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Worksheetsmadras cardio ex.2
Total questions: 85
Worksheet time: 54mins
Hyperlipidemia
Elevation total CHO, LDL, or TG, and low HDL or combination
Decrease total CHO, LDL, or TG, and low HDL or combination
Only lipid
all
transport fatty acids (TG contain fatty acids) and CHO derived from diet (postprandial state) or synthesized in small intestines from gut to liver
Exogenous pathway:
Endogenous pathway:
delivers CHO and TG from liver to peripheral cells in fasting state and back to liver
Exogenous pathway
Endogenous pathway
Lipoprotein classes
- LDL
HDL
VLDL
IDL
Transports TG and CHO from diet or made in intestine from gut to
liver, skeletal muscle, adipose tissue
- Not present in plasma after 12-14 hour fast
Chylomicron
Chylomicron remnant
Very-low density lipoprotein (VLDL)
After most of TG removed in muscle & adipose tissue capillar beds by lipoprotein lipase
Chylomicron
Chylomicron remnant
Very-low density lipoprotein (VLDL)
Formed mainly in liver
- Mainly transports TG > CHO (carries 15-20% of blood CHO) from
liver to periphery
- Major lipid component: endogenous TG
-(fibrates increase lipoprotein lipase activity) → removed TG converted to fatty acids and stored as energy
Chylomicron
Chylomicron remnant
Very-low density lipoprotein (VLDL)
Derived from VLDL in capillaries of adipose tissue & muscle after
extraction of TG by LPL in capillary beds
- Major lipid component: endogenous cholesterol (CHO > TG)
Intermediate-density lipoprotein (IDL)
Very-low density lipoprotein (VLDL)
High-density lipoprotein (HDL)
Mostly derived from VLDL catabolism and cellular synthesis
- Major lipid component: endogenous cholesterol
- Major atherogenic lipoprotein (carries 60-70% of blood CHO)
- Main target for lipid-lowering medications
Low-density lipoprotein (LDL)
Intermediate-density lipoprotein (IDL)
Very-low density lipoprotein (VLDL)
Transport cholesterol FROM cells to liver (reverse cholesterol
transport) for secretion into bile or transfer to either VLDL and LDL
- Carries 20-30% of blood CHO
- Major lipid component: cholesterol
- Clears peripheral tissue (coronary arteries) of too much CHO and
some of protective effects
High-density lipoprotein (HDL)
Intermediate-density lipoprotein (IDL)
Low-density lipoprotein (LDL)
Causes of reduced HDL
Smoking
Obesity
Sedentary and lifestyle
Beta-blockers
Causes of increased HDL
➢smoking cessation
Moderate alcohol ingestion (< 2 drinks/day)
Physical exercise
and Weight loss
Oral contraceptives
Phenytoin
Lipoprotein a:
- Variation of LDL (formed by LDL-like particle with apoprotein B-100 and apoprotein(a) )
↑ atherosclerotic progression and thrombosis
True
False
Apolipoproteins exist in: A-I, A-II, B-100, C, E
Protein components on outer surface of lipoproteins
function is Receptor binding
→ transfer CHO from
lipoprotein into cell)
both
First stage chylomicron: Dietary CHO and TG Absorbe in intestine
VLDL : Lipoprotein secrete by liver
IDL: Intermediate in digestion fat
LDL Final stage "Bad CHO "release the CHO in bloodstream
HDL Final stage "Good cholesterol" pick up the CHO floating free bloodstream
SEE PPT16
True
False
Nonpharmacological Treatment
Diet
Regular Physical Exercise: ↑ HDL, ↓ TG
- Weight loss → ↓ LDL
note initial goal: lose 10% body weight)
Smoking cessation: slightly ↓ cholesterol levels, change risk profile, ↑ HDL
↓ BP
which are Statins select apply
Lovastatin, simvastatin,
atorvastatin,
rosuvastatin
pitavastatin
pravastatin, fluvastatin,
none
Resulting Medical Conditions Atherosclerosis Pathogenesis
Angina
Arrhythmias
MI, Stroke
or sudden death
Peripheral Arterial Disease
Abdominal aortic aneurysm
Secondary Causes of Lipoprotein Abnormalities
Hypercholesterolemia
Hypertriglyceridemia
Hypocholesterolemia
Hear Diases
C-Reactive Protein select which is true
Acute phase protein elevated during severe infection & inflammation
Synthesized and released by liver
Elevated levels with no hyperlipidemia associated with increased risk of coronary events
Synthesized and released by Intestines
Acute phase protein decrease during severe infection & inflammation
Atherosclerosis (MI, ischemic stroke, CHD, PVD) partly due to chronic inflammation by vascular injury induced by oxidized LDL, diabetes, infection
True
False
Statins Contraindications
Persistent elevation of LFTs
Active liver disease
Unexplained
Lactation
none
Associated with Increased hs-CRP Levels (high-sensitivity C-reactive protein)
↑ BP
↑ BMI
Cigarette smoking
DM
Metabolic syndrome
Low HDL/high TG
Chronic infections (bronchitis)
Chronic inflammation (RA)
Estrogen/progesterone use
Associated with Decreased hs-CRP Levels
high-sensitivity C-reactive protein
Medications
- Statins, fibrates, niacin, pioglitazone,
rosiglitazone
Weight loss
Exercise
Moderate alcohol consumption
none
1st line medication to lower cholesterol
statin
Fibrate
Niacin
all
Plant Sterols/Stanols
Inhibit intestinal absorption of dietary & biliary CHO
Avoid if have sitosterolemia (rare)
↓ LDL 6-15% (2-3 gm/day)
Nausea, indigestion, gas, diarrhea, constipation
all
Stanol: decrease beta-carotene absorption
Sterol: decrease absorption of alpha and beta carotene, vitamin E
true
false
drugs cause Hypercholesterolemia:
Thiazides, cyclosporine, glucocorticoids,
beta-blockers, progestins, mirtazapine,
Oral estrogens, glucocorticoids, bile acid sequestrants
DM, Obsety , chronic liver disease
Nephrotic syndrome, hypothyroidism, etc.
Drugs cause Hypertriglyceridemia
Oral estrogens, glucocorticoids, bile acid sequestrants, mirtazapine, antifungal, alcohol, beta blockers, thiazides, tamoxifen,
raloxifene
AIDS, chronic liver disease,
all
Diabetes, obesity, pregnancy,
Drug cause Hypocholesterolemia
Malabsorption, malnutrition, AIDS, chronic liver disease, etc
obesity, progestins, non-ISA beta blockers, isotretinoin, etc
hiazides, cyclosporine, glucocorticoids, protease inhibitors, isotretinoin,
beta-blockers, progestins, mirtazapine, sirolimus, etc.
- Nephrotic syndrome, hypothyroidism, etc.
Drug cause Low HDL:
obesity, progestins, non-ISA beta blockers, isotretinoin, etc
Malabsorption, malnutrition, AIDS, chronic liver disease, etc.
Oral estrogens, glucocorticoids, bile acid sequestrants, mirtazapine,
- Diabetes, obesity, pregnancy, etc.
none
apply Bile Acid Sequestrants
block enterohepatic circulation of bile
acids from intestinal lumen to liver
Colestipol, cholestyramine, colesevelam
↑ CHO synthesis → ↑ VLDL → ↑ TG
↓ LDL
↑ CHO synthesis → ↑ VLDL →↓ TG
↑ LDL
colesevelam indication: INCREASE LDL and improve glycemic control in type 2 DM adult pts
FALSE
TRUE
Biles sequestrate adverse effect and indication
GI: constipation, bloating, flatulence, nausea, abdominal pain
Mix with water, non-carbonated beverage (ex: apple juice, grape juice, pulpy
juice-orange juice)
Mix with water, carbonated beverage
No effect GI
Bile sequestrants ↓ absorption of medications (ex: warfarin, niacin, digoxin, etc)
Administer medications at least 1-4 hours before or 4-6 hours after
bile acid sequestrant (medication specific)
True
False
Statins MOA
Inhibit HMG CoA reductase (rate limiting step) in CHO synthesis
DO NOT Inhibit HMG CoA reductase (rate limiting step) in CHO synthesis
Most potent LDL & total CHO lowering agents & best tolerated
SECOND Most potent LDL & total CHO lowering agents & best tolerated
STATIN METABOLIZED IN
LIVER
GI
INTESTINE
ALL
Primary prevention of CVD
pt. HTN, low HDL, smoking, or family hx
premature CHD,)
Indicated to:
Reduce risk of stroke
Reduce risk of MI
Reduce risk of arterial revascularization procedures
Rosuvastatin Indication
Artrovastatin Indication
lovastatin Indication
all
Statins Adverse Effects/Interactions
- Increase in blood glucose reported
-Dyspepsia
-Elevations in LFTs
-
Myopathy/rhabdomyolysis
gemfibrozil, niacin, CYP 3A4 inhibitors
(interaction)
myalgia:
Rosuvastatin: dipstick + proteinuria and microscopic hematuria
(esp with ≥ 40mg/day)
High Intensity Statin
(Lowering LDL by
≥ 50%)
Atorvastatin (40t)-80 mg
Rosuvastatin 20 (40) mg
Atorvastatin 10mg
Rosuvastatin 10mg
Atorvastatin (40t)-80 mg
Rosuvastatin10 mg
Simvastatin20-40 mg
Rosuvastatin 20 (40) mg
Moderate Intensity Statin
(Lowering LDL by
30-49%)y
Atorvastatin 10 Mg
Fluvastatin 40 mg bid
Rosuvastatin10mg
Simvastatin20-40 mg
Pravastatin 40 mg
Lovastatin 40 mg
Low Intensity Statin
(Lowering LDL by
< 30%)
Pravastatin10-20 mg
Lovastatin 20 mg
Atorvastatin 20
Rosuvastatin 20 (40) mg
ACC/AHA 2018 Lipid Guidelines
4 Statin Groups
Secondary ASCVD preventionT
Severe hypercholesterolemia (LDL ≥ 190 mg/dL)
Primary prevention: Adults 40-75 YO with DM AND NO ASCVD AND
LDL ≥ 70 mg/dLYo
Primary Prevention: Adults 40-75 YO AND LDL 70-189 mg/dL AND
NO Diabetes AND NO ASCVD AND ≥ 7.5% 10-year ASCVD risk
Severe hypercholesterolemia (LDL ≥ 100mg/dL)
Clinical ASCVD defined:(all .of atherosclerotic origin)
ACS Acute Coronary syndrome
MI
Stroke
Peripheral artery disease PAD
transient ischemic attack (TIA)
Aortic aneurisma
stable or unstable angina or coronary
HF
Ver high-risk defined: "multiple major ASCVD events OR 1 major ASCVD
event and multiple high-risk conditions"
True
False
pregnant → D/C statin 1-2 months before try to become
true
false
40-75 YO
LDL 70-189 mg/dL
10-year ASCVD risk ≥ 7.5%
CKD NOT on dialysis OR treated by kidney transplantation
moderate-intensity statin or moderate-intensity statin in combination with ezetimibe
high intensity statin or moderate-intensity statin in combination with ezetimibe
only ezetimibe
moderate-intensity statin or moderate-high intensity statin in combination with ezetimibe
CDK PATIENT LIPID GUIDELINE
Advanced kidney disease ON dialysis AND taking statin: continuing statin
Advanced kidney disease ON dialysis: do NOT start statin
Advanced kidney disease ON dialysis AND should stop taking statin:
all
Risk factors for myopathy with fibrates and statins:
Age > 70 YO
- Female
Renal disease
- Liver disease
- Diabetes
Hypothyroidism
Excessive alcohol intake
- Heavy exercise
Age < 70 YO
- Female
Renal disease
- Liver disease
- Diabetes
Hyperthyroidism
Coenzyme Q10 recommended for routine use if taking statin or to treat statin-associated muscle symptoms
true
false
Avoid consumption of grapefruit and grapefruit juice
lovastatin
atorvastatin
simvastatin
rosuvastatin
all
↑ warfarin
Lovastatin,
simvastatin,
rosuvastatin:
atorvastatin:
pitavastatin
Rosuvastatin: take aluminum and magnesium hydroxide combination antacid at least 2 hours after rosuvastatin
true
false
Bempedoic Acid (Nexletol)=Adenosine triphosphate-citrate lyase (ACL) inhibitor
↓ synthesis of CHO in liver
main effect ↓ LDL
↑ synthesis of CHO in liver
adverse effects:
hyperuricemia,
increased LFTs (liver failure test, tendon rupture
main effect ↑LDL
Bempedoic Acid (Nexletol) CAUSE Myopathy risk increases with use
and the Check lipid panel within weeks after starting medication
Avoid with doses > 20 mg of simvastatin
- Avoid with doses > 40 mg of pravastatin
Avoid with doses > 20 mg of rovastatin
- Avoid with doses > 40 mg of pravastatin
8-12
4-12
Fibrates
Gemfibrozil (Lopid)
Fenofibrate (Tricor, Triglide, Antara, Lofibra, TriLipix, Lipofen, Fibricor, Fenoglide)
stimulate PPAR alpha receptors (found in liver, heart kidney, muscle)
↓ VLDL↓ TG
increase LDL
↓ VLDL↓ TG
decrease LDL
Febrate Preferable over Niacin when TG < 400
false
true
Ezetimibe (Zetia®)
Cholesterol absorption inhibitor and
Inhibits exogenous pathway
↓ hepatic stores of CHO
↓ LDL,↓ TG↑ HDL
↓ LDL,↑ TG ↓HDL
can combination
with statin
True LDL CALCULATION
LDL = Total CHO – (HDL + TG/5)
LDL = Total CHO + (HDL + TG/5)
LDL accurate if TG are < 400 (cannot calculate if TG > 400)
LDL accurate if TG are > 400 (cannot calculate if TG <400)
Formula VLDL
VLDL = TG
5
VLDL = 5
TG
Nicotinic Acid
Niaspan lipid effects
↓ LDL 10-15%
- ↓ TG 20-30%
- ↑ HDL 15-25% (most potent)
Niaspan lipid effects
↓ LDL 10-15%
- ↑ TG 20-30%
-↓HDL 15-25% (most potent)
ADRSFlushing (tolerance
Myopathy
Hyperglycemia
Hyperuricemia
Hepatotoxicity
ALL
Long duration of DM (type 2: ≥ 10 years; type 1: ≥ 20 years)
Albuminuria ≥ 30 mcg of albumin/mg creatinine
eGFR < 60 mL/min/1.73 m2
Retinopathy
Neuropathy
ABI < 0.9
INTERMIDEATED-intensity statin
LOW-intensity statin
high-intensity statin
40-75 YO AND LDL 70-189 mg/dL AND 10-year ASCVD risk ≥ 7.5% chronic inflammatory conditions (ex: SLE, RA, psoriasis), HIV are types of risk-enhancing factors → moderate or high-intensity statin
True
False
Moderate
hypertriglyceridemia
(fasting or nonfasting)
150 to 499 mg/dL
> 500 mg/dL
Severe
hypertriglyceridemia
(fasting)
150 to 499 mg/dL
> 500 mg/dL
avoid refined carbohydrates and alcohol; omega-3 fatty acids AND fibrate (fenofibrate) if needed
not avoid refined carbohydrates and alcohol; omega-3 fatty acids AND fibrate (fenofibrate) if needed
▪ ASCVD or cardiac risk factors taking statin and controlled LDL
→ elevated TG (135-499 mg/dL) → no consider adding icosapent ethyl
to reduce cardiovascular risk
true
false
ACC/AHA 2018 Lipid Guidelines Hypertriglyceridemia
1) ≥ 20 YO AND moderate hypertriglyceridemia;lifestyle modification
2) 40-75 YO AND moderate OR severe hypertriglyceridemia AND ASCVD risk ≥ 7.5%:start or increase statin
3) 40-75 YO AND severe hypertriglyceridemia (fasting TG ≥ 500 mg/dL) AND ASCVD risk ≥ 7.5%: start statin
True
False
Primary Prevention: Adults 40-75 YO AND LDL 70-189 mg/dL AND NO Diabetes
with Estimate 10-year ASCVD risk (fatal and nonfatal MI or stroke) by using PCE that is race and sex specific (strong recommendation)
select apply
High risk: ≥ 20% (use high-intensity statin and reduce LDL > 50%)
▪ Intermediate-risk: moderate-intensity statin (strong recommendation) Intermediate-risk: reduce LDL > 30%
▪ Intermediate-risk: High intensity statin (strong recommendation) Intermediate-risk: reduce LDL > 30%
intermediate risk: ≥ 20% (use high-intensity statin and reduce LDL > 50%)
Combination Therapy not recommend
statin/fibrate
statin/niacin
statin/fish oil
Which decrease LDL
Statins
Bempedoic Acid:
PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) inhibitor, inhibits apo B-100 translation:
Bile acid sequestrants
Ezetimibe:
Nicotinic acid
↓ TG and ↑ HDL
Statins
Fibrates
Fish oil:
Ezetimibe:
↓ LDL, ↓ TG, and ↑ HDL
Nicotinic acid
Fish oil
Ezetimibe
all
↓ TG
Fibrates
Bile acid sequestrants:
Fish oil
none
↓ LDL
Statins
Bempedoic Acid:
Bile acid sequestrants
Ezetimibe:
PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) inhibitor, inhibits apo B-100 translation: ↓ L
Vascepa®(icosapent ethyl): true
Fish Oil
EPA (omega 3 fatty acid)
4 grams/day
bid with food
djunct to maximally tolerated statinreduce risk of MI, stroke, coronary
with increased TG (≥ 150 mg/dL)
all
Fish Oil medication
Lovaza
Epanova® (omega-3-carboxylic acids)
Vasepa
none
Evolocumab (Repatha)
PCSK9 inhibitor
Monoclonal AB
REduce risk of MI, stroke, and coronary revascularization in adults with CVD
sq INJECTION
DECREASE LDL
primary treatment of hyperlipidemia
(including heterozygous familial hypercholesterolemia)
iv INJECTION
DECREASE LDL
primary treatment of hyperlipidemia
(including heterozygous familial hypercholesterolemia)
Alirocumab (Praluent)
PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) inhibitor
↓ LDL
Obtain LDL levels within 4-8 weeks
Nasopharyngitis, injection site reactions, influenza, increase LFT
Protect from light
sq only
none
Lomitapide (Juxtapid)
Administer orally , bbw :hepatoxicity,
ORALLY
VLDL synthesis inhibition reduces LDL
TG transfer prote inhibitor
ACC/AHA 2018 Lipid Guidelines Primary Prevention: Diabetes Mellitus
> 75 YO with DM and taking statin: keeping on statin MODERATE
Adults with DM and 10-year ASCVD risk > 20% ADD ezetimibe to decrease LDL by > 50%
20-39 YO with DM and long duration (type 2: ≥ 10 years; type 1: ≥ 20 years), albuminuria (≥ 30 mcg of albumin/mg creatinine), eGFR < 60 mL/min/1.73 m2, retinopathy, neuropathy, or ABI (< 0.9): moderate-intensity statin
NONE
Primary Prevention: Diabetes Mellitus
40-75 YO with DM and LDL ≥ 70mg/dL
moderate-intensity statin
BEGIN WITH MODERATE INTENSITY
then high-intensity statin if have multiple risk
TRUE
FALSE
50-75 YO with DM: high-intensity statin reasonable (goal: reduce LDL by > 30%, )
High-intensity statin preferred
FALSE
TRUE
1) 40-75 YO with DM AND without atherosclerotic CVD: moderate-intensity statin
2) DM at higher risk (especially if have multiple atherosclerotic CVD risk factors OR 50-70 YO OR ASCVD risk > 20%): high-intensity statin
TRUE
FALSE
Lovastatin Extended-Release interaction
Strong CYP3A inhibitors: Erythromycin, clarithromycin,ketoconazole,
Cyclosporine
Gemfibrozil
Avoid grape juice
Dialtazem , verapamil Maximum of 20 mg/day lovastatin.
And amidarone 40mg/day
simvastatin interaction
Verapamil, diltiazem
Maximum of 10 mg/day
Amiodarone, amlodipine,
ranolazine
Maximum of 20 mg/day
contraindicate :Strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, erythromycin, clarithromycin, ), gemfibrozil, cyclosporine, danazol
avoid grape juice
