SHORT PRESENTATION ABOUT ARTHEROSCLEROSIS AND FACTOR RESPONSIBLE FOR IT AND ITS MANAGEMENT .

2. OVERVIEW
 Epidemiology
 Introduction
 Structure of the arterial wall
 Definition of atherosclerosis and its hypothesis
 Lipoproteins and related biochemistry
 Atheroma: Morphology
 Risk factors
 AHA classification
 Common sites
 Common clinical syndromes
 Complications
 Preventions
 Treatment

3. EPIDEMIOLOGY
Coronary artery disease is most common cause of death
worldwide,3.8 million men and 3.4 million women die from
cardiovascular disease(CVD) each year(WHO). It has also
been estimated that CAD is responsible for 10% of disability-
adjusted life years in low-income countries and 18% in high-
income ones. The death rates from CAD in the UK are among
the highest in western Europe but are falling, particularly in
younger age groups.

4. EPIDEMIOLOGY(cont…)
 Recent study of Bangladesh (1986-2006) shows increment
in CVD mortality rate in Males by 30 fold (16 deaths per
100,000 to 483 deaths per 100,000) and in Females by 47
fold (7 deaths per 100,000 to 330 deaths per 100,000).
(Indian Heart Journal)
 Occult CAD is common in those who present with other
forms of atherosclerosis vascular disease, such as
intermittent claudication or stroke, and is an important
cause of morbidity and mortality in these patient.

5. INTRODUCTION
Arteriosclerosis literally means “hardening of the
arteries”. It is a generic term used to describe arterial wall
thickening and loss of elasticity.
Three (3) distinctive patterns of arteriosclerosis are:
1. Arteriolosclerosis: Involves small arteries and arterioles.
It is of 2 types: Hyaline and Hyperplastic. It is primarily
associated with hypertension.

6. INTRODUCTION(cont…)
2. Monckeberg medial sclerosis: Characterized by calcification of
the walls of the small to medium sized muscular arteries (i.e.
femoral, tibial, radial, ulnar and genital arteries), typically in the
internal elastic membrane. This usually occurs after the age of 50
years and is unrelated to atherosclerosis. The lesions are non-
obstructive therefore, are clinically insignificant.
3. Atherosclerosis: It comes from Greek root words arthere means
“gruel” and sclerosis means “hardening”. It is the most frequent
and clinically more important.

7. STRUCTURE OF THE ARTERIAL WALL
Arterial wall consists of organized connective tissue
composed of cells and matrix fibers that are
arranged in three tunicae: Intima, Media and
Adventitia.
1. Intima: The innermost layer, extending from
lumen to internal elastic lamina. It is lined by
endothelial cells. Basal lamina consists of 2
zones: inner clear zone contains glycoproteins
(laminin); outer dense fibrillar zone contains
collagen (type-IV). Finally, internal elastic
lamina, it contains of smooth muscles cells.

8. STRUCTURE OF THE ARTERIAL WALL (cont…)
2. Media: It extends from internal elastic lamina to
adventitia (external elastic lamina). The media composed
of closely packed smooth muscle cells associated with
elastin and collagen fibres.
3. Adventitia: It extends from external elastic lamina to a
boundary that is rather difficult to define; usually it is
continuous with the perivascular connective tissues. It
contains vasa vasorum and nerves.

9. TYPES OF SMOOTH MUSCLE CELLS
There are two distinctive patterns of smooth muscle cells, namely:
“synthetic” and “contractile”.
Intimal smooth muscle cells are more synthetic whereas medial
smooth muscle cells are more contractile. Intimal synthetic
smooth muscle cells has high proliferative index, more readily
migratory, expresses much extracellular matrix, proteases and
inflammatory cytokines. These can produce 25-46 times more
collagen than the contractile smooth muscle cells.

10. DEFINITION OF ATHEROSCLEROSIS
Atherosclerosis is a slowly progressive disease of large to medium
sized muscular and large elastic arteries characterized by elevated
intimal-based fibro-fatty plaques composed of lipid, proliferating
smooth muscle cells and increased extracellular matrix. As we know
this is a slow progressive disease so now we will discuss briefly
initiation, progression and outcome of it.
Hypothesis for initiation of atherosclerosis are described below:-

11. HYPOTHESIS OF ATHEROGENESIS:-
1. Lipid hypothesis
2. Response to injury hypothesis
3. Monoclonal hypothesis

12. LIPOPROTEINS AND ITS BIOCHEMISTRY
 Apo-lipoproteins are the proteins that binds
with lipid and forms the lipoproteins (apoA,
apoB, apoC, apoD, apoE, apoH) .
 Cholesterols are carried by esterification
and packed with the hydrophobic cores of
lipoproteins.
Apo: Apo-lipoprotein
C: Cholesterol
T: Triglycerides
Green: Phospholipids Fig: Chylomicron

13. LIPOPROTEINS AND ITS BIOCHEMISTRY(cont...)
 Depending of cholesterol density, there are 4 types of lipoproteins
namely: HDL, LDL, VLDL and Chylomicrons. However, for
atherosclerosis LDL, VLDL and HDL carry significant interest where
as chylomicrons deals with transfer of exogenous i.e. dietary lipid
from intestine to liver and other part of body.
 Apo-lipoprotein B-100 (apoB-100) is the carrier protein for LDL and
VLDL. LDL is called “bad cholesterol” as it deposits the cholesterols
to arterial wall whereas HDL the “good cholesterol” mobilizes the
cholesterol from the cells and from the atheroma.

14. LIPID HYPOTHESIS
Goldstein and Brown in 1985 won Nobel prize as a recognition of their
work on defective gene associated with familial
hypercholesterolemia. Cholesterol biosynthesis is regulated by
HMG CoA reductase (rate limiting enzyme) which in turn being
regulated by LDL not by the HDL. Cellular uptake of LDL is
absolutely requires LDL receptor. Genetic deficiency of LDL
receptors result in decreased bound-LDL, which in turn suppresses
the HMG CoA reductase. Therefore hypercholesterolemia results.
This increased cholesterol results in atherosclerosis.

15. RESPONSE TO INJURY HYPOTHESIS
1) Endothelial injury
2) Accumulation of lipoproteins
3) Monocyte adhesion to the
endothelium and formation of
foam cells.
4) Platelet adhesion
5) Factor release
6) SMC proliferation and ECM
production.
7) Lipid accumulation

16. Figure 11-11 Sequence of cellular
interactions in atherosclerosis.
Hyperlipidemia, hyperglycemia,
hypertension, and other influences cause
endothelial dysfunction. This results in
platelet adhesion and recruitment of
circulating monocytes and T cells, with
subsequent cytokine and growth factor
release from inflammatory cells leading to
smooth muscle cell migration and
proliferation as well as further
macrophage activation. Foam cells in
atheromatous plaques derive from
macrophages and smooth muscle cells
that have accumulated modified lipids
(e.g., oxidized and aggregated low density
lipoprotein [LDL]) via scavenger and LDL-
receptor-related proteins. Extracellular
lipid is derived from insudation from the
vessel lumen, particularly in the presence
of hypercholesterolemia, as well as from
degenerating foam cells. Cholesterol
accumulation in the plaque reflects an
imbalance between influx and efflux;
high-density lipoprotein (HDL) likely
helps clear cholesterol from these
accumulations. In response to the
elaborated cytokines and chemokines,
smooth muscle cells migrate to the
intima, proliferate, and produce
extracellular matrix, including collagen
and proteoglycans. IL-1, interleukin-1;
MCP-1, monocyte chemoattractant
protein-1.

17. MONOCLONAL HYPOTHESIS
This hypothesis suggests that each lesion of atherosclerosis is
derived from a single smooth muscle cell which serves as a
precursor cell for clonal expansion of proliferating smooth
muscle cells. However, this theory is being challenged and
remained controversial.

18. MORPHOLOGY
Two distinctive types of morphologic features are observed.
1. Fatty streaks
2. Atherosclerotic plaques

19. Fatty streaks : Morphology
Fatty streaks are composed of lipid-filled foamy
macrophages. Beginning as multiple minute flat
yellow spots, they eventually coalesce into elongated
streaks 1 cm long or longer. These lesions are not
sufficiently raised to cause any significant flow
disturbances. It may present in patients as young as 1
year old. A causal relationship between fatty streaks
and atheromatous plaques is suspected but remains
unproved.

20. Atherosclerotic plaques (atheroma): morphology
 Atheroma: Greek “athere”, -- “porridge like gruel” and atheromatous plaque is a
raised white yellow intimal based lesion, protruding into the vessel lumen having a
soft yellow grumous core of lipid (mainly cholesterol and cholesterol ester) covered
by a firm white fibrous cap.

21. RISK FACTORS:
Non modifiable (Constitutional):
 Genetic abnormality
 Family history
 Increasing age
 Male gender
Modifiable:
 Hyperlipidemia
 Hypertension
 Cigarette smoking
 Diabetes
Additional risk factors:
 Obesity
 Physical inactivity
 Stress (type-A personality)
 Estrogen deficiency
 High carbohydrate intake
 Alcohol
 Lipoprotein Lp(a)

22. AHA CLASSIFICATION/STAGING

23. COMMON SITES:
In descending frequency:
1. Abdominal aorta
2. Coronary arteries
3. Popliteal arteries
4. Descending thoracic aorta
5. Internal carotid arteries
6. Circles of Willi’s
7. Other arteries specially in the ostia of bifurcation where there is change
is laminar flow pattern. (renal arteries, mesenteric arteries, etc)

24. COMMON CLINICAL SYNDROMES
A) Ischemic heart disease:-
- sudden death
- myocardial infraction
- heart failure
B) Cerebrovascular disease:-
- cerebral infraction
- transient ischemic attacks
- dementia
C) Peripheral vascular disease:-
- intermittent claudication
- gangrene

25. CORONARY SYNDROMES

26. COMPLICATIONS:
1) Rupture, ulceration or erosion of plaque
2) Hemorrhage into a plaque
3) Atheroembolism
4) Aneurysm formation
5) Occulusion by thrombus
6) Critical stenosis

27. COMPLICATIONS OF ATHEROSCLEROSIS

28. PREVENTION
Look for the risk factors, like:-
a) Reduce dietery cholesterol and moderate fat
intake not more than 20-25gm per day.
b) Intake of green leafy vegetable.
c) Regular exercise and walk minimum 1.5 km per
day.
d) Avoid smoking and alcohol

29. TREATMENT
According to the diseases:-

30. REFERENCES
 Coronary Artery Disease: A Review, A.K.M. Monwarul Islam et al, Indian Heart
Journal 65 (2013), 424-435.
 Robbins and Cortan Pathologic Basis of Disease, 9th edition.
 Rutherford’s Vascular Surgery 8th edition.
 Davidson’s principles and practice of Medicine, 23rd edition.
 Muir’s text book of pathology, 14th edition.