Atherosclerosis, Cholesterol, Hyperlipidemia

Front 1

This starts with injury to the blood vessel wall. Initially it is characterized by the accumulation of excessive LDL beneath the endothelium, which becomes oxidized by oxidative wastes produced by blood vessel cells and which triggers endothelial cells to produce chemicals that attract monocytes, which then trigger an inlfammatory response.

Back 1

Atherosclerosis

Front 2

Monocytes become macrophages, which then phagocytize oxidized LDL until they become packed with fat droplets, at which time they are known as?

Back 2

Foam Cells

Front 3

This is visible accumulation of foam cells beneath the vessel lining?

Back 3

Fatty streak

Front 4

This is the earliest form of an atherosclerotic plaque?

Back 4

Fatty streak

Front 5

Later in the course of the disease, _______ precipitates in the plaque, causing the affected vessel to become hard so that it cannot easily distend?

Back 5

Calcium

Front 6

These release chemicals that break down connective tissue fivers, weakening the plaques fibrous cap?

Back 6

Foam cells

Front 7

What causes a throbus/clot to form?

Back 7

When an enlarging atherosclerotic plaque breaks through the weakened endothelial lining that covers it, blood is exposed to the underlying collagen, which allows platelets to adhere to it forming a clot which is also known as a thrombus.

Front 8

If a clot breaks loose, it then becomes known as?

Back 8

an embolus

Front 9

What are the factors associated with atherosclerosis?

Back 9

Genetic predisposition

Obesity

Advanced Age

Smoking

Hypertension

Lack of Exercise

Elevated C-Reactive Protein or homocysteine

Infectious agents

Elevated Cholesterol

Front 10

What are the two main sources of cholesterol?

Back 10

Diet and the liver

Front 11

What are the three major lipoproteins in the blood?

Back 11

HDL, LDL, VDL

Front 12

Cholesterol is used in the production of what three things?

Back 12

Plasma Membranes

Steroid Hormones

Bile Salts

Front 13

Cells take up cholesterol from the blood by?

Back 13

Synthesizing LDL receptors

Front 14

This transports cholesterol to the liver, which then secretes cholesterol as well as cholesterol derived bile salts into the intestine.

Back 14

HDL

Front 15

This is an accumulation of macrophages containing droplets of lipids.

Yellow-brown, pinkish, or orange macules, papules, plaques, nodules, or infiltrations in tendons.

Some are associated with high plasma LDL cholesterol levels.

Back 15

Xanthomas

Front 16

What is the most common of all xanthomas? It is a soft polygonal yellow orange papules and plaques localized to upper and lower eyelids and around inner canthus.

Back 16

Xanthelasma

Front 17

This is yellow or skin colored subcutaneous tumors that move with extensor tendons. A symptom of familial hypercholesterolemia.

Back 17

Xanthoma tendineum

Front 18

This is a yellow nodule located especially on the elbows and knees found with patients with inheritable forms of hyperlipidemia?

Back 18

Xanthoma Tuberosum

Front 19

Discrete inflammatory type papules that erupt suddently, appearing typically on the buttocks, elbows, lower arms and knees seen in inheritable forms of hyperlipidemia as well as uncontrolled diabetes.

Back 19

Eruptive Xanthoma

Front 20

This is yellow-orange, flat or elevated infiltrations of the volar creases of palms and fingers seen in type III familial dyslipidemia.

Back 20

Xanthoma striatum palma

Front 21

On a regular fasting lipid profile, the lab only includes what four things?

Back 21

TC, HDL, TG and calculates the LDL for you.

Front 22

What must you order specifically if you want it?

Back 22

LDL

Front 23

If TG are over ___ then you must order a direct LDL because the calculated LDL will not be accurate?

Back 23

400

Front 24

If all three components of the lipids are high, what is the order of priority?

Back 24

1. LDL
2. TG
3. HDL

Front 25

For each lipid, there is a goal to be met, and for each there is a specific measure for that goal, what are they for each?

Back 25

LDL - It's simply a goal LDL

For TG - It's modified and called a goal non-HDL (TC-HDL) - basically atherogenic, set at thirty points higher than goal LDL

For HDL, it's the TC:HDL ratio - TC:HDL ratio >4.5 is assocaited with increased cardiovascular risk

Front 26

T or F

Hyperlipidemia is a well established risk factor for coronary artery disease?

Back 26

True

Front 27

T or F

Hyperlipidemia is a well established risk factor for acute ischemic stroke?

Back 27

False, because studies are unclear

Front 28

What are CHD equivalents?
4 of them

Back 28

Peripheral vascular disease

Carotid Stenosis

Abdominal Aortic Aneurysm

Diabetes Mellitus type I and II

Front 29

What are the independent risk factors for CHD other than high LDL?

Back 29

Age and gender (male 45+, female 55+)

Hypertension (treated or untreated)

Cigarette Smoking

HDL <40

Family History (1st degree M<55, F<65)

Front 30

What is considered a negative risk factor in HD?

Back 30

HDL > 60

Front 31

What are the screening recommendations for low risk adults?

Back 31

Fasting lipids every five years from age 20+

If > 30 below goals, repeat in 5 years

If < 30 below goals, repeat 1 years

Front 32

What are the screening recommendations for high risk adults?

Back 32

If multiple risk factors, CHD or CHD equivalent, yearly or more frequently depending on situation.

Front 33

Some people may require further risk assessment if it is felt that the Framingham/ATP criteria underestimate their true risk. What are the four tests to study emerging risk factors?

Back 33

Cardiac calcium scoring

Carotid intima media thickening

ABI

hs-CRP = C reactive protein

Front 34

What are the secondary causes of dyslipidemia?

Back 34

Diabetes mellitus

Hypothyroidism

Nephrotic Syndrome

Chronic Renal Failure

Obstructive Liver Dz

Front 35

What are the drugs that can act as secondary causes of dyslipidemia?

Back 35

Progestins
Anabolic steroids
corticosteroids
protease inhibitors
thiazides
beta blockers
isotretinoin

Front 36

NCEP ATP III definition - LDL

100-129 ?
130-159 ?
160-189 ?
190 + ?

Back 36

100-129 near optimal/above optimal

130-159 Borderline High

160-189 High

190 + Very High

Front 37

NCEP ATP III Definition - Total Cholesterol

<200 ?
200-239?
240+?

Back 37

<200 desirable

200-239 borderline high

240+ High

Front 38

NCEP ATP III Definition Triglycerides

<150 ?
150-199 ?
200-499 ?
500+ ?

Back 38

<150 normal
150-199 borderline high
200-499 high
500+ Very High

Front 39

NCEP ATP III Definition - HDL

<40?
60+?

Back 39

<40 Low
60+ High

Front 40

For the highest risk patients a goal LDL of what is optional?

Back 40

<70

Front 41

For a high risk patient who has just suffered a heart attack what is often initiated irrespective of LDL level?

Back 41

Statin

Front 42

If there is no CHD or equivalent, what can be tried for 3-6 months?

Back 42

Therapeutic lifestyle changes

Front 43

What are the three therapeutic lifestyle changes?

Back 43

Diet, Exercise/Weight management, Tobacco cessation

Front 44

What is the Tx for LDL?

Back 44

Consider drug simultaneously with TLC for CHD and CHD equivalents

Consider adding drug to TLC after 3-6 months for other risk categories.

Front 45

What are the four main drugs for lowering LDL?

Back 45

Statins
Bile Acid Sequestrants
Niacin
Fibrates

Front 46

If you have a non HDL Goal exceeded and triglycerides are 200-499 what are the three ways of managing?

Back 46

First meet LDL goal

Start with TLC, remove alcohol, remove as much fat as possible from diet

Give drugs if not effective, options are to increase initial LDL lowering drug or add niacin or fibrate.

Front 47

If you have a non HDL Goal exceeded and triglycerides are 500+ what are three ways of managing?

Back 47

First priority is to prevent pancreatitis

Start with drugs Niacin and Fibrate

In addition to TLC - Very low fat diet, avoidence of alcohol, weight management/physical activity.

Front 48

What is the most frequent risk factor associated with premature CHD?

Back 48

Low HDL

Front 49

What are the causes for low HDL?

Back 49

Cigarettes
Obesity
Sedentary lifestyle
Beta-blockers
Anabolic steroids - too many androgens

Front 50

What are the list of items, and how many of them do you have to have in order to have a diagnosis of metabolic syndrome?

Back 50

Elevated TG
Low HDL
Abdominal Obesity
Hypertension
Fasting Glucose

You must have three of these for a diagnosis of metabolic syndrome

Front 51

This is a part of metabolic syndrome, and it is frequently associated with premature CHD?

Back 51

Atherogenic dyslipidemia

Front 52

What is the primary management of metabolic syndrome?

Back 52

TLC: Weight loss, increased physical activity

Treat hypertension
Treat dyslipidemia
Aspirin for CHD patients

Front 53

What is the most effective medication for lowering LDL?

Back 53

Statins

Front 54

What are the two most effective medications for lowering triglycerides?

Back 54

Fibrates and Niacin

Front 55

What drug is the most effective for raising HDL?

Back 55

Niacin

Front 56

these are often used second line to statins to lower LDL?

Back 56

Bile Acid Resins

Front 57

What are the three Bile acid resins?

Back 57

Cholestyramine

Colestipol

Colesevelam

Front 58

These are the drugs of choice for lowering LDL in children and women of childbearing age.

Back 58

Bile Acid Resins

Front 59

What is the mechanism of bile acid resins?

Back 59

Trap bile in the intestine, so that it is excreted. Leads to increased conversion of liver cholesterol into bile. Ultimately leads to up regulation of liver LDL receptors.

Front 60

What is a contraindication for bile acid resins?

Back 60

May raise TG, contraindicated if TG >300.

Do not use if GI motility disorder

May interfere with drug absorption, warfarin, digoxin, synthroid.

Front 61

What are two other benefits of statins besides lowering LDL?

Back 61

Cardioprotective (beyond LDL lowering)

May be beneficial for gallstones

Front 62

What are the Potential Cardioprotective Effects (other than LDL lowering) for statins

Back 62

Improved endothelial function
Increased plaque stability
Decreased inflammation
Decreased oxidation of lipoproteins
Decreased platelet aggregation

Front 63

These statins have long half-lives and can be taken at any time of the day

Back 63

Atorvastatin (Lipitor) & rosuvastatin (Crestor)

Front 64

What statin is best for use in children with familiar hypercholesterolemia?

What three for age 11+

What statin for age 8+

Back 64

Age 11+ : Atorvastatin, Lovastatin, Simvastatin

Age 8+ : Pavastatin

Front 65

What are two cautions with statins?

Back 65

elevated LFTs

Myopathy

Front 66

What three statins are metabolized by CYP-3A4; adding a drug that inhibits CYP-3A4 increases the risk for rhabdomylosis?

Back 66

Atorvastatin, simvastatin, & lovastatin

Front 67

What two statins are not extensively metabolized by CYP3A4 and are less liklely to induce rhabdomyolysis when used with one of the predisposing drugs

Back 67

Pravastatin & fluvastatin

Front 68

Cholesterol Absorption Inhibitor

Decreases intestinal delivery of cholesterol to liver, decreasing liver stores, and enhancing clearance of cholesterol from the blood

Back 68

Ezetimibe

Front 69

Synergizes with statin to lower LDL

Back 69

Ezetimibe

Front 70

Combination product
Ezetimibe (Zetia) + Simvastatin (Zocor)

Back 70

Vytorin

Front 71

Drugs of choice for lowering Triglycerides

By also raising HDL, may also be helpful for atherogenic dyslipidemia

Exact mechanism somewhat unclear
Increases TG clearance and decreases TG synthesis from Liver

Effect on lipids may depend, in part, on initial lipid profile

Back 71

Fibrates

Front 72

What are the two fibrates?

Back 72

Gemfibrozil (Lopid)

Fenofibrate (Various Formulations)

Front 73

Fibrates have an increased risk of causing myopathy if combined with?

Back 73

Increased risk for myopathy if combined with statins

Fenofibrate appears to be the least likely to interfere with statin metabolism

Front 74

As a general rule, statins may be used in combination with one of the predisposing drugs if the statin is administered at no more than __% of maximal dose?

Back 74

25%

Front 75

A 34 year old male taking atorvostatin presents to urgent care complaining of cough X 3 weeks, now with fever and dyspnea, CXR reveals an infiltrate, what ABX would you avoid?

Back 75

Azithromycin, macrolides cause statin interaction

Front 76

BH is a 34 year old male who started atorvostatin therapy 4 months ago. He presents complaining of feeling like he strained his forearm. With absolutely no causitive history for a forearm strain. You consider a statin induced myopathy. Which lab do you order?

Back 76

Creatinine Kinase

Front 77

Fibrates are contraindicated in what five situations?

Back 77

Children

Pregnant or lactating

Gallstone Disease
All fibrates increase lithogenicity of bile

Hepatic Dysfunction (relative)
Fibrates may cause elevated LFTs

Renal Failure (relative)
Avoid statin-fibrate combination
Reduce dosage of fibrate

Front 78

What are the two omega three fatty acids?

Back 78

Fish Oils

Lovazza

Front 79

Inhibits hepatic VLDL production

Approved ONLY to lower very high TG (> 500)

Seems to inhibit platelets

Back 79

Lovazza

Front 80

Omega 3 fatty acids will help with what?

Back 80

Will help Triglycerides, but not LDL

Front 81

Decreases hepatic TG synthesis

Enhances Lipoprotein Lipase activity

Decreases fractional clearance of ApoA-I, accounting for increased HDL

Drug of choice for treating low HDL

More potent HDL raising effect ( 35%) than any other agent

Back 81

Niacin

Front 82

What are the lipid effects of niacin?

Back 82

Increases HDL
Decreases TG
Decreases LDL
The only medication that decreases Lp(a)

Front 83

What are some negative side effects of niacin?

Back 83

Flushing
GI Upset
Hepatotoxicity
Insulin resistance
Elevated Uric Acid
Birth Defects
Eye toxicity (rare)

Front 84

Niacin can reactivate what?

Back 84

peptic ulcer disease

Front 85

Hepatotoxicity

More common with _______, especially at doses > 2 grams/day

Can cause fulminant liver failure

Back 85

Long acting niacin

Front 86

While taking a niacin regimine, reductions in _____________ in a patient taking niacin should be viewed as a sign of toxicity

Back 86

Reduction in LDL of 50% or more in a patient taking niacin should be viewed as a sign of toxicity.

Front 87

When starting a niacin regimine, what should be monitored?

Back 87

LFTs, Glucose, & Uric Acid at baseline and every 2 – 4 weeks until stable dose achieved

Then every 3 – 6 months

Front 88

What are the contraindications with Niacin?

Back 88

Peptic Ulcer Disease
Liver Dz
Pregnancy
Gout (relative)
Diabetes Mellitus (relative)

Front 89

Niacin may interfere with _____ metabolism?

Back 89

Statin

Front 90

This is a type of niacin that releases slower than immediate-release, possibly reducing flushing
Releases faster than long-acting, possibly reducing hepatotoxicity

Back 90

Extended-release (Niaspan)

Front 91

Niacin that (causes flushing)
Niacin that (causes hepatotoxicity)

Back 91

Short-acting

Front 92

Niacin that (causes hepatotoxicity)

Back 92

Long-acting

Front 93

Extended release Niacin + lovastatin

Lovastatin 20 mg (because max dose is 80 mg and is metabolized by 3A4)
Niacin ER 500 or 1000 mg

For patient who requires TG control beyond that achieved by statin alone

Back 93

Advicor

Front 94

May be reasonable option for combined hyperlipidemia

For patients with low LDL who also have low HDL and high Triglycerides

Back 94

Advicor