Dyslipidemia (Wendt & Gonzalvo)

Question 1

Apoplipoproteins Role:

ApoA-1

Answer 1

(structural in HDL)

mediates reverse of cholesterol transport

Question 2

Apoplipoproteins Role:

ApoB-100

Answer 2

structural in VLDL; IDL; LDL; LDL receptor ligand made in liver

Question 3

Apoplipoproteins Role:

ApoB-48

Answer 3

produced in intestines/structural in chylomicrons

Question 4

Apoplipoproteins Role:

ApoE

Answer 4

does reverse cholesterol transport with HDL;

Question 5

Apoplipoproteins Role:

ApoCIII

Answer 5

inhibits LPL and interferes w/ ApoB and ApoE binding to hepatic receptors

Question 6

ApoB48 will be found on ______

Answer 6

chylomicrons

Question 7

ApoB-100 will be found on _______

Answer 7

VLDLs; IDLs; LDLs

Question 8

Ratio of what two things is important for assessing CVD risk (per Wendt lecture)

Answer 8

ratio of Total Cholesterol: HDL cholesterol

Question 9

Diseases assoc. with Hypertriglyceridemia

Answer 9

Pancreatitis
Xanthomas
Increased risk in CHD

Question 10

Diseases assoc. w/ Hypoerlipoproteinemia

Answer 10

Atherosclerosis
Premature CAD
Neurologic disease- stroke

Question 11

What TC:HDL ratio is considered increase risk for CVD

Answer 11

> 4.5

Question 12

There are ____ receptors on endothelial cells - helps lead to atherosclerosis

Answer 12

LDL

Question 13

Atheroslerosis

LDL in blood gets into ________ which leads to ______ cells then _______

Answer 13

monocytes; foam cells; fatty streak

Question 14

How Statins Increase LDL Receptors:

Statins cause there to be less ______ in the blood, therefore the _______ are no stuck anymore and can go _______

Answer 14

cholesterol(sterols); proteases (arent stuck anymore); go cleave transcription factors (that will increase LDL receptor transcription)

Question 15

which statins should be taken in the evening with meals (for absorption)

Answer 15

Simvastatin and Lovastatin

Question 16

which statins have CYP3A4 metabolism?

Answer 16

Simvastatin; Lovastatin; Atorvastatin

Question 17

which statin does not have metabolism via CYP enzyme? and how is it metabolized?

Answer 17

pravastatin; sulfation!

Question 18

what is Zetia’s MOA?

Answer 18

inhibits NPC1L1 – aka will inhibit intestinal absorption of cholesterol from dietary sources and reabsorption of cholesterol in the bile

Question 19

what drugs inhibit Apo B lipoprotein synthesis

Answer 19

Lomitapide; Mipomersen

Question 20

what is the fibrate class of drugs’ MOA?

Answer 20

fibrate binds to PPAR-alpha and aso RXR; all of that binds to PPRE with drives LPL expression! it also increase expression of ApoA1 (aka HDL expression)

Question 21

what is PSCK9s normal job (not talking about drugs)

Answer 21

PCSK9 = promotes degradation of LDL receptors in the liver

Question 22

MOA for Omega 3 fatty acids

Answer 22

inhibits synthesis of TGs in liver –bc it is a poor substrate for enzymes that make TGs

Question 23

Niacin will reduce TGs by:

• increase ______ activity to increase _____ clearance
• decrease _______ production
• strongly increase _______ levels

Answer 23

increase Lipase; increase VLDL clearance

decrease VLDL production

increase HDL levels

Question 24

Niacin works in ______ tissue and which organ?

Answer 24

adipose; liver

Question 25

Niacin: | works in adipose tissue by decreasing Fatty Acid transport to liver by _________

Answer 25

inhibiting TG lipolysis by hormone sensitive lipase

Question 26

Niacin: | works in liver by inhibiting ________ and ______

Answer 26

fatty acid synthesis and esterification

Question 27

what things can reduce HDL

Answer 27

- smoking - T2DM - Obesity - Malnutrition - Drugs (anabolic steroids and Beta blockers)

Question 28

what things can lead to elevated LDL

Answer 28

- hypothyroidism - nephrotic syndrome - cholestasis - anorexia nervosa - Drugs: Thiazides; cyclosporine; tegretol

Question 29

steps for Pathogenesis of Atherosclerosis:

Answer 29

- endothelial injury - inflamm. response - macrophage infiltraiton - platelet adhesion - smooth muscle proliferation - extracellular muscle accumulation

Question 30

Common signs for dyslipidemia

Answer 30

- pancreatitis - eruptive xanthomas - peripheral polyneuropathy - increased BP - Waise Size (> 40 in in men; > 35 in women) - BMI > 30 kg/m^2)

Question 31

Common Sx of Dyslipidemia

Answer 31

- chest pain/palpitations - Sweating/anxiety/SOB - Loss of consciousness - Difficulty w/ speech or movement - abdominal pain - sudden death

Question 32

how to calculate LDL

Answer 32

LDL = TC - HDL - TG/5

Question 33

what lab parameters are used for dyslipidemia

Answer 33

HDL; TC; TG; LDL

Question 34

what things are needed for BOTH Framingham and Pooled cohort eqns

Answer 34

- gender - age - HDL - Systolic BP - Tx for HTN - Smoking - Total Cholesterol

Question 35

what things are needed for pooled cohort eqn and NOT framingham

Answer 35

race; diabetes

Question 36

Statins and Muscle Injury: | if CK is ______ times the upper limit - stop the statin!

Answer 36

10

Question 37

why is grapefruit juice a possible issue with statins

Answer 37

grapefruit juice is a CYP3A4 inhibitor - will elevate statin levels --- higher risk of muscle injury

Question 38

when to monitor Statins?

Answer 38

baseline 4 - 12 weeks after starting statin initiation every 3 - 12 months as clinically indicated

Question 39

ADEs of Bile acid resins

Answer 39

impaired absorption of fat soluble vitmains hypernatremia hyperchloremia GI obstruction

Question 40

Niacin will _____ LFTs and lead to _____uricemia and ______glycemia _____ statin levels

Answer 40

increase; hyper; hyper; increase

Question 41

Fibrates will increase the levels of what drugs

Answer 41

- statins - zetia - sulfonylureas - warfarin

Question 42

which lipid drug is an oligonucleotide inhibitor of ApoB-100 synthesis

Answer 42

Mipomerson

Question 43

which lipid drug is an inhibitor of a triglyceride transfer protein

Answer 43

lomitapide

Question 44

what are guidelines used for Lipid therapy | and in the order they were implemented

Answer 44

``` NECP ACC/AHA NLA ACC - non statin NLA - PCSK9 ```

Question 45

what are 4 statin benefit groups

Answer 45

- Clinical ASCVD - LDL > 190 - Diabetes and ages 40 - 75 - ASCVD risk > 7.5% and ages 40 - 75

Question 46

if someone has clinical ASCVD what type of statin should they be on

Answer 46

if > 75 yo - moderate intensity | if < 75 yo - high intensity

Question 47

if someone is b/w ages 40 - 75 and has diabetes what type of statin should they be on

Answer 47

if ASCVD risk > 7.5% - high intensity | if ASCVD risk < 7.5% - moderate intensity

Question 48

if someone has an LDL > 190 and has diabetes what type of statin should they be on

Answer 48

high intensity

Question 49

what are the high intensity statins

Answer 49

ator. 40 - 80 | rosuv 20 - 40

Question 50

what are the major risk factors for ASCVD (for NLA statin)

Answer 50

- Age: M > 45; W > 55 - HDL: M < 40; F: 50 - HTN? - Smoker? - FH of early CHD: first degree relative ---- M: < 55; F < 65

Question 51

goals for NON- HDL and LDL if put into NLA VERY high risk group

Answer 51

NON-HDL < 100 | LDL < 70

Question 52

goals for NON- HDL and LDL if put into NLA low, mod, or high risk group

Answer 52

NON-HDL < 130 | LDL < 100

Question 53

NLA Guidelines: | Who is low risk

Answer 53

0 - 1 major risk factor

Question 54

NLA Guidelines: | who is mod risk

Answer 54

2 major risk factors + ASCVD risk b/w 5 - 15%

Question 55

NLA Guidelines: | who is very high risk

Answer 55

Clinical ASCVD OR DM with 2+ Risk Factors

Question 56

NLA Guidelines: | who is high risk

Answer 56

- CKD 3B/4 - LDL > 190 - DM w/ 0 - 1 risk factors - 3+ risk factors - 2 risk factors + (pooled: > 15%; framingham >10%)