Lipoprotein & Lipid Disorders - Gleeson Flashcards Preview

M2 Cardiovascular > Lipoprotein & Lipid Disorders - Gleeson > Flashcards

Flashcards in Lipoprotein & Lipid Disorders - Gleeson Deck (43):
1

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

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

2

How is LDL-C calculated?

Non-HDL?

Friedwald equation:

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

3

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

pancreatitis

4

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

  • LDL-C > 100
  • HDL < 40

5

Total cholesterol

What is (mg/dL):

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

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

6

Triglycerides (TG)

What is (mg/dL):

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

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

7

HDL

What is (mg/dL):

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

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

8

LDL

What is (mg/dL):

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

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

9

Non-HDL

What is (mg/dL):

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

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

10

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

11

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

12

Type IIa genetic hyperlipidemia is also known as what?

What is the common presentation?

Familial hypercholesterolemia

CAD < age 60

13

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

14

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

Severe hypertriglyceridemia (Type I genetic hyperlipidemia)

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?

TG > 2000 mg/dL

  1. LPL or apoC2 or apoC3 defect
  2. chylomicrons

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?

TC > 275, LDL-C > 190

  1. LDL-R
  2. LDL

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?

TC and TG both 200-500

  1. apoE2 + overproduction
  2. VLDL, IDL

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?

TG > 1000

  1. LPL or apoC3
  2. VLDL, chylomicrons

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?

TG 500-1000

  1. LPL or apoC3
  2. VLDL

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?

LDL 100, TG 200-500, HDL < 40

  1. overproduction of apoB100
  2. LDL, VLDL

21

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

Type I Chylomicronemia

22

Describe the defect in Type II familial hypercholesterolemia

LDL-R is defective, so LDL accumulates

23

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

24

Describe the defect in type III dysbetalipoproteinemia

apoE2/E2 defect and environmental factors

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

25

Describe the defect in type IV hypertriglyceridemia

apoC2 or apoC3 on VLDL is defective, so VLDL accumulates

26

Describe the defect in Type V familial hypertriglyceridemia

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

27

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

  • Chylomicrons
  • VLDL
  • IDL

28

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)

29

Describe the following triglyceride disorders:

  1. Type I hyper-chylomicronemia
  2. Type IIB familial combined hyperlipidemia
  3. Type IV
  4. 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

30

LDL contains approximately what percentage of circulating cholesterol?

90%

31

What two lipid particle types are especially atherogenic?

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

32

Describe some lipid disorders that increase risk of ASCVD

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

33

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)

34

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

35

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

36

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

statins

37

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

Due to the founder effect:

French Canadians

South Afrikaners

Ashkenazi Jews

38

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

How is this treated?

Familial hypercholesterolemia

Start statin therapy immediately if age >12

39

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

40

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!)

41

Describe the underlying conditions seen with type IIb dyslipidemia

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

42

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

43

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