Dyslipidemia Managment Flashcards
difference between cholesterol and triglycerides
role of lipoproteins
Cholesterol
- used for cell membrane flexibility
- vitamin D synthesis
- sex hormone production
- use in bile acid
Triglycerides
- used as energy!
- directly transported to the muscles
- stored in adipose tissue later for energy
these cant circulate in the body alone– need to be packaged in lipoproteins to travel
different lipoproteins contain differnt amounts of triglyceride and cholesterol
chylomicron: majority TG (80-95%)
VLDL: 55-80% TG
LDL: 60-70% cholesterol
HDL: low amounts of both cholesterol and TG
apolipoprotein (non-HDL) are the lipid delivery pathway made from the liver or metablism
Apo-a-1 protiens: (HDl) are part of reverse lipid trasnport from cells back to the TG or cholesterol form
- reverse cholesterol transport back to liver
- reverse cholesterol to exchange with the others (LDL, VLDL, etc.)
formation of LDL (smaller particles) from VLDL and chylomicrons —> release TG (as fatty acids) as they change into LDL
LDL taken up by liver or peripheral cells (turning into an atherosclerotic palque!!!)
what constitutes atherosclerotic cadriovascular disease (ASCVD)
how do VLDL, LDL and chylomicrons play a role
cholesterol causing ischemia!!
- MI
- TIA/Stroke
- stable or unstable angina
- cornary/arterial revascularization
- PAD
things due to atherosclerotic origin a clot issue
LDL – increased LDL = increased cholesterol = atherosclerosis
VLDL – increased VLDL = increased TG = atherosclerosis (because its on itsway to become a LDL)
Chylomicrons – increased chylomicrons = incread TG = acute pancreatitis (want TG < 500)
non-pharm recommendations too…
- lower LDL
- lower TG
- raise HDl
- reduce ASCVD risk
lower LDL
- increase fiber
- phytosterol supplementation
increase HDL
- increase exercise
- stop smoking
Raise HDL
- loose weight
- increase exercise
- stop drinking alcohol
- reduce sugar and carb intake
Lower ASCVD
- avoid trans fats
- increse veggies and fruit
- reduce intake of cholesterol and sodium foods
- get exercise
- stoke smoking
Statins
- MOA
- when are they used
- what groups of people benefit from statin use
Statins- focus on lowering LDL levels by 18-55%
MOA
- specifically: works to decrease the amount of cholesterol being produced within the liver –> therefore forcing the liver to increase the amount of receptors it has on its surface to attract more out of the serum!
- act by blocking HMG-CoA reductase to stop the prodcution of cholesterol in the liver
Purpose
- to lower the ASCVD risk for individuals – #1 treatment choice
- they lower LDL, non-HDL lipoproteins & TG
- additionally –> can stabilize a pre-formed atherosclerotic plaque, and decrease inflammation
- inhibits platlet aggregation & thrombin generation
- depending on risk factors – used as moderate or high dose therapy
- atorvostain and rousuvastain= can be high dose treatment
Populations who benefit
- secondary prevention: for those who have HAD an ASCVD event ( MI,stroke,PAD or revascualrization) –> give high intensity statin
- primary prevention:for those…
- 1. who have severe hypercholesteremia ( LDL > 190)
- 2. who have DM (age 40-75) & LDL > 70
- 3. who have ASCVD risk score > 7.5% & LDL > 70 (age 40-75)
how to differentiate between high risk and very high risk ASCVD in secondary prevention
treatment pathways for each
considered to be VERY high risk ASCVD if…
1. history of 2 major ASCVD events (MI/stroke,etc.)
OR
2. 1 major ASCVD event + 2 high-risk conditions (older lage, DM, HTN, CKD, smoker)
(*if not of the above, but still had ASCVD at any point – they’re just “high risk secondary prevention”)
Treatment
VERY high risk ASCVD
- initiate high intensitity statin
- if LDL still > 70 = add ezetimibe
- if STILL LDL > 70 = add PSK-9 inhibitor
High Risk ASCVD
- initiate high intensitiy statin
- if LDL still > 70 = add ezetimbie
remeber thresholds are not goal thearpies – just when to consider stepping up treatment
the only goal is the % reduction in LDL by statins
treatment decisions for severe hypercholesteremia (LDL > 190) in primary prevention
what type of PCSK9 for heterzygote or homozygote FH?
PRIMARY PREVENTION: pt. has LDL > 190
1. start them immediately on a high intensity statin treatment (no need for the ASCVD risk score tool here)
if the LDL is > 100 still….
2. add ezetimibe
if the LDL is STILL > 100….
- add PCSK9inhibitor or
- bempedoic acid or
- bile aceid seqestrant
pts. with this high of LDL may have familial hypercholesterolemia….
heterozygote: do statin + (alirocumab or bempedoic acid)
homozygote: statin + evolucumab
in severe primary hypercholesteremia, what non-statin meds can we use?
how do they work? MOA
PCSK9 inhibitors (alirocumab = hetero) or Evolocumba = for heterzygote or homozygote pts. age 10+
Ezetimibe (off-label use): in homozygotes age 10+
Bile acide sequesterants: in heterozygotes ages 10-17
treatment decisions for those
primary prevention
ages 40-75
DM
- start mod. intensty statin
- can calcuate ascvd score, if its >20% or they have lots of risk factors = start a high intensitiy one
after starting hig-intensity – still not redcued LDL by 50%? add ezetimibe
treatment decisions for
primary prevention
LDL > 70
age 40-75
no DM
if ascvd < 5% = lifestyle changes
if ascvd 5-7.4% + risk factors = mod. statin
if ascvd 7.5-19.9% + risk factors = mod statin
ascvd 20% = high intensity
risk factors include
- CKD
- metabolic syndrome
- south asian
- inflammatory disease
- preeclampsia
primary prevention
pt. 40-75
LDL > 70
no DM
but the risk factors are mehhh
and then ascvd risk score is intermediate
what do you do
look at cornary artery calcium score
for those in boardeline or intermediate risk ASCVD groups
CAC = 0 reassecc score in 5-10 years
CAC = 1-99 favors use of statin
CAC = > 100 or 75% occulsion initiate statin
how do you monitor lipids
when do you recheck
recheck lipid panel after 4-12 weeks of initiating or adusting meds
if the goal % drop is achieved — > continue and reassess in 3-12 months
if the goal % drop is not –> assess other causes, reinforced med adhearace and repeat 4-12 weeks
still no? inc. statin or add meds
Statins
drug names
who is metabolized at CYP3a4
how does tirating the statin dose up help?
Atrovastatin & rousuvistatin = can be used at high does
- avoid use of simvistatin and lovastatin – too many interactions
who is metabolized at 3A4? so careful with cyp3a4 inhibitors!! (azoles)
- lovastatin
- simvistatin
- atrovastatin
avoid statin use with gemfibrozil
dont drink more thant 1 quart of grapefruit juice a day
how dose doubling the dose work?
- will only increase the amount of LDL lowering by 6%
special populations and statin use
asians should avoid what? use what dose of other?
japanese should do what
pregnant
children
Asian
- avoid simvastatin!!
- use rousuvastatin starting low dose 5mg
Japanese
- may require lower doses of statins
- rousuv., pravas & pita
pregnant
- usually stop
- but high risk pt. assess risks
children
- rousuvistatin: can be used at age 8 (7 if FC)
- prava and pita: 8 years
- lova, simva & ator: 10 years
Statin adverse effects
3 big ones
who is at risk for these
what is statin intolerance?
- SAMS- statin assocaited muscle symptoms
- myalgias, myopathy, rhabdomyolysis - increased liver enzymes
- transient – monitor baseline prior to initial dose - new DM
- increased risk with increased dose
who is at risk for these?
- those with co-morbid (liver and kidney issues)
- previous muscle or statin issues
- unexaplined ALT elevation
- drug-interactions
- older thant 75
- asians
- the dose of the stain plays a big role here
have a side effect? retry it and see
Statin Intolerance
- people who tried statins a minimum of at least 2 different kinds, with one at their lowest dose and still couldnt handle it
find the max they can tolerate and maybe leave there (or add non statin)
what is monitored during statin treatment
- if they present with muscle symptoms = check creatine
- if they have signs of hepatotoxicity = check liver enzymes and bilirubuin/alk. phosphate
no routine measurement of these is necessary
