Hypercholesterolemia (+ familial)

Question 1

how does cholesterol help your body? (4)

Answer 1

1. precursor to bile salts
2. helps maintain rigidity and fluidity of cell membranes
3. essential to steroid hormone production
4. production of vitamin D from sunlight

Question 2

where is cholesterol synthesized?

Answer 2

liver

Question 3

how much cholesterol should pts include in diet?

Answer 3

trick question, none!
the liver creates all the cholesterol that is required by the body

if anything, get more HDL-C

Question 4

how is cholesterol synthesized?

Answer 4

1. glucose is broken down
2. glycolysis and Krebs
3. you have 3x acetyl-CoA
4. use HMG-CoA reductase (rate limiting enzyme)
5. squalene
6. 7-dehydrocholesterol
7. cholesterol!

Question 5

is saturated fat bad for you? what does it do to your cholesterol levels?

Answer 5

yes, increases the fat deposition in the liver and more cholesterol production in the liver

Question 6

is unsat fat bad for you? what does it do to your cholesterol?

Answer 6

no, it reduces blood cholesterol

Question 7

how does cholesterol travel and move throughout the body?

Answer 7

1. synthesized in liver or taken in from dietary fat/cholesterol
2. dietary cholesterol is packed with apoproteins into a chylomicron to travel in the lymph system
3. cholesterol synthesized in the liver is released as VLDL into the blood stream
4. both chylomicron and VLDL is broken down into LDL
5. free fatty acids can be deposited into adipose tissue, in the peripheral tissues (muscles) via LDL receptors on cells
6. HDL is synthesized by the liver and intestines and goes out into the blood stream to pick up cholesterol and bring back to liver for excretion

Question 8

Apolipoprotein B is an important carrier for _______

Answer 8

chylomicrons, LDL, and apoA

Question 9

the function of an apolipoprotein is to _____

Answer 9

bind to lipids to form lipoproteins to help transport them through the blood, cerebrospinal fluid, and lymph

Question 10

ApoA is an important protein for _________ cholesterol

Answer 10

HDL

Question 11

what is the clinical significance of lipoprotein(a)?

Answer 11

lipoprotein(a) is a LDL
genetics play a large role in how much lipoprotein(a) a pt may have, it cannot be controlled with diet and exercise

having high levels puts the pt at a significantly higher risk of CVD

can be tested once in a pt’s lifetime with inital screening for dyslipidemia

Question 12

what is hypercholesterolemia?

Answer 12

elevation of
- Total cholesterol
- LDL-C
- non-HDL-C (encompasses chylomicron remnants, VLDL, LDL, IDL, Lp(A))
- triglycerides

OR

decrease of
- HDL-C
- apolipoprotein A

Question 13

What are some risk factors for hyperchoelsterolemia?

Answer 13

• older age
• obesity
• FH of premature atherosclerotic CVD/dyslipidemia
• HTN
• DM
• Smoking
• low HDL-C
• inflammatory diseases
• COPD
• Chronic kidney disease

Question 14

Who should be screened for dyslipidemia? Name 5

Answer 14

• Men >= 40Y
• Women >= 40Y or postmenuopausal

All ppl with the below regardless of age:
- pts w/ atherosclerosis
- AAA
- DM
- HTN
- current smoker
- stigmata of hydlipidemia
- FH of premature CVD, dyslipidemia
- chronic kidney disease
- obesity
- inflammatory diseases ➔ RA, SLE, PsA, AS, IBD
- HIV infection
- erectile dysfunction
- COPD
- history of hypertensive disorder or pregnancy

Question 15

what is familial hypercholesterolemia?

Answer 15

a group of genetic defects that affects how LDL-C is processed by the body. Allows LDL-C levels to rise in serum at a younger age

Question 16

what type of genetic defects might we see in familial hypercholesterolemia?

Answer 16

• LDL receptor defects ➔ LDL-C not taken up by cells, so increased [serum]
• ApoB ➔ no or defective ApoB, then LDL-C is unable to bind to LDL-receptor on cells, so increased [serum]
• PCSK9 ➔ increased PCSK9, PCSK9 binds to LDL-receptors so it cannot be used by LDL-C to go into the cells, so increased [serum]

Question 17

what s/s could we see in hypercholesterolemia?

Answer 17

xanthomas: fat build up under the surface of the skin
- eyes ➔ xanthelasma: yellow deposits around the eyelid
- tendons ➔ tendinous xanthoma: most common in the Achilles tendon

angina
corneal arcus - white/grey ring around iris
bruits on physical exam

Question 18

What ix would you order to screen for hypercholesterolemia?

Answer 18

1. lipid panel – TC, LDL-C, HDL-C, non-HDL-c, TG ➔ repeat with fasting if TG is high
2. Lp(a) - once in a lifetime
3. fasting plasma glucose or A1c
4. creatinine ➔ eGFR

Consider
1. ApoB
2. TSH
3. liver biochemistries - AST/ALT/ALP/GGT
4. Genetic testing for familial hypercholesterolemia

Question 19

What is the Simon Broome Diagnostic criteria used for and what is a part of it (7)?

Answer 19

used to diagnose familial hypercholesterolemia

1. age
2. total cholesterol
3. LDL-C
4. tendon xanthomas
5. DNA evidence of a LDLR, PCSK9 or APOB mutation
6. FH of premature CVD event
7. FH of extremely high cholesterol

Question 20

how do you treat hypercholesterolemia?

Answer 20

1. pt education - diet, exercise, smoking cessation, wt loss
2. statins
3. bile acid sequestrants
4. ezetimibe
5. PCSK9 inhibitors (mAbs)

Could consider LDL aphaeresis for severe familial hypercholesterolemia

Question 21

how would you decide what treatment someone with hypercholesterolemia you would give? how would it influence the plan?

Answer 21

calculate framingham risk score

low risk - pt education
medium/higher risk - medicinal therapy (statins, bile acid sequestrants, cholesterol absorption inhibitors, PCSK9 mAb)

Question 22

what do you need calculate framingham risk score (7)?

Answer 22

1. age
2. sex
3. smoker
4. Total cholesterol
5. HDL-C
6. systolic BP
7. BP history