Module 7: CV Risk Assessment Study Questions

Question 1

Describe the postulated reasons for increased atherosclerosis development in the presence of cigarette smoking, hypertension, and diabetes.

Answer 1

Cigarette smoking:
- Cigarette smoke contains a large # of harmful chemicals that become dissolved in blood upon inhalation and damage the lining of arteries. These chemicals and the damage to the endothelium itself lead to constriction of blood vessels and reduction of BF to tissues inc the heart

Hypertension:
- Chronic high BP can lead to DAMAGE to ENDOTHELIUM and a THICKENING of artery WALLS, impaired relaxation of arteries, which puts additional stress on the heart to pump against the higher resistance

Diabetes:

• Diabetics show an increased small, dense LDL, elevated TGs, and low HDL
• glycosylation of proteins due to chronic high glucose has been thought to play a role in this risk

Question 2

What are the primary mechanisms proposed for elevated levels of low density lipoproteins promoting atherosclerosis development, and for elevated levels of high density lipoproteins protecting against atherosclerosis?

Answer 2

1. LDL: Elevated LDL accumulate in the artery wall and be taken up either as aggregated LDL or oxidized LDL by macrophages or smooth muscle cells in the artery, leading to foam cell formation and atherosclerotic lesions
2. HDL: has ability to remove excess cholesterol delivered to arterial cells by LDL. Can also induce relaxation of the artery wall

Question 3

Describe two emerging biomarkers for and their proposed relationship with increased risk for CHD

Answer 3

1. Lipoprotein a; Lp(a)
   - composed of one molecule of LDL with an additional protein, apo (a), unrelated to apoA-I on HDL, attached to the apoB portion of LDL via a disulfide linkage
   - produced in liver and circulates in blood
   - Statins (who lower LDL lvls) do not lower Lp(a)
   - can be lowered through reducing plasma LDL lvls
   - independent inc in risk of CVD associated w/elevated Lp(a) lvls. Likely due to high Lp(a) causing inc leakiness in blood vessel endothelium or inc tendency to form blood clots
2. CRP
   - marker of inflammation in the body
   - produced by liver in response to inc lvls of inflammatory molecules inc tumor necrosis alpha and interleukin 6 released from sites of inflammation
   - sites of inflammation inc developing atherosclerotic lesions in artery walls, visceral fat in people w/abdominal obesity, inflamed tissues in people w/rheumatologic disease e.g. rheumatoid arthritis or lupus, lungs of people w/chronic lung disease
   - independent risk factor for CHD, likely contributes to atherosclerosis or blood clotting by itself
   - high sensitivity CRP test should be given to individuals at the intermediate risk of CHD based on FRS in whom finding a high CRP would lead to change in their management, inc use of cholesterol-lowering treatment