Lipoprotein & Lipid Disorders - Gleeson Flashcards
When testing lipids, what is included in the ‘classic’ lipid profile?
- total cholesterol
- triglycerides
- HDL
- LDL (calculated)
- non-HDL (calculated)
How is LDL-C calculated?
Non-HDL?
Friedwald equation:
- LDL-C = TC - (HDL-C + VLDL-C)
- Non-HDL = TC - HDL
A triglyceride level >1000 mg/dL is a significant risk for what?
pancreatitis
What LDL-C and HDL levels are considered risks for ASCVD?
- LDL-C > 100
- HDL < 40
Total cholesterol
What is (mg/dL):
- optimal?
- normal?
- clearly abnormal?
- < 150
- <200
- >325
Triglycerides (TG)
What is (mg/dL):
- optimal?
- normal?
- clearly abnormal?
- < 75
- < 150
- > 150
HDL
What is (mg/dL):
- optimal?
- normal?
- clearly abnormal?
- M > 40; F > 50
- M > 40; F > 50
- < 35
LDL
What is (mg/dL):
- optimal?
- normal?
- clearly abnormal?
- < 70
- < 130
- > 260
Non-HDL
What is (mg/dL):
- optimal?
- normal?
- clearly abnormal?
- << 100
- < 160
- > 290
What type(s) of genetic lipid disorder(s) are usually dormant until lifestyle and/or other diseases ‘unmask’ them?
Types IIB, III, IV, and V
What type(s) of genetic lipid disorder(s) are predominantly genetic, with little-to-no influence from lifestyle or other diseases?
Types I and IIA
Type IIa genetic hyperlipidemia is also known as what?
What is the common presentation?
Familial hypercholesterolemia
CAD < age 60
Type IIb genetic hyperlipidemia is also known as what?
What is the common presentation?
Familial combined hyperlipidemia or with metabolic syndrome
CAD risk 2X normal despite borderline/normal lipid numbers
A child presenting with triglycerides >2000 mg/dL is likely to be diagnosed with what?
Severe hypertriglyceridemia (Type I genetic hyperlipidemia)
What is the main abnormal lipid seen in Type I genetic hyperlipidemia?
- What is the primary defect?
- What is the excess lipoprotein?
TG > 2000 mg/dL
- LPL or apoC2 or apoC3 defect
- chylomicrons
What is the main abnormal lipid seen in Type IIa genetic hyperlipidemia?
- What is the primary defect?
- What is the excess lipoprotein?
TC > 275, LDL-C > 190
- LDL-R
- LDL
What is the main abnormal lipid seen in Type III genetic hyperlipidemia?
- What is the primary defect?
- What is the excess lipoprotein?
TC and TG both 200-500
- apoE2 + overproduction
- VLDL, IDL
What is the main abnormal lipid seen in Type V genetic hyperlipidemia?
- What is the primary defect?
- What is the excess lipoprotein?
TG > 1000
- LPL or apoC3
- VLDL, chylomicrons
What is the main abnormal lipid seen in Type IV genetic hyperlipidemia?
- What is the primary defect?
- What is the excess lipoprotein?
TG 500-1000
- LPL or apoC3
- VLDL
What is the main abnormal lipid seen in Type IIb genetic hyperlipidemia?
- What is the primary defect?
- What is the excess lipoprotein?
LDL 100, TG 200-500, HDL < 40
- overproduction of apoB100
- LDL, VLDL
What disease features defective LPL, apoC2, or apoC3 on chylomicrons, resulting in failure to remove TG from chylomicrons
Type I Chylomicronemia
Describe the defect in Type II familial hypercholesterolemia
LDL-R is defective, so LDL accumulates
Describe the lipoprotein changes of visceral adiposity and insulin resistance
- insulin resistance increases central adiposity
- central adiposity exports FFA and TG to the liver
- The liver releases more VLDL
- VLDL drives increased CETP activity
- increased CETP activity drives further LPL/HL activity
Describe the defect in type III dysbetalipoproteinemia
apoE2/E2 defect and environmental factors
apoE2/E2 on IDL is poorly recognized by LDL-R
Describe the defect in type IV hypertriglyceridemia
apoC2 or apoC3 on VLDL is defective, so VLDL accumulates
Describe the defect in Type V familial hypertriglyceridemia
apoC2 or apoC3 on both VLDL and chylomicrons do not work. Both VLDL and chylomicrons accumulate.
Name 3 lipid particle types that are predominantly filled with triglycerides (TG):
- Chylomicrons
- VLDL
- IDL
Name some medical conditions that increase triglycerides
What else might increase triglycerides?
- metabolic syndrome, insulin resistance
- diabetes
- hypothyroidism
- anorexia
- HIV
- pregnancy
- alcohol
- fructose >50g/day
certain medications will also increase triglycerides (examples: estrogens, birth control, thiazide diuretics, steroids, protease inhbitors, etc)
Describe the following triglyceride disorders:
- Type I hyper-chylomicronemia
- Type IIB familial combined hyperlipidemia
- Type IV
- Type I
- Type I hyperchylomicronemia
- children, TG > 2000
- inherited loss of LPL or defective apoC3 or apoC3
- chylomicrons fill with TG in the gut (at enterocytes) but cannot offload TG to peripheral cells
- Type IIB familial combined hypertriglyceridemia
- TG 200 to 500
- over-production of VLDL. Inherited, but also seen with insulin resistance, metabolic syndrome, inflammation, and visceral adiposity
- Type IV
- TG 500 to 1000
- dysfunctional LPL, resulting in large VLDL particles
- combination of genetics and environment
- Type I
- TG > 1000
- results in excessive TG and chylomicrons
LDL contains approximately what percentage of circulating cholesterol?
90%
What two lipid particle types are especially atherogenic?
IDL (a.k.a. VLDL remnants) and VLDL
Describe some lipid disorders that increase risk of ASCVD
- Elevated total cholesterol or LDL levels
- Excess apoB lipoproteins
- Depressed HDL levels
- Elevated Lp(a)
What medical conditions result in increased LDL-C?
What else might contribute to increased LDL-C?
- hypothyroidism
- renal disease
- obstructive liver disease
- anorexia
- polycystic kidney disease
- pregnancy
some medications also increase LDL-C (examples: anabolic steroids, cyclosporines
progestins, thiazide diuretics)
Name some factors/behavior that increase HDL
Lower HDL
- Raise HDL
- aerobic exercise
- alcohol
- estrogens
- Lower HDL
- insulin resistance and metabolic syndrome
- anabolic steroids
- progestins
- trans-fats
- smoking
Why is elevated Lp(a) a risk factor for ASCVD?
- Lp(a) is homolgous between LDL and plasminogen
- Lp(a) may compete with plasminogen, reducing the fibrinolytic capacity of the blood, increasing the chance of atheroscerotic plaque and thrombus formation
If a patient’s 10-year risk of ASCVD is >7.5%, what treatment should be started?
statins
Familial hypercholesterolemia (type IIa) is particularly prevalent in what 3 populations? Why?
Due to the founder effect:
French Canadians
South Afrikaners
Ashkenazi Jews
LDL 2-5 times normal since bith is indicative of what?
How is this treated?
Familial hypercholesterolemia
Start statin therapy immediately if age >12
What is the most common mutation seen in Familial Hypercholesterolemia?
What other mutations might be commonly seen?
90%: LDL-R mutation (decreased number or function, over 1600 mutations)
also: apoB mutation or PCSK9 gain-of-function mutation
What is result of a PCSK9 gain-of-function mutation?
PCSK9 loss-of-function mutation?
Familal hypercholesterolemia, leading to increased catabolism of LDL-R, resulting in fewer available LDL-R to remove LDL from circulation. LDL levels rise.
Loss-of-function decreases LDL-R catabolism, leading to increased LDL-R, lowering circulating LDL (significant drug target!)
Describe the underlying conditions seen with type IIb dyslipidemia
- metabolic syndrome
- insulin resistance (environmental or genetic)
- visceral adiposity
- western lifestyle
- diabetes
What is atherogenic dyslipidemia? What causes it?
TG:HDL > 4; LDL-P >> LDL-C
Increased LDL-P, increased VLDL remnants (IDL) -> both very atherogenic
metabolic syndrome
Name the criteria for metabolic syndrome
Require 3:
- Waist M >=40; F >=35
- TG > 150
- HDL M<40; F<50
- BP > 135/85 or Rx
- FBG >=100
