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

Pathophysiology and Evaluation of Dyslipidemia Flashcards

(103 cards)

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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
Friedewald equation
used to estimate LDL from FLP LDL calculation not valid when TG > 400 mg/dl LDL = TC - HDL - TG/5
26
1st step for managment strategies
nonpharmacologic treatment
27
Lifestyle management
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
28
DASH dietary pattern, USDA food pattern, or AHA diet
vegetables, fruits, and whole grains low fat dairy products, poultry, fish, legumes non-tropical vegetable oils and nuts limits sweets and red meats
29
Reduce percent of calories from saturated and trans fat
5-6% calories from saturated fats (of total calories)
30
Lower sodium intake
<1,500 mg of sodium daily aim for reduction of at least 1,000 mg/day for most adults
31
Engage in moderate-to-vigorous intensity aerobic physical activity
90-150 minutes of exercise a week divided into 3-4 sessions/week for about 40 min/session
32
Recommend appropriate therapeutic lifestyle changes for a patient diagnosed with hyperlipidemia
reduced intake of saturated fats and cholesterol soluble fiber to decrease LDL plant stanols and sterols weight reduction increased physical activity smoking cessation
33
Soluble fiber to decrease LDL
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
34
Plant stanols and sterols
2-3 gms daily of sterols decrease LDL 6-15%
35
Weight reduction
weight and BMI monitored at each visit if overweight, 10% weight loss recommended
36
Increased physical activity
moderate intensity activity for 40 min daily 3-4 days a week
37
Omega-3 fatty acids
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
38
Pharmacologic treatment options
HMG-CoA reductase inhibitors (statins) bile acid resins (bile acid sequestrants) niacin cholesterol absorption inhibitor fibrates PCSK9 inhibitors/monoclonal antibodies inclisiran bempedoic acid
39
Effects of pharmacologic agents
all decreases serum LDL except for omega-3 FAs (increase 4-49%) all increase serum HDL all decrease serum TG
40
Effects of pharmacologic agents on serum LDL
statin: decrease 20-60% BARs: decrease 15-30% ezetimibe: decrease 17% PCSK9 mAb: decrease 60-70% inclisiran: decrease 48-52% bempedoic acid: decrease 18%
41
Effect of pharmacologic agents on serum TG
gemfibrozil: decrease 35-50% fenofibrate: decrease 41-53% omega-3 FAs: decrease 23-45% niacin: decrease 25-30%
42
HMG-CoA reductase inhibitors
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
Statin intensity
low intensity moderate intensity high intensity
44
Low intensity
simvastatin 10 mg pravastatin 10-20 mg lovastatin 20 mg fluvastatin 20-40 mg
45
Moderate intensity
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
High intensity
atorvastatin 40-80 mg rosuvastatin 20-40 mg
47
Properties of statins: lipophilic or hydrophilic
lipophilic: fluvastatin, pitavastatin, lovastatin, simvastatin, atorvastatin hydrophilic: pravastatin, rosuvastatin
48
Properties of statin: CYP450
lovastatin, simvastatin, atorvastatin: 3A4, simvastatin also 3A5; cause you to decrease dose of statin or avoid it
49
Statins important considerations
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
Characteristics predispoding individuals to statin adverse effects
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
Statin adverse effects
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
Statin contraindications
acute liver disease unexplained, persistent elevations of serum transaminases pregnancy breastfeeding
53
Statins and muscle injury
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
Managment of muscle injury from statins
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
Statin alternative dosing strategies
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
Contraindicated with simvastatin
itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine, danazol
57
Simvastatin considerations
do not exceed 10 mg simvastatin daily with: verapamil, diltiazem do not exceed 20 mg simvastatin daily with amiodarone, amlodipine, ranolazine
58
Statin and hyperglycemia
although it increases BS, benefit outweighs this risk
59
Statin monitoring
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
Bile acid resins (BARs)
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
BARs
decrease LDL and cholesterol disadvantages: may increase TG, take other meds 1 hour before or 4 hrs after BAR
62
BARs adverse effects
GI side effects: constipation, bloating, nausea, flatulence AEs: impaired absorption of fat-soluble vitamins (A, D, E, K), hypernatremia, hyperchloremia, GI obstruction
63
BAR contraindications
cholestyramine: complete biliary obstruction colesevelam: Hx bowel obstruction, serum TG > 500 mg/dL, Hx hypertriglyceridemia-induced pancreatitis
64
BARs interactions
may decrease effect of: acetaminophen, TZDs, oral contraceptives, corticosteroids, ezetimibe, fibrates, thiazide diuretics, warfarin, digoxin
65
Niacin
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
Niacin prostaglandin mediated flushing and itching
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
Niacin contraindications
active hepatic disease significant or unexplained persistent liver transaminase elevations active peptic ulcer arterial hemorrhage
68
Cholesterol absorption inhibitor
ezetimibe (zetia) combo product with simvastatin - vytorin can further decrease LDL by 12-20% when combined with statin therapy
69
Ezetimibe adverse effects
fatigue, diarrhea, GI upset
70
Ezetimibe contraindications
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
Fibrates
typically for your elevated TGs
72
Fibrates side effects and contraindications
SEs: GI disturbances, rash, myalgia, dizziness contraindications: history of gallbladder disease, ESRD or dialysis, persistent liver disease
73
Fibrates increase levels of
statins, ezetimibe, sulfonylureas, warfarin
74
PCSK9 monoclonal antibodies
alirocumab (praluent) and evolocumab (repatha) indication: adjunct to diet and statin to reduce LDL in familial heterozygous hypercholesterolemia or atherosclerotic CVD
75
PCSK9 monoclonal antibodies MOA
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
PCSK9 monoclonal antibodies adverse effects
GI upset, increased LFTs, injection site rxn, myalgia, influenza
77
PCSK9 mAbs should be considered for
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
Inclisiran
leqvio decrease LDL and cholesterol indication: adjunct to diet and statin to reduce LDL in familial heterozygous hypercholesterolemia or atherosclerotic CVD
79
Inclisiran MOA
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
Inclisiran adverse effects
injection site reactions arthralgia urinary tract infection diarrhea bronchitis pain in extremities dyspnea
81
Inclisiran dosing
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
Bempedoic acid
nexletol, nexlizet indication: adjunct to diet and statin to reduce LDL in familial heterozygous hypercholesterolemia or atherosclerotic CVD
83
Bempedoic acid adverse reactions and warnings/precautions
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
Bempedoic acid MOA
bempedoic acid CoA inhibits ACLY and therefore cholesterol synthesis
85
Red yeast rice
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
lomitapide
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
Lomitapide MOA
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
Evinacumab
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
Evinacumab MOA
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
Coronary artery calcium (CAC) test
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
Pt groups considered for non-statin treatment
want to maximize statin does 1st, then consider adding secondary agent 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
Non-statin recommendations (after maximally tolerated statin)
1st line 2nd line other
93
1st line
ezetimibe use if LDL is not at goal according to condition, or if pts with DM have an ASCVD risk of 20%
94
2nd line
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
Other
BAS - bile acid sequestrants ACC/AHA: if <50% reduction in LDLc on maxiamlly tolerated statin + ezetimibe and have TG >/= 300 mg/dL
96
Categories of hypertriglyceridemia
persistent hypertriglyceridemia moderate severe
97
Persistent hypertriglyceridemia
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
Moderate (150-499 mg/dL)
excess TGs carried in very low-density lipoprotein (VLDL)
99
Severe (>500 mg/dL)
excess TGs carried in VLDL and chylomicrons VLDL is atherogenic, elevated chylomicrons impart increased risk of acute pancreatitis
100
Secondary factors in those >/= 20yo with moderate hypertriglyceridemia
lifestyle: obesity, metabolic syndrome, excess alcohol use secondary disorders: DM, hypothyroidism, chronic liver disease, CKD, nephrotic syndrome
101
Lifestyle modifications to reduce TG
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
Pharmacologic treatment of TG
use of statin therapy in moderate and severe hypertriglyceridemia other therapies in severe hypertriglyceridemia: initiate statin tx + fibrate OR omega-3 FAs
103
Pharmacologic treatment of TG
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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