Dyslipidemia Flashcards
What does fasting lipid Profile includes?
1) LDL
2)HDL
3)TG
4)Chol
how to calculate LDL levels when TG < 400mg/dL?
LDL = Total Chol - (TG/5+HDL)
What does Dyslipidemia leads to?
Atherosclerotic Cardiovascular disease (ASCVD)
Coronary artery disease
Cerebrovascular disease
Peripheral Vascular disease
What is the target of Lipid lowering therapy?
Lower LDL
How is LDL removed?
50% of LDL is removed from blood by liver
50% of LDL is taken by peripheral cells or deposited in arteries where atherosclerotic will form
What is the aim of HDL?
Transport Chol from periphery to liver
how to calculate the non HDL levels? and for what aim?
non HDL = total Chol - HDL
What are the traits of Polygenic Hypercholesterolemia?
- Most prevalent
- Mild to moderate increase in LDL
- Caused by combination of:
o Environmental factors
o Genetic factors
What is Atherogenic hypercholesterolemia
moderate increase in TG & LDL
decrease in HDL
patients are overweight (increase in waist circumstances) &/or diabetic
What are Familial hypercholesterolemia 2 types?
Autosomal Dominant disorder
Defective clearance –> defective receptor gene –> hi LDL
Associated with premature CAD (before age 20)
Deposition of LDL in tendons (Xanthomas) & iris & Arteries (atheromas)
Two types:
Heterozygotes: 1/2 the LDL receptor are function (LDL 250-450 mg/dL)
Homozygotes: No functional LDL receptors (LDL >500mg/dL)
What is Another type of Familial hypercholesterolemia?
Familial defective apoprotein B 100
cant distinguish clinically from Heterozygous FH
defective apolipoprotein B —> Decrease binding to LDL receptors –> decrease clearance
Definitive diagnosis require : Molecular screening
what are the drug induced Dyslipidemia ?
7 drugs!!
Transient and mild:
Thiazide diuretics (HCTZ ) + Beta blockers (olol)
Moderate- Severe:
Oral contraceptive (estradiol …)
Glucocorticoids (sone - solone)
isotretinoin
Cyclosporine
Protease inhibitors (navir)
What are the desired levels for Total Chol ; LDL ; HDL;TG
Total Chol <200 mg/dL
LDL: primary prevention: <100mg/dL
secondary prevention: <70mg/dL
HDL: Men > 40mg/dL
Female > 50 mg/dL
TG: < 150mg/dL
How are patients divided? (4 categories)
- Clinically evident ASCVD (history of MI , multiple major ASCVD events; stable or unstable angina ; multiple high risk conditions)
- Age 20-75 & LDL levels > or = 190mg/dL
- Age 40-75 with DM and LDL >or= 70mg/dL
- Age 40-75 and LDL > or = 70mg/dL
what are Major ASCVD events?
- Recent acute coronary syndrome (within past 12 months)
- History of myocardial infarction
- History of ischemic stroke
- Symptomatic peripheral arterial disease (claudication)
What are high risk conditions?
- Age > or = 65 years
- Heterozygous familial hypercholesterolemia
- History of prior coronary bypass surgery or PCI outside of the major ASCVD
- DM
- Hypertension
- CKD (eGFR 15-59 mL/min/1.73m2)
- Current smoking
- Persistently elevated LDL – C > or = 100mg/dL
- History of congestive Heart Failure
How to manage patient with clinical ASCVD?
Use high intensity statin or maximally tolerated statin therapy :
1) Atorvastatin 40-80 mg
2) Rosuvastatin: 20-40 mg
====> Ezetimibe may be added in high risk ASCVD ( if LDL > or = 70mg/dL)
====>PSCK9 inhibitor might be added to ezetimibe with Statin if LDL > or = 70
How to manage patient with the age of 20-75 & LDL>or =190mg/dL
Use high intensity statin or maximally tolerated statin therapy :
1) Atorvastatin 40-80 mg
2) Rosuvastatin: 20-40 mg
====> Ezetimibe may be added if LDL > or = 100mg/dL
====>PSCK9 inhibitor might be added to ezetimibe with Statin if LDL > or = 100 + high risk ASCVD
How to manage patient with the age of DM and Age 40-75 & LDL> or = 70mg/dL
Use Moderate intensity statin:
1) Atorvastatin 10-20 mg
2) Rosuvastatin: 5-10 mg
3) Simvastatin 20-40mg
4)Pravastatin 40-80mg
5)lovastatin 40mg
6)Extended release Fluvastatin 80mg
7)Fluvastatin 40mg BID
8) Pitvastatin 2-4 mg
When do we use High intensity statin for DM patient who age btw 40-75 and LDL >or = 70
In patients with:
A- DM risk enhancers
- Albuminuria > or = 30mcg/mg Cr
- ABI <0.9
-GFR < 60mL/min
-Long duration of DM ( > or = 10 years for TYPE II ; > or = 20 years for type I)
- neuropathy
-Retinopathy
B- Several ASCVD risk factors
- family history
- persistent LDL>or =160
-metabolic syndrome
-CKD
- Pre-eclampsia or premature menopause + age < 40
- Chronic inflammatory disorder
- High risk ethnicity (South Asians)
- persistent TG> or = 175
- APO B > or = 130 mg/dL
- CRP > or = 2 mg/L
- ABI <0.9
-lipoprotein A > or = 50 mg/dL
How to manage patient with the age of Age 40-75 & LDL> or = 70mg/dL
Calculate ASCVD 10yr risk factor
> or = 20% –> high intensity
btw 7.5 and 20 & risk enhancers ASCVD –> moderate intensity
5-7.5 & risk enhancers ASCVD –> may use moderate
what to do if decision about statin therapy is uncertain ?
Consider Coronary Artery Calcium (CAC):
if CAC =0 —> withhold or delay statin except in: smoker + strong family history
if CAC = 1-99 —> statin therapy especially if age > 55
if CAC > 100 or > 75th percentile —> indicated statin therapy
what are the brand names of each Statin?
Atorvastatin = lipitor
Fluvastatin = lescol
Lovastatin = Mevacor
Pravastatin = Pravachol
Rosuvastatin = crestor
Simvastatin = Zocor
Pitavastatin = Livalo
which statins are the most efficacious? ( list 3 drugs from most to least)
1) Rosuvastatin
2) atorvastatin
3) Simvastatin
When it is better to administer a Statin?
Do we have statins that can be administered anytime? (what is the reason?)
Atorvastatin (Lipitor)
Rosuvastatin (Crestor)
Pitavastatin (Livalo)
due to their long t1/2
What are the SE of Statin? (Mild-Transient / Serious)
Mild- Transient:
- headache
-myalgia
- GI
- increase glucose
Rare but serious:
- increase LFTs
- Myopathy
- Hemorrhagic stroke
What are the contraindications of statin?
Pregnancy
Active liver disease
who are the patients that are predisposed to adverse statin effects?
1) impaired renal or hepatic function
2) History of statin intolerance
3) Concomitant use of drugs affecting statin metabolism
4) Age > 75
5) ALT > 3 times the upper limit of normal
Can statin lead to myalgia?
Yes,
if it was:
- bilateral
- involve proximal muscles
- onset of weeks/months of statin therapy
- Improves upon statin discontinuation
what are the serious SE of statin?
- increase LFTs > x3 upper limit
- myositis ( increase CPK > 10x upper limit
- rare: rhabdomyolysis , myoglobinuria , Acute tubular necrosis
what inhibits statin? and what induce it?
inhibit: Gemfibrozil
Induce: Grapefruit
what are the monitoring used for safety?
-LFTs
-CPK
-Renal Function
which statin is less likely to cause muscle toxicity?
- pravastatin
- Fluvastatin
which statin is used during severe renal impairment?
- Atorvastatin
-Fluvastatin
which statin aren’t metabolized by CYP3A4 ?
- Pravastatin
- Fluvastatin
- Rosuvastatin
How to monitor statin therapy? and when?
- Adherence
- Response to therapy —> lipid panel
- Adverse effects
—-> first time 1-3 m after initiation or change in therapy —–> then 3-12 month
what are other Dyslipidemia Drugs can be used?
1) Ezetimibe (zetia)
decrease LDL
SE: Diarrhea + arthralgia + cough + fatigue
A choice in pregnancy
2) PCSK9 I : SC q 2-4 w
a- alirocumab
b- evolocumab
60% decrease in LDL
high cost
3) Fibrates:
a- gemfibrozil (Lopid) —–> mild GI upset ====> dont use with statin
b- Fenofibrate (triCor)
c- Clofibrate (Atromid)
d- Bezafibrate (EUROPE)
e- Ciprofibrate (EUROPE)
decrease TG and LDL + increase HDL & LFTs & incidence of Chol Gallstones
4) Bile acid resins:
a- colestipol (colestid)
b- cholestyramine (Questran)
c- colesevelam (Welchol)
Decrease LDL with addition to statin & absorption of fat soluble vitamin & folic acid + increase TG (avoid TG> 300mg/dL)
SE: GI ( less in colesevelam)
Colestipol + cholestyramine –> decrease absorption of anionic drugs (beta blockers + thiazide diuretics + warfarin + thyroxine + digoxin) –> space 1 hr before or 4 hrs after resin dose
5) Niacin : VITB3
decrease LDL & TG + increase HDL
Lack efficacy in reducing ASCVD
SE: flushing , hyperglycemia , hepatotoxicity
CI: active liver disease or peptic ulcers
6) Omega 3 (PUFA)
a- Decosahexaenoic acid (DHA)
b-Eicosapentaenoic aicd (EPA)
Lovaza & Icosapent ethyl (vascepa) –> decrease risk of CV if TG> 150 & established ASCVD / DM+ >or = 2 risk factors
Decrease TG by 50% –> high dose 2-4 g/d
SE: GI + A fib + fishy aftertaste + increase risk of bleeding
7) Bempedoic Acid:
decrease Chol in liver —> decrease LDL 23%
With ezetimibe –> decrease LDL by 48%
SE: increase risk of tendon rupture & increase uric acid
8) Mipomersen ( Kynamro) & lomitapide (Juxtapid) –> added in homozygous FH
SE: hepatotoxicity
9) Inclisiran :
decrease LDL by 50% with twice yearly dosing
10) FIber: or add psyllium (metamucil) – oat bran …. —> modest decrease in LDL
what is Hypertriglyceridemia and its causes?
TG> 150mg / dL
TG> 500 –> increase risk of pancreatitis
secondary causes :
- chronic renal failure
- DM
- Alcohol
- Sedentary lifestyle
- Obesity
- Drugs (beta blocker + estrogen + steroids)
How to manage Hypertriglyceridemia?
Omega 3 PUFA OR fibrates 1st line
ASCVD > or = 7.5 % –> statin
what are the causes of low HDL?
<40 in men
<50 in women
Causes:
- insuin resistance
- Physical inactivity
- DM
- Cigarette smoking
- hi Carbs
- Drugs
How to manage low HDL?
- weight reduction
- increased physical activity
-smoking cessation
-Drug therapy as needed
