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PHRM 844 Module #2 > Pathophysiology and Evaluation of Dyslipidemia > Flashcards

Pathophysiology and Evaluation of Dyslipidemia Flashcards

1
Q

Describe the pathophysiological consequences of hyperlipidemia

A

lipoprotein abnormalities can contribute to increased risk for coronary, cerebrovascular, and peripheral arterial disease
major risk factor for coronary heart disease (CHD); coronary atherosclerosis contributes to ischemic heart disease

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2
Q

Name the major steps in the development of atherosclerotic plaques

A

endothelial injury –> inflammatory response –> macrophage infiltration –> platelet adhesion –> smooth muscle cell proliferation –> extracellular matrix accumulation

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3
Q

Lipids

A

cholesterol
cholesterol esters
triglycerides
phospholipids

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4
Q

Lipoproteins

A

LDL
HDL
VLDL

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5
Q

Apolipoproteins

A

Apo-B
Apo-A1
Apo-CIII

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6
Q

Want to look at these for every patient for screening purposes

A

LDL
HDL
triglycerides

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7
Q

Name the clinical guidelines referenced for treatment of dyslipidemias

A

NCEP ATP III (gold standard)
ACC/AHA guidline on the treatment of blood cholesterol
NLA recommendations for the patient-centered management of dyslipidemia
ACC recommendations for role of non-statin therapy
NLA PCSK9 recommendations
multisociety guideline on the management of blood cholesterol

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8
Q

ACC/AHA guidelines

A

in adults greater than or equal to 20YO with clinical ASCVD or at high-risk of ASCVD what are the magnitude of benefits in individual endpoints and composite ischemia events and magnitude of harm in terms of adverse events derived from LDLc lowering in large RCTs with statin therapy plus a second lipid-modifying agent compared with statin alone

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9
Q

ACC/AHA guideline

A
  1. is it primary or secondary prevention?
  2. is their LDL >190?
  3. does the pt have diabetes?
  4. age
  5. ASCVD risk
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10
Q

Primary prevention

A

pts with no previous ASCVD event
primary hypercholesterolemia, DM, age >75yo
ASCVD risk >/= 20%, high risk

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11
Q

Risk enhancing factors for primary prevention

A

family history of premature ASCVD, persistently elevated LDLc >/=160 mg/dL, CKD, persistently elevated TG >/= 175 mg/dL, pre-eclampsia, premature menopause, inflammatory disease, ethnicity, metabolic syndrome, other elevated labs (apoB, Hs-CRP, Lp(a)), decreased ankle-brachial index

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12
Q

Secondary prevention

A

pts with previous ASCVD event - MI, stable/unstable angina, revascularization, stroke, TIA, PAD, aortic aneurysm

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13
Q

High-risk conditions for secondary prevention

A

age 65 yo or older, heterozygous familial hypercholesterolemia, history of prior CABG or PCI outside of major ASCVD events, DM, hypertension, CKD, current smoker, elevated LDLc despite maximally tolerated statin adn ezetimibe, history of CHF, chronic coronary disease

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14
Q

General pts benefiting from statin use

A

clinical ASCVD at any age, primary hypercholesterolemia LDL >/= 190 mg/dL, pts aged 45-70 yo with DM, familial hypercholesterolemia, pts aged 40-75 w/o DM, risk discussion and clinical decision for other pts with elevated LDLc

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15
Q

Follow-up and monitoring recommendations

A

initiate statin –> follow up in 4-12 weeks until dose stable –> follow up every 3-12 months

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16
Q

Identify common symptoms associated with the clinical presentation of dyslipidemias

A

largely asymptomatic (most pts don’t have symptoms until they really progress)
symptoms: depending on severity and duration of disease: chest pain, palpitations, sweating, anxiety, SOB, loss of consciousness, difficulty with speech or movement, abdominal pain, sudden death

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17
Q

Identify common signs associated with the clinical presentation of dyslipidemias

A

signs: pancreatitis (concerned oncer over 400-500); eruptive xanthomas; peripheral polyneuropathy; increased BP; waist size: >40in in men and >35in in women; BMI > 30 kg/m2

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18
Q

Name lab parameters typically ordered for evaluation, monitoring, and assessment of dyslipidemia

A

increase in non-HDL-C, TC, LDL-C, TG, Apo-B, CRP, LDL-P; decrease in HDL
if not fasting, triglycerides may be higher than they really all

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19
Q

LDL-C

A

amount of cholesterol in LDL particles

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20
Q

LDL-P

A

number of LDL particles; not routinely ordered

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21
Q

Non-HDL-C

A

amount of cholesterol in atherogenic particles; not routinely reported; non-HDL-C = TC - HDL

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22
Q

Apo-B

A

number of atherogenic particles; not routinely ordered

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23
Q

ApoB, LDL-P and Non-HDL-C

A

all valid in non-fasting sample and with elevated TG levels
all more predictive of future CVD risk than LDL-C alone

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24
Q

What is included in a fasting lipid panel

A

TC, TG, HDL-C, LDL-C (calculated using friedewald equation)

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25
Q

Friedewald equation

A

used to estimate LDL from FLP
LDL calculation not valid when TG > 400 mg/dl
LDL = TC - HDL - TG/5

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26
Q

1st step for managment strategies

A

nonpharmacologic treatment

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27
Q

Lifestyle management

A

DASH dietary pattern, USDA food pattern, or AHA diet
reduce percent of calories from saturated and trans fat
lower sodium intake
engage in moderate-to-vigorous intensity aerobic physical activity

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28
Q

DASH dietary pattern, USDA food pattern, or AHA diet

A

vegetables, fruits, and whole grains
low fat dairy products, poultry, fish, legumes
non-tropical vegetable oils and nuts
limits sweets and red meats

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29
Q

Reduce percent of calories from saturated and trans fat

A

5-6% calories from saturated fats (of total calories)

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30
Q

Lower sodium intake

A

<1,500 mg of sodium daily
aim for reduction of at least 1,000 mg/day for most adults

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31
Q

Engage in moderate-to-vigorous intensity aerobic physical activity

A

90-150 minutes of exercise a week
divided into 3-4 sessions/week for about 40 min/session

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32
Q

Recommend appropriate therapeutic lifestyle changes for a patient diagnosed with hyperlipidemia

A

reduced intake of saturated fats and cholesterol
soluble fiber to decrease LDL
plant stanols and sterols
weight reduction
increased physical activity
smoking cessation

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33
Q

Soluble fiber to decrease LDL

A

oat bran
pectins or gums
psyllium products - binds cholesterol in gut and reduced hepatic production and clearance, psyllium seed 10-15 gms daily may decrease TC and LDL by 20%
metamucil

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34
Q

Plant stanols and sterols

A

2-3 gms daily of sterols decrease LDL 6-15%

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35
Q

Weight reduction

A

weight and BMI monitored at each visit
if overweight, 10% weight loss recommended

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36
Q

Increased physical activity

A

moderate intensity activity for 40 min daily 3-4 days a week

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37
Q

Omega-3 fatty acids

A

eating fish once weekly can reduce CV mortality risk
fish oil/omega-3 FAs: EPA/DHA, reduces TG, may increase LDL by 4-49%
most OTC
lovaza (Rx) - 2-4 gms daily or divided BID
vascepa (Rx) - 2 gs PO BID with food; icosapent ethyl, the only triglyceride; risk based nonstatin therapy FDA approved; for ASCVD risk reduction

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38
Q

Pharmacologic treatment options

A

HMG-CoA reductase inhibitors (statins)
bile acid resins (bile acid sequestrants)
niacin
cholesterol absorption inhibitor
fibrates
PCSK9 inhibitors/monoclonal antibodies
inclisiran
bempedoic acid

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39
Q

Effects of pharmacologic agents

A

all decreases serum LDL except for omega-3 FAs (increase 4-49%)
all increase serum HDL
all decrease serum TG

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40
Q

Effects of pharmacologic agents on serum LDL

A

statin: decrease 20-60%
BARs: decrease 15-30%
ezetimibe: decrease 17%
PCSK9 mAb: decrease 60-70%
inclisiran: decrease 48-52%
bempedoic acid: decrease 18%

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41
Q

Effect of pharmacologic agents on serum TG

A

gemfibrozil: decrease 35-50%
fenofibrate: decrease 41-53%
omega-3 FAs: decrease 23-45%
niacin: decrease 25-30%

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42
Q

HMG-CoA reductase inhibitors

A

rate limiting step in our liver when making cholesterol
lovastatin (altoprev, mevacor)
pravastatin (pravachol)
pitavastatin (livalo)
simvastatin (zocor)
fluvastatin (lescol)
atorvastatin (lipitor)
rosuvastatin (crestor)

43
Q

Statin intensity

A

low intensity
moderate intensity
high intensity

44
Q

Low intensity

A

simvastatin 10 mg
pravastatin 10-20 mg
lovastatin 20 mg
fluvastatin 20-40 mg

45
Q

Moderate intensity

A

atorvastatin 10-20 mg
rosuvastatin 5-10 mg
simvastatin 20-40 mg
pravastatin 40-80 mg
lovastatin 40-80 mg
fluvastatin 40 mg BID
fluvastatin XL 80 mg
pitavastatin 1-4 mg

46
Q

High intensity

A

atorvastatin 40-80 mg
rosuvastatin 20-40 mg

47
Q

Properties of statins: lipophilic or hydrophilic

A

lipophilic: fluvastatin, pitavastatin, lovastatin, simvastatin, atorvastatin
hydrophilic: pravastatin, rosuvastatin

48
Q

Properties of statin: CYP450

A

lovastatin, simvastatin, atorvastatin: 3A4, simvastatin also 3A5; cause you to decrease dose of statin or avoid it

49
Q

Statins important considerations

A

usually well tolerated
obtain LFTs at baseline: repeat LFTs when clinically indicated, DC if LFTs 3x upper limit of normal
serious muscle toxicity: myopathy, rhabdomyolysis (more pain involved, proteins released from muscle –> kidney failure)
watch for unusual muscle pain and darkened urine
avoid large quantities of grapefruit juice (>1 quart daily)
contraindicated in pregnancy or to women who may become pregnant

50
Q

Characteristics predispoding individuals to statin adverse effects

A

impaired renal or hepatic function, prior statin intolerance or muscle disorders, unexplained ALT elevations > 3 x ULN, other drugs that affect statin metabolism, >75 years of age

51
Q

Statin adverse effects

A

pt experiences muscle symptoms or fatigue while on statin: DC statin and evaluate for rhabdomyolysis; evaluate for exacerbating conditions; restart same or lower dose statin once symptoms resolve

52
Q

Statin contraindications

A

acute liver disease
unexplained, persistent elevations of serum transaminases
pregnancy
breastfeeding

53
Q

Statins and muscle injury

A

muscle injury is uncommon with statin monotherapy: myalgias 2-11%, myositis 0.5%, rhabdomyolysis <0.1%
may experience myalgias without elevated creatine kinase (CK), CK >10x upper limit of normal, DC statin
risk of muscle injury is increased when taking statins extensively metabolized by CYPA3A4 and drugs that interfere with CYP3A4: trial CoQ10 150-200 to help prevent adverse muscle side effects

54
Q

Managment of muscle injury from statins

A

ensure pt has valid indications for statins; assess is muscle pain is excerise related; DC statin and see if muscle pain resolves; switch to lower risk statin (hydrophilic); consider alternative dosing strategies; consider DC the statin/using alternative agents

55
Q

Statin alternative dosing strategies

A

every other day and once weekly statin dosing
for atorvastatin, fluvastatin, and rosuvastatin - double daily dose is necessary for every other day dosing to achieve similar LDL lowering

56
Q

Contraindicated with simvastatin

A

itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine, danazol

57
Q

Simvastatin considerations

A

do not exceed 10 mg simvastatin daily with: verapamil, diltiazem
do not exceed 20 mg simvastatin daily with amiodarone, amlodipine, ranolazine

58
Q

Statin and hyperglycemia

A

although it increases BS, benefit outweighs this risk

59
Q

Statin monitoring

A

FLP: baseline, 4-12 weeks following statin initiation, every 3-12 months as clinically indicated
consider: baseline CK in individuals with increased risk of adverse muscle effects, CK while on statin therapy in individuals with muscle symptoms, hepatic function in individuals with s/sxs of hepatoxicity

60
Q

Bile acid resins (BARs)

A

traps the bile, liver uses cholesterol to try to get more bile to be created, decrease cholesterol
cholestyramine (questran, prevalite)
colestipol (colestid)
colesevelam (welChol)

61
Q

BARs

A

decrease LDL and cholesterol
disadvantages: may increase TG, take other meds 1 hour before or 4 hrs after BAR

62
Q

BARs adverse effects

A

GI side effects: constipation, bloating, nausea, flatulence
AEs: impaired absorption of fat-soluble vitamins (A, D, E, K), hypernatremia, hyperchloremia, GI obstruction

63
Q

BAR contraindications

A

cholestyramine: complete biliary obstruction
colesevelam: Hx bowel obstruction, serum TG > 500 mg/dL, Hx hypertriglyceridemia-induced pancreatitis

64
Q

BARs interactions

A

may decrease effect of: acetaminophen, TZDs, oral contraceptives, corticosteroids, ezetimibe, fibrates, thiazide diuretics, warfarin, digoxin

65
Q

Niacin

A

niacor, niaspan, slo-niacin
numerous OTC products: not federally regulated in the US; preparations marked “no flush” may have no free nicotinic acid and are ineffective in treating dyslipidemia; some sustained-release formulations are associated with an increased risk of hepatotoxicity

66
Q

Niacin prostaglandin mediated flushing and itching

A

to prevent flushing: administer: ASA 325 mg 30 min before taking niacin, take close to meal times, avoid alcohol and hot drinks which worsen flushing, start with lower doses and titrate up slowly, increase LFTs, hyperuricemia and hyperglycemia, may increase levels of statins

67
Q

Niacin contraindications

A

active hepatic disease
significant or unexplained persistent liver transaminase elevations
active peptic ulcer
arterial hemorrhage

68
Q

Cholesterol absorption inhibitor

A

ezetimibe (zetia)
combo product with simvastatin - vytorin
can further decrease LDL by 12-20% when combined with statin therapy

69
Q

Ezetimibe adverse effects

A

fatigue, diarrhea, GI upset

70
Q

Ezetimibe contraindications

A

concomitant use with a statin and active hepatic disease or unexplained persistent serum transaminase elevations
pregnancy (when used concomitantly with a statin)
breastfeeding (when used concomitantly with a statin)

71
Q

Fibrates

A

typically for your elevated TGs

72
Q

Fibrates side effects and contraindications

A

SEs: GI disturbances, rash, myalgia, dizziness
contraindications: history of gallbladder disease, ESRD or dialysis, persistent liver disease

73
Q

Fibrates increase levels of

A

statins, ezetimibe, sulfonylureas, warfarin

74
Q

PCSK9 monoclonal antibodies

A

alirocumab (praluent) and evolocumab (repatha)
indication: adjunct to diet and statin to reduce LDL in familial heterozygous hypercholesterolemia or atherosclerotic CVD

75
Q

PCSK9 monoclonal antibodies MOA

A

SQ injection that inhibits the binding of PCSK9 to LDL receptors and upregulate the recycling of LDL receptors, resulting in a drastic decrease in LDLc (43-64% reduction)

76
Q

PCSK9 monoclonal antibodies adverse effects

A

GI upset, increased LFTs, injection site rxn, myalgia, influenza

77
Q

PCSK9 mAbs should be considered for

A

ASCVD (on maximally tolerated statin therapy +/- ezetimibe and LDLc greater than or equal to 70 mg/dL or non-HDLc greater than or equal to 100 mg/dL)
very high risk/statin intolerance
further reduction of LDLc if pretreatment LDLc is greater than or equal to 190 (on maximally-tolerated statin therapy ezetimibe)

78
Q

Inclisiran

A

leqvio
decrease LDL and cholesterol
indication: adjunct to diet and statin to reduce LDL in familial heterozygous hypercholesterolemia or atherosclerotic CVD

79
Q

Inclisiran MOA

A

long-acting synthetic small interfering ribonucleic acid (siRNA) that inhibits translation of PCSK9 protein thus inhibiting PCSK9 production
this prolongs the activity of LDL receptors

80
Q

Inclisiran adverse effects

A

injection site reactions
arthralgia
urinary tract infection
diarrhea
bronchitis
pain in extremities
dyspnea

81
Q

Inclisiran dosing

A

initial dose of one prefilled syringe of leqvio 284 mg/1.5mL, then another at 3 months
every 6 months (2 doses a year)

82
Q

Bempedoic acid

A

nexletol, nexlizet
indication: adjunct to diet and statin to reduce LDL in familial heterozygous hypercholesterolemia or atherosclerotic CVD

83
Q

Bempedoic acid adverse reactions and warnings/precautions

A

AEs: URTI, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, and elevated liver enzymes
warning and precautions: may increase blood uric acid levels and lead to the development of gout; risk of tendon rupture; avoid concomitant use with simvastatin >20mg and pravastatin >40mg (myopathy)

84
Q

Bempedoic acid MOA

A

bempedoic acid CoA inhibits ACLY and therefore cholesterol synthesis

85
Q

Red yeast rice

A

active ingredient: lovastatin
shown to lower TC, LDLc, and TG as well as CV events and total mortality; possibly increases HDLc
same AEs, interactions, and precautions as statins
no regulation of active ingredient strength
no recommendations by ACC/AHA for its use

86
Q

lomitapide

A

juxtapid
microsomal truglyceride transfer protein inihibitor indicated as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis to reduce LDLc, TC, apo B and non-HDLc in pts with homozygous familial hypercholesterolemia
only available through REMS program
boxed warning for hepatotoxicity

87
Q

Lomitapide MOA

A

directly binds and inhibits microsomal triglyceride transfer protein, preventing assembly of apo B containing lipoprotiens in enterocytes and hepatocytes –> inhibits synthesis of chylomicrons and VLDL –> leads to reduced levels of plasma LDLc

88
Q

Evinacumab

A

evkeeza
recombinant human monoclonal antibody indicated as an adjunct to other lipid-lowering therapies to reduce LDLc in adults and pediatric pts (>12YO) with homozygous familial hypercholesterolemia

89
Q

Evinacumab MOA

A

binds to and inhibits ANGPTL3 (angiopoietin-like protein 3) and rescues/allows LPL and EL to promote VLDL processing and clearance of LDL formation

90
Q

Coronary artery calcium (CAC) test

A

tests how much calcium buildup they have
CT of chest to measure calcium buildup; use rarely if risk decision is uncertain to determine initiation of statin
CAC = 0: assess other risk factors to determine need
CAC = 1-99: favors statin therapy, especially age 55+
CAC>/= 100: initiate at least moderate-intensity statin

91
Q

Pt groups considered for non-statin treatment

A

want to maximize statin does 1st, then consider adding secondary agent
age </= 75 w/ clinical ASCVD on statin for secondary prevention - consider PCSK9
age >/= 21 w/o clinical ASCVD on statin for primary prevention - add ezetimibe if LDL > 100 mg/dL
age 40-75 w/o clinical ASCVD and w/ DM on statin for primary prevention - add ezetimibe if ASCVD risk >20%

92
Q

Non-statin recommendations (after maximally tolerated statin)

A

1st line
2nd line
other

93
Q

1st line

A

ezetimibe
use if LDL is not at goal according to condition, or if pts with DM have an ASCVD risk of 20%

94
Q

2nd line

A

PCSK9 inhibitors
can consider if LDL and/or non-HDL still not at goal
also may be considered if pts cannot tolerate statin and/or ezetimibe

95
Q

Other

A

BAS - bile acid sequestrants
ACC/AHA: if <50% reduction in LDLc on maxiamlly tolerated statin + ezetimibe and have TG >/= 300 mg/dL

96
Q

Categories of hypertriglyceridemia

A

persistent hypertriglyceridemia
moderate
severe

97
Q

Persistent hypertriglyceridemia

A

fasting TG > 150 mg/dL following at least 4-12 weeks of lifestyle intervention, a stable dose of a maximally tolerated statin and a secondary cause evaluation

98
Q

Moderate (150-499 mg/dL)

A

excess TGs carried in very low-density lipoprotein (VLDL)

99
Q

Severe (>500 mg/dL)

A

excess TGs carried in VLDL and chylomicrons
VLDL is atherogenic, elevated chylomicrons impart increased risk of acute pancreatitis

100
Q

Secondary factors in those >/= 20yo with moderate hypertriglyceridemia

A

lifestyle: obesity, metabolic syndrome, excess alcohol use
secondary disorders: DM, hypothyroidism, chronic liver disease, CKD, nephrotic syndrome

101
Q

Lifestyle modifications to reduce TG

A

targeting 5-10% weight loss = 20% decrease in TG
very low fat dieat (10-15% of diet), restriction of alcohol, sugar, and refined carbs
moderate or higher intensity physical activity (>/=150 min per week) = 20-50% decrease in TG

102
Q

Pharmacologic treatment of TG

A

use of statin therapy in moderate and severe hypertriglyceridemia
other therapies in severe hypertriglyceridemia: initiate statin tx + fibrate OR omega-3 FAs

103
Q

Pharmacologic treatment of TG

A

although statins are known to reduce TGs, they alone cannot prevent acute pancreatitis in the setting of secondary causes
fibrates or omega-3 FAs are the go-to pharmacological therapies to decrease the risk of acute pancreatitis
ACC/AHA guidelines give passing mention to niacin as a TG lowering therapy but do not explicitly recommend it

PHRM 844 Module #2 (23 decks)

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