VASCULAR: ATHEROSCLEROSIS I

Question 1

arterioscelerosis

Answer 1

Arteriosclerosis: “hardening of the arteries” due to arterial wall thickening and loss of elasticity

Question 2

atherosclerosis

Answer 2

Atherosclerosis: hardening due to intimal lesions (atheromas or atherosclerotic plaques)

Question 3

structure of atherosclerosis

Answer 3

Structure: soft, yellow, cholesterol-rich core - white fibrous cap - protrude into vessel lumens

Plaques common at aorta, coronary and carotid arteries- particularly at bifurcation points

Question 4

Describe 3 cardiovascular effects of atheroscelerosis

Answer 4

1. Plaques decrease the effective vessel radius
   atheromas increase resistance to flow
   In the coronary arteries: atheromas impede local reflex vasodilation → vasodilator reserve is reduced → tolerance to exercise is reduced
2. Plaque rupture exposes collagen and other thrombogenic substances; local thrombus can cause clot; partial and complete vessel occlusion possible
3. Increased risk of embolism (debris becoming lodged downstream); thromboembolism (thrombus or debris from ruptured plaque (embolus) occludes a downstream vessel)

Question 5

What are the 2 risk factors for atherosclerosis

Answer 5

1. Hypercholesterolemia: a lipid disorder in which your low-density lipoprotein (LDL), or bad cholesterol, is too high
2. Dyslipidemia: imbalance of lipids; altered ratio of low density lipoprotein (LDL)

Obesity
Diabetes mellitus (uncontrolled)
Smoking
Sedentary lifestyle
Hypertension
Males have a higher risk; based on fat distribution; post menopausal results in decreased estrogen; now males and females have more equal risk
Hyperlipidemia

Question 6

Why is LDL bad and HDL good?

Answer 6

LDL transports cholesterol from liver → tissues

HDL transports cholesterol from tissues → liver

Question 7

Tangier Disease

Answer 7

Tangier Disease: congenital mutation in ABC protein; ABC enables cholesterol to exit tissue and bind ApoA1 of HDL; genetic defect → ↓ HDL cholesterol in blood ↑ risk of CV disease

Question 8

Familial hypercholesterolemia

Answer 8

Familial hypercholesterolemia: mutation in tissue LDL receptor. Increased LDL cholesterol in blood and increased risk of cardiovascular disease

Question 9

How do we know that lipids are involved?

Answer 9

1. epidemiological studies
2. studying genetic disorders
3. studies on transgenic mice ; scientists cause overexpression of ApoB (lipoprotein associated with LDL)→ development of atherosclerosis and CHD and increased risk of cardiovascular disease
4. Pharmacological interventions (lipid lowering drugs) treat atherosclerosis
   - ex: statins and alirocumab and inclisiran

Question 10

Describe statins

Answer 10

Statins: reduce cholesterol synthesis by blocking HMG-coA reductase in the liver; has a secondary anti-inflammatory effect; ↓ risk of CV disease

Question 11

Describe alirocumab

Answer 11

Alirocumab: inhibitor of PCSK9 which decreases LDL levels; PCSK9 degrades the LDL receptor in the liver → ↑ LDL

Question 12

Diagnostic indicators of atherosclerosis

Answer 12

C-reactive protein: released from the liver in response to cytokines - an indicator of inflammation and infection
e.g. IL-6 from activated macrophages

Bacteria/viruses: implicated in atherosclerosis; chronic inflammation, leukocyte & lipid accumulation; increase plaque formation
bacteria and viruses found in plaques (Chlamydia pneumoniae, Helicobacter pylori, Herpes)

Hyperhomocystinemia: ↑ [homocysteine] blood associated with CHD (↑ oxidative stress);
folic acid reduces homocysteines but there is uncertain therapeutic efficacy

Lipoprotein A: genetic variant of LDL; if someone has a greater proportion of this it is associated with ↑ coronary and cerebrovascular disease
Blood Iron concentration - contributes to lipid peroxidation - pre-menopausal women are protected - some advise to reduce red meat intake

Platelet aggregation - increased susceptibility to aggregation = increased risk

Erectile dysfunction - may be a warning sign of impaired vascular health - high C-reactive protein promotes endothelial dysfunction

Peridontal disease - 20% higher risk of CHD due to inflammatory risk