approximately 1.3 million people have angina.
Disease of the coronary arteries is almost always
due to atheroma and its complications, particularly
thrombosis. Occasionally, the coronary arteries are
involved in other disorders such as aortitis,
polyarteritis and other connective tissue disorders.

39. 39

40. 40
Coronary artery disease: clinical manifestations and pathology
Clinical problem Pathology
Stable angina Ischaemia due to fixed atheromatous stenosis of one
or more coronary arteries
Unstable angina Ischaemia caused by dynamic obstruction of a
coronary artery due to plaque rupture or erosion with
superimposed thrombosis
Unstable angina Myocardial necrosis caused by acute occlusion of a
coronary artery due to plaque rupture or erosion with
superimposed thrombosis
Heart failure Myocardial dysfunction due to infarction or
ischaemia
Arrhythmia Altered conduction due to ischaemia or infarction
Sudden death Ventricular arrhythmia, asystole or massive myocar-
dial infarction

41. Stable angina
41
Angina pectoris is the symptom complex caused
by transient myocardial ischaemia and constitutes
a clinical syndrome rather than a disease. It may
occur whenever there is an imbalance between
myocardial oxygen supply and demand. Coronary
atheroma is by far the most common cause of
angina, although the symptom may be a
manifestation of other forms of heart disease,
particularly aortic valve disease and hypertrophic
cardiomyopathy

42. Factors influencing myocardial oxygen supply and demand
Oxygen demand: cardiac work
• Heart rate
• BP
• Myocardial
contractility
• Left ventricular hypertrophy
• Valve disease, e.g. aortic
stenosis
Oxygen supply: coronary blood flow
• Duration of diastole
• Coronary perfusion
pressure (aortic diastolic
minus coronary sinus or
right atrial diastolic
pressure)
• Coronary vasomotor tone
• Oxygenation
(Haemoglobin Oxygen
saturation)
42

43. 43
Clinical features
The history is the most important
factor in making the diagnosis.
Stable angina is characterised by
central chest pain, discomfort or
breathlessness that is precipitated
by exertion or other forms of
stress, and is promptly relieved by
rest.
Some patients find the discomfort
comes when they start walking,
and that later it does not return
despite greater effort (‘warm-up
angina’).

44. 44
Investigations
1. Resting ECG:
2. Exercise ECG
3. Myocardial perfusion scanning, Stress
echocardiography
4. Coronary arteriography

45. 45
A positive exercise test (chest leads only). The resting 12-lead
ECG shows some minor T-wave changes in the inferolateral
leads but is otherwise normal. After 3 minutes’ exercise on a
treadmill, there is marked planar ST depression in leads V4 and
V5 (right offset). Subsequent coronary angiography revealed
critical three-vessel coronary artery disease.
45

46. 4646
A myocardial perfusion scan showing reversible anterior myocardial
ischaemia. The images are cross-sectional tomograms of the LV. The
resting scans (left) show even uptake of the 99technetium-labelled
tetrofosmin and look like doughnuts. During stress (e.g. a dobutamine
infusion), there is reduced uptake of technetium, particularly along the
anterior wall (arrows), and the scans look like crescents (right).
At rest
During stress

47. 4747

48. 4848

49. 4949

50. 5050

51. 51
Management
1. Antiplatelet therapy :75 mg aspirin
2. Anti-anginal drugs: Nitrates, Beta-
blockers, Ca+2 channel antagonists,
K+ channel activators, If channel
antagonist
3. Percutaneous coronary intervention
4. Coronary artery bypass grafting

52. 52
Acute coronary syndrome
ACS is a term that encompasses both unstable
angina and myocardial infarction (MI).
It 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.

53. 53
Criteria for acute myocardial
infarction
Detection of a rise and/or fall of cardiac biomarker
values (preferably cardiac troponin) with at least
one of the following:
1. Symptoms of ischaemia
2. New significant ST–T changes or new LBBB.
3. Development of pathological Q waves.
4. Imaging evidence of new loss of viable
myocardium or new regional wall motion
abnormality.
5. Identification of an intracoronary thrombus by
angiography or post-mortem.

54. 54
The time course of MI. The relative proportion of ischaemic, infarcting
and infarcted tissue slowly changes over a period of 12 hours. In the
early stages of MI, a significant proportion of the myocardium in
jeopardy is potentially salvageable.
54

55. Clinical features of acute coronary syndromes
Symptoms
• Prolonged cardiac pain:
chest, throat, arms,
epigastrium or back
• Nausea and vomiting
• Breathlessness
• Collapse/syncope
• Anxiety and fear of impending
death
Physical signs
• Signs of sympathetic
activation: pallor, sweating,
tachycardia
• Signs of vagal activation:
vomiting, bradycardia
• Signs of tissue damage: fever
• Signs of complications: e.g.
mitral regurgitation,
pericarditis
• Signs of impaired myocardial
function: Hypotension,
oliguria, cold peripheries,
Narrow pulse pressure,
Raised JVP, Third heart
sound, Quiet first heart
sound, Diffuse apical
impulse, Lung crepitations
55

56. 56
Investigations
1. Electrocardiography.
2. Plasma cardiac biomarkers.
3. Other blood tests: CBC, ESR, CRP.
4. Chest X-ray
5. Echocardiography

57. 57
The serial evolution
of ECG changes in
transmural MI.
57

58. 5858

59. 5959

60. 6060

61. 6161

62. 6262

63. 63
Complications of acute
coronary syndrome
1. Arrhythmias: Ventricular fibrillation, Atrial
fibrillation, Bradycardia,
2. Ischaemia
3. Acute circulatory failure
4. Pericarditis
5. Mechanical complications: Rupture of the
papillary muscle, Rupture of the interven-
tricular septum, Rupture of the ventricle.
6. Embolism
7. Impaired ventricular function, remodelling and
ventricular aneurysm.

64. 64
Immediate management: the
first
12 hours
1. Analgesia: morphine sulphate 5–10
mg or diamorphine 2.5–5 mg plus
metoclopramide 10 mg
2. Antithrombotic therapy:
• Antiplatelet: 300 mg aspirin +
clopidogrel 600 mg
• Anticoagulants: unfractionated
heparin, fractioned heparin or a
pentasaccharide

65. 65
3. Anti-anginal therapy: Sublingual
glyceryl trinitrate (300–500 μg), β-
blockers (e.g. atenolol 5–10 mg),
Ca+2 channel antagonist (e.g.
nifedipine or amlodipine)
4. Reperfusion therapy:
STEMI: PCI in the first 12h,
Thrombolysis (Alteplase)
Non-STEMI: No thrombolytic
therapy, no need for coronary
revascularisation in first 12h.

66. 66
3. Anti-anginal therapy: Sublingual
glyceryl trinitrate (300–500 μg),
β-blockers (e.g. atenolol 5–10
mg), Ca+2 channel antagonist (e.g.
nifedipine or amlodipine)

67. 67
Later in-hospital management
1. Risk stratification and further
investigation: GRACE score
2. Lifestyle and risk factor
modification: stop smoking,
lowering serum cholestrol, reduce
weight ... etc.
3. Mobilisation and rehabilitation
4. Secondary prevention drug therapy

68. 68
Stroke
⊷85% of the cerebral infarction is
due to inadequate blood flow to
part of the brain.
⊷Cerebral infarction is mostly
caused by thromboembolic disease
secondary to atherosclerosis in the
major extracranial arteries (carotid
artery and aortic arch).

69. 6969

70. 70
Transient ischaemic attack (TIA):
describes a stroke in which symptoms
resolve within 24 hours, The term
TIA traditionally also includes
patients with amaurosis fugax, usually
due to a vascular occlusion in the
retina.
<

71. 71
Stroke: describes those events in
which symptoms last more than 24
hours.
>

72. 72
Progressing stroke (or stroke in
evolution): describes a stroke in
which the focal neurological deficit
worsens after the patient first
presents. Such worsening may be due
to increasing volume of infarction,
haemorrhagic transformation or
increasing cerebral oedema.

73. 73
Completed stroke: describes a stroke
in which the focal deficit persists and
is not progressing.

74. 74
⊷The risk factors for ischaemic
stroke reflect the risk factors for
the underlying vascular disease.
⊷About 5% are due to rare causes,
including vasculitis, endocarditis,
and cerebral venous disease.

75. Risk factors for stroke
Fixed risk factors
• Age
• Gender (male > female
except at extremes of
age)
• Race (Afro-Caribbean >
Asian > European)
• Previous vascular event:
(Myocardial infarction, Stroke,
Peripheral vascular disease)
• Heredity
• High fibrinogen
Modifiable risk factors
• Blood pressure
• Cigarette smoking
• Hyperlipidaemia
• Heart disease: (Atrial
fibrillation, Congestive
cardiac, failure, Infective
endocarditis)
• Diabetes mellitus
• Excessive alcohol intake
• Oestrogen-containing drugs:
(Oral contraceptive pill,
Hormone replacement
therapy)
• Polycythaemia75

76. 7676

77. 77
Clinical features
⊷Acute stroke and TIA are characte-
rised by a rapid-onset (over
minutes), focal deficit of brain
function.
⊷It is ‘negative’ in character (i.e.
abrupt loss of function without
positive features such as abnormal
movement).
⊷If symptoms progress over hours
or days, other diagnoses must be
excluded.

78. Characteristic features of stroke and stroke mimics
Feature Stroke Stroke mimics
Symptom onset Sudden (minutes) Often slower onset
Symptom
progression
Rapidly reaches
maximum severity
Often gradual onset
Severity of
deficit
Unequivocal May be variable/
uncertain
Pattern of
deficit
Hemispheric
pattern
May be non-specific
with confusion,
memory loss,
balance disturbance
Loss of
consciousness
Uncommon More common
78

79. 79
Investigations
1. CT
2. MRI
3. lumbar puncture
4. ECG), 24-hour, ECG Echo
5. FBC, Cholesterol Blood glucose
6. Duplex ultrasound of carotids
7. MRA, CTA, contrast angiography
8. ESR, Serum protein electropho-
resis, clotting/thrombophilia
screen

80. 80

81. 81

82. 82
Management
1. Supportive care
2. Intravenous thrombolysis with
recombinant tissue plasminogen
activator (rt-PA)
3. Aspirin: reduces the risk of early
recurrence
4. Heparin
5. coagulation abnormalities should
be reversed as quickly as possible
6. Management of risk factors

83. 83
Chronic lower limb arterial disease
PAD affects the leg eight times more
often than the arm.

84. 84
Intermittent claudication
This term describes ischaemic pain
affecting the muscles of the leg upon
walking. The pain is usually felt in
the calf because the disease most
commonly affects the superficial
femoral artery.

85. 85
Typically, the pain comes on after a
reasonably constant ‘claudication
distance’ and rapidly subsides on
stopping walking. Resumption of
walking leads to a return of the pain.

86. 86
only 1–2% per year will deteriorate to
a point where amputation and/or
revascularisation are required.
Annual mortality rate exceeds 5%, 2–
3 times higher than in an equivalent
nonclaudicant population because IC
is nearly always found in association
with widespread atherosclerosis, so
that most claudicants succumb to MI
or stroke.

87. 87
Treatment
⊷Smoking cessation, exercise
⊷Antiplatelet agent (aspirin 75 mg
or clopidogrel 75 mg daily)
⊷Reduction of cholesterol
⊷Dx and Tx of DM
⊷Dx and Tx of frequently associated
conditions (e.g. HT, anaemia, HF)
⊷vasodilator (cilostazol)
⊷angioplasty, stenting, endarterect-
omy or bypass

88. 88
Critical limb ischaemia
Rest (night) pain, requiring opiate
analgesia, and/or tissue loss
(ulceration or gangrene), present for
more than 2 weeks, in the presence of
an ankle BP of less than 50 mmHg.

89. 8989

90. “
90
Diabetic vascular disease
Approximately 5–10% of patients with
PAD have DM, If the blood supply is
adequate, then dead tissue can be
excised in the expectation that healing
will occur, provided infection is
controlled and the foot is protected from
pressure. Sadly, most PT present lately
which accounts for the high amp-
utation rate.

91. 9191

92. 92

93. “
93
Chronic upper limb arterial
disease
Arm claudication (rare).
• Atheroembolism (blue finger syndrome).
Small emboli lodge in digital arteries and
may be confused with Raynaud’s
phenomenon but, in this case, the
symptoms are unilateral. Failure to make
the diagnosis may eventually lead to
amputation.

94. Managment
94

95. Primary prevention
95
Two strategies; population and targeted strategies:
The population strategy aims to modify the risk factors
of the whole population through diet and lifestyle
advice, on the basis that even a small reduction in
smoking or average cholesterol, or modification of
exercise and diet will produce worthwhile benefits.
The targeted strategy aims to identify and treat high-risk
individuals, who usually have a combination of risk
factors and can be identified by using composite scoring
systems

96. 96
For example, a 65-year-old man with an average BP of
150/90 mmHg, who smokes and has diabetes mellitus, a
total : HDL cholesterol ratio of 8 and left ventricular
hypertrophy on ECG, will have a 10-year risk of
coronary artery disease of 68% and a 10-year risk of
any cardiovascular event of 90%. Lowering his
cholesterol will reduce these risks by 30% and lowering
his BP will produce a further 20% reduction; both
would obviously be worthwhile.

97. 97
Conversely, a 55-year-old woman who has an identical
BP, is a non-smoker, does not have diabetes mellitus
and has a normal ECG and a total : HDL cholesterol
ratio of 6 has a much better outlook, with a predicted
coronary artery disease risk of 14% and cardiovascular
risk of 19% over the next 10 years. Although lowering
her cholesterol and BP would also reduce risk by 30%
and 20% respectively, the value of either or both
treatments is questionable.

98. Secondary prevention
98
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.

99. 99
The energetic correction of modifiable risk factors,
particularly smoking, hypertension and
hypercholesterolaemia, is important.
All patients with coronary artery disease should be
given statin therapy, irrespective of their serum
cholesterol concentration.
BP should be treated to a target of 140/85 mmHg or
lower.
Aspirin and ACE inhibitors are of benefit in patients
with evidence of vascular disease.
Betablockers benefit patients with a history of MI or
heart failure.

100. Thank You
100