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
