What are components of lipid transport?
Cholesterol (C), Triglycerides (TGs), Lipoproteins (LPs), and apolipoproteins (ALPs)
What is cholesterol for?
cell membranes (steroid hormones - cortisol)
What are TGs for?
nutrients (energy)...they carry fatty acids
What are the sizes of LPs?
chylomicrons > chylomicron remnants > VLDL > IDL > LDL > HDL
VLDL is made by liver.
IDL is metabolized to LDL metab to HDL
What are apolipoproteins?
"biochemical keys" - allow LP access to specific sites for delivery, modification
What is exogenous lipid metabolism?
Dietary fats acquire APLs (from HDL) to form chylomicrons.
TGs hydrolyzed by lipoprotein lipase (LPL) to free fatty acids to go to adipose/storage or muscle/energy.
The do not contribute to AS, but remnants removed by liver can be taken up by macrophages and contribute to AS.
What is endogenous lipid metabolism?
Fats into liver are either stored or exported as VLDL (not atherogenic).
LPL act on VLDL>>>fatty acids released into tissues & VLDL metab to IDL (not atherogenic).
IDL metab to LDL in liver which has C & LPs, but no TGs.
Most LDL is taken up by liver, but some to tissues>>>taken up by macrophages, oxidized and contribute to AS. (LDL is seen more in pts w/high TGs)
What is a rare genetic defect in RCT (reverse cholesterol transport)?
CETP(C ester transfer protein) defect which is high HDL but high CV events
What are lipid-activated nuclear receptors?
Fibrates activate PPARs (peroxisome proliferator-activated receptors) which accelerate fatty oxidation in liver & elevate HDL.
Glitazones active PPARs in muscle/adipose.
PPAR agonists & CETP inhibitors have no benefit.
What do Liver X receptors do?
They promote FA & TG synthesis and stim conversion of C to bile acid.
What does niacin do?
Blocks release of FA from adipose.
What does resins do?
Decrease bile acids from being absorbed>>> dec C in liver>>>in LDL receptors in liver>>> dec LDL (but inc TGs)
How does liver get rid of cholesterol?
Turns it into bile.
What are disorders of lipid metabolism?
FH (familial hypercholesterolemia)
FCH (familial combined hyperlipidemia)
FHT (familial hypertriglyceridemia)
What is FH?
Autosomal Dom; 1/500
High C, LDL & NL TGs
w/xanthomas (knees & hands), xanthelasma, & arthralgias
How is FH caused?
mutation of LDL receptor gene
What is FCH?
Autosomal Dom; 1/50
High TG; High LDL; High TG & LDL; or High TG & low HDL (FH w/premature CAD)
What is FHT?
Autosomal Dom; 1/50
What is chylomicronemia syndrome?
xanthomas on back, butt, knees, elbows
pancreatitis, hepatosplenomegaly, SOB, lymphadenopathy, memory loss, peripheral neuropathy
How is chylomicronemia syn caused?
LPL gene defect; TGs>2000
Occurs w/FCH or FHT + DM, obese, or steroid/estrogen tx.
How tx chylomicronemia syn?
Elim fat from diet to dec lipids.
Insulin to control DM.
What is DM dyslipidemia?
How tx DM dyslipidemia?
Insulin will dec TG & LDL, but wt gain will dec HDL
What are secondary causes of hyperlipidemia?
DM, ETOH, hypothyroidism, diuretics (BBs), diuretics, estrogens, & antipsychotics
What labs are for hyperlipidemia?
12h fast (q 5yrs if NL)
Calculated LDL = C - HDL - (TG/5)
TG - normal = <150 (500 is very high)
How tx high TGs?
Niacin or fibrate +/- fish oil to prevent pancreatitis
What is high risk of hyperlipidemia?
10yr risk >20% (CAD, DM, AAA, carotid dz, peripheral vascular dz)
What is the goal for high risk?
LDL <100 (or <70)
What is goal for 2+ risk factor and <20% 10y risk?
LDL < 130
What is goal for <2 risk factors and <10% 10y risk?
LDL < 160
What is tx for hyperlipidemia?
lower LDL <100 w/CAD...and change lifestyle
What do statins (HMG CoA reductase inhibitors) do?
lower LDL by 40%
Stop if liver enzymes 3 x NL or inflammed
What are SE of statins?
myalgia, rhabdomyolysis (inflam muscle) is rare
What does niacin (nicotin acids) do?
lowers TG, inc HDL, lower LDL
What are SE of niacin?
Flushing (so take ASA before)
What do ezetimibe do?
lowers LDL & TG (use w/statin)
What do resins (bile acid sequestrants) do?
lowers LDL....may inc TGs
What are SE of resins?
constipation, dyspepsia (better w/colesevelam)
What do fish oils do?
lowers TGs....may inc LDL
What do fibric acids do?
Use fenofibrate over gemfibrozil