Hyperlipidemia

Question 1

What is the function of lipoproteins?

Answer 1

Because lipids are insoluble in plasma, circulating lipids are carried in these
Used for energy, storage, hormone production and bile acid formation

Question 2

What happens after abnormal lipoprotein metabolism?

Answer 2

Atherosclerosis (usually genetic because of defective receptors so there is overproduction/impaired removal of lipoproteins)

Question 3

What are the 5 types of lipoproteins?

Answer 3

Chylomicrons, VLDL, IDL, LDL and HDL

Question 4

Function of chylomicrons

Answer 4

Carry dietary lipids from intestine to liver, skeletal muscle and adipose tissue

Question 5

Function of VLDLs

Answer 5

Carry newly synthesized triglycerides from liver to adipose tissue

Question 6

Function of IDLs

Answer 6

Intermediate between VLDL and LDL (usually not detectable in blood)

Question 7

Function of LDLs

Answer 7

Carry cholesterol from liver to body’s cells

Question 8

Function of HDLs

Answer 8

Collect excess cholesterol from body’s tissues (including vascular endothelium) and return it to the liver
Basically reverse cholesterol transport to provide protection against heart disease

Question 9

What do you want to suspect in anyone with a family history of premature atherosclerotic cardiovascular disease?

Answer 9

An inherited increased lipid disorder (familial hypercholesterolemia, polygenic hypercholesterolemia or familial combined hyperlipidemia)

Question 10

What is familial hypercholesterolemia?

Answer 10

Monogenic and very rare
Homozygotes have much more LDL than heterozygotes
Treat with a statin (and maybe add on)

Question 11

What is polygenic hypercholesterolemia?

Answer 11

Very similar to familial but multiple genes!
Increased LDL with premature onset of CHD
Treat with a statin (and maybe add on)

Question 12

What is familial combined hyperlipidemia?

Answer 12

Polygenic with a wide variety of lipid abnormalities
Present in almost half of people with familial CHD
Treat with a statin (and maybe add on)

Question 13

What is secondary hyperlipidemia?

Answer 13

Etiology that does not relate to lipid metabolism (diabetes and excessive alcohol most common, also obesity, smoking, renal/liver disease, drugs etc)

Question 14

Process of atherosclerosis

Answer 14

LDLs diffuse through endothelium at a rate that is dependent on the concentration in the blood!
Macrophages follow, absorb them, become foam cells and then die to release cholesterol and form deposits
Body reacts with increased collagen to form a cap
Cap ruptures and thrombus forms leading to a potential infarct

Question 15

When is it recommended to screen?

Answer 15

Between 9-11 and again at 17-21 yrs

Question 16

Non-modifiable risk factors of CHD

Answer 16

Family history of premature ASCVD
Age (male over 45 and female over 55)
Male
Symptomatic cardiovascular disease (angina etc)
Chronic kidney disease

Question 17

Modifiable risk factors of CHD

Answer 17

HTN (BP over 140/90 or on antihypertensive)
DM
Smoking
Obesity
Hyperlipidemia or HDL<40

Question 18

What is a negative risk factor of CHD?

Answer 18

HDL > 60

Question 19

What is on a fasting lipid panel?

Answer 19

Total cholesterol, triglycerides, LDL and HDL

Total cholesterol= HDL + LDL + (TAGs/5)

Question 20

Why do you need to 12 hour fast before a fasting lipid panel?

Answer 20

Cholesterol isn’t really affected by eating but TAGs are and they are done at the same time

Question 21

Cholesterol levels and acute MI

Answer 21

Levels can drop 24-48 hrs after acute MI and can persist up to 60 days

Question 22

Lipid profile cutoffs

Answer 22

Cholesterol: <200 mg/dL good, 240 high risk
TAGs: <150 good, 200-499 high risk
HDL: 60 good, <35 high risk
LDL: 60-130 good, 160-189 high risk

Question 23

What are plane xanthomas?

Answer 23

Cholesterol-filled, soft, yellow plaques that appear in various places (can indicate familial or secondary causes)

Question 24

What are tuberous xanthomas?

Answer 24

Yellow-orange nodules often over knees and elbows (can also be in tendons)
Associate with familial hypercholesterolemia

Question 25

What are eruptive xanthomas?

Answer 25

Crops of small red-yellow papules with ABRUPT ONSET Seen on extensor surfaces and butt Caused by elevated TAGs >1500 (indicate familial HLD

Question 26

What is corneal arcus?

Answer 26

White or grey ring around the cornea | Abnormal in pts under 40!

Question 27

What is the approach to lipid management?

Answer 27

Diet, exercise and meds

Question 28

DASH diet

Answer 28

For HTN/hyperlipidemia Rich in fruits and veggies, moderate low fat dairy, low animal protein, plant sources of protein, low sodium Goal is to decrease BP, LDL and hopefully decrease risk of CHD and stroke

Question 29

What can increase HDL cholesterol?

Answer 29

Exercise

Question 30

Types of medications used

Answer 30

``` HMG Co-A reductase inhibitors (statins) Fibrates Nicotinic acid Bile acid sequestrants Cholesterol absorption inhibitors PCSK9 inhibitors ```

Question 31

Why are statins used?

Answer 31

To decrease incidence of major vascular events and coronary mortality Think they stabilize vulnerable plaques and reduce inflammation

Question 32

How do statins work?

Answer 32

Inhibit HMG-CoA reductase (rate limiting step in cholesterol synthesis in liver) Less cholesterol is produced to decrease blood levels Liver enzymes sense this and increase LDL receptors Relocate to membrane and bind LDL and VLDL to take more cholesterol out of blood LDL and VLDL goes to liver and gets digested

Question 33

Lipid panel changes with a statin

Answer 33

Lower LDL by 20-60% | Lower TAGs by 15-30%

Question 34

Adverse effects of statins

Answer 34

Mild GI, liver toxicity, myalgia, myositis, myopathy, rhabdo

Question 35

Contraindications of statins

Answer 35

Absolute: Active liver disease and pregnancy Caution: use of other CYP3A4 inhibitors and various drugs, chronic kidney/liver disease

Question 36

What baseline should you obtain before statin therapy?

Answer 36

Lipid panel, LFTs and creatine kinase levels

Question 37

What should you consider when there is a poor response or intolerance to statin therapy?

Answer 37

Reinforce adherence to meds and lifestyle changes Exclude secondary causes Investigate statin intolerance

Question 38

When should the addition of a nonstatin LDL lowering agent be considered?

Answer 38

In ppl at high ASCVD risk that are getting the maximum tolerated statin and there is an insufficient response

Question 39

What are bile acid sequestrants (resins)?

Answer 39

Ex: cholestyramine, colesevelam, colestipol Bind bile acids in the intestine to inhibit their absorption Decrease LDL by up to 24% Act synergistically with statins Safe in pregnancy!

Question 40

Adverse effects of resins

Answer 40

Constipation, gas, may interfere with fat soluble vitamin absorption, affect warfarin management, increase TAGs

Question 41

Contraindications of resins

Answer 41

Absolute: TAGs >400 Relative: TAGs >200

Question 42

What does nicotinic acid do?

Answer 42

Reduce production of LDL, increase HDL and may reduce TAGs

Question 43

Adverse effects of nicotinic acid

Answer 43

Flushing and pruritus, liver damage, safety concerns when combo with statin

Question 44

Contraindications of nicotinic acid

Answer 44

Absolute: active liver disease Relative: hyperuricemia, hyperglycemia, unstable angina Don't use in pregnancy

Question 45

What do fibric acid derivatives do?

Answer 45

(Gemfibrozil, fenofibrate, bezafibrate) Mostly lower TAGs, raise HDL Don't usually use in pregnancy

Question 46

Adverse effects of fibric acid derivatives

Answer 46

May induce gall stones, hepatitis and myositis

Question 47

Contraindications of fibric acid derivatives

Answer 47

Absolute: severe hepatic or renal disease, preexisting gallstones, taking simvastatin Relative: other statin use (risk of myopathy), concurrent warfarin use

Question 48

What does Ezetimibe do?

Answer 48

Blocks intestinal absorption of dietary and biliary cholesterol via transporter Lower LDL up to 17% Can use with statin Contra: do not use with statin in active liver disease and pregnancy

Question 49

PCSK9 inhibitors

Answer 49

(Evolocumab, alirocumab) | Limited experience and data but should reduce LDL levels

Question 50

What are the 4 statin benefit groups?

Answer 50

Individuals with clinical ASCVD (acute coronary syndromes, history of MI, stable or unstable angina) Individuals with LDL>190 Individuals with diabetes aged 40-75 yrs with LDL 70-189 and without clinical ASCVD Individuals without ASCVD or diabetes with LDL 70-189 and estimated 10 yr ASCVD risk is >7.5%

Question 51

What statin level is used for people with clinical ASCVD?

Answer 51

Less than 75: high intensity | Over 75: moderate intensity

Question 52

What statin level is used for group 2?

Answer 52

High intensity

Question 53

What statin level is used for group 3?

Answer 53

Moderate intensity (high when 10 yr wisk is over 7.5%)

Question 54

What statin level is used for group 4?

Answer 54

Moderate to high

Question 55

What is the biggest contributor to ASCVD risk calculator?

Answer 55

Age

Question 56

What factors can also be used to initiate stain therapy if not in the 4 groups?

Answer 56

LDL >160, family history of premature ASCVD, Hs-CRP>2 mg/L, ABI