Download Lipids and Coronary Heart Disease: Objectives

Lipids and Coronary Heart Disease: Objectives
1. How does the accumulation of cholesterol in the arterial wall result in coronary heart disease?
a. Progression of Atherothrombotic Disease:
i. Normal, Fatty Streak (foam cells), lipid-rich plaque (fibrous cap + lipid core),
plaque rupture, thrombus (clot)
b. Starts in the uterus
i. Everyone has it to different degrees
ii. With increasing age, accumulation is increased
iii. Less blood flow to heart, leads to heart pumping harder
iv. Blockage of arteries results in heart attacks and strokes
2. How is the arterial wall progressively modified to abnormally accumulate cholesterol?
a. There is a compensatory expansion of the artery’s diameter, so as to maintain a
constant lumen space
b. When it can no longer continue expanding, the lumen eventually is narrowed and filled
in with accumulated cholesterol
c. Oxidation of LDL causes endothelial dysfunction
i. Risk factors (#3) injure the endothelium
ii. LDL-C and cells enter the endothelium
iii. LDL-C is oxidized
iv. Foam cells, cytokines, and plaque rupture
v. ALSO: Decreases Nitric oxide synthetase, and increases angiotension converting
enzyme
1. Reducing vascular reactivity, leading to arterial hypertension
3. What are the CVD risk factors and how do they potentiate artherosclerosis?
a. Risk Factors include:
i. Dyslipidemia
ii. Hyperhomocysteinemia
iii. Hypertension
iv. Genetic abnormalities
v. Smoking & Obesity
vi. Diabetes & Insulin Resistance
vii. Ischemia & Peripheral Artery Disease
viii. Inflammation
b. How they potentiate artherosclerosis
i. Oxidation of LDL causes endothelial dysfunction
1. Risk factors (#3) injure the endothelium
2. LDL-C and cells enter the endothelium
3. LDL-C is oxidized
4. Foam cells, cytokines, and plaque rupture
5. ALSO: Decreases Nitric oxide synthetase, and increases angiotension
converting enzyme
a. Reducing vascular reactivity, leading to arterial hypertension
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Lipids and Coronary Heart Disease: Objectives
ii. Chronic inflammation at the sites of plaque formation
1. Immune cells release cytokines
2. Cell interacts in same way as in: rheumatoid arthritis, cirrhosis, etc.
iii. High C-Reactive Protein (CRP) levels  incr risk of CVD & MI
1. Is a marker for inflammation
4. What is the difference between a stable plaque and a vulnerable plaque?
a. Stable Plaque:
i. Thick, fibrous cap
ii. Smooth muscle cells (more extracellular matrix)
iii. Plaque is lipid-poor
b. Vulnerable Plaque:
i. Thin, fibrous cap (rupture can occur more easily)
ii. Inflammatory cells are present
iii. The plaque is lipid-rich
5. Name two methods for reversing artherosclerosis.
a. Statins:
i. LDL-C levels are reduced because statins are competitive inhibitors of HMG-CoA
Reductase (an enzyme involved in the synthesis of cholesterol)
ii. Reduction in plaque volume
iii. Can be assisted by increase in HDL
b. Lifestyle:
i. Exercise
ii. Stress reduction
iii. Healthy diet (veggies/fiber, fruits…low sat and trans fats)
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