Chapter 13 - Hyperlipidemia Flashcards
5 major lipoproteins
1) Chylomicron 2) VLDL 3) IDL 4) LDL 5) HDL
Chylomicron distinguinshing particle
one Apo B48
VLDL particle distinguishing feature
Apo C and E and Apo B-100
Adult treatment panel 3 guidelines on levels of LDL, HDL, TG
TABLE 13.2
MARS study on IDL
associated with carotid artery intima-media thickness
Another name for IDL
Remnant lipoprotein
LDL receptor
Discovered by Nabel and Braunwald (nobel prize 1985) liver has 70% of this higher expression means better = lower circulating LDL level reduces with syndrome X
HDL protein and physiology
Liver secrets Apo A-I = no lipid Forms cholesterol ester by lecithin-cholesterol acyltransferase HDL spherical –> return to liver
Reverse cholesterol transport
HDL exchange cholesterol for TG from VLDL through cholesterol ester transfer protein (CETP)
Atherosclerosis steps
Mononuclear cells in blood –> cholesterol enriched Intracellular droplets of cholesterol accumulate –> foam cells Foam cells adhere and damage endothelium –> migrate to intima layer Foam cells accumulate under endothelium = fatty streak APOPTOSIS lipid spills out = lipid core of atherosclerotic plaque Wall expand = positive remodeling plaque thicken and encroach lumen = negative remodeling cap break = platelet rich clot = thrombosis
Most predictive lipoprotein fraction for determining atherosclerotic risk
LDL-C
Non-HDL-C =
LDL-C + IDL-C + VLDL-C + lipoprotein A
Risk factors for CHD otherthan elevated LDL-C
1) smk 2) HTN > 140/90 3) low HDL < 40 4) FHx 5) age > 45 male; > 55 female
Family history that counts towards CHD risk factor
1) CHD in male 1st degree relative < 55 years 2) CHD in female first degree relative < 65 years
ATP pannel 1, 2 and 3 recommenadtions
ATP-1 = education and lifestyle intervention ATP-2 = patient with known CHD should have more aggressive LDL-C target ATP-3 = aggressive approach to risk assessment and therapy
CHD risk equivalents
1) other clinical forms: PAD, AAA, symp Carotid 2) diabetes 3) multiple risk factors with 10 year risk CHD > 20%
Comparison of LDL and non-HDL target by risk ATP-3
TABLE 13.3
ACC/AHA guidelines on targets for LDL-C and non-HDL-C at different risks
TABLE 13.4
ATP 3 treatment target and when to start TLC and DRUGS
TABLE 13.5
PREDIMED study in Spain
7447 patients with CVD risk Mediterranean diet supplemented with olive oil or nuts –> decrease major CV events
Essential components of therapeutic lifestyle changes
LDL-RAISING NUTRIENTS 1) sat fat < 7% total calories 2) dietary cholesterol < 200 mg/day LDL lowering 1) plant stanols/sterols 2g/day 2) soluble fiber 10-25g/day 3) total calories to prevent weight gain 4) physical activity to expend 200 kcal/day
Statin effect on LDLC HDLC
Lower LDL-C by 18-60% HDLC 5-20% TG 7-30% additional double statin dose = 6% reduction LDLC
Side effect of statin
1) transient elevation of transaminase level 2) rhabdo 4/10000
Contraindication to statin use
ABSOLUTE 1) active/chronic liver disease RELATIVE 1) cyclosporine, macrolide, antifungal, cytochrome P450 inhibitor (fibrates, nicotinic acid)
Starting dose and max dose for different statins
Lovastatin 20 mg - 80 mg Pravastatin 20-80 Simvastatin 20-40 fluvastatin 20-80 atorvastatin 10-80 rosuvastatin 5-40 pitavastatin 2-4
Scandinavian simvastatin survival study
lipid lowere therapy reduce mortality
HPS study
simvastatin 40 mg/day reduce major vascular event
Prospective study of pravastatin in the elderly at risk
PROSPER study reduce LDLC and CHD mortality and major CV events
Treating to new targets study
TNT aggressive LDL lowering improves survival
Justification for the use of statins in prevention an intervention trial evaluating rosuvastatin
JUPITER rosuvastatin lower CRP and improve CV events and death
Niacin effect on HDL, LDL
HDL increase 15-35% LDL down 5-25%
Side effect of niacin
hepatotoxicity
COMPELL study
niacin + statin has better synergistic effects
Fibrates effect on HDL, LDL
TG 25-50% HDL 5-15% LDL 10-20%
Bile acid sequestrant types
Colestipol cholestyramine colesevelam
Fibrates types
Gemfibrozil Fenofibrate peroxisome proliferator alpha agonist
Ezetimibe effect
LDL 15-20%
Omega 3 fatty acid types
Eicosapentaenoic acid (EPA) docosahexaenoic acid (DHA)
Other agents to lower cholesterol
Cholesterol ester transfer protein inhibitor (CETP) proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9)
Care in using gemfibrozil
cannot be used with statin increase toxicity of statins
