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
Familial hypercholesterolemia - genetic defect?
90%: LDL receptor (LDLR)
Other:
apoB (APOB)
proprotein convertase subtilisin-kexin type 9 (PCSK9)
LDL receptor adaptor protein 1 (LDLRAP1)
how to dx Familial hypercholesterolemia
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 hyperlipidemia causes?
hypothyroidism
poorly controlled diabetes,
nephrotic syndrome,
obesity/ insulin resistance
hepatitis
Medications (steroids, isotretinoin and, in females, OCP)
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
Causes of secondary dyslipidemia
● 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
hyperlipidemia - what to look for on exam
i. Xanthomas – tendon, tuberous, or planar
(Tendon xanthomata in children are highly suggestive of homozygous FH)
ii. arcus corneae
iii. Xanthelasma
genetic causes of hyperTG
1) Familial Hyperchylomicronemia (Usually TGs are above 10 mmol/L)
1. LPL gene mutation
2. LMF1 mutation
3. GPIHBP mutation
4. Apo A-V mutation
5. Apo C-II mutation
2) FCH
1. Combined VLDL and LDL elevations raise TG and cholesterol
2. Due to excess VLDL production
3. Exact genetic mutation is unknown
3) Familial dysbetalipoproteinemia
1. High cholesterol and TG because ApoE2 presence makes it hard to clear remnants, and LDL subsequently builds up as well as VLDL and chylomicron remnants
4) Familial hypertriglyceridemia (also known as endogenous or mixed lipemias)
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
