ATHEROSCLEROSIS

ATHEROSCLEROSIS
Natural history and main
consequences
DEF:-

 >Atherosclerosis is characterized by intimal lesion

called atheroma or fibrofatty plaques which
obstruct vascular lumen.
 >life time risk of developing CAD in males over 40
years 50% and in woman over 40 years is 32%
CLASSIFICATION

Type 1
 Formation of foam cell .
 Intra cellular lipid accumulation . > mainly
intracellular lipid accumulation .

 Type 2
 > formation of fatty streak .
> fatty streak are the known risk factor for
artherosclerosis especially serum lipoprotein
cholesterol concentration and smoker.
 Type 3
 > Charecterized by small extracellular lipid pools.

Starts from 3rd decade.

Type 4
 Type 1, 2 and 3 are clinically silent. …> Known as
atheroma lesion.

 > of core of extracellular lipid.

 > Onset from 3rd decade
 Type 5
 > Known as fibroatheroma lesion.
 Consist of lipid core and fibrotic layer
 .
 Onset from 4rd decade

 Type 6

Complicated lesion .
 Charecterized by surface defect hematoma haemorrhage and thrombus.
 > Onset from 4th decade
 > Type 4,5 and 6 may be clinically silent or overt.


TIMELINE
More cosequnences
ANGIOGRAPHIC FINDINGS
MORPHOLOGY
 THE KEY PROCESS IN ATHEROSCLEROSIS IS
INTIMAL THIKENING AND LIPID
ACCUMULATION
 ATHEROMATOUS PLAQUE CONSIST OF
RAISED FOCAL LESION INITIATING WITHIN
THE INTIMA,HAVING A
SOFT,YELLOW,GRUMOUS CORE OF
LIPID,COVERED BY WHITE FIBROUS CAP
 ATHEROMATOUS PLAQUES APPEAR WHITE
TO WHITISH YELLOW AND IMPINGE ON
THE LUMEN OF THE ARTERY
 SIZE VARIES FROM 0.3 TO 1.5cm BUT MAY
COALESCE TO FORM LARGER MASSES
 USUALLY INVOLVE ONLY PARTIAL
CIRCUMFERENCE OF THE VESSEL
 THE ATHEROSCLEROTIC PLAQUES THAT
WERE INITIALLY FOCAL LATER BECOME
DIFFUSE AND NUMEROUS AS THE DISEASE
PROGRESSES
 IF THE ATHEROMA IS PRESENT IN A SMALL
ARTERY MAY CAUSE ISCHEMIC INJURY TO
DISTANT ORGANS
 ABDOMINAL AORTA IS MORE COMMONLY
INVOLVED THAN THORACIC AORTA AND
THE LEISONS ARE MUCH MORE
PROMINENT AROUND THE ORIGIN(OSTIA)
OF MAJOR BRANCHES
 SEVERE DISEASE
WITH DIFFUSE AND
COMPLICATED
LESIONS IN THE
AORTA
COMPONENTS OF
ATHEROSCLEROTIC PLAQUES
 3 PRINCIPAL COMPONENTS-
 CELLS-including SMCs,macrophages and other
leucocytes
 ECM-including collagen,proteoglycans and
elastin fibers
 INTRACELLULAR AND EXTRACELLULAR
LIPIDS
 TYPICALLY THE SUPERFICIAL FIBROUS CAP
IS COMPOSED OF SMCs AND DENSE ECM
 BENEATH IS THE CELLULAR AREA
CONSISTING OF MACROPHAGES,SMCs AND
T LYMPHOCYTES
 STILL DEEPER IS A NECROTIC CORE
,CONSISTING OF A DISORGANISED MASS
OF LIPID,CHOLESTEROL CLEFTS,DEBRIS
FROM DEAD CELLS,FOAM
CELLS,FIBRIN,VARIABLLY ORGANISED
THROMBUS AND OTHER PLASMA
PROTIENS
FOAM CELLS
 FOAM CELLS ARE LARGE,LIPID LADEN
CELLS DERIVED FROM
MONOCYTES(TISSUE MACROPHAGES),BUT
SMCsCAN ALSO IMBIBE LIPID AND BECOME
FOAM CELLS
 PLAQUES PROGRESSIVELY ENLARGE THROUGH
CELL DEATH AND DEGENERATION,SYNTHESIS
AND DEGRADATION OF ECM AND
ORGANISATION OF THROMBUS
 LATER ON,THESE ATHEROMAS MAY UNDERGO
CALCIFICATION
RISKS OF ADVANCED LESIONS
 FOCAL RUPTURE,ULCERATION OR
EROSION OF THE LUMINAL SURFACE OF
ATHEROMATOUS PLAQUES MAY RESULT IN
EXPOSURE OF THROMBOGENIC
SUBSTANCES THAT INDUCE THROMBUS
FORMATION,PRODUCING
MICROEMBOLI(ATHEROEMBOLI)
 HEMORRHAGE INTO A PLAQUE MAY BE
INITIATED BY RUPTURE OF EITHER THE
OVERLYING FIBROUS CAP OR THIN
WALLED CAPILLARIES THAT VASCULARISE
THE PLAQUE.
 A CONTAINED HAEMATOMA MAY EXPAND
THE PLAQUE OR INDUCE PLAQUE
RUPTURE
 SUPERIMPOSED THROMBOSIS MAY OCCUR
ON DISRUPTED LESIONS AND MAY
PARTIALLY OR COMPLETELY OCCLUDE THE
LUMEN
 THROMBI MAY HEAL OR MAY WORSEN
THE ARTERY BLOCKADE
 ANEURYSMAL DILATATION MAY RESULT
FROM ATH-INDUCED ATROPHY OF
UNDERLYING MEDIA,WITH LOSS OF
ELASTIC TISSUE,CAUSING WEAKNESS AND
POTENTIAL RUPTURE
EPIDEMIOLOGY
&
RISK FACTORS
EPIDEMIOLOGY

 Major cause of death & premature disability in

developed countries
 Less prevalent in Asia & Africa
 By 2020 cardiovascular diseases notably
atherosclerosis will be leading cause of total
disease burden
• PREVALENCE OF ATHEROSCLEROSIS: 17 PER
1000

 Death rate expectoration for atherosclerosis(USA):

41deaths per day
 40% of middle aged men have evidence of
ischaemia due to atherosclerosis

 Between 1963-2000, 50% ↓ in death rate from

ischemic heart disease & 70%↓ in death rate from
strokes

 ↓ mortality lead to ↑ average life expectancy by 3 yrs

 Significant coronary sclerosis was found in
approximately two-thirds of the subjects above the
age of 20 years
 Nearly one out of every three apparently healthy
males beyond 30 had a rather severe grade of
coronary sclerosis.
RISK FACTORS
MAJOR
Non modifiable modifiable

 ↑ Age • Hyperlipidemia
 Male gender • Hypertension
 Family history • Cigarette smoking
 Genetic abnormalities • Diabetes
 Male >females
 oestrogen in females : ↓incidence of artherosclerosis
↑ risk in post menopausal women

 Age
 Men ≥ 45 yrs
 Women ≥ 55yrs
5 fold ↑ incidence of MI above 40-65 yrs of age
 Genetic abnormalities
 Hypertension & diabetes are most common
 Familial hypercholesterolemia may be a cause.
 Hyperlipidemia
Cholesterol
 <200: normal
 200-240: borderline
>240: drug therapy
LDL
 <130 :normal
 130-160: borderline
>160: drug therapy
HDL
<40 : increased RISK
 Hypertension
 BP≥ 140/90 : low risk
 BP ≥ 169/95: high risk
 Smoking

≥ 1 PACK/DAY for several years ↑

death rate by 200%
 Diabetes
2 fold ↑ in MI than non diabetics.

 100 fold ↑ risk of gangrene in lower extremities

OTHER CAUSES
 Life style risk factors
 Obesity (BMI≥ 30kg/m2)
 Physical inactivity
 Stress (type A personality)
 Alcohol

 Hardened unsaturated fat intake

ALCOHOL AND
ATHEROSCLEROSIS
ALCOHOL INCREASES HDL
 Emerging risk factors
 Lipoprotein Lp(a)
 Homocysteine

 Prothrombotic factors
 Proinflammatory factors
 Impaired fasting glucose
 Infectious agents
 Chlamydia pneumoniae
 cytomegalovirus
 EFFECTS &
PREVENTION
CLINICOPATHOLOGIC
EFFECTS

VASCULAR CHANGES-COMPLEX
DYNAMIC INTERACTION AMONG
FIXED ATHEROSCLEROTIC
IMPAIRED CORONARY NARROWING OF EPICARDIAL
PERFUSION RELATIVE TO CORONARY ARTERIES
MYOCARDIAL
INTRALUMINAL THROMBOSIS
DEMAND(MYOCARDIAL
ISCHEMIA) PLATELET AGGREGATION

VASOSPASM
 PREVENTION

SSEECC
N
ND OO
DA ARR
YY
 DELAYING
PRIMARY PREVENTION
CAUSING
REGRESSION OF
ATHEROMA
ESTABLISHED
FORMATION
LESION
RISK FACTOR MODIFICATION
 CESSATION OF CIGARETTE SMOKING
 CONTROL OF HYPERTENSION
 WEIGHT REDUCTION
 INCREASED EXERCISE
 MODERATION OF ALCOHOL CONSUMPTION
 LOWERING TOTAL & LDL BLOOD
CHOLESTROL LEVELS
 INCREASING HDL LEVELS
SECONDARY PREVENTION

PREVENT RECURRENCE OF
EVENTS MYOCARDIAL INFARCTION
MODIFICATION SHOULD
BEGIN IN CHILDHOOD
 STUDIES SHOW DISEASE BEGINS IN
CHILDHOOD
 CARDIOVASCULAR RISK FACTORS IN
CHILDREN PREDICT ADULT PROFILE
 SERUM CHOLESTROL AND SMOKING
IMPORTANT DETERMINANTS OF EARLY
STAGES OF ATHEROSCLEROSIS
THANK
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