DYSLIPIDEMIA

Question 1

*high total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglycerides
*low high-density lipoprotein (HDL) cholesterol
*a combination of these abnormalities

Answer 1

dyslipidemia

Question 2

familial history

Answer 2

genetic predisposition for:
dyslipidemia,
hypertension, &
type II diabetes

Question 3

diabetes mellitus

Answer 3

glucose excess alters endothelial cell metabolism
↓
direct damage to arterial endothelium

Question 4

hypertension

Answer 4

chronic, high-pressure forces act on the artery wall
↓
direct damage to arterial endothelium

Question 5

smoking

Answer 5

inhaled free radicals enter the blood
↓
direct damage to arterial endothelium

worsens dyslipidemia via unclear mechanisms
↓
dyslipidemia (high LDL, low HDL)
↓
more LDL diffuses across damaged endothelium, & accumulate in the intima layer of the artery wall
↓
LDL in intima is oxidized into lipids that trigger chronic inflammation in the vessel wall
↓
inflammation recruits monocytes into the vessel wall, which then differentiate into macrophages
↓
macrophages phagocytose the oxidized LDL & become filled with fat, called “foam cells”
↓
over time, foam cells accumulate in the intima to form an enlarging “lipid core”, fibrous connective tissue accumulates around the lipid core, forming “fibrous cap”
↓
development of “atheroma” (lipid filled plaque that can enlarge & eventually impinge on the vessel lumen) in the artery wall (ATHEROSCLEROSIS)

Question 6

LDL in intima is oxidized into lipids that trigger chronic inflammation in the vessel wall

Answer 6

Elevation of systemic markers of inflammation

*can be evaluated as an independent predictor of atherosclerosis:
Elevated Serum CRP

Question 7

macrophages phagocytose the oxidized LDL & become filled with fat, called “foam cells”

Answer 7

streaks of fatty tissue can be observed b/w the endothelium & the smooth muscle layer (media) of the artery

*seen on pathological specimens, early indicator of developing atherosclerosis:
Fatty Streaks

Question 8

over time, foam cells accumulate in the intima to form an enlarging “lipid core”, fibrous connective tissue accumulates around the lipid core, forming “fibrous cap”

Answer 8

foam cells can also release many inflammatory mediators w/c ↑ proliferation of media smooth muscle cells

cells detach, enter the lipid core & further enlarge it

Question 9

development of “atheroma” (lipid filled plaque that can enlarge & eventually impinge on the vessel lumen) in the artery wall (ATHEROSCLEROSIS)

Answer 9

the atheroma can calcify & further enlarge, & can either remain stable (not rapture) or rupture

complications of atherosclerosis

Question 10

*aids in the transport of LDL from the periphery back to the liver for breakdown

Answer 10

HDL

Question 11

allow for more rapid accumulation of LDL in the vessel walls

Answer 11

low levels of HDL

Question 12

a condition where the arteries become narrowed and hardened due to the buildup of fatty deposits, cholesterol, and other substances (called plaque) on the artery walls

Answer 12

Atherosclerosis

Question 13

atherosclerosis

if the plaque’s fibrous cap remains stable (does not rapture)

Answer 13

↓
plaque expansion intrudes into lumen of the blood vessel, severely occluding blood flow
↓
persistent O2 supply-demand mismatch, especially on exertion
↓ ↓
coronary stable angina
artery
stenosis on
angiography
↓
embolization of thrombotic material on plaque
↓
transient ischemic attack (TIA)
↓
aorta➔ vessel occlusion & calcification/ weakening of the aortic wall ➔ parts of the wall bulge out ➔ Aortic Aneurysm (can rapture & hemorrhage)
↓
legs➔ occlusion of iliac, popliteal, or other leg arteries ➔ peripheral vascular disease ( can lead to claudication, gangrene & amputation)

Question 14

-refers to pain, cramping, or discomfort in the muscles, typically in the legs
-Often a symptom of peripheral artery disease (PAD), a condition where the arteries in the legs become narrowed or blocked due to atherosclerosis (plaque buildup).

Answer 14

Claudication

Question 15

atherosclerosis

rupture of the fibrous cap overlying the atheromatous plaque

Answer 15

⬇
the rough surfaces of the fibrous cap & the contents of the lipid core are exposed to the lumen of the artery with local activation of coagulation pathway
⬇ ⬇
thrombosis embolism of
at rupture thrombus
site
⬊ ⬋
Acute Coronary Syndrome (ACS)
⬇ ⬇
if no myocyte if myocytes have
death died
⬇ ⬇
unstabe angina myocardial
infarction (MI)
⬊ ⬋
total occlusion of artery lumen
⬇
cerebrovascular accident (CVA)
aka Stroke

Question 16

thrombus

Answer 16

blood clot

Question 17

thrombosis

Answer 17

formation of blood clot

Question 18

embolism

Answer 18

movement of the clot (thrombus) to a different part of the body where it causes blockage

Question 19

primary chylomicronemia (familial lipoprotein lipase, cofactor deficiency, other)

Answer 19

chylomicrons, VLDL increased

Question 20

familial hypertriglyceridemia

Answer 20

VLDL increased
Chylomicrons may be increased

Question 21

familial combined hyperlipoproteinemia

Answer 21

VLDL predominantly ⬆
LDL predominantly ⬆
VLDL, LDL ⬆

Question 22

familial dysbetalipoproteinemia

Answer 22

VLDL remnants,
Chylomicrons remnants ⬆

Question 23

familial hypercholesterolemia
heterozygous

Answer 23

LDL ⬆

Question 24

familial hypercholesterolemia
HOMOZYGOUS

Answer 24

LDL ⬆

Question 25

familial ligand-defective apoB-100

Answer 25

LDL ⬆

Question 26

Lp(a) hyperlipoproteinemia

Answer 26

Lp(a) ⬆

Question 27

primary hyperlipoproteinemias type : lipoprotein elevation:

Answer 27

I chylomicrons IIa LDL IIb LDL + VLDL III IDL (LDL1) IV VLDL V VLDL + Chylomicrons

Question 28

HMG-CoA Reductase Inhibitors (STATINS) chemistry:

Answer 28

*structural analogs of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) *Pravastatin, Simvastatin- chemically modified derivatives of Lovastatin *Lovastatin, Simvastatin- inactive Lactone prodrugs, hydrolyzed in the GIT to open B-hydroxyl derivatives *Pravastatin- open, active Lactone ring *Atorvastatin, Fluvastatin, Rosuvastatin - fluorine-containing active synthetic compounds

Question 29

HMG-CoA Reductase Inhibitors (STATINS) MOA

Answer 29

*competitive inhibition of HMG-CoA reductase -reducing the conversion of HMG-CoA to Mevalonate, the rate limiting step of De Novo Cholesterol synthesis *induce an increase in high affinity LDL receptors, increasing both the catabolic rate of LDL & the hepatic extraction of LDL precursors (VLDL remnants) from the blood, thus, reducing LDL *also impair the synthesis of isoprenoids (ubiquinone (Q10) & dolichol, & prenylation of proteins)

Question 30

HMG-CoA Reductase Inhibitors (STATINS) Effects:

Answer 30

* MOST effective & best-tolerated agent in decreasing LDL *linear does-response relationship *not effective in Homozygous familial hypercholesterolemia (NO LDL receptors) *maximal in 7-10 days *decreases TG levels >250mg/dL (especially the potent Atorvastatin, Rosuvastatin, Simvastatin) *moderately increases HDL

Question 31

HMG-CoA Reductase Inhibitors (STATINS) Pharmacokinetics:

Answer 31

*Absorption *40-70% except Fluvastatin (almost completely absorbed) *high hepatic first pass metabolism *M: t1/2 *Lovastatin, Fluvastatin, Pravastatin, Simvastatin (1-3h) - must be given at night *Atorvastatin (14h), Pitavastatin (12h), Rosuvastatin (19h) - may be given any time of the day *cholesterol synthesis is maximal at 12-2 am

Question 32

high intensity statins

Answer 32

*lower LDL concentrations by >/-50% *atorvastatin 40-80mg *rosuvastatin 20-40mg

Question 33

moderate intensity statins

Answer 33

*lower LDL-C by 30- <50% *atorvastatin 10mg (to 20mg) *fluvastatin 40mg twice daily *fluvastatin XL 80mg *lovastatin 40mg (to 80mg) *pitavastatin 1-4mg *pravastatin 40mg (to 80mg) *rosuvastatin (5mg) to 10mg *simvastatin 20-40mg

Question 34

low intensity statins

Answer 34

lower LDL-c, on average, by <30% *fluvastatin 20-40mg *lovastatin 20mg *pravastatin 10-20mg *simvastatin 10mg

Question 36

HMG-CoA Reductase Inhibitors (STATINS) Uses:

Answer 36

*the HALLMARK of drug therapy of DYSLIPIDEMIAS *monotherapy or in combination w/: -Ezetimibe -PCSK9 MABs -Resins, -Niacin, or -Bempedoic Acid in reducing levels of LDL *first line treatment for elevated risk of ASCVD to reduce the occurrence of ASCVD events (primary & secondary prevention) -40-70 y/o with known history of clinical ASCVD or DM -LDL-C >/- 190mg/dL *children w/ heterozygous familial hypercholerolemia: -atorvastatin, lovastatin, simvastatin = 11yo -pravastatin = 8yo

Question 37

HMG-CoA Reductase Inhibitors (STATINS) ADR:

Answer 37

*asymptomatic AST/ALT elevation (3x) *myopathy/rhabdomyolysis -CK elevation -myoglobinuria ➔ kidney injury *rare: hypersensitivity syndromes (lupus-like disorder, dermatomyositis, peripheral neuropathy, autoimmune myopathy) *small but significant increase in incidence of type II DM *red yeast rice -highly variable statin content -may contain Citrinin, a nephrotoxin

Question 38

HMG-CoA Reductase Inhibitors (STATINS) Drug Interactions:

Answer 38

*Lovastatin, Simvastatin, Atorvastatin (CYP3A4 metabolism) *enzyme inhibitors: macrolides antibiotics, cyclosporins, ketoconazole, HIV protease inhibitors, tacrolimus, nefazodone, fibrates, paroxetine, venlafaxine, amiodarone *enzyme inducers: phenytoin, griseofulvin, barbiturates, rifampicin, & thiazolidinediones *Fluvastatin, Rosuvastatin, Pitavastatin, (CYP2C9 metabolism) *enzyme inhibitors: ketoconazole, metronidazole, sylfinpyrazone, amiodarone, cimetidine *increases risk of myopathy: -Gemfibrosil 38% -cyclosporine 4% -digoxin 5% -warfarin 4% -macrolides 3% -azole antifungals 1%

Question 39

HMG-CoA Reductase Inhibitors (STATINS) Pleiotropic effects:

Answer 39

secondary effects: 1- improved endothelium function 2- reduced oxidative stress 3- atherosclerotic plaque stabilization 4- anti-inflammatory effects

Question 40

Niacin (Nicotinic Acid)

Answer 40

niacin nicotinic acid vitamin B3 *generic only: extended release niacin (Niaspan)

Question 41

Niacin (Nicotinic Acid) Chemistry & PK:

Answer 41

*almost completely absorbed *converted to amide, w/c is incorporated into NAD & NADP to function as a vitamin *excreted in the urine unchanged & as metabolites *Niacin (but not as amide) has lipid lowering effect

Question 42

Niacin (Nicotinic Acid) MOA:

Answer 42

*⬇ VLDL (TGs) & LDL *in adipose tissue: inhibits lipolysis of TGs by Hormone Sensitive Lipase, w/c reduce transport of free Fatty Acids to the liver & hepatic TG synthesis *in the Liver: reduces TG synthesis by inhibiting the synthesis & esterification of the Fatty Acids *in extrahepatic tissues: enhances LPL activity, promoting clearance of Chylomicrons & VLDL TGs *reduce TG synthesis ➔ ⬇ hepatic VLDL production ➔ ⬇ LDL levels *⬆ HDL: ⬇ fractional clearance of apoA-I in HDL

Question 43

inhibits the synthesis of triacylglycerol to fatty acids

Answer 43

niacin

Question 44

Niacin (Nicotinic Acid) effects:

Answer 44

*favorably affects all lipid parameters *MOST effective agent for increasing HDL (by 30-40%) *⬇ TG by 35-50% (as effective as fibrates and statins) *the only lipid lowering drug that ⬇ Lp(a) levels significantly

Question 45

Niacin (nicotinic Acid) uses:

Answer 45

*combined hyperlipidemia (hypertriglyceridemia + hypercholesterolemia) *heterozygous familial hypercholesterolemia *dysbetalipoproteinemia *Niacin + Statin: no further reduction in ASCVD risk *monotherapy in a statin intolerance

Question 46

Niacin (nicotinic Acid) ADR:

Answer 46

*flushing (cutaneous dilation) with sensation of warmth & pruritus -prevented by aspirin prior to niacin intake -minimized by starting at lower doses *dyspepsia, upper GI distress *skin rashes, dry skin -prevented by taking after meal *AST & ALT elevation, serum albumin lowering -less with niacin ER *hyperglycemia due to impaired glucose tolerance/insulin resistance *acanthosis nigricans - a condition that causes areas of dark, thick velvety skin in body folds and creases (maitim na batok) *atrial arrhythmia *macular edema *pregnancy: category C

Question 47

Niacin (nicotinic Acid) special precaution:

Answer 47

diabetes hyperurcemia

Question 48

Niacin (nicotinic Acid) CI:

Answer 48

*chronic liver disease *peptic ulcer disease *severe gout

Question 49

Niacin (nicotinic Acid) DI:

Answer 49

*potentiation of anti-hypertensive drugs *myopathy with statins *increased risk of flushing with alcohol

Question 50

FIBRIC ACID DERIVATIVES FIBRATES

Answer 50

*Fenofibrate *Gemfibrozil

Question 51

FIBRIC ACID DERIVATIVES FIBRATES

Question 52

FIBRIC ACID DERIVATIVES FIBRATES PK:

Answer 52

*absorbed rapidly & efficiently (>90%) when given with meal *highly bound to albumin (>95%) *t1/2 *1.1h gemfibrozil *20h fenofibrate (prodrug) *glucuronide conjugation *urinary excretion *gemfibrozil crosses the placenta

Question 53

FIBRIC ACID DERIVATIVES FIBRATES MOA

Answer 53

PPARA activation ⟶ ⬆ FA oxidation in hepatocytes & striated muscle ⟶ ⬇ TG synthesis⟶ ⬇ plasma triglycerides PPARA activation ⟶ ⬇ apoC-III, ⬆ LPL ⟶ ⬆ lipoprotein TG lpolysis & VLDL clearance ⟶ ⬇ plasma triglycerides PPARA activation ⟶ ⬆ apoA-1, apoA-II ⟶ ⬆ Plasma HDL

Question 54

FIBRIC ACID DERIVATIVES FIBRATES effects:

Answer 54

*varies among patients depending on the lipid profile *MAIN: decreases TGs (VLDL) by up to 50% *⬆ HDL by 15% (fenofibrate> gemfibrozil) *⬇ LDL in normotriglyceridemia/mild hypertriglyceridemia (<400mg/dL) *potential antithrombotic effects: inhibition of coagulation & enhancement of fibrinolysis

Question 55

FIBRIC ACID DERIVATIVES FIBRATES uses:

Answer 55

*type III hyperlipoproteinemia (dysbetalipoproteinemia) -- MOST sensitive responders to Fibrates *decreases elevated triglyceride & cholesterol levels dramatically *DOC for treating severe hypertriglyceridemia (>1000mg/dL) who are at risk for pancreatitis *DOC for Chylomicronemia syndrome *fenofibrate + statin *fibrate of choice for use in combination with a statin *no further reduction of ASCVD risk

Question 56

FIBRIC ACID DERIVATIVES FIBRATES ADR:

Answer 56

generally well tolerated *rashes *GI symptoms *myopathy/myositis - in combination w/ statins *arrhythmias *hypokalemia *impotence *elevated aminotransferases or alkaline phosphatase *cholesterol gallstones *anemia/leukopenia

Question 57

FIBRIC ACID DERIVATIVES FIBRATES SP:

Answer 57

biliary tract disease

Question 58

FIBRIC ACID DERIVATIVES FIBRATES CI:

Answer 58

*children *pregnant *severe renal disease *severe liver disease

Question 59

FIBRIC ACID DERIVATIVES FIBRATES DI:

Answer 59

potentiation of warfarin action

Question 60

BILE SEQUESTERANTS / RESINS

Answer 60

oldest & safest lipid lowering drugs *cholestyramine *colesevelam *colestipol

Question 61

BILE SEQUESTERANTS / RESINS chemistry;

Answer 61

large polymeric cationic resins that are insoluble in water

Question 62

BILE SEQUESTERANTS / RESINS MOA:

Answer 62

binding of (-) charged bile acids & bile salts in the small intestine ⬇ excretion of resin/bile acid complex in the feces (10x) ⬇ decreased return of bile acids to the liver by enterohepatic circulation ⬇ lower bile acid concentration ⬇ increased hepatic conversion of cholesterol to bile acids via 7a-hydroxylation ⬇ increased production of LDL receptors ⬇increased hepatic uptake of cholesterol containing LDL ⬇ decrease plasma LDL

Question 63

BILE SEQUESTERANTS / RESINS effects:

Answer 63

*MAIN: ⬇ LDL by 12-18% w/o GI symptoms *⬆ VLDL in hypertriglyceridemia (TG>250mg/dL) *improves glucose metabolism in diabetes due to increased secretion of the incretin glucagon-like-peptide-1

Question 64

BILE SEQUESTERANTS / RESINS uses:

Answer 64

*primary hypercholesterolemia *combined hyperlipidemia- combined w/ other agents (fibrates, niacin) *2nd line treatment if statin therapy does not lower LDL_C levels sufficiently or in cases of statin intolerance *heterozygous familial hypercholesterolemia -recommended for patients 11-20yo *helpful in relieving pruritus in cholestasis & bile salt accumulation

Question 65

BILE SEQUESTERANTS / RESINS ADR: cholestipol, cholestyramine

Answer 65

*generally safe (not absorbed) *hyperchloremic acidosis (due to administration as chloride salts) *unpleasant gritty sensation of slurry *dyspepsia & bloating -reduced by completely suspending in liquid several hours before ingestion -relieved by increasing dietary fiber *constipation -relieved by increasing water & dietary fiber/psyllium intake *steatorrhea- in pre-existing bowel disease or cholestasis *malabsorption of Vit K- hypoprothrombinemia

Question 66

BILE SEQUESTERANTS / RESINS SP

Answer 66

cholestipol, cholestyramine *hypertriglyceridemia (>200mg/dL) *diverticulitis

Question 67

BILE SEQUESTERANTS / RESINS CI:

Answer 67

colestipol, cholestyramine *hypertriglyceridemia (>400mg/dL) *dysbetalipoproteinemia

Question 68

BILE SEQUESTERANTS / RESINS DI:

Answer 68

colestipol, cholestyramine *binds & ⬇ absorption of thiazides, furosemides, propanolo, tetracycline, iron salts, thyroxine, digoxin, warfarin, pravastatin, fluvastatin, ezetimibe, folic acid, ascorbic acid, aspirin, phenylbutazone *general rule: additional medication (except niacin) should be given 1hr before or 2 h after the resin *colesevelam- does not bind digoxin, warfarin, or reductase inhbitors

Question 69

EZETIMIBE PK:

Answer 69

*conjugated in the intestine to an active glucuronide & then readily absorbed *enters enterohepatic circulation

Question 70

EZETIMIBE MOA:

Answer 70

selective inhibition of intestinal absorption of cholesterol & phytosterols via Niemann-Pick C1-like-1 transport protein, NPC1L1 ⬇ decreased incorporation of cholesterol into chylomicrons ⬇ decrease delivery of cholesterol to the liver by chylomicron remnants ⬇ increased production of LDL receptors ⬇ increased hepatic uptake of cholesterol-containing LDL ⬇ decreased plasma LDL

Question 71

EZETIMIBE uses:

Answer 71

*combination therapy with other lipid lowering drugs (except BAS) *primary hypercholesterolemia- monotherapy in statin intolerance *DOC for patients in phytosterolemia

Question 72

EZETIMIBE ADR:

Answer 72

rare: hypersensitivity, reversible liver dysfunction, & myositis

Question 73

EZETIMIBE DI:

Answer 73

BAS: prevents absorption of ezetimibe

Question 74

FISH oil

Answer 74

*contains omega-3 PUFAs: eicosapentaenoic acid (EPA) & docosahexaenoic adic (DHA) *MOA: activation of PPAR-a *EFFECT: *main: ⬇ VLDL TGs *anti-inflammatory & antithrombotic effects *⬆ LDL-C in severe hypertriglyceridemia USES: adjunct in severe hypertriglyceridemia (>1000mg/dL) *Lovasa- concentrated fish oil w/ EPA 465mg & DHA 375mg *Vascepa- w/ 1- or 0.5g of icosapent ethyl, a highly purified ethyl ester of EPA ADR: *high doses (EPA 15-30g/day) may prolong bleeding time *arthralgia, nausea, fishy burps, dyspepsia, ⬆ LDL-C omega-3 fatty acids-marine Lovasa

Question 75

PCSK9 inhibitors chemistry

Answer 75

humanized monoclonal antibodies *alirocumab praluent *evolocumab repatha

Question 76

PCSK9 MOA:

Answer 76

inhibitors of protein convertase subtilisin / kexin type 9 *pcsk9- a protease that binds hepatic LDL receptors & enhances lysosomal degradation of LDL receptors, resulting in higher plasma LDL-C Effects: * ⬇ LDL by up to 70% alone or up to 60% in those using statins *⬇ TGs & Lp(a)

Question 77

PCSK9 inhibitors uses:

Answer 77

*given alone, or with statin, bempedoic acid, &/or ezetimibe *established ASCVD- lower risk of MI, stroke, & UA requiring hospitalization *HeFH- lower LDL-C as adjunctive therapy alone or in combination with other LDL-C lowerigndrugs *HoFH- lower LDL-C as adjunctive therapy in combination with other LDL-C lowering drugs ADR: *most common: injection site reactions (<10%) *<1% risk of neurocognitive effects *slightly ⬆ risk for infections CI: pregnancy

Question 78

PCSK9 inhibitors

Answer 78

Alirocumab *primary hyperlipidemia *75mg SC every 2W *300mg SC every 4W Evolocumab *homozygous familial hypercholesterolemia *420mg once monthly *primary hyperlipidemia *140mg SC every 2W *420mg SC once monthly *prevention of cardiovascular events *140mg SC every 2W *420mg SC once monthly

Question 79

RNAi inhibitor of PCSK9: Inclisiran

Answer 79

*a small siRNA *⬇ LDL-C by about 50% *adjunct to diet & maximally tolerated statin therapy in adults with HeFH or clinical ASCVD who require additional reduction in LDL-C

Question 80

BEMPERDOIC ACID

Answer 80

Chemistry: *a dicarboxylic acid PK: *a prodrug that is metabolized to the active bempedoic acid-CoA by very long chain acyl-CoA synthase-1 MOA: *competitive inhibition of ATP citrate lyase of hepatic de novo cholesterol synthesis *ACL- cytoplasmic enzyme that converts citrate to oxaloacetate & acteyl-CoA Effects: ⬇ LDL-C by 15-25% *precipitates compensatory increase in cholesterol absorption USE: *HeFH & established ASVD- adjunct to diet & maximally tolerated statin therapy to further lower LDL-C *alternative in statin intolerance ADR: *hyperuricemia *tendon rupture

Question 81

LOMITAPIDE

Answer 81

MOA: inhibition of microsomal triglyceride transfer protein (MTP) ⟶⬇ VLDL secretion ⟶ ⬇ plasma LDL *MTP- essential for the intracellular addition of TGs to nascent VLDL & chylomicrons EFFECT: ⬇ LDL by 50% USES: *HoFH- adjunct to diet & maximally tolerated statin for lowering LDL-C, total cholesterol, apoB, & non-HDL-C lipoproteins *used in combination with maximally tolerated statin therapy Lomitapide (Juxtapid)

Question 82

LOMITAPIDE ADR

Answer 82

*under an FDA risk evaluation & mitigation strategy -diarrhea, vomiting, & abdominal pain -hepatotoxicity & hepatic steatosis -steatorrhea- prevented by strict low fat diet CI: *pregnancy

Question 83

EVINACUMAB-DGNB

Answer 83

CHEMISTRY: *human monoclonal lgG4 antobody MOA: inhibition of angiopoietin-like-3 *ANGPTL3- a member of angiopoietin-like-protein family expressed in the liver, an inhibitor of LPL & endothelial lipase (EL) EFFECTS: *⬇ LDL-C by 49% by promoting of VLDL processing & clearance upstream of LDL formation *⬇ HDL-C & TGs USES: *HoFH- an addition to lipid lowering medications & diet

Question 84

TREATMENT COMBINATIONS USEFUL WHEN:

Answer 84

*VLDL levels are significantly increased during treatment of hypercholesterolemia with a Resin *LDL & VLDL levels are both elevated initially *LDL or VLDL levels are not normalized with a single agent or *an elevated level Lp(a) or an HDL deficiency coexists with other hyperlipidemias *the lowest effective doses should be used in combination therapy & the patient should be monitored more closely for evidence of toxicity

Question 85

GOALS FOR TREATMENT

Answer 85

*reducing the risk of fatal and nonfatal atherosclerotic cardiovascular disease (ASCVD) events: *acute coronary syndromes *MI *stable or unstable angina *arterial revascularization *transient ischemic attack *peripheral arterial disease *LDL-C- primary target of lipid lowering therapy in preventing ASCVD

Question 86

ASCVD risk assessment & primary prevention age: 0-19yo

Answer 86

***lifestyle*** to prevent or reduce ASCVD risk diagnosis of familial hypercholesterolemia ➔ *statins*

Question 87

ASCVD risk assessment & primary prevention age: 20-39yo

Answer 87

*** estimate lifetime risk to encourage lifestyle to reduce ASCVD risk ***consider statin* ** if family history premature ASCVD & LDL-C >/- 160mg/dL

Question 88

ASCVD risk assessment & primary prevention age: 40-75yo & LDL-C >/-70 <190mg/dL w/out diabetes mellitus

Answer 88

***10year ASCVD risk percent begins risk discussion**

Question 89

LDL-C >190mg/dL (>/-4.9mmol/L)

Answer 89

*no risk assessment *high intensity statins (classI)

Question 90

diabetes mellitus & age 40-75yo

Answer 90

moderate intensity statins (class I) *diabetes mellitus & age 40-75yo **risk assessment to consider high intensity statins (class IIa)

Question 91

age: >75yo

Answer 91

| **clinical assessment *****risk discussion**

Question 92

# ASCVD risk assessment & primary prevention <5% low risk

Answer 92

risk dscussion: emphasize lifestyle to reduce risk factors (class I)

Question 93

# ASCVD risk assessment & primary prevention <5% - <7.5% borderline risk

Answer 93

risk discussion: if risk enhancers are present then the risk discussion regarding moderate-intensity statin therapy (class 2b)

Question 94

-/>7.5% - <20% intermediate risk

Answer 94

if risk estimate + risk enhancers favor statin: initiate moderate-intensity statin to reduce LDL-C by 30%- 49% (class I)

Question 95

-/> 20% high risk

Answer 95

| risk discussion: initiate statin to reduce LDL-C >/- 50% (class I)

Question 96

-/>7.5% - <20% intermediate risk *if risk decision is uncertain:

Answer 96

consider measurng CAC in selected adults: CAC=zero (lowers risk, consider no statin, unless diabetes, family history of premature CHD, or cigarette smoking is present) CAC=1.99 favors statin (especially after age 55) CAC= 100+ &/or 75th percentile, initiate statin therapy

Question 97

ASCVD risk enhancers

Answer 97

*family history of premature ASCVD *persistent elevated LDL-C (>/-160mg/dL or 4.1mmol/L) *CKD *metabolic syndrome *preeclampsia, menopause *inflammatory disease (rheumatoid arthritis, psoriasis, HIV) *ethnicity (south asean ancestry) higher risk