Dyslipidemia Flashcards
1) Define hyperlipidemia/dyslipidemia
2) What is the goal with Tx?
3) Is it preventable?
4) Is it addressed in isolation?
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
1) Chylomicrons transport fats from the intestinal mucosa to the __________.
2) What do they then do?
3) When does LDL-C form?
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
LDL-C delivers fat and cholesterol to the cells (endothelium of vessels), which when oxidized forms fatty streaks and __________________, leading to atherosclerosis
atheromatous plaques
What does high LDL result in?
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”
What results in bruits? What are bruits a sign of?
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
What can HDL-C do?
Carry fat and cholesterol back to the liver for excretion and high HDL-C levels can remove cholesterol from atheromatous plaques and stabilize them
Familial hypercholesterolemia:
1) What is it?
2) What will labs show?
3) What is it a common cause of?
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
Secondary or acquired hypercholesterolemia
1) What is the main cause?
2) What will the labs show?
3) Who is this cause common in?
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
Secondary or acquired hypercholesterolemia: What are some other causes?
1) Poorly controlled T2DM
2) Metabolic syndrome
3) Hepatic and renal disease
4) Corticosteroid, progestin, anabolic steroids, and ETOH use
1) Elevated _________ increases risk ASCVD
2) Elevated __________ decreases risk of ASCVD
3) What is a risk enhancer, factor in metabolic disease, pancreatitis?
1) LDL-C
2) HDL-C
3) Elevated TG
List some risk factors for dyslipidemia/ hyperlipidemia
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
What are the Sx of dyslipidemia?
Often asymptomatic until ACS, ischemic stroke, claudication, CKD
Dyslipidemia PE:
1) What are Xanthomas?
2) Where are Xanthoma palpebrarum?
3) Where are Tendonous xanthomas?
1) Accumulations of lipid laden macrophages in the skin
2) Eyelids
3) Calcaneal tendon
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?
Arcus senilius
What will labs show with dyslipidemia?
1) Increased serum total cholesterol, LDL-C, & TG
2) Decreased serum HDL-C
1) Define lipoprotein
2) Give examples
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)
Define apolipoprotein and give examples
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.
True or false: Apolipoproteins and lipoproteins are not routinely measured in most patients
True
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?
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
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?
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
Lipoprotein A:
1) What are elevated levels assoc. with?
2) What is a risk factor?
1) Elevated levels associated with ASCVD
2) ACC: Lpa > 50 mg/dL is a risk enhancing factor
Apolipoprotein B (Apo B)
1) What is it?
2) What levels are considered an ASCVD risk enhancer?
1) Major lipoprotein in chylomicrons, VLDL, LDL
2) APO-b >130 mg/dL
What are the 5 ACC/AHA steps of recommendations for Tx?
1) Assess risk, det. mgmt group
2) Lifestyle therapies
3) Appropriate-intensity statin
4) Monitor response
5) Non-statin therapy for certain subgroups
Use ACC ASCVD calculator to estimate 10-year risk:
What are the 3 main groups of risk factors? Describe each
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)
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?
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
What are the 4 groups of risk of ASCVD over the next 10 years?
1) Low risk: < 5%
2) Borderline risk: 5 - 7.4%
3) Intermediate risk: 7.5 – 19.9 %
4) High risk 20% +
What are 2 criticisms of the 10 year ASCVD risk factor calculator?
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
The ___________________ diet has the most consistent evidence for cardiovascular disease prevention
Mediterranean
List the 3 optimal lifestyle interventions
1) Combination of diet and physical activity counseling to achieve weight loss = improve cardiovascular health
2) Smoking cessation
3) Avoid heavy alcohol consumption
What are the 4 Aha/acc statin benefit groups?
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
True or false: Secondary prevention is for very high-risk patients (i.e. with ASCVD)
True
Secondary prevention:
1) What is the Tx?
2) What is the goal?
3) What may be needed to reach the goal?
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
Define clinical ASCVD (very high risk)
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
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?
1) Maximally tolerated high intensity statin is recommended
2) May need add on therapy to reach goal
3) Same as secondary prevention
Describe primary prevention for 40-75 y/o with Diabetes mellitus (No ASCVD; LDL-C 70-189)
Moderate-intensity statin
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
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
Describe primary prevention for age 40-75 y/o w. no ASCVD and no DM
LDL-C < 70 mg/dL: assess lifetime risk, TLC, and monitor
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))
1) LDL-C goal is < 100 mg/dL
2) LDL-C goal is < 70 mg/dL
3) LDL-C goal is < 55 mg/dL
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?
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
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?
1) Reduction of LDL-C ~ 30-49%
2) Most have LDL-C goal of < 100 mg/dL
List the risk enhancing factors that can influence statin decisions
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 ofpre-eclampsiaor 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
When is it reasonable to get a coronary artery calcium (CAC) score?
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
Describe how to interpret CAC scores
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
Describe monitoring response to therapy
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
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?
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
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?
1) Fluvastatin, lovastatin, pravastatin, simvastatin
-At night
2) Atorvastatin, Fluvastatin, Pitavastatin, Rosuvastatin
-Any time of day
Statin MOA:
1) What does inhibition of HMG-CoA reductase site do?
2) What are the results of this?
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%.
Statins may have additional non–lipid-related effects, such as what?
1) Stabilization of atherosclerotic plaques, anti-inflammatory, immunomodulatory and antithrombotic effects
2) Effects on bone metabolism, and reduced risk of dementia.
Adverse effects of statins: Describe the myopathy
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
Besides myopathy, list other side effects of statins
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
Statin related muscle Sx:
1) Myalgias
2) Myositis
2) Rhabdomyolysis
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
Statins: When do you need to adjust based on CK?
1) Routine CK monitoring is not recommended
2) d/c or adjust statin if CK >10x upper limit of normal
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?
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
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?
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
List the doses for the following moderate intensity statins:
1) Fluvastatin
2) Pitavastatin
1) Fluvastatin XL 80mg, or Fluvastatin 40mg BID
2) Pitavastatin 1-4mg
Describe what to do abt statins and cataracts
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
Describe non-statin therapy for High-risk patients (>20% 10-year risk of ASCVD and or known ASCVD or FHL)
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
Ezetimibe (Zetia):
1) What does it do?
2) What dose and when?
3) Is it well tolerated?
1) Inhibits the absorption of cholesterol from thesmall 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
Pcsk9 inhibitors:
1) How many are there? Name them
2) How are they administered?
3) What do they require? When should they be used?
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
1) Describe the site of action/ MOA of statins
2) What are 2 side effects?
1) Hepatocytes
-HMG-CoA reductase inhibitor reduces LDL-C in hepatocytes and increases LDL surface receptors. Net effect – lowers LDL
2) Myopathy, transaminase
Ezetimibe:
1) What is the site of action/ MOA?
2) Side effect?
1) Small intestines
-Reduces absorption of cholesterol
2) Transaminase
PSCK9i
1) Site of action/ MOA?
2) Net effect?
3) Side effects?
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
Omega 3 fatty acids:
1) When are they used?
2) Primary MOA?
1) For primary and secondary prevention of ASCVD
2) Modest lowering of TG
What did the 2018 Cochrane systemic review find abt omega 3 fatty acids??
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
Bempedoic Acid (Nexletol):
1) What is it/ when is it used?
2) What is the dose and cost?
3) What is the MOA?
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)
Bempedoic Acid (Nexletol):
1) What are the side effects?
2) What is an issue with this?
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
1) Ezetimibe works in the ________
2) PSCK9i works at the surface of the ____________ effectively increasing LDL-C receptors
1) intestine
2) Hepatocyte
Fibric acid Derivatives: What are the 3 effects on lipids?
1) Significant decrease serum TG
2) Moderate reduction in LDL-C
3) Moderate increase in HDL-C
List the 3 main parts of the MOA of Fibric acid Derivatives
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
Describe the side effects of Fibric acid Derivatives
Similar to statins
1) Mild GI upset - dyspepsia
2) Myopathy
3) Decreased synthesis of bile …. Increased risk of gall stones (cholelithiasis)
Fibrates/ Fibric acid Derivatives: List 2, and their doses
1) Fenofibrate (TriCor) 200 mg daily
2) Gemfibrozil (Lopid) 600 mg BID
Bile acid sequestrants
1) What are they/ what do they do?
2) What is their effect?
3) What are the side effects?
1) Resins that disrupt theenterohepatic circulationofbile acidsby 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
How are bile acid sequestrants classified?
In general, they are classified ashypolipidemic agents, although they may be used for purposes other than lowering cholesterol such as chronic diarrhea
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
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
BLUF: What work in hepatocyte to inhibit production of cholesterol?
Statins
Add-on Rxs; list the MOAs for:
1) Ezetimibe
2) PCSK9i
3) Inclisiran
4) Icosapent ethyl
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
81
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?
1) TG > 500
2) Metabolic syndrome; risk enhancers
3) Affected by diet; if non-fasting and elevated, consider repeat with fasting
1) What is the first step to addressing elevated TGs?
2) How can this be done non-pharmacologically?
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
Addressing elevated TGs:
1) What should you assess and manage? How?
2) What is the TG goal?
1) LDL-C; statin group
2) TG goal is < 500 mg/dL
Addressing elevated TGs: What 2 things should you consider adding to lower it?
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
Which form of fibrate is recommended more?
Fenofibrate 145 mg PO QD : less risk of myopathy with statins than gemfibrozil
What is no longer recommended to Tx high TGs? Why?
Niacin is no longer recommended: too many side effects, questionable efficacy
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?
1) High intensity statin, try to get below 100 LDL.
2) Probably change drugs before you start a statin, or reduce dose.
