Lipids Flashcards
dyslipidemia criteria?
LDL-C ≥ 3.4mmol/L
what is a statin?
HMG-CoA reductase inhibitors
- Block hepatic HMG Co-A reductase (rate limiting enzyme in cholesterol biosynthesis)
- Leads to increased LDL receptor and decreased serum cholesterol
adverse effects of statins?
Headaches, myalgias, hepatotoxicity, myopathy, rhabdomyolysis
Most common: elevated LFTS (improves after d/c)
***Teratogenic
meds for hyperlipidemia besides statins
Resins = Bile acid sequestrants
Cholesterol absorption inhibitors (ezetimibe)
Fibric acids
Nicotinic acid
Omega 3 fatty acids
what to monitor once starting statin
Serum ALT, AST, CK and lipids 1 month after initiating therapy
Monitor every 3-6 months
Monitor for growth abnormalities and secondary sexual characteristics
FH - gene
90%: LDL receptor (LDLR)
Other:
apoB (APOB)
proprotein convertase subtilisin-kexin type 9 (PCSK9)
LDL receptor adaptor protein 1 (LDLRAP1)
how to dx FH
LDL-C >/= 4.0
PLUS ONE OF
- DNA mutation
- tendon xanthoma
- LDL-C >/= 8.5
if none of those but have FDR w elevated LDL or with early CVD, probably FH
goal of statin therapy?
An LDL-C 2.6 mmol/L or less, or a minimum of 50% reduction from baseline.
secondary hyperCh causes
● Endocrine:
○ Hypothyroidism
○ T1DM/T2DM
○ Pregnancy
○ PCOS
○ Lipodystrophy
● Renal
○ CKD
○ HUS
○ Nephrotic syndrome
● Hepatic:
○ Obstructive liver disease/cholestatic conditions
○ Biliary cirrhosis
○ Alagille syndrome
● Inflammatory disease
○ SLE
○ JIA
● Storage disease
○ Glycogen storage disease
○ Gaucher disease
○ Cystine storage disease
○ Juvenile Tay-Sachs disease
○ Niemann-Pick disease
● Others
○ Anorexia Nervosa
○ Kawasaki disease
○ Solid organ transplantation
○ Childhood cancer survivor
○ Idiopathic hypercalcemia
○ Klinefelter syndrome
○ Werner syndrome
● Drugs – corticosteroids, some OCPs
meds that cause hyperlipidemia
glucocorticosteroids
isotretinoin
OCP
insulin
thiazide diuretics
fibrates
if testing for familial hypercholesterolemia, what genes to test for?
LDLR, APOB and PCSK9
exam findings in hyperCh
i. Xanthomas – tendon, tuberous, or planar
(Tendon xanthomata in children are highly suggestive of homozygous FH)
ii. arcus corneae
iii. Xanthelasma
how does DM cause hyperTG
1) insulin def causes markedly decreased transcription of the LPL gene (administration of insulin usually helps restore normal TG levels within days, however LDL may rise due to beta effect where VLDL → LDL; this takes much longer to resolve)
2) increased flux of FFA to liver stimulates production of TGs and their secretion in VLDL
causes of elevated LDL with normal TG
i. Familial hypercholesterolemia (LDLR mutation)
ii. Autosomal dominant hypercholesterolemia (PCSK9 activating mutation)
iii. Autosomal recessive hypercholesterolemia (protein affected that allows LDLR endocytosis)
iv. ApoB100 mutation
v. Anorexia
what is the pathophys for Dysbetalipoproteinemia
genetic mutation in Apo E (most commonly E2)
if CK is elevated when on a statin, what do you do
stop the medication and consider restarting
The threshold for worrisome level of CK is 10 times above the upper limit of reported normal
CHILD-1 diet
<10% diet is fat and <300 mg cholesterol a day
CHILD-2 diet
<7% of diet is fat and <200 mg cholesterol a day
hyperTG and abdo pain
pancreatitis
referral to endo criteria for lipids
- LDL > 3.4 mmol/L
- HDL < 0.9 mmol/L
- TG > 2.3 mmol/L
why is it so important to tx children w hyperCh?
- Atherosclerosis is the basis of CV disease
- Begins in youth
○ Often clinically SILENT
○ Only see on labs
○ And atherosclerotic changes seen starting in childhood, before clinically apparent signs - Directly linked to CV risk factors including dyslipidemia
Identification and management of dyslipidemia in childhood might serve to delay the onset and slow the progression of atherosclerotic CVD, particularly in high-risk populations.
what is the function of Ch in the body
Ch steroids
membranes
bile acids
what is the structure of FFA
3 TG bound to a glycerol backbone
what is the role of TG in the body
fuel source to
- heart, muscle
undergo B-oxidation in mitochondria
to produce acetyl CoA
what lipoproteins have more TG and what have more ChE?
more TG: chylomicrons, VLDL
more ChE: LDL, HDL
what apoproteins are for:
structure
ligand
to activate LPL
structure: B48 and B100
ligand: B100 and E
to activate LPL: CII
what does ApoE bind to and why
LRP1 to exit the endogenous pathway and go into the liver
what binds to LDL-R
B-100
when are the Apo-B’s involved?
endogenous pathway
(not exogenous)
what is PCSK9
binds to LDL-R and causes its degradation
where is hepatic lipase
in the blood
what are apolipoproteins
transport proteins that bind to lipids to form lipoproteins
what does ApoA1 do?
reverse pathway
cholesterol uptake from cells
activates LCAT
what Ch does ApoA1 define
HDL
(A is Awesome
B is Bad)
what is the role of LDL
deliver Ch to cells
what Ch is ApoB100 in
LDL
IDL
VLDL
how does HDL transfer Ch to VLDL and LDL
via CETP
Lipoprotein (a)
strongly atherogenic
what level of TG makes LDL not measurable
4.5
LDL levels in FH
hetero: 2-3X UL
homo: 4-6X UL
PSCK9 mutation
PSCK9 -> degradation for LDLR
GOF mutation -> increased degradation
Ch profile in HF
high LDL
normal TG, HDL
Ligand-defective apoB100
Lipid profile
features
Moderate to markedly high LDL normal TGs
Caused by poor binding of the LDL particle to the LDLR, because of a mutation in apoB-100
results in a decreased clearance of LDL from plasma
tendon xanthomas
primary hyperTG DDx
- = just hyperTG
*LPL deficiency
*Apo-CII deficiency
*Familial chylomicronemia syndrome
*Familial hypertriglyceridemia - Dysbetalipoproteinemia
- Familial LPL inhibitor
- Familial combined hyperlipidemia
Causes of hyperTG
- Diabetes: insufficient insulin therapy, as insulin is required for LPL activity
- Uncontrolled T1DM
- Uncontrolled T2DM
- Hypopituitarism
– GH Deficiency (incr VLDL production and dcr VLDL clearance)
– Hypothyroidism - GSD
- Renal Failure
- Nephrotic syndrome (upregulation of cholesterol synthesis due to protein loss, upregulation of HMG Co-Reductase)
- Pregnancy (elevated estrogen that causes incr VLDL production and dcr LPL)
- Acute hepatitis
- EtOH (large amounts can cause incr VLDL and impaired lipid metabolism)
- HIV (?secondary to incr inflammation)
- Medications:
— Glucocorticoids (incr VLDL production)
— PEG-asparginase (incr VLDL production and dcr LPL activity)
— Estrogens (incr VLDL secretion and dcr hepatic lipase)
— Anti-psychotics
Eruptive xanthomas - what dx
hyperTG
Lipemia retinalis - what dx
hyperTG
mgmt hyperTG
fibrates
omega-3 FA
insulin in acute
what level of TG are you at risk of pancreatisi
10-11
how to dx LPL def
LPL activity
physical exam in hyperTG
Eruptive xanthomas
Lipemia retinalis
what is the most common cause of hyperCh?
Familial combined dyslipidemia
Familial combined dyslipidemia
Caused by hepatic overproduction of lipoprotein particles containing apoB-100, namely VLDL and LDL
Elevated TG, LDL, low HDL
no exam findings
Familial Dysbetalipoproteinemia
Abnormal ApoE which is important for uptake of TG rich chylomicrons + VLDL
labs:
Elevated TGs, low LDL & HDL
palmar and tuberous xanthomas
DIS BETA RAPPER
hypolipoproteinemia
aka
gene
Tangier disease
ABCA1
very low HDL
cellular cholesterol build up
tonsils orange
Secondary Dyslipidemia causes
R/O CHAN always
Cholestasis
Hypothyroidism
Anorexia nervosa
Nephrotic syndrome
Other causes:
ENDO
- DM
- Pregnancy
- PCOS
RENAL
- Nephrotic syndrome
- CKD
HEPATIC
- Obstructive liver disease/cholestatic conditions
- Biliary cirrhosis
IMMUNOLOGIC
- HIV
RHEUM
- JIA
- SLE
DRUGS
- Glucocorticoid
- Alcohol
□ XS: Increased TG
□ Mod alcohol can increased HDL
- OCP
- Atypical antipsychotics
- Isotretinoin
- Bile acid sequestrants
- Cyclophosphamide
obesity related dyslipidemia
lipid profile
Mild-moderate hyperTG
Low HDL-C
lipid profile in DM
high TG
low HDL
normal LDL
universal screening for children, when?
between 9 and 11 years of age
again at 17-21 years of age
what constitutes “Fhx early CVD”
- parent, grandparent, aunt, or uncle
– <55 years for men and <65 years for women
–history of angina, myocardial infarction, coronary artery disease, or sudden cardiac death
Corneal arcus, xanthelasmas or tendon xanthomas suggest?
high LDL
Lipemia retinalis and eruptive xanthomas over extensor surfaces and buttocks
high TG
palmar and tuberous xanthomas
Dysbetalipoproteinemia
what is Etezimibe
bile acid sequestrant
PCSK9 inhibitors
s/e
flu-like symptoms, site reactions, myalgias, fatigue
meds that cause high TG
steroids, estrogen, beta-blockers, HAART, isotretinoin, BAS, antipsychotics
