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DR KAMALESH LENKA
• Atherosclerosis is characterized by intimal lesions called atheromas
(or atheromatous or atherosclerotic plaques) that impinge on the
vascular lumen and can rupture to cause sudden occlusion
Epidemiology of Atherosclerosis
• Atherosclerosis is virtually ubiquitous among most developed nations
• The mortality rate for IHD in the United States is among the highest in
the world, approximately five times higher than that in Japan.
• However, IHD is increasing in Japan,
• Furthermore, Japanese emigrantswho come to the United States and
adopt American lifestyles and dietary customs acquire the same
atherosclerosis risk as U.S.-born individuals
RISK FACTORS
• Constitutional Risk Factors
• Genetics.-Family history is the most important independent risk factor
for atherosclerosis
• Certain mendelian disorders are strongly associated with
atherosclerosis (e.g., familial hypercholesterolemia)
• Age.-
• Atherosclerosis usually remains clinically silent until lesions reach a
critical threshold in middle age or later.
• Thus, the incidence of myocardial infarction increases 5-fold between
40 and 60 years of age.
• Gender-
• All other factors being equal, premenopausal women are relatively
protected against atherosclerosis
• Thus, myocardial infarction and other complications of atherosclerosis
are uncommon in premenopausal women in the absence of other
predisposing factors such as diabetes, hyperlipidemia,hypertension
• After menopause, however, the incidence of atherosclerosis-related
disease increases and can even exceed that in men.
Modifiable Major Risk Factors
• Hyperlipidemia-
• and, more specifically, hypercholesterolemia— is a major risk factor
for development of atherosclerosis and is sufficient to induce
lesions in the absence of other risk factors
• The main cholesterol component associated with increased risk is
low-density lipoprotein (LDL) cholesterol (“bad cholesterol”);
• By contrast, high-density lipoprotein (HDL) cholesterol (“good
cholesterol”) mobilizes cholesterol from developing and existing
vascular plaques and transports it to the liver for biliary excretion.
• High dietary intake of cholesterol and saturated fats (e.g., present in
egg yolks, animal fats, and butter) raises plasma cholesterol levels
• Omega-3 fatty acids (abundant in fish oils) are beneficial
• whereas (trans)-unsaturated fats produced by artificial hydrogenation
of polyunsaturated oils (used in baked goods and margarine)
adversely affect cholesterol profiles.
• Exercise and moderate consumption of ethanol raiseHDL levels
• whereas obesity and smoking lower them.
• Statins are a widely used class of drugs that lower circulating
cholesterol
• Hypertension-risk factor for development of atherosclerosis.
• On its own, hypertension can increase the risk for IHD by
approximately 60%
• Cigarette smoking-
• is a well-established risk factor in men and probably accounts for the
increasing incidence and severity of atherosclerosis in women
• Prolonged (years) smoking of one or more packs of cigarettes per day
doubles the rate of IHD-related mortality
• while smoking cessation reduces the risk.
• Diabetes mellitus-
• is associated with raised circulating cholesterol levels and markedly
increases the risk for atherosclerosis.
• disorder is associated with an increased risk for stroke and a 100-fold
increase in atherosclerosis-induced gangrene of the lower
extremities.
• Additional Risk Factors-
• There is some evidence that a systemic pro-inflammatory state is
associated with the development of atherosclerosis and hence
measures of systemic inflammation have been used in risk
stratification.
• systemic markers of inflammation, determination of C-reactive
protein (CRP) has emerged as one of the simplest and most sensitive
• CRP is an acute-phase reactant synthesized primarily by the liver
• Hyperhomocysteinemia.-Serum homocysteine levels correlate with
coronary atherosclerosis, peripheral vascular disease, stroke, and venous
thrombosis
• Metabolic syndrome-Associated with central obesity this clinical entity is
characterized by
• insulin resistance,
• hypertension,
• dyslipidemia (elevated triglycerides and depressed HDL),
• hypercoagulability,
• and a pro-inflammatory state, which may be triggered by cytokines
released from adipocytes.
• Lipoprotein(a) levels.-Lipoprotein(a) is an LDL-like particle that
contains apolipoprotein B-100 linked to apolipoprotein(a).
Adrenergic stimulation
VULNERABLE Plaques:
• ontain large areas of foam cells and extracellular lipids-with thin
fibrous caps
• *collagen represents the major structural component of the fibrous
cap and accounts for its mechanical strength and stability
• -contain few smooth muscle cells
• -have clusters of inflammatory cells
• *STATINS stabilize plaques by reducing plaque inflammation
ACUTE PLAQUE CHANGE-
• Peak time of onset of acute myocardial infarction is between 6 AM
and 12 NOON
CONSEQUENCES OF ATHEROSCLEROTIC
DISEASE
• THROMBOSIS
• *VASOCONSTRICTION
• compromises lumen size and by increasing local mechanical forces
can potentiate plaque disruption-stimulated by
• :1. Adrenergic agonists
• 2. Local platelet contents
• 3. impaired secretion of cell relaxing factors
• 4. mediators released from perivascular inflammtory cell