Lipid Disorders - Exam 4

Question 1

What are lipids composed of? What are the two main lipids?

Answer 1

glycerol and fatty acids

main lipids: cholesterol and triglycerides

Question 2

What is the role of cholesterol? Triglycerides?

Answer 2

essential element of all animal cell membranes and forms the backbone of steroid hormones and bile acids synthesis

assist in the transfer of energy into cells

Question 3

What is the function of apolipoproteins? Where are they found? Where are they synthesized?

Answer 3

activate enzymes for lipoprotein metabolism and act as ligands for cell surface receptors

proteins found on the surface of lipids that

synthesized: liver and small intestine

Question 4

Where is the primary source, lipoprotein association and function of the following: ApoB-48, ApoB-100, ApoC-I, ApoC-II, ApoC-III, ApoE

Answer 4

Question 5

What are lipoproteins composed of? What is their role?

Answer 5

are complex molecules made up of lipids and apolipoproteins.

transporting cholesterol, triglycerides and fat-soluble vitamins to and from tissues

Question 6

What is the core of a lipoprotein made out of?
What is the shell composed of?

Answer 6

core: hydrophobic liquid
triglyceride (aka triglycerols)
Free cholesterol
cholesterol esters (bound to free fatty acids)

shell: hydrophilic lipids
phospholipids
apolipoproteins (apo)

Question 7

How are lipoproteins classified? How is that determined?

Answer 7

based on density

Density is determined by the presence of triglycerides and apolipoproteins

Question 8

Which is more dense, triglycerides or apolipoproteins? What are the 5 types?

Answer 8

triglycerides are less dense; apolipoproteins are more dense

chylomicrons
VLDL - Very-low-density
IDL - Intermediate-density
LDL - Low-density
HDL - High-density

Question 9

What are the 2 lipoprotein metabolic pathways? Give a short summary of each

Answer 9

Exogenous lipid pathway: absorption of dietary lipids and formation of chylomicrons

Endogenous lipid pathway: secretion of VLDL by the liver, transition to IDL and LDL

Question 10

Exogenous pathways Step 1:

Dietary TG’s, cholesterol, fatty acids and retinol (vit. A) are absorbed in small intestine combined with _____ to form _____. They then pick up ____ and ____ from HDL and travel to the capillaries.

Answer 10

apolipoprotein (apoB-48)

chylomicrons

apoC

apoE

Question 11

Exogenous pathways Step 2: These _____ are absorbed into capillaries where they are utilized in the _____ via ____. TG’s are broken down by ______ into FFA which can be converted to energy for use/storage in muscle and adipose tissue

Answer 11

chylomicrons

peripheral tissue

apoC

lipoprotein lipase (LPL)

Question 12

Exogenous pathways Step 3: The ____ remnant then travels to the ____ where it is taken up via _____ with the help of ____. _____ is also lost in this process to another receptor

Answer 12

chylomicron

liver

LDL receptors (LDLR)

apoE

ApoB48

Question 13

Endogenous Pathway Step 1: ____ and _____ are combined in the liver along with ____ to create VLDL

Step 2: ____ acquires apoE and ____ via transfer from ____molecules when leaving the ___

Answer 13

Cholesterol

triglycerides

apoB-100

VLDL

apoC

HDL

liver

Question 14

Endogenous pathway Step 3: VLDL is utilized in the _____ as TG’s are broken down by ____ for energy (lipolysis) and now are referred to as _____

Step 4: 40-60% of ___ is taken up by the liver (via _____, the remaining IDL is further broken down by ____ during systemic circulation to form ____

Answer 14

peripheral tissues (apoC)

LPL

IDL

IDL

apoE and the LDLR

hepatic lipase (HL)

LDL

Question 15

Endogenous pathway Step 5: 70% of the ____is removed from circulation by the liver _____ , the remaining 30% is used up by the ______.

Step 6: ____ removed from circulation by the ____ is broken down and the _____ is excreted in the bile

Answer 15

LDL

(via apoB & LDLR)

peripheral tissues (lipolysis)

LDL

liver

cholesterol

Question 16

HDL: Immature HDL with ____ sees the macrophages full of ____ and “sweeps” up the ____ → HDL matures

Answer 16

ApoA1

LDL

excess LDL

Question 17

Mature ____ can drop off ____ into peripheral tissues to create more ____ as well as take ____ from lower density lipoproteins

Answer 17

HDL

cholesterol

hormones

triglycerides

Question 18

Finally, HDL can deposit _____ cholesterol in the ____ for breakdown/excretion and process starts over. What is an additional function of HDL?

Answer 18

“sweeped up”

liver

other functions of HDL include “donating”
apoproteins for lipid metabolism

Question 19

What are some key differences between LDL and HDL?

Answer 19

LDL: bad
-deposits cholesterol in the blood vessel wall which build up can impede blood flow
-High level of cholesterol esters

HDl: good
-can “sweep” cholesterol out of the blood vessel keeping them clear of build-up
-Picks up cholesterol from peripheries to deposit into the liver
-High protein levels

Question 20

Watch ninja nerd video included in the lecture about lipoprotein metabolism

Answer 20

DO IT!!

Question 21

What are 4 pathways that lead to dyslipidemia

Answer 21

1. Excessive hepatic secretion of VLDL
2. Impaired lipolysis of triglyceride-rich lipoproteins
   chylomicrons and VLDL
3. Impaired hepatic uptake of ApoB containing lipoproteins
   all lipoproteins except HDL
4. Inherited low levels of HDL-C

Question 22

**______ is one of the MC cause for dyslipidemia. Will fasting TG and HDL be high or low? What are some factors that increase VLDL secretion? **What is the major one?

Answer 22

Excessive Hepatic Secretion of VLDL

elevated fasting TGs
low HDL-C levels

factors:
Obesity
Insulin resistance
High-carb diet
**Nephrotic syndrome
ETOH use
Cushing’s Syndrome

Question 23

_____ results from a dysfunction in lipoprotein lipase (LPL). What does TGs and HDL look like? What are 2 causes?

Answer 23

Impaired Lipolysis of Triglyceride Rich Lipoproteins aka impaired breakdown

elevated TGs
low HDL-C

**genetic disorder
insulin resistance

Question 24

______ a down regulation of the LDL receptor (LDLR) in the liver leads to elevated serum LDL-C. What are some common causes?

Answer 24

Impaired Hepatic Uptake of ApoB Containing Lipoproteins

saturated fat intake reduces LDL activity
hypothyroidism
estrogen deficiency
chronic kidney and liver disease
**multiple drugs
thiazides, cyclosporin, carbamazepine
genetic disorders

Question 25

_____ accelerated catabolism of HDL and its apoA. What are 3 causes?

Answer 25

Disorders of low HDL cholesterol causes: obesity insulin resistance genetic disorders

Question 26

**How is dsylipidemia defined? What are 2 contributing factors? Increases risk for ______.

Answer 26

as elevated levels of LDL-C and triglycerides as well as low HDL aka due to increased LDL, more foam cells = increased risk of heart attack genetics and environmental factors increases risk for atherosclrotic cardiovascular disease (ASCVD)

Question 27

patches on skin (MC -buttock) due to lipid deposition yellow, pink, brown, or skin-colored can be pruritic or painful What am I? What values are normally high?

Answer 27

Eruptive Xanthomas extremely high chylomicrons (TG’s) or VLDL

Question 28

_____ are lipid deposit nodules in the tendons of the hands, feet, and heel. What value is high?

Answer 28

tendinous xanthomas seen with high LDL

Question 29

_____ milky appearance of the veins and arteries of the retina. What value is high?

Answer 29

lipemia retinalis extremely high triglycerides

Question 30

Serum changes in the blood after it is drawn are due to high _____. Describe it

Answer 30

triglycerides often look opalescent or milky serum

Question 31

When do you start screening for ASCVD? What test do you order?

Answer 31

adults starting at age 20 or kids beginning at age 2 if family hx of early CVD or significant primary hypercholesterolemia textbook answer: Total cholesterol (TC) and HDL (fasting sample is preferred but non-fasting is acceptable)

Question 32

What are the indications if a full lipid panel should be ordered?

Answer 32

Total Cholesterol > 250 HDL-C is < 40 non-fasting may result in higher TG’s leading falsely elevated results

Question 33

**What are the normal ranges for : TC, LDL, HDL, TG. How long do they need to fast?

Answer 33

TC < 200 mg/dL LDL < 100 mg/dL - UNLESS THEY HAVE EXISTING ASCVD! HDL 40-59 mg/dL (> 60 mg/dL is cardioprotective) TG’s < 150 mg/dL 9-12 hours prior to collection

Question 34

How often should you screen for hyperlipidemia?

Answer 34

~5 years for the average adult 3 years for lipid levels close to those warranting therapy - if they’re borderline Annually for those on treatment not a definitive answer! guideline only

Question 35

What are some secondary causes of hyperlipidemia?

Answer 35

hyperglycemia nephrotic syndrome/chronic renal insufficiency hepatitis/cholestasis hypothyroidism

Question 36

What effect does oral contraceptives have on lipids? alcohol use?

Answer 36

increase triglycerides and total cholesterol increased triglycerides and HDL due to carbs and sugar, liver dysfunction

Question 37

What are the 4 guidelines we need to consider about statin therapy?

Answer 37

clinical ASCVD DM LDL > or equal to 190mg primary prevention with ASCVD risk of over 7.5%

Question 38

** What are the 6 risk factors for ASCVD?

Answer 38

1. Tobacco use 2. DM 3. HTN 4. Obesity (BMI ≥ 30) 5. Family hx of premature heart disease 55 y/o in males 65 y/o in females 6. Personal hx of CAD or non-coronary atherosclerosis: abdominal aortic aneurysm, peripheral artery disease, carotid artery stenosis

Question 39

**What are the 4 major ASCVD events that put you in the VERY high risk category? How many of the MAJOR event do you need to be considered VERY high risk?

Answer 39

ACS within past 12 months History of MI (other than ACS above) History of ischemic stroke Symptomatic PAD 2+

Question 40

**What are the high risk conditions? What is the second way to be considered VERY high risk?

Answer 40

Age ≥ 65 years CKD (GFR 15-59 mL/min) Coronary bypass or percutaneous intervention Current smoker Diabetes Hereditary Familial Hyperlipidemia History of heart failure Hypertension LDL-C ≥ 100 mg/dL despite max tolerated statin + ezetimibe 1 of the major and 2+ of the high risk conditions to be very high risk

Question 41

When should you start high intensity versus moderate intensity statin therapy?

Answer 41

High intensity statin - Very high risk ASCVD or ≤ 75 years of age Moderate intensity statin - Not “Very High Risk” and older than 75

Question 42

**What drugs (with dosages) are considered high-intensity statins? What percent do they lowered LDL? Which one has mild evidence to decrease existing plaque?

Answer 42

Rosuvastatin 20mg 40mg Atorvastatin 40mg 80mg greater than 50% Rosuvastatin

Question 43

How much does moderate statin therapy decrease LDL? Low intensity? What are the low intensity statins with dosages?

Answer 43

Moderate: 30-49% Low: 30% Simvastatin 10mg Pravastatin 10mg 20mg Lovastatin 20mg Fluvastatin 20-40mg

Question 44

What are the 2 goals of lipid management? How often should you monitor?

Answer 44

Reassess lipid panel after 4-12 weeks then every 3-12 months

Question 45

For a person WITHOUT ASCVD and LDL at or above 190? What is the tx? monitoring? goals?

Answer 45

tx: high intensity statin Rosuvastatin 20mg 40mg Atorvastatin 40mg 80mg monitor: Reassess lipid panel after 4-12 weeks then every 3-12 months goals: Goal #1 - 50% reduction in LDL-C Goal #2 - LDL-C of <100 mg/dL

Question 46

For a pt age 40-75 with DM and LDL 70-190, what is the protocol?

Answer 46

Step 1: Calculate an estimated 10-year ASCVD risk Step 2: Review diabetes-specific high-risk features

Question 47

What is the ASCVD risk estimator calculator tool? What are the criteria?

Answer 47

Predicts 10-year risk for first ASCVD event among patients who are between 20 and 79 years of age Sex, Age, Race TC/HDL SBP Tx for HTN/DM Smoking status

Question 48

Picking statin therapy for pts 40-75 with DM and LDL between 70-190 depends on what two factors? Do they have to have both or one?

Answer 48

ONE FACTOR **10 year risk ≥ 7.5% or (+) Diabetes specific risk enhancers **know greater than or equal to 7.5% risk**

Question 49

**Picking statin therapy for pts 40-75 with DM and LDL between 70-190 and the answer is YES! What is the tx? What are the 2 goals?

Answer 49

Question 50

**Picking statin therapy for pts 40-75 with DM and LDL between 70-190 and the answer is no. What is the tx? What are the 2 goals?

Answer 50

Question 51

For borderline pts between 40-75 without ASCVD or DM and LDL is between 70-189. What are the next steps?

Answer 51

1. calculate ASCVD risk tx depends on risk %

Question 52

**Aged 40–75 without clinical ASCVD or DM and whose LDL-C is between 70–189 mg/dL and ASCVD risk is between 7.5 and 19.9 need to consider _____. What is it? What do the results indicate?

Answer 52

measuring coronary artery calcium (CAC) CAC - utilizes a low dose CT scan of the heart, assessing the amount of calcium plaque build up on the vascular walls. Score ranges from 0-400. CAC ≥100 - consider adding statin CAC 1-99 - consider adding statin if age ≥ 55 years CAC score of zero - focus on lifestyle modifications reassess in 5-10 years, indicates low 10-15 year risk

Question 53

What are the 3 lifestyle modifications? How long does it take to see an effect?

Answer 53

aerobic exercise weight loss diet changes 3-6 months

Question 54

**______ inhibit HMG-CoA, a key enzyme in cholesterol synthesis in the liver increases the number of LDL receptors on the hepatocyte cell membrane. Where are they metabolized? What do you need to order before starting?

Answer 54

statins in the liver need to order baseline LFTs, 2-3 months after starting/changing dose and annually

Question 55

What is the MC SE of statins? What drugs have LESS likelyhood of SE?

Answer 55

Myalgias- normal CK Myopathy/Rhabdomyolysis- with elevated CK pravastatin and fluvastatin

Question 56

_____ occurs in those predisposed to DM and use of high intensity statin

Answer 56

hyperglycemia

Question 57

What are the CI to statin therapy?

Answer 57

active liver dz preg and nursing mothers

Question 58

What is the effect of taking statin and CYP450 meds together?

Answer 58

worsening the SE of statins

Question 59

What if a pt cannot tolerate a statin or its not doing its job, then what?

Answer 59

try a different statin, fluvastatin, pravastatin - most likely to be tolerated but not as effective 2nd line: ezetimibe, PCSK9 inhibitors, bempedoic acid, inclisiran 3rd: -bile acid sequestrants, fenofibrate, niacin (kinda)

Question 60

______ : blocks appx 60% of dietary cholesterol absorption. Works best when ?? What does it NOT have an effect on?

Answer 60

Ezetimibe (Zetia) works best in combo with statin **no effect on HDL or TG** but statins do

Question 61

_____ monoclonal antibodies inhibit PCSK9 from binding to LDL receptors decreasing LDL receptor degradation and increasing LDL clearance. What is the route? Any CI?

Answer 61

PCSK9 Inhibitors alirocumab (Praluent), evolocumab (Repatha) injection q 2 weeks no limitation in renal or liver impairment

Question 62

______ inhibits adenosine triphosphate-citrate lyase (ACL) inhibiting cholesterol synthesis in the liver. increases the number of LDL receptors on the hepatocyte cell membrane stimulates LDL catabolism. When it is commonly used?

Answer 62

Bempoic Acid (Nexletol) Used as adjunct therapy when we need additional LDL reduction after maximally tolerated statin therapy

Question 63

bempoic acid/ezetimibe = ____. What is the effect? What are the SE? (includes just normal bempoic acid)

Answer 63

Nexlizet synergistic effect with statins gout/hyperuricemia, cold/flu s/s, tendon rupture, muscle spasms, abdominal pain

Question 64

_____ Blocks the production of mRNA needed for PCSK9 production resulting in less LDL. What is the route?

Answer 64

Inclisiran (Leqvio) Injection day 1, then at 3 months, then q6m thereafter (must be in a clinical setting)

Question 65

_____ Binds bile acids in the intestines requiring the liver to excrete more bile. The liver uses hepatic cholesterol to make bile which results in the liver taking up more LDL-C from the systemic circulation. What % reduction in LDL? What is the pt education?

Answer 65

Bile Acid Sequestrants cholestyramine, colestipol and colesevelam (Welchol) 10-24% take it by itself NOT with other drug. take other drugs 1 hour before or 4 hours after bile acid sequestrants

Question 66

What is the preferred lowing lipid med for preg pts?

Answer 66

Bile Acid Sequestrants: cholestyramine, colestipol and colesevelam (Welchol)

Question 67

**How do you define hypertriglyceridemia? **What is a complication?

Answer 67

Defined by a plasma/serum level >150 mg/dL pancreatitits: triglycerides over 400

Question 68

what is the tx for pts older than 20 with triglycerides between 175-499?

Answer 68

treat underlying conditions Avoid medications that worsen lipid levels **Avoid refined carbohydrates, saturated and trans fatty acids **Watch your “white” foods! Avoid alcohol

Question 69

**When is statin therapy indicated for hypertriglycerdimia?

Answer 69

40-75 y/o with severe hypertriglyceridemia ≥ 500 mg/dL with an ASCVD risk of ≥ 7.5% Severe hypertriglyceridemia >1000 mg/dL alone

Question 70

_____ stimulate LPL activity (enhances TG clearance from blood) reduce apoC-III synthesis (enhances lipoprotein remnant clearance) promote breakdown of fatty acids may reduce VLDL-TG production How much do they reduce TGs?

Answer 70

Fibrates: gemfibrozil (Lopid), fenofibrate (Trilipix, Tricor) by 50% or more

Question 71

dyspepsia, increase risk of gallstones, myopathy, hepatotoxicity are all SE of _____

Answer 71

fibrates: gemfibrozil (Lopid), fenofibrate (Trilipix, Tricor)

Question 72

**What is a drug interaction of gemfibrozil (Lopid), fenofibrate (Trilipix, Tricor)? When do you need to be cautious?

Answer 72

Drug interaction: increases warfarin caution in CKD pts: excreted by the kidneys - dose reduction required

Question 73

______ inhibit the release of TG’s from the liver (reducing VLDL). Stimulates LPL (increases clearance of TG’s from the plasma).

Answer 73

Omega 3 Fatty Acids

Question 74

Where are Omega 3 Fatty Acids naturally found? What dose is beneficial?

Answer 74

Naturally found in fish and flaxseed, OTC supplement can reduce TG’s by 50% or more - requires up to 4 grams a day to be beneficial

Question 75

_____ stronger version of omega 3 fatty acid - contains >95% omega 3 fatty acids in comparison to 30-50% in OTC combinations

Answer 75

Vascepa (Icosapent ethyl) expensive

Question 76

What is considered severe for a fasting triglyceride level?

Answer 76

TG greater than or equal to 500 elevated VLDL and chylomicrons

Question 77

______ inhibits breakdown of TG in adipose tissue. Increases LPL activity (increases clearance of TG’s). Inhibits synthesis of TG in liver (reduces VLDL secretion and subsequently LDL levels). Reduces clearance of apoA-I. What are the SE? What is a way to combat it?

Answer 77

Niacin SE: niacin flush-> give ASA 81mg 30min prior to reduce flush also raises uric acid levels- avoid with hx of gout

Question 78

_____ is approved for use in Europe for patients with genetically confirmed monogenic chylomicronemia but is not approved for clinical use in the United States.

Answer 78

APO C3 Inhibitor