Hyperlipidemia Flashcards
process of atherogenesis
abnormal accumulation of lipids, cells, and extracellular matrix within the arterial wall THESE form plaques
plaques either narrow or rupture causing oxygen deprivation
primary event in atherogenesis
vessel injury or endothelial dysfunction (via toxic chemical environments)
endothelial dysfunction causes
impairment in permeability, release of cytokines increases desire to clot
atherogenesis is is a chronic ____ condition
inflammatory
includes accumulation of lipids in intima, recruitment of leukocytes and smooth muscle cells, deposit in ECM
causing dysfunction
why do we care about hyperlipidemia
atherosclerosis can be prevented
primary prevention treatment can get successful results
management strategies provided prior to the onset of CVD related events
primary prevention
management plan for those who have already experienced CV event
secondary prevention
efforts to prevent progression and/or reoccurrence
modification of identifiable risk factors can…
significantly decrease morbidity and mortality
cholesterol reduction leads to consistent reduction in mortality
high cholesterol = atherosclerosis
non modifiable risk factors
can’t control or change
family history, male sex,
hereditary and hyperlipidemia
runs in family
familial hypercholesterolemia (increased LDL at birth)
age and sex
men have higher LDL when younger then when they get older, women have worse
modifiable risk factors
blood lipid abnormalities
DM, HTN, sedentary lifestyle. abdominal obesity, cigarette smoking, diet, increased alcohol
lack of physical activity and hyperlipidemia
= weight gain, increased LDL, decreased HDL, increased total LDL
hyperlipidemia can result from
over production and/or defective clearance of vLDL or increased conversion vLDL to LDL
defective clearance of LDL can be caused by
genetically determined structural defects
diminished binding of ApoB to otherwise normal LDL
where do fats typically come from
saturated fats, animal products (meat and dairy)
unsaturated fats (seeds, nuts, veggie oils)
sources of cholesterol
egg yolks, organ meats and milk
what diet is typically the cause of high cholesterol
high in saturated fats and cholesterol
which lipoprotein is exclusively cholesterol
LDL
which lipoprotein has more TGs than cholesterol
more TG then cholesterol
main source of plasma LDL
vLDL
levels of which lipoprotein correlate with atherosclerosis?
LDL
high levels in blood cause it to accumulate in the lumen
LDL metabolism
liver removes it
hepatocytes that specifically bind to ApoB
ligand associated with LDL that binds with LDL receptors
removes LDL from circulation
LDL and plaque
LDL that is not removed from circulation by macrophages
migrate into arterial walls where they become foam cells of atherosclerotic plaques
foam cells harden which causes atherosclerosis
hyperlipidemia and CVD risk
increases progressively high levels of LDL cholesterol
this risk declines with high HDL levels
very high LDL levels
190 mg/dL and higher
good HDL values
40-59 mg/dL
minimum HDL levels for females = 50
high TG levels
> 500 = risk of pancreatitis
declines in serum cholesterol can be skin in ___
acute illness
TGs are ELEVATED in presence of pancreatitis
CRP
Hs-CRP is NOT a screening tool for lipids, it is a produce of hyperlipidemia
high lipids predict CVD
Farmingham study
predicative score based on age, gender, LDL, HDL. BP, DM, smoking
End points of risk = CHD death, nonfatal MI, unstable angina, stable angina
started with just generational, ID risk factors of everyone
smoking cessation
programmatic and/or group support with pharmacologic therapy
smoking cessation is most cost effective preventative measures
ATPIII
elimination of diabetes and addition of wider age range
LDL is still best way to decrease risk
predictive variables in ACC?AHA cohort calc
age, gender, total cholesterol, HDL, BP, DM, smoking
end points of ACC/AHA
CHD death
nonfatal MI
fatal stroke
nonfatal stroke
treatment decisions based on:
clinical CV disease or DM
Pt’s age
LDL cholesterol >190
est. 10 yr risk
smoking cessation is most cost effective preventative measures
what should an effective diet include
giggles, fruits, whole grains
low fat dairy produces, poultry, fish, legumes
healthy oils and nuts
pharm management of hyperlipidemia
goal is to lower LDL levels (no specific value, just 10%)
should start on ASA
HMG-CoA reductase inhibitors
aka statins
block rate limiting enzyme in cholesterol synthesis
cholesterol isn’t synthesized in liver so have to increase serum LDL uptake
Statin administration and SE
take once at night
myalgia, rhabdomyolysis, mysoitis, liver failure
high intensity statin therapy
Lower LDL by 50%
atorvastatin (Lipitor) 40-80mg
tosuvastatin (Crestor) 20-40,g
moderate intensity statins
lower LDL by 30-50%
Atorvastatin (Lipitor) 10-20 Rosuvastatin (Crestor) 5-10 simvastatin (Zocor) 20-40 Pravastatin (pravachol) 40-80 lovastatin (Mevacer) 40
low intensity statin therapy
lowers LDL by <30%
simvastatin (Zocor)
Pravastatin (Pravachol) 10-20
Lovastatin (Mevacor) 20mg
four groups that continually benefit from statins
- those w/atherosclerotic CV dz
- LDL >190
- 40-75 DM pos w/ LDL >70
- no other dz 40-75, LDL >70-189, 10 yrs factor of 7.5%+
ezetemide
Zeita
inhibits intestinal absorption of cholesterol, blocks its movement across wall
only med W.O. side effects!!!!
bile acid sequestrants
Cholestryamine (PRevalite) Colesevelam (Welchol) Colestipol (Colestid)
bile removed, causes liver to use up more LDL to maintain levels
only lipid SAFE in pregos
Bile Acid Binding resins SE
abdomina discomfort, flats, n/v
INCREASES TG levels and may interfere with fat soluble vitamin absorption
Niacin (Nicotinic Acid)
known to increase HDL (35-35%)
not used bc increased HDL doesn’t really lower risk, and nasty side effects (FLUSHING< hot flashes and parities)
PCSK9 inhibitors
ALirocuman (Praluent) Vcolocuman (repatha)
blocks gene that degrades LDL-r on liver, found to lower levels 50-60%
SQ injection, COSTLY but no muscle toxicity
Fibric acid derivative
Gemfibrozil (lipid)
fenofibrate (Fenoglide, Fibricor, lofibra)
increase vLDL catabolism, fatty acid oxidation and elimination of TG rich particles
increases HDL and reduces TG
SE of fibric acid derivatives
hepatitis, dyspepsia, n/v, muscle issues (rhabdo, myalgia, myositis)
esp. worse off if you combine with statins
Triglyceride specific pharm therapy?
Fibric Acid Derivatives if TGs are >500 and pt is at risk of pancreatitis
could add nicotinic acid agent or omega 3
if TGs< 499…
tx with statin to get to LDL goal
if still high when meet that goal, add nicotinic or intensify statin
how to treat elevated TGs
primarily diet
avoid alcohol, simple sugar, refined starches, saturated and transfatty acids, monitor calories
Tx for pt >21 and LDL >190
assess secondary hyperlipidemia cause
initiate statins (highest intensity possible)
primary prevention for its w/DM and LDL of 70-189
40-75 yr with DM should start or continue statin
if 10 yr risk >7.5% high intensity stain reasonable
primary prevention pt w/o diabetes and LDL 70-189
moderate intensity statins if reasonable
or could try and work with patient on a treatment plan
ASCVD risk
> 7.5%
high intensity statin
ASCVD risk
5%- 7.5%
consider moderate intensity statin
what do you asses 4-12 weeks following statin imitation
adherence
response to therapy
adverse effects
measure fasting lipid levels
continue w/emphasis on DM management if pt. is DM
secondary causes of dyslipidemia
DM hypothyroidism excessive alcohol liver, renal dz obesity, smoking, drugs
xanthelasma
yellowish plaques that occur most commonly near inner cantles of eye and seen more often on upper lid than lower lid
eruptive xanthoma
skin, red, yellow papular eruptions
firm pea-shaped bumps
found on buttocks, papule may be pyritic
plasma TGs
Tendon xanthoma
high LDL concentrations found on achilles, patella, back of hand
indicates familial hypercholesterolemia
familial hypercholesterolemia
increased LDL from birth
causes tendon xanthoma, early onset CVD
impairment in function of these receptors = reduced LDL clearance
increased LDL uptake in marophages = and foam cells
homozygous familial hypercholesterolemia
VERY rare
high incidence of supra aortic stenosis
heterozygous familial hypercholesterolemia
high LDL levels form birth, premature CVD, family hx of hypercholesterolemia, tendon xanthomata
