Dyslipidemia

Question 1

1) Define hyperlipidemia/dyslipidemia
2) What is the goal with Tx?
3) Is it preventable?
4) Is it addressed in isolation?

Answer 1

1) Systemic disease
2) Goal is to reduce/prevent ASCVD and related morbidity and mortality
3) Most ASCVD is preventable
4) No; one component in risk of ASCVD

Question 2

1) Chylomicrons transport fats from the intestinal mucosa to the __________.
2) What do they then do?
3) When does LDL-C form?

Answer 2

1) liver
2) Release triglycerides, cholesterol into hepatocytes
3) Hepatocytes form LDL-C that transports lipids to the body’s cells, HDL-C transports lipids back to the liver

Question 3

LDL-C delivers fat and cholesterol to the cells (endothelium of vessels), which when oxidized forms fatty streaks and __________________, leading to atherosclerosis

Answer 3

atheromatous plaques

Question 4

What does high LDL result in?

Answer 4

1) Cellular proliferation of smooth muscle and fibrous tissue
2) This causes narrowing of arterial lumen, fibrous tissue stiffens the artery (atherosclerosis)
3) Calcium precipitate lipids into bony hard calcifications; these processes referred to as “hardening of the arteries”

Question 5

What results in bruits? What are bruits a sign of?

Answer 5

Atheromatous plaques protruding into the lumen result in turbulent flow (bruits) - attract platelet aggregation – plaques are prone to rupture…..leading to acute formation of thrombus or emboli and distal ischemia

Question 6

What can HDL-C do?

Answer 6

Carry fat and cholesterol back to the liver for excretion and high HDL-C levels can remove cholesterol from atheromatous plaques and stabilize them

Question 7

Familial hypercholesterolemia:
1) What is it?
2) What will labs show?
3) What is it a common cause of?

Answer 7

1) Gene mutation: results in over production and defective clearance of TG and LDL-C and/or low HDL-C
2) Very high LDL-C (above 200), TG (above 500), low HDL-C (20s-30s).
3) Dyslipidemia in kids/young adults

Question 8

Secondary or acquired hypercholesterolemia
1) What is the main cause?
2) What will the labs show?
3) Who is this cause common in?

Answer 8

1) Primarily lifestyle – sedentary lifestyle, diet - high in saturated fats, cholesterol, and trans fats
2) Varies, LDL-C above 100, TG above 150
3) In adults, but also now in kids

Question 9

Secondary or acquired hypercholesterolemia: What are some other causes?

Answer 9

1) Poorly controlled T2DM
2) Metabolic syndrome
3) Hepatic and renal disease
4) Corticosteroid, progestin, anabolic steroids, and ETOH use

Question 10

1) Elevated _________ increases risk ASCVD
2) Elevated __________ decreases risk of ASCVD
3) What is a risk enhancer, factor in metabolic disease, pancreatitis?

Answer 10

1) LDL-C
2) HDL-C
3) Elevated TG

Question 11

List some risk factors for dyslipidemia/ hyperlipidemia

Answer 11

1) Diet (calories, saturated fats)
2) Age
3) Central obesity
4) Exercise
5) Family or personal h/o early CVD - heart, stroke, & peripheral n(carotid, aortic, PAD)
-Men < 55 y/o
-Women < 65 y/o
6) Medications: thiazides, B-blockers, OCPs, OCS
7) Previous diagnosis: pancreatitis, hepatic, & renal disease

Question 12

What are the Sx of dyslipidemia?

Answer 12

Often asymptomatic until ACS, ischemic stroke, claudication, CKD

Question 13

Dyslipidemia PE:
1) What are Xanthomas?
2) Where are Xanthoma palpebrarum?
3) Where are Tendonous xanthomas?

Answer 13

1) Accumulations of lipid laden macrophages in the skin
2) Eyelids
3) Calcaneal tendon

Question 14

Dyslipidemia PE: What is common/normal in patient’s over 50, but in younger patients may be sign of underlying issue – elevated cholesterol, TG, alcohol use?

Answer 14

Arcus senilius

Question 15

What will labs show with dyslipidemia?

Answer 15

1) Increased serum total cholesterol, LDL-C, & TG
2) Decreased serum HDL-C

Question 16

1) Define lipoprotein
2) Give examples

Answer 16

1) Lipoprotein is an assembly of molecules whose function is to transport hydrophobiclipids in watery media including water and extracellular fluid
2) HDL, LDL, IDL, VLDL, ULDL (chylomicrons)

Question 17

Define apolipoprotein and give examples

Answer 17

1) Apolipoprotein is a protein bound to lipids in order to form lipoproteins.
2) Apolipoprotein A, B, C, D, E, H, L, and apolipoprotein(a) are the classes of Apolipoproteins.

Question 18

True or false: Apolipoproteins and lipoproteins are not routinely measured in most patients

Answer 18

True

Question 19

1) What is a standard lipid panel?
2) What 3 things are measured that are not affected by TG levels?
3) What 2 things are affected by recent eating?

Answer 19

1) Calculates LDL-C = TC – (HDL+TG/5) – LDL levels affected by TG levels
2) Direct LDL-C, HDL, & TC
3) TG & calculated LDL-C

Question 20

1) Fasting and non-fasting TC:HDL-C levels appear to have similar prognostic value & association with what?
2) When is fasting recommended?
3) What is best?
4) What does TC mean? What abt TG?

Answer 20

1) CVD outcomes
2) If you are concerned about TG or TGs are > 400 mg/dL & using calculated LDL-C
3) Consistency is best
4) TC= total cholesterol, TG= triglycerides

Question 21

Lipoprotein A:
1) What are elevated levels assoc. with?
2) What is a risk factor?

Answer 21

1) Elevated levels associated with ASCVD
2) ACC: Lpa > 50 mg/dL is a risk enhancing factor

Question 22

Apolipoprotein B (Apo B)
1) What is it?
2) What levels are considered an ASCVD risk enhancer?

Answer 22

1) Major lipoprotein in chylomicrons, VLDL, LDL
2) APO-b >130 mg/dL

Question 23

What are the 5 ACC/AHA steps of recommendations for Tx?

Answer 23

1) Assess risk, det. mgmt group
2) Lifestyle therapies
3) Appropriate-intensity statin
4) Monitor response
5) Non-statin therapy for certain subgroups

Question 24

Use ACC ASCVD calculator to estimate 10-year risk:
What are the 3 main groups of risk factors? Describe each

Answer 24

1) Demographics: Age, Sex, Ethnicity
2) Tests/Labs: BP mm Hg, TC mg/dL, HDL-C mg/dL
3) Medical history: treatment for HTN, DM status, current smoker

(Ask about these in HPI/ROS, PMHx)

Question 25

ACC ASCVD 10-year risk calculator: 1) What is it? 2) Is it a good tool? 3) What does fair calibration mean? 4) How can it be used?

Answer 25

1) 4 pooled cohort risk equations 2) Very good discrimination – ability to discriminate those at high risk from those a lower risk 3) Fair calibration – the equations tend to overestimate actual numeric risk 4) As “opener” in the risk discussion

Question 26

What are the 4 groups of risk of ASCVD over the next 10 years?

Answer 26

1) Low risk: < 5% 2) Borderline risk: 5 - 7.4% 3) Intermediate risk: 7.5 – 19.9 % 4) High risk 20% +

Question 27

What are 2 criticisms of the 10 year ASCVD risk factor calculator?

Answer 27

1) Calculator may overestimate 10-year risk of myocardial infarction and stroke; major influencer is AGE 2) Borderline risk: risk enhancers such as metabolic syndrome, coronary artery calcium score, etc. may favor use of statins

Question 28

The ___________________ diet has the most consistent evidence for cardiovascular disease prevention

Answer 28

Mediterranean

Question 29

List the 3 optimal lifestyle interventions

Answer 29

1) Combination of diet and physical activity counseling to achieve weight loss = improve cardiovascular health 2) Smoking cessation 3) Avoid heavy alcohol consumption

Question 30

What are the 4 Aha/acc statin benefit groups?

Answer 30

1) **Secondary prevention:** Clinical ASCVD 2) **Primary prevention:** Age 20-75, severe elevated cholesterol (LDL-C > 190 mg/dl) 3) **Primary prevention:** Diabetes Mellitus (No ASCVD, non-severe elevated cholesterol; LDL-C 70-189 mg/dL) 4) **Primary prevention:** General pop.; use ASCVD calculator

Question 31

True or false: Secondary prevention is for very high-risk patients (i.e. with ASCVD)

Answer 31

True

Question 32

Secondary prevention: 1) What is the Tx? 2) What is the goal? 3) What may be needed to reach the goal?

Answer 32

1) High intensity statin 2) Goal: LDL-C < 70 mg/dL with secondary Goal of < 55 mg/dL 3) Add on therapy to reach goal

Question 33

Define clinical ASCVD (very high risk)

Answer 33

1) Acute coronary syndrome 2) Previous ischemic stroke 3) Symptomatic peripheral artery disease 4) A patient is also very high risk if he or she has multiple high-risk conditions: like familial hypercholesterolemia, age of at least 65 years, hypertension, diabetes, chronic kidney disease, tobacco use, heart failure, or LDL level greater than 100 mg /dL (2.59 mmol per L) despite maximal statin plus ezetimibe therapy

Question 34

Primary prevention for ages 40-75 y/o w. severely elevated cholesterol (LDL-C > 189 mg/dL): 1) What prevention is recommended? 2) What may be needed? 3) What is the goal if assoc. with familial HC?

Answer 34

1) Maximally tolerated high intensity statin is recommended 2) May need add on therapy to reach goal 3) Same as secondary prevention

Question 35

Describe primary prevention for 40-75 y/o with Diabetes mellitus (No ASCVD; LDL-C 70-189)

Answer 35

Moderate-intensity statin

Question 36

Describe primary prevention for the general population age 40-75 w. no DM or clinical CVD (LDL-C 70-189 mg/dL) based on 10 yr ASCVD risk

Answer 36

1) Low risk (< 5%): lifestyle and risk reduction education, no statin 2) Boarder line risk (5 - 7.4%) + risk enhancing factors: lifestyle, statin may be considered in select patient 3) Intermediate risk (7.5% - 19.9%) – moderate intensity statin 4) High risk (> 20%): high intensity statin

Question 37

Describe primary prevention for age 40-75 y/o w. no ASCVD and no DM

Answer 37

LDL-C < 70 mg/dL: assess lifetime risk, TLC, and monitor

Question 38

2022 ACC recommended LDL-C goals, list them for: 1) General population without heart disease 2) Secondary prevention CVD 3) Very high-risk patients (secondary prevention, familiar hypercholesterolemia or high Lipoprotein(a))

Answer 38

1) LDL-C goal is < 100 mg/dL 2) LDL-C goal is < 70 mg/dL 3) LDL-C goal is < 55 mg/dL

Question 39

Statin intensity and LDL-C reduction: High intensity 1) How much does it reduce LDL? 2) What is the goal for most of these patients? 3) What abt some of these patients? 4) What med?

Answer 39

1) Reduction of LDL-C ~ 50% or more 2) Most patients on high intensity statins have LDL-C goal of < 70 mg/dL 3) Some < 55 mg/dL (secondary prevention, patients with familiar HL) 4) Atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily

Question 40

Statin intensity and LDL-C reduction: Moderate intensity 1) How much does it reduce LDL? 2) What is the goal for most of these patients?

Answer 40

1) Reduction of LDL-C ~ 30-49% 2) Most have LDL-C goal of < 100 mg/dL

Question 41

List the risk enhancing factors that can influence statin decisions

Answer 41

1) + family history of premature ASCVD (male < 55 y/o, female < 65 y/o) 2) persistent elevation of LDL-C levels > 160 mg/dL 3) metabolic syndrome 4) chronic kidney disease 5) a history of pre-eclampsia or premature menopause (< 40 years old) 6) chronic inflammatory disorders (e.g.,  rheumatoid arthritis, psoriasis, SLE, or chronic HIV) 7) high-risk ethnic group (south Asian) 8) TG >175 mg/dL 9) Lipoprotein a (Lp a)> 50 mg/dL, Apolipoprotein b (Apo b)> 130 mg/dL 10) Coronary artery calcium score > zero

Question 42

When is it reasonable to get a coronary artery calcium (CAC) score?

Answer 42

1) Patient is not on a statin 2) Patients 40 to 75 years of age with an LDL-C level of 70 to 189 mg per dL and a 10-year ASCVD risk of 5% to 19.9% if a decision about statin therapy is uncertain

Question 43

Describe how to interpret CAC scores

Answer 43

1) If the CAC score is zero, statin not indicated unless the patient is a cigarette smoker, has diabetes, or has a strong family history of premature ASCVD 2) A CAC score of 1 to 99 suggests elevated risk & statin therapy should be considered, particularly for patients 55 years and older 3) CAC score is >100 or > 75th percentile, statin therapy is indicated

Question 44

Describe monitoring response to therapy

Answer 44

1) Lipid measurement should be repeated four to 12 weeks after initiating or changing dose of a statin to assess adherence & response of LDL-C lowering medications and lifestyle changes 2) When at goal and stable, lipid measurement should be repeated every three to 12 months PRN

Question 45

Monitoring: 1) If you use a statin, LDL-C goal is ______mg/dL 2) Secondary prevention or FHL LDL-C goal is _______ mg/dL 3) What should you do if inadequate response?

Answer 45

1) < 100 2) <55 3) check for patient compliance to Rx and lifestyle may need to titrate statin or add adjunct Rx Ask about side effects … see next slides

Question 46

1) Which statins have a **short** half life? -When do they need to be administered? 2) Which have a **long** half life? -When do they need to be administered?

Answer 46

1) Fluvastatin, lovastatin, pravastatin, simvastatin -At night 2) Atorvastatin, Fluvastatin, Pitavastatin, Rosuvastatin -Any time of day

Question 47

Statin MOA: 1) What does inhibition of HMG-CoA reductase site do? 2) What are the results of this?

Answer 47

1) Blocks the conversion of HMG-CoA to mevalonic acid within the hepatocyte 2) Reduces hepatic cholesterol synthesis which leads to: -Increased cell surface LDL receptor expression & increased clearance of LDL-C by 20% to 55%.

Question 48

 Statins may have additional non–lipid-related effects, such as what?

Answer 48

1) Stabilization of atherosclerotic plaques, anti-inflammatory, immunomodulatory and antithrombotic effects 2) Effects on bone metabolism, and reduced risk of dementia.

Question 49

Adverse effects of statins: Describe the myopathy

Answer 49

1) Myalgias < 10% - but patients complain frequently 2) Myositis or rhabdomyolysis, leading to ARI – rare 3) Usually bilateral achy, weakness, sore, stiff, crampy, tender, +/- general fatigue

Question 50

Besides myopathy, list other side effects of statins

Answer 50

1) Headaches, GI upset, sleep disturbance 2) Transaminase elevations/hepatic toxicity- infrequent/rare 3) New onset T2DM – depends on population – higher risk for T2DM … maybe 4) Cataracts – unclear (no pun intended) 5) CYP metabolism – lots of drug interactions, use Lexicomp or other Rx cross check

Question 51

Statin related muscle Sx: 1) Myalgias 2) Myositis 2) Rhabdomyolysis

Answer 51

1) Myalgias = sore muscles, normal CK … 5-10% of statin users?? 2) Myositis = sore muscles, elevated CK, no myoglobinuria - rare 3) Rhabdomyolysis = sore muscles, elevated CK, + myoglobinuria/acute RI - rare

Question 52

Statins: When do you need to adjust based on CK?

Answer 52

1) Routine CK monitoring is not recommended 2) d/c or adjust statin if CK >10x upper limit of normal

Question 53

Statin related muscle Sx: 1) What should you do before starting statins? 2) What should you do at followups? 3) Why? 4) What can help evaluate side effects?

Answer 53

1) Baseline clinical MSK condition (rather than labs (CK)) 2) Ask at follow up visits “any change in MSK conditions?” -Change statins or dosing 3) Improves compliance 4) ACC tool to evaluate side effects related to statin

Question 54

1) What is Simvastatin most likely to cause? What is the max dose? 2) What 2 meds are least likely to cause this? When should they be used & why?

Answer 54

1) Muscle symptoms; FDA does not recommend dosing beyond 40 mg daily 2) Fluvastatin and Pitavastatin; reserve for patients with true statin intolerance due to muscle soreness Can only achieve moderate intensity statin therapy

Question 55

List the doses for the following moderate intensity statins: 1) Fluvastatin 2) Pitavastatin

Answer 55

1) Fluvastatin XL 80mg, or Fluvastatin 40mg BID 2) Pitavastatin 1-4mg

Question 56

Describe what to do abt statins and cataracts

Answer 56

1) Currently, the benefits of statin therapy outweigh any presumed risk of cataract development. 2) For patients concerned about cataract development, recommend ways to reduce other risk factors such as smoking cessation, reducing ultraviolet sun exposure (sunglasses) & remind patients of the importance of regularly scheduled eye exams

Question 56

Describe non-statin therapy for High-risk patients (>20% 10-year risk of ASCVD and or known ASCVD or FHL)

Answer 56

1) LDL-C goal < 70 mg/dL 2) If LDL-C is > 70 mg/dL on max tolerated statin, consider adding ezetimibe (Zetia) 3) If still above LDL-C goal on max tolerated statin and ezetimibe, then it would be reasonable to consider a PCSK9i following shared decision on net benefit, safety, & cost

Question 57

Ezetimibe (Zetia): 1) What does it do? 2) What dose and when? 3) Is it well tolerated?

Answer 57

1) Inhibits the absorption of cholesterol from the small intestine, thus decreases the amount of cholesterol normally available to hepatocytes, thus leading them to absorb more cholesterol from circulation, thus lowering levels of circulating cholesterol. 2) 10 mg daily, anytime, typically as add on to max tolerated statin if LDL-C not at goal or consider if statin intolerant 3) Generally well tolerated, may increase transaminases but more likely due to statin -Now available in combo pills with statins

Question 58

Pcsk9 inhibitors: 1) How many are there? Name them 2) How are they administered? 3) What do they require? When should they be used?

Answer 58

1) 2 FDA approved drugs: Alirocumab (Praluent) and Evolocumab (Repatha) 2) SQ injection every 2-4 weeks, no dose titration 3) ~14,000 dollars/year: prior authorization Add on therapy when max tolerated statin +/- ezetimibe not at goal LDL-C in highrisk patients

Question 59

1) Describe the site of action/ MOA of statins 2) What are 2 side effects?

Answer 59

1) Hepatocytes -HMG-CoA reductase inhibitor reduces LDL-C in hepatocytes and increases LDL surface receptors. Net effect – lowers LDL 2) Myopathy, transaminase

Question 60

Ezetimibe: 1) What is the site of action/ MOA? 2) Side effect?

Answer 60

1) Small intestines -Reduces absorption of cholesterol 2) Transaminase

Question 61

PSCK9i 1) Site of action/ MOA? 2) Net effect? 3) Side effects?

Answer 61

1) Extracellular -Binds PSCK9 particles, allows for increased LDL receptor recycling, effectively increasing density of LDL recrptor on hepatocyte surface. 2) Lowers LDL levels 3) Injection site irritation, expensive

Question 62

Omega 3 fatty acids: 1) When are they used? 2) Primary MOA?

Answer 62

1) For primary and secondary prevention of ASCVD 2) Modest lowering of TG

Question 63

What did the 2018 Cochrane systemic review find abt omega 3 fatty acids??

Answer 63

1) EPA and DHA has little to no effect on all cause deaths and CV events and probably makes little to no difference to CVD deaths 2) Marine omega-3 FA may have role in elevated TG; Icosapent ethyl

Question 64

Bempedoic Acid (Nexletol): 1) What is it/ when is it used? 2) What is the dose and cost? 3) What is the MOA?

Answer 64

1) FDA approved adjunct to diet + max tolerated statin for treatment ASCVD or familiar hypercholesterolemia in patients requiring additional (beyond statin benefit) LDL-C reduction 2) 180 mg PO daily, 30-day cost ~$ 350 added to existing therapy 3) Inhibits ATP citrate lyase (ACL)

Question 65

Bempedoic Acid (Nexletol): 1) What are the side effects? 2) What is an issue with this?

Answer 65

1) Hyperuricemia, acute gouty arthritis; myalgia, arthralgias; anemia 2) Potential for significant drug interactions; dose limitations for some statins are recommended during concurrent use – recommend using drug interaction software

Question 66

1) Ezetimibe works in the ________ 2) PSCK9i works at the surface of the ____________ effectively increasing LDL-C receptors

Answer 66

1) intestine 2) Hepatocyte

Question 67

Fibric acid Derivatives: What are the 3 effects on lipids?

Answer 67

1) Significant decrease serum TG 2) Moderate reduction in LDL-C 3) Moderate increase in HDL-C

Question 68

List the 3 main parts of the MOA of Fibric acid Derivatives

Answer 68

1) Alter transcription of genes coding for proteins that control lipoprotein metabolism 2) Enhanced catabolism of TG and reduction of secretion of VLDL particles and LDL-C 3) Changes in LDL apolipoprotein expression raises HDL-C levels

Question 69

Describe the side effects of Fibric acid Derivatives

Answer 69

Similar to statins 1) Mild GI upset - dyspepsia 2) Myopathy 3) Decreased synthesis of bile …. Increased risk of gall stones (cholelithiasis)

Question 70

Fibrates/ Fibric acid Derivatives: List 2, and their doses

Answer 70

1) Fenofibrate (TriCor) 200 mg daily 2) Gemfibrozil (Lopid) 600 mg BID

Question 71

Bile acid sequestrants 1) What are they/ what do they do? 2) What is their effect? 3) What are the side effects?

Answer 71

1) Resins that disrupt the enterohepatic circulation of bile acids by combining with bile constituents and preventing their reabsorption from the gut. 2) Minimal to modest lowering of LDL-C No action on TG 3) GI side effects: constipation, gas, bloating, nausea, elevated transaminase

Question 72

How are bile acid sequestrants classified?

Answer 72

In general, they are classified as hypolipidemic agents, although they may be used for purposes other than lowering cholesterol such as chronic diarrhea

Question 73

BLUF 1) When should you use calculation tools to assist in determining initial risk group? What tools specifically? 2) What do you need to eval and manage? 3) Statins are the work horse for what? 4) Describe add on therapy w newer agents

Answer 73

1) Age 40-75; 10-year score to determine initial risk group (low, intermediate, moderate, high risk) 2) Statin intolerance 3) Both primary and secondary prevention of ASCVD 4) May have a role in select patients (high risk) but have ?? Long-term benefit in patient outcomes that matter

Question 74

BLUF: What work in hepatocyte to inhibit production of cholesterol?

Answer 74

Statins

Question 75

Add-on Rxs; list the MOAs for: 1) Ezetimibe 2) PCSK9i 3) Inclisiran 4) Icosapent ethyl

Answer 75

1) Inhibit GI absorption 2) Bind PCSK9 on surface of hepatocyte 3) Reduce production of PSCK9 molecules in hepatocyte 4) Omega3 FA little benefit regarding ASCVD

Question 76

81

Question 77

1) What is associated with increased risk of pancreatitis, risk enhancer for ASCVD? 2) TG level are component criteria for what? 3) TG levels are measured, what are they affected by? How is this applicable clinically?

Answer 77

1) TG > 500 2) Metabolic syndrome; risk enhancers 3) Affected by diet; if non-fasting and elevated, consider repeat with fasting

Question 78

1) What is the first step to addressing elevated TGs? 2) How can this be done non-pharmacologically?

Answer 78

1) Address modifiable risk factors: e.g., T2DM, Rx that raise TG 2) Manage other ASCVD risk factors: HTN, smoking, inactivity -Moderate exercise 150 min/week or vigorous exercise 75 min/week -Diet -EtOH intake

Question 79

Addressing elevated TGs: 1) What should you assess and manage? How? 2) What is the TG goal?

Answer 79

1) LDL-C; statin group 2) TG goal is < 500 mg/dL

Question 80

Addressing elevated TGs: What 2 things should you consider adding to lower it?

Answer 80

1) Consider marine omega-3 FA (Icosapent ethyl) 2) Consider adding fibrate a) Fenofibrate 145 mg PO QD – less risk of myopathy with statins than gemfibrozil

Question 81

Which form of fibrate is recommended more?

Answer 81

Fenofibrate 145 mg PO QD : less risk of myopathy with statins than gemfibrozil

Question 82

What is no longer recommended to Tx high TGs? Why?

Answer 82

Niacin is no longer recommended: too many side effects, questionable efficacy

Question 83

You have a 54 y/o male with PMHx of HTN on ACEi and hydrochlorothiazide and an LDL-C 210 mg/dL. 1) What do you do? 2) What if the pt is already on amlodipine?

Answer 83

1) High intensity statin, try to get below 100 LDL. 2) Probably change drugs before you start a statin, or reduce dose.