Page 411 - Textbook of Pathology, 6th Edition

4th decade and beyond. Evidence in support comes from the 10. Markers of inflammation such as elevated C reactive protein, 395
high death rate from IHD in this age group. an acute phase reactant, correlate with risk of developing
atherosclerosis.
2. SEX. The incidence and severity of atherosclerosis are
more in men than in women and the changes appear a decade Pathogenesis
earlier in men (>45 years) than in women (>55 years). The
prevalence of atherosclerotic IHD is about three times higher As stated above, atherosclerosis is not caused by a single
in men in 4th decade than in women and the difference slowly etiologic factor but is a multifactorial process whose exact
declines with age but remains higher at all ages in men. The pathogenesis is still not known. Since the times of Virchow,
lower incidence of IHD in women, especially in a number of theories have been proposed.
premenopausal age, is probably due to high levels of Insudation hypothesis. The concept hypothesised by
oestrogen and high-density lipoproteins, both of which have Virchow in 1856 that atherosclerosis is a form of cellular
anti-atherogenic influence. proliferation of the intimal cells resulting from increased

3. GENETIC FACTORS. Genetic factors play a significant imbibing of lipids from the blood came to be called the ‘lipid
role in atherogenesis. Hereditary genetic derangements of theory’. Modified form of this theory is currently known as
lipoprotein metabolism predispose the individual to high ‘response to injury hypothesis’ and is now-a-days the most
blood lipid level and familial hypercholesterolaemia. widely accepted theory.
Encrustation hypothesis. The proposal put forth by
4. FAMILIAL AND RACIAL FACTORS: The familial Rokitansky in 1852 that atheroma represented a form of
predisposition to atherosclerosis may be related to other risk encrustation on the arterial wall from the components in the
factors like diabetes, hypertension and hyperlipopro- blood forming thrombi composed of platelets, fibrin and
teinaemia. Racial differences too exist; Blacks have generally leucocytes, was named as ‘encrustation theory’ or ‘thrombogenic
less severe atherosclerosis than Whites. theory’. Since currently it is believed that encrustation or
thrombosis is not the sole factor in atherogenesis but the
EMERGING RISK FACTORS components of thrombus (platelets, fibrin and leucocytes)

There are a number of nontraditional newly emerging risk have a role in atheromatous lesions, this theory has now been CHAPTER 15
factors for which the role in the etiology of atherosclerosis is incorporated into the response-to-injury hypothesis
yet not fully supported. These factors are as under: mentioned above.
1. Higher incidence of atherosclerosis in developed Though, there is no consensus regarding the origin and
countries and low prevalence in underdeveloped countries, progression of lesion of atherosclerosis, the role of four key
suggesting the role of environmental influences. factors—arterial smooth muscle cells, endothelial cells, blood
2. Obesity, if the person is overweight by 20% or more, is monocytes and dyslipidaemia, is accepted by all. However,
associated with increased risk. the areas of disagreement exist in the mechanism and
3. Use of exogenous hormones (e.g. oral contraceptives) by sequence of events involving these factors in initiation,
women or endogenous oestrogen deficiency (e.g. in post- progression and complications of disease. Currently,
menopausal women) has been shown to have an increased pathogenesis of atherosclerosis is explained on the basis of
risk of developing myocardial infarction or stroke. the following two theories:
4. Physical inactivity and lack of exercise are associated with 1. Reaction-to-injury hypothesis, first described in 1973, and
modified in 1986 and 1993 by Ross.
the risk of developing atherosclerosis and its complications. 2. Monoclonal theory, based on neoplastic proliferation of The Blood Vessels and Lymphatics
5. Stressful life style, termed as ‘type A’ behaviour pattern, smooth muscle cells, postulated by Benditt and Benditt in
characterised by aggressiveness, competitive drive, 1973.
ambitiousness and a sense of urgency, is associated with
enhanced risk of IHD compared with ‘type B’ behaviour of 1. REACTION-TO-INJURY HYPOTHESIS. This theory is
relaxed and happy-go-lucky type. most widely accepted and incorporates aspects of two older
6. Patients with homocystinuria, an uncommon inborn error historical theories of atherosclerosis—the lipid theory of
of metabolism, have been reported to have early Virchow and thrombogenic (encrustation) theory of
atherosclerosis and coronay artery disease. Rokitansky.
7. There are some reports which suggest that moderate The original response to injury theory was first described
consumption of alcohol has slightly beneficial effect by raising in 1973 according to which the initial event in atherogenesis
the level of HDL cholesterol. was considered to be endothelial injury followed by smooth
8. Prothrombotic factors and elevated fibrinogen levels favour muscle cell proliferation so that the early lesions, according
formation of thrombi which is the gravest complication of to this theory, consist of smooth muscle cells mainly.
atherosclerosis. The modified response-to-injury hypothesis described sub-
9. Role of infections, particularly of Chlamydia pneumoniae and sequently in 1993 implicates lipoprotein entry into the
viruses such as herpesvirus and cytomegalovirus, has been intima as the initial event followed by lipid accumulation in
found in coronary atherosclerotic lesions by causing the macrophages (foam cells now) which according to
inflammation. Possibly, infections may be acting in modified theory, are believed to be the dominant cells in early
combination with some other factors. lesions.