Ans. is ‘a’ i.e., Left anterior descending artery

Ans. is ‘c’ i.e., Lipids in LDL gets oxidized

Answer is C (Decreased fibrinogen levels)

Increased levels of _.fibrinogen (and not decreased fibrinogen levels) are associated with increased risk of atherosclerosis.

• Fibrinogen Levels

‘Fibrinogen levels correlate with coronary risk and provide information regarding coronary risk independent of lipoprotein profile. Elevated fibrinogen levels might promote a thrombotic diathesis’.

• Waist Hip Ratio : This refers to a characteristic ‘male’ distribution of adipose tissue i.e. excess of fat in the abdomen compared with that in hips.

`An elevated waist/hip ratio has been associated with symptomatic cardiovascular disease and cerebrovascular disease in both men and women. – Pubmed (NCBI – website)

Hyperhomocvsteinemia and low HDL levels are known risk factors for Atherosclerosis (as depicted in the following table).

Major risk Factors for Atherosclerosis

• Cigarette smoking
• Hypertension (BP > 140/90mm/hg) or (on Antihypertensive medication)
• Low HDL cholesterol
• Diabetes mellitus
• Family history of CHD
• Age (Men > 45 years; Women > 55 years)
• Life style risk factors Obeity (BMI > 30 kg/m2)

Physical inactivity Atherogenic diet

Emerging risk factors

• Lipoprotein (a)
• Homocystine             •
• Prothrombotic factors (Fibrinogen)
• Pro inflammatory factors
• Impaired fasting glucose
• Subcl inical atherogenesis

Answer is B (Homocysteine)

• There is a strong positive correlation between atherosclerosis and circulating levels of Homocysteine’‘
• Hyperhomocysteinemia has been most consistently linked with atherosclerosis and coronary thrombotic events
• “Patient with clinical and angiographic evidence of coronary artery disease tend to have higher levels of plasma homocysteine. The relationship has not been extended to cerebrovascular and peripheral vascular disease”- CMDT
• “A large body of literature suggests a relationship between hyperhomocysteinemia and coronary events. Several mutations in the enzymes involved in homocysteine accumulation correlate to thrombosis and (in some studies) coronary risk”
• An increase of 5 micromol / L of homocysteine in serum elevates the risk of coronary artery disease by as much as cholesterol increase of 20 mg /dl.
• Homocysteine interacts with lysyl residues of collagen interfering with collagen cross linking.
• It forms homocysteine thiolactone, a highly reactive free radical which thiolates LDL particles.
• These particles tend to aggregate, are endocytosed by macrophages and increase the tendency for atherogenesis.
• Providing adequate quantity of pyridoxine, vitamin B12 and folic acid will keep homocysteine in blood in normal levels.
• Maternal hyperhomocysteinemia is known to increase the chances of neural tube defects in foetus. So, high doses of folic acid are advised in pregnancy.

Answer is C (Cigarette Smoking)
Cigarette smoking is the single most important modifiable risk factor for atherosclerosis.

• Smoking is the single most important modifiable risk factor for the development of Peripheral Artery Disease (PAD)
• Smoking cessation is the single most important target Pr coronary artery disease (CAD) Prevention
• Hypertension continues to be the most important of all modifiable risk factors for stroke

Answer is A (Intake of Unsaturated Fatty Acids is associated with decreased risk)

The maximal benefit is observed with Omega 3 Poly-unsaturated Fatty Acids, however Mono-unsaturated Fatty Acids also have consistent anti-atherosclerotic benefits and both Poly-unsaturated Fatty Acids (PUFA) and Mono­unsaturated Fatty Acids (MUFA) are considered Cardioprotective Fatty Acids.

Hypercholestoremia alone may increase the risk of Atherosclerosis

`Hyperlipidemia and more specifically hypercholesterolemia is a major risk factor lb,. atherosclerosis. Even in the absence of other factors, h^ypercholesterolemia is sufficient to stimulate lesion development’. – Robbins 8th/497 Extent of Athrosclerosis is more severe in arteries than in veins

Atherosclerosis is always severe in areas where pressure and velocity are high (as in arteries) in contrast to areas where pressure and velocity are low (as in veins).

‘Overall atherosclerosis is more severe in high-pressure arteries than in pulmonary arteries with lower blood pressure. It is least severe in veins where pressure and velocit^y are lowest’ – ‘Pan – Vascular Medicine’ by Topol (2002)/90 Abdominal Aorta is more commonly involved than Thoracic Aorta

`Abdominal Aorta is more commonly involved than Thoracic Aorta. Within the abdominal aorta lesions tend to be more prominent around the ostia’ – `Med Essentials’ (Kaplan Publishing) 2007/249

`In the systemic circulation  severity is accentuated in the abdominal aorta and large arteries of the lower limb where pulse wave reflection and summation effect elevate the pulse and systolic pressures. The disease is more severe in large  rather than small vessels indicating the importance of mural tension and Reynolds number both of which are proportional to radius increasing the likelihood and severity of effects of blood flow disturbance at arterial forks, junctions and curvatures’.- ‘Pan Vascular Medicine’

Ans. is ‘a’ i.e., Chronic inflammatory disorder of vessel wall

Facts about atherosclerosis

Is a chronic inflammatory and healing response of the arterial wall to endothelial injury.

Atherosclerosis progresses in the following sequence:

Endothelial injury and dysfunction → Accumulation of lipoproteins (mainly LDL) Monocyte adhesion to the endothelium, followed by migration into the intima and transformation into macrophages and foam cells → Platelet adhesion factor release from activated platelets, macrophages, and vascular wall cells → Smooth muscle cell proliferation, extracellular matrix production, and recruitment of T cells → Lipid accumulation both extracellularly and within cells (macrophages and smooth muscle cell).

In descending order, the most extensively involved vessels are the lower abdominal aorta, the coronary arteries, the popliteal arteries, the internal carotid arteries, and the vessels of the circle of Willis. In humans, the abdominal aorta is typically involved to a much greater degree than the thoracic aorta.

Ans. is ‘a’ i.e., Oxidized LDL

Morphology of atherosclerotic plaque

There are three major components of an atherosclerotic plaques :-

i) Cells : Smooth muscle cell and macrophages are the major cells with some contribution from foam cells (lipid-laden macrophages), and lymphocytes. Advanced atherosclerotic plaque may lack smooth muscles as smooth muscle cells undergo apoptosis.

ii) Extracellular matrix : Collagen, elastic fibers, proteoglycans.

iii) Lipids : Both intracellular and extracellular, with cholesterol and cholesterol ester being the major lipids.

Ans. is ‘b’ i.e., Obesity

Ans. is ‘c’ i.e., Convex part formed by fibrous cap

• The convex part is formed by the fibrous cap, which consists of smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin and proteoglycans.
• The central necrotic core is formed of cell debris, cholesterol crystals, foam cells and calcium.
• The concave part is formed by the tunica media of the vessel

Ans. is ‘d’ i.e., Endothelium

• The most acceptable hypothesis for the pathogenesis of atherosclerosis is “the response to injury hypothesis”.
• According to this hypothesis, atherosclerosis is a chronic inflammatory response of the arterial wall initiated by injury to endothelium.

Pathogenesis of atherosclerosis

• Following stages occurs in the pathogenesis of Atherosclerosis:
• Endothelial injury
• Earliest stages of the development of atherosclerosis are mediated by the inflammatory cascade.
• Inflammation mediated injury to endothelium is the cornestone in the development of atherosclerosis.
• After injury, endothelium is activated and there is increased expression of adhesion molecule-VCAM-1 and
• there is increased permeability to endothelium.
• TNF is the major cytokine to induce this expression.

Migration of leukocytes

• When VCAM-1 is expressed on endothelium, leukocytes adhere to the endothelium.
• Leukocytes than cross the endothelial barrier and begin to accumulate in subendothelial intimal space.
• Macrophages engulf LDL cholesterol and form foam cells → formation of earliest lesion, i.e. fatty streak.
• Macrophages also form oxygen free radicals that cause oxidation of LDL to yield oxidized LDL (modified LDL).
• Smooth muscle cell migration and proliferation
• Inflammatory cells in subendothelial intimal space secrete cytokines, mainly PDGF, TGF-ct and FGF which cause migration of smooth muscle cells from media to subendothelial intimal space as well as their proliferation.

Maturation of plaque

• Smooth muscle cells synthesize extracellular matrix (especially collegen) and convert a fatty streak into a mature fibrofatty atheroma, and contribute to the progressive growth of atherosclerotic lesions.

Ans:C.)Complicated Plaque
Schematic Evolution of Lesions in Atherosclerosis.
[img id=6454] 
MORPHOLOGIC FEATURES

1. FATTY STREAKS AND DOTS. 

• Grossly, the lesions may appear as flat or slightly elevated and yellow.
• They may be either in the form of small, multiple dots, about 1 mm in size, or in the form of elongated, beaded streaks.
• Microscopically, fatty streaks lying under the endothelium are composed of closely-packed foam cells, lipid containing elongated smooth muscle cells and a few lymphoid cells. 

2. GELATINOUS LESIONS.

• They are round or oval, circumscribed grey elevations, about 1 cm in diameter.
• Microscopically, gelatinous lesions are foci of increased ground substance in the intima with thinned overlying endothelium.

3. ATHEROMATOUS PLAQUES.

• A fully developed atherosclerotic lesion is called atheromatous plaque, also called fibrous plaque, fibrofatty plaque or atheroma.
• Grossly, atheromatous plaques are white to yellowish white lesions, varying in diameter from 1-2 cm and raised on the surface by a few millimetres to a centimetre in thickness.
• Cut section of the plaque reveals the luminal surface as a firm, white fibrous cap and a central core composed of yellow to yellow-white, soft, porridgelike material.
• Microscopically, the following features are invariably present :
• Superficial luminal part of the fibrous cap is covered by endothelium, and is composed of smooth muscle cells, dense connective tissue and extracellular matrix containing proteoglycans and collagen.
• Cellular area under the fibrous cap is comprised by a mixture of macrophages, foam cells, lymphocytes and a few smooth muscle cells which may contain lipid.
• Deeper central soft core consists of extracellular lipid material, cholesterol clefts, fibrin, necrotic debris and lipid laden foam cells.

4. COMPLICATED PLAQUES.

• Various pathologic changes that occur in fully-developed atheromatous plaques are called the complicated lesions. 
• These changes include calcification, ulceration, thrombosis, haemorrhage and aneurysmal dilatation.