VASCULAR: ATHEROSCLEROSIS I Flashcards
arterioscelerosis
Arteriosclerosis: “hardening of the arteries” due to arterial wall thickening and loss of elasticity
atherosclerosis
Atherosclerosis: hardening due to intimal lesions (atheromas or atherosclerotic plaques)
structure of atherosclerosis
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
Describe 3 cardiovascular effects of atheroscelerosis
- 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 - Plaque rupture exposes collagen and other thrombogenic substances; local thrombus can cause clot; partial and complete vessel occlusion possible
- Increased risk of embolism (debris becoming lodged downstream); thromboembolism (thrombus or debris from ruptured plaque (embolus) occludes a downstream vessel)
What are the 2 risk factors for atherosclerosis
- Hypercholesterolemia: a lipid disorder in which your low-density lipoprotein (LDL), or bad cholesterol, is too high
- 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
Why is LDL bad and HDL good?
LDL transports cholesterol from liver → tissues
HDL transports cholesterol from tissues → liver
Tangier Disease
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
Familial hypercholesterolemia
Familial hypercholesterolemia: mutation in tissue LDL receptor. Increased LDL cholesterol in blood and increased risk of cardiovascular disease
How do we know that lipids are involved?
- epidemiological studies
- studying genetic disorders
- studies on transgenic mice ; scientists cause overexpression of ApoB (lipoprotein associated with LDL)→ development of atherosclerosis and CHD and increased risk of cardiovascular disease
- Pharmacological interventions (lipid lowering drugs) treat atherosclerosis
- ex: statins and alirocumab and inclisiran
Describe statins
Statins: reduce cholesterol synthesis by blocking HMG-coA reductase in the liver; has a secondary anti-inflammatory effect; ↓ risk of CV disease
Describe alirocumab
Alirocumab: inhibitor of PCSK9 which decreases LDL levels; PCSK9 degrades the LDL receptor in the liver → ↑ LDL
Diagnostic indicators of atherosclerosis
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
