Hypercholesterolemia (+ familial) Flashcards
how does cholesterol help your body? (4)
- precursor to bile salts
- helps maintain rigidity and fluidity of cell membranes
- essential to steroid hormone production
- production of vitamin D from sunlight
where is cholesterol synthesized?
liver
how much cholesterol should pts include in diet?
trick question, none!
the liver creates all the cholesterol that is required by the body
if anything, get more HDL-C
how is cholesterol synthesized?
- glucose is broken down
- glycolysis and Krebs
- you have 3x acetyl-CoA
- use HMG-CoA reductase (rate limiting enzyme)
- squalene
- 7-dehydrocholesterol
- cholesterol!
is saturated fat bad for you? what does it do to your cholesterol levels?
yes, increases the fat deposition in the liver and more cholesterol production in the liver
is unsat fat bad for you? what does it do to your cholesterol?
no, it reduces blood cholesterol
how does cholesterol travel and move throughout the body?
- synthesized in liver or taken in from dietary fat/cholesterol
- dietary cholesterol is packed with apoproteins into a chylomicron to travel in the lymph system
- cholesterol synthesized in the liver is released as VLDL into the blood stream
- both chylomicron and VLDL is broken down into LDL
- free fatty acids can be deposited into adipose tissue, in the peripheral tissues (muscles) via LDL receptors on cells
- 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
Apolipoprotein B is an important carrier for _______
chylomicrons, LDL, and apoA
the function of an apolipoprotein is to _____
bind to lipids to form lipoproteins to help transport them through the blood, cerebrospinal fluid, and lymph
ApoA is an important protein for _________ cholesterol
HDL
what is the clinical significance of lipoprotein(a)?
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
what is hypercholesterolemia?
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
What are some risk factors for hyperchoelsterolemia?
- older age
- obesity
- FH of premature atherosclerotic CVD/dyslipidemia
- HTN
- DM
- Smoking
- low HDL-C
- inflammatory diseases
- COPD
- Chronic kidney disease
Who should be screened for dyslipidemia? Name 5
- 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
what is familial hypercholesterolemia?
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
what type of genetic defects might we see in familial hypercholesterolemia?
- 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]
what s/s could we see in hypercholesterolemia?
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
What ix would you order to screen for hypercholesterolemia?
- lipid panel – TC, LDL-C, HDL-C, non-HDL-c, TG ➔ repeat with fasting if TG is high
- Lp(a) - once in a lifetime
- fasting plasma glucose or A1c
- creatinine ➔ eGFR
Consider
1. ApoB
2. TSH
3. liver biochemistries - AST/ALT/ALP/GGT
4. Genetic testing for familial hypercholesterolemia
What is the Simon Broome Diagnostic criteria used for and what is a part of it (7)?
used to diagnose familial hypercholesterolemia
- age
- total cholesterol
- LDL-C
- tendon xanthomas
- DNA evidence of a LDLR, PCSK9 or APOB mutation
- FH of premature CVD event
- FH of extremely high cholesterol
how do you treat hypercholesterolemia?
- pt education - diet, exercise, smoking cessation, wt loss
- statins
- bile acid sequestrants
- ezetimibe
- PCSK9 inhibitors (mAbs)
Could consider LDL aphaeresis for severe familial hypercholesterolemia
how would you decide what treatment someone with hypercholesterolemia you would give? how would it influence the plan?
calculate framingham risk score
low risk - pt education
medium/higher risk - medicinal therapy (statins, bile acid sequestrants, cholesterol absorption inhibitors, PCSK9 mAb)
what do you need calculate framingham risk score (7)?
- age
- sex
- smoker
- Total cholesterol
- HDL-C
- systolic BP
- BP history
