Lipoprotein & Lipid Disorders - Gleeson

Question 1

When testing lipids, what is included in the ‘classic’ lipid profile?

Answer 1

• total cholesterol
• triglycerides
• HDL
• LDL (calculated)
• non-HDL (calculated)

Question 2

How is LDL-C calculated?

Non-HDL?

Answer 2

Friedwald equation:

• LDL-C = TC - (HDL-C + VLDL-C)
• Non-HDL = TC - HDL

Question 3

A triglyceride level >1000 mg/dL is a significant risk for what?

Answer 3

pancreatitis

Question 4

What LDL-C and HDL levels are considered risks for ASCVD?

Answer 4

• LDL-C > 100
• HDL < 40

Question 5

Total cholesterol

What is (mg/dL):

1. optimal?
2. normal?
3. clearly abnormal?

Answer 5

1. < 150
2. <200
3. >325

Question 6

Triglycerides (TG)

What is (mg/dL):

1. optimal?
2. normal?
3. clearly abnormal?

Answer 6

1. < 75
2. < 150
3. > 150

Question 7

HDL

What is (mg/dL):

1. optimal?
2. normal?
3. clearly abnormal?

Answer 7

1. M > 40; F > 50
2. M > 40; F > 50
3. < 35

Question 8

LDL

What is (mg/dL):

1. optimal?
2. normal?
3. clearly abnormal?

Answer 8

1. < 70
2. < 130
3. > 260

Question 9

Non-HDL

What is (mg/dL):

1. optimal?
2. normal?
3. clearly abnormal?

Answer 9

1. << 100
2. < 160
3. > 290

Question 10

What type(s) of genetic lipid disorder(s) are usually dormant until lifestyle and/or other diseases ‘unmask’ them?

Answer 10

Types IIB, III, IV, and V

Question 11

What type(s) of genetic lipid disorder(s) are predominantly genetic, with little-to-no influence from lifestyle or other diseases?

Answer 11

Types I and IIA

Question 12

Type IIa genetic hyperlipidemia is also known as what?

What is the common presentation?

Answer 12

Familial hypercholesterolemia

CAD < age 60

Question 13

Type IIb genetic hyperlipidemia is also known as what?

What is the common presentation?

Answer 13

Familial combined hyperlipidemia or with metabolic syndrome

CAD risk 2X normal despite borderline/normal lipid numbers

Question 14

A child presenting with triglycerides >2000 mg/dL is likely to be diagnosed with what?

Answer 14

Severe hypertriglyceridemia (Type I genetic hyperlipidemia)

Question 15

What is the main abnormal lipid seen in Type I genetic hyperlipidemia?

1. What is the primary defect?
2. What is the excess lipoprotein?

Answer 15

TG > 2000 mg/dL

1. LPL or apoC2 or apoC3 defect
2. chylomicrons

Question 16

What is the main abnormal lipid seen in Type IIa genetic hyperlipidemia?

1. What is the primary defect?
2. What is the excess lipoprotein?

Answer 16

TC > 275, LDL-C > 190

1. LDL-R
2. LDL

Question 17

What is the main abnormal lipid seen in Type III genetic hyperlipidemia?

1. What is the primary defect?
2. What is the excess lipoprotein?

Answer 17

TC and TG both 200-500

1. apoE2 + overproduction
2. VLDL, IDL

Question 18

What is the main abnormal lipid seen in Type V genetic hyperlipidemia?

1. What is the primary defect?
2. What is the excess lipoprotein?

Answer 18

TG > 1000

1. LPL or apoC3
2. VLDL, chylomicrons

Question 19

What is the main abnormal lipid seen in Type IV genetic hyperlipidemia?

1. What is the primary defect?
2. What is the excess lipoprotein?

Answer 19

TG 500-1000

1. LPL or apoC3
2. VLDL

Question 20

What is the main abnormal lipid seen in Type IIb genetic hyperlipidemia?

1. What is the primary defect?
2. What is the excess lipoprotein?

Answer 20

LDL 100, TG 200-500, HDL < 40

1. overproduction of apoB100
2. LDL, VLDL

Question 21

What disease features defective LPL, apoC2, or apoC3 on chylomicrons, resulting in failure to remove TG from chylomicrons

Answer 21

Type I Chylomicronemia

Question 22

Describe the defect in Type II familial hypercholesterolemia

Answer 22

LDL-R is defective, so LDL accumulates

Question 23

Describe the lipoprotein changes of visceral adiposity and insulin resistance

Answer 23

• 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

Question 24

Describe the defect in type III dysbetalipoproteinemia

Answer 24

apoE2/E2 defect and environmental factors

apoE2/E2 on IDL is poorly recognized by LDL-R

Question 25

Describe the defect in type IV hypertriglyceridemia

Answer 25

apoC2 or apoC3 on VLDL is defective, so VLDL accumulates

Question 26

Describe the defect in Type V familial hypertriglyceridemia

Answer 26

apoC2 or apoC3 on both VLDL and chylomicrons do not work. Both VLDL and chylomicrons accumulate.

Question 27

Name 3 lipid particle types that are predominantly filled with triglycerides (TG):

Answer 27

* Chylomicrons * VLDL * IDL

Question 28

Name some medical conditions that increase triglycerides What else might increase triglycerides?

Answer 28

* 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)

Question 29

Describe the following triglyceride disorders: 1. Type I hyper-chylomicronemia 2. Type IIB familial combined hyperlipidemia 3. Type IV 4. Type I

Answer 29

* 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

Question 30

LDL contains approximately what percentage of circulating cholesterol?

Answer 30

90%

Question 31

What two lipid particle types are especially atherogenic?

Answer 31

IDL (a.k.a. VLDL remnants) and VLDL

Question 32

Describe some lipid disorders that increase risk of ASCVD

Answer 32

* Elevated total cholesterol or LDL levels * Excess apoB lipoproteins * Depressed HDL levels * Elevated Lp(a)

Question 33

What medical conditions result in increased LDL-C? What else might contribute to increased LDL-C?

Answer 33

* hypothyroidism * renal disease * obstructive liver disease * anorexia * polycystic kidney disease * pregnancy some medications also increase LDL-C (examples: anabolic steroids, cyclosporines progestins, thiazide diuretics)

Question 34

Name some factors/behavior that increase HDL Lower HDL

Answer 34

* Raise HDL * aerobic exercise * alcohol * estrogens * Lower HDL * insulin resistance and metabolic syndrome * anabolic steroids * progestins * trans-fats * smoking

Question 35

Why is elevated Lp(a) a risk factor for ASCVD?

Answer 35

* 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

Question 36

If a patient's 10-year risk of ASCVD is \>7.5%, what treatment should be started?

Answer 36

statins

Question 37

Familial hypercholesterolemia (type IIa) is particularly prevalent in what 3 populations? Why?

Answer 37

Due to the founder effect: French Canadians South Afrikaners Ashkenazi Jews

Question 38

LDL 2-5 times normal since bith is indicative of what? How is this treated?

Answer 38

Familial hypercholesterolemia Start statin therapy immediately if age \>12

Question 39

What is the most common mutation seen in Familial Hypercholesterolemia? What other mutations might be commonly seen?

Answer 39

90%: LDL-R mutation (decreased number or function, over 1600 mutations) also: apoB mutation or PCSK9 gain-of-function mutation

Question 40

What is result of a PCSK9 gain-of-function mutation? PCSK9 loss-of-function mutation?

Answer 40

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!)

Question 41

Describe the underlying conditions seen with type IIb dyslipidemia

Answer 41

* metabolic syndrome * insulin resistance (environmental or genetic) * visceral adiposity * western lifestyle * diabetes

Question 42

What is atherogenic dyslipidemia? What causes it?

Answer 42

TG:HDL \> 4; LDL-P \>\> LDL-C Increased LDL-P, increased VLDL remnants (IDL) -\> both very atherogenic metabolic syndrome

Question 43

Name the criteria for metabolic syndrome

Answer 43

Require 3: * Waist M \>=40; F \>=35 * TG \> 150 * HDL M\<40; F\<50 * BP \> 135/85 or Rx * FBG \>=100