Dyslipidemia and CVD part 1 Flashcards
hypolipoproteinemias 3 examples
- abetalipoproteinemia
2. familial hypobetalipoproteinemia 3. tangier disease ( alpha-lipoprotein deficiency )
abetalipoproteinemia
defect in app B synth
- no chiylo, VLDL, LDL and TG accumulate in the liver and intestine
familial hypobetalipoproteinemia
LDL concentration is 10-50% of normal but chill formation occurs
tangier disease
absence of HDL, CE accumulate in tissues, chill, VLDL, LDL all normal,
most common hyperlipoproteinemia phenotypes
IIb (LDL and VLDL- mutation of LDL receptor and app B) and IV (VLDL)- but no marker
majority of genotype for apo-E
60% have E-3/E-3
what’s the bad one of apo-E
E-2/E-2 bc it does not bind to the LDL receptor so increased VLDL
primary dyslipidemia classification?
single or poly-genetic abnormality affecting lipoprotein function resulting in hyper to hip lipidemia
type 1 - hyperchylomicronemia
high TG, low HDL, skin xANTHOMAS, PANCREATITIS,
type IIa- hypercholesterolemia
high LDL and Tg normal or high,
symptoms: xanthekasma, vascular disease
type IIb- combined hyperlipoproteinemia
high LDL and VLDL and high apo-B
serum: high chol, high TG and low HDL
type III- dysbetalipoproteinemia
high b-VLDL IDL
and high LDL and VLDL
type IV- hypertriglyceridem a
high VLDL
type V- mixed hyperlipidemia
high VLDL, and CM
Total CH
less than 5.2mmol/L
HDL levels
want more than 1.0 men
more than 1.3 in women
LDL levels
want less than 2.6
TG levels
want less than 1.7
apoproteins
primary determinant of the metabolic fate of lipoproteins
VLDL major apoproteins
B-100 and E and C
LDL major apoprotein
B-100
HDL major apoprotein
A1, AII, C, E
CM major apoproteins
B-48, E, A1, AIV, C11, C111
Apo e-2 does not bind to
LDL receptor ( so higher VLDL ruminants)
defect in app B synth ( no CM, VLDL, LDL formed and TG accumulate in liver and intestine
abetalipoproteinemia
LDL is 10-15% of normal but CM still occurs
familial hypobetalipoprotinemia
Tangier disease
absence of HDL
- no apo A-II
- can’t take away CE from tissues ( so accumulate)
CM, VLDL, LDL are normal
which hyperlipidemias have the greatest CVD risk? why?
IIb ( combined hyperlipoprotinemia) and III dysbetalipoproteinemia)
- bc high in both LDL and VLDL
hyperchylomicronemia
no CVD risk
this is when there is low LPL so CM accumulatie, leading to high TG and low HDL
Hypercholesterolemia
polygenic- affecting LDL receptors and means that there are higher levels of LDL-C circulating but normal TG ( or high) ( + CVD risk)
combined hyperlipoproteinemia
+++ CVD risk
- mutation in LDL receptor or APO B such that there is high LDL and VLDL
( so high CE and high TG with low HDL)
dys-beta-lipo-protein-emia
E2/E2
high TG and VLDL ?
IV- hypertriglyceridemia
in type V- why is there a white band at the top?
CM floating ( the least dense) - this is mixed hyperlipidemia ( with high VLDL - like in hypertriglyceridemia) but this one is different bc also has high CM
when will blood look more white?
when there is accumulation of TG from CM or VLDL
why does IIA ( hypercholesterolemia look normal?
high CH, from LDL but TG are normal
what are some medications that can cause secondary dyslipidemia?
thiazide diuretics, B- blockers, corticosteroids, estrogens,
HSL role in obesity and lipoprotein metabolism
activity is increased bc high adipose tissue and if insulin resistance there is a lot of insulin being produced levels
- end result is increased substrate flux to the liver
describe the effect of alcohol on VLDL levels
ethanol blocks the pathway of acyl-CoA to oxidation ( for energy) so more acetyl-CoA will get converted to TG and get packaged in VLDL
- more VLDL, more lipolysis, more TG uptake into tissues ( fat deposit)
effect of obesity on lipoprotein metabolism
over production of VLDL, increased lipolysis ( normal levels of VLDL but higher fat deposit)
how does hyper-triglyceremia happen with obesity?
VLDL defect. lipolytic effect (high TG if high VLDL)
how would hyper-cholesterolemia come from obesity?
LDL
- if there was a defect in the LDL receptor
- a diet very high in sat fats
posible mechanism for reduced HDL in obesity?
CE get transferred to VLDL and HDL takes up a TG, when this happens excessively, increased catabolism of HDL bc lots more adipose tissue
2 factors associated with low HDL in obesity?
severity (BMI)
- inverse relationship between HDL ( this is a stronger affect than the effect of raised LDL and obesity)
and distribution ( abdominal)
what casues the decrease in HDL in obesity?
enhanced uptake of HDL2 by adipocytes and and increase in catabolism of apolipoprotein A-1
who should be screened?
all mena nd women over the age of 40
- abdominal aortic aneurysm, obesity, Diabetes, hypertension, family history of premature CVD
FRS
is a test that estimates your 10-year cardiovascular disease risk
we use this information to stratify the risk - so if FRS is above20% high risk, if between 10-19% intermediate risk
when does FRS double?
if person is aged 30-55 without diabetes and has a relative with premature CVD
which are the 5 statin indicated conditions
- atherosclerosis, 2.diabetes, 3.chronic kidney disease, 4.abdominal aortic aneurysm
- LDL more than 5mmol/L
CVD intermediate risk ?
FRS of 10-19%
LDL > 3.5 ( should be under 2.6)
non-HDL > 4.3
or men or women with one of more psi factor that are one the age of 50 ( men and 60 women)
what 2 methods as alternatives for LDL
non-HDL-C and apo-B as alternative targets
primary target for high risk (>20% FRS)
<2.0 LDL
primary target if intermediate risk and LDL is greater that 3.5?
<2.0 LDL
primary target if low risk but LDL is greater than 5.0 so we initiate treatment ( <10% FRS)
> 50% decrease in LDL-C
