L2: Hyperlipidemia Flashcards
What do chylomicrons do?
Carry dietary lipids from intestine to liver, skeletal muscle, and adipose tissue
What do VLDL’s do?
Carry newly synthesized triglycerides from liver to adipose tissue
What do IDL’s do?
Intermediate between VLDL and LDL; not usually detectable in blood
What do LDL’s do?
Carry cholesterol from liver to body’s cells
What do HDL’s do?
Collect cholesterol from body’s tissue and return it to liver (the good cholesterol)
What are the 2 forms of exogenous lipid metabolism?
- Diet
- Chylomicrons
What are the 2 forms of endogenous lipid metabolism/
- Liver (produces fats)
- VLDL, LDL, IDL
What is the 1 form of reverse cholesterol transport lipid metabolism?
HDL
What are the 3 types of inherited lipid disorders?
- Familial hypercholesterolemia
- Polygenic hypercholesterolemia
- Familial combined hyperlipidemia
What are the gene requirements for familial hypercholesterolemia?
Monogenic disorder:
- Heterozygotes (2x normal value of LDL)
- Homozygotes (8x normal value of LDL)
Which inherited hyperlipidemias are polygenic?
- Polygenic hypercholesterolemia
- Familial combined hyperlipidemia
Of the 3 inherited disorders, which is most common?
Familial combined hyperlipidemia
What is FCH different from PH or FH?
PH and FH have increased levels of LDL while FCH has a wide variety of lipid abnormalities.
How do you treat the inherited hyperlipidemias (in general)?
Statins
What are the types of secondary hyperlipidemias? (8)
- Diabetes
- Excessive alcohol
- Smoking
- Obesity
- Hypothyroidism
- Chronic renal disease
- Medications
When should children with a family hx of hyperlipidemia be screened?
Between ages 9-11 and again at 17-21 years old or earlier if high suspicion
What are the modifiable risk factors for CHD (coronary heart disease)?
- HTN (BP >/= 140/90 or on antihypertensive)
- DM
- Tobacco use
- Obesity
- Hyperlipidemia or HDL <40
What HDL level is considered a risk factor? What HDL level is considered a negative risk factor?
Risk factor: HDL <40
Negative risk factor: HDL >/= 60
What is the primary form of testing for hyperlipidemia? Describe the process.
Fasting lipid panel
- Consists of total cholesterol, triglycerides, LDL, and HDL
- Total cholesterol = HDL + LDL + (triglycerides/5)
- 12 hour fast (mostly for the triglycerides)
What can cause falsely low levels when taking a fasting lipid panel?
Acute coronary syndrome (cholesterol/LDL/HDL levels can drop 24-48 hours after acute MI and persist for 60 days)
What is the desirable, borderline, and high risk levels for cholesterol on a lipid profile?
Desirable: <200
Borderline: 200-239
High risk: 240
What is the desirable, borderline, and high risk levels for triglycerides on a lipid profile?
Desirable: <150
Borderline: 150-199
High risk: 200-499
What is the desirable, borderline, and high risk levels for HDL on a lipid profile?
Desirable: 60
Borderline: 35-45
High risk: <35
What is the desirable, borderline, and high risk levels for LDL on a lipid profile?
Desirable: 60-130
Borderline: 130-159
High risk: 160-189
What are 4 possible exam findings you may see in a patient with hyperlipidemia?
- Plane xanthomas
- Tuberous xanthoma
- Eruptive xanthoma
- Corneal arcus
***But remember PE may be completely normal
What are plane xanthomas? Which disorders would this finding indicate?
- Cholesterol filled, soft, yellow plaques that appear in various places
- Can indicate familial or secondary causes
What are cholesterol filled, soft, yellow plaques that appear in various places?
Plane xanthomas
What are tuberous xanthomas? Which disorders would this finding indicate?
- Yellow-orange nodules often located over knees and elbows (can also be in the tendons = tendinous xanthoma)
- Associated with familial hypercholesterolemia
What are yellow-orange nodules often located over knees and elbows?
Tuberous xanthomas
What are crops of red-yellow papules with abrupt onset, most commonly located on the extensor surfaces and buttocks?
Eruptive xanthomas
What are eruptive xanthomas? Which disorders would this finding indicate?
- May indicated familiar HLD
- Caused by elevated triglycerides often >1500mg/dL
What level of triglycerides can cause eruptive xanthomas?
> 1500mg/dL
What is a corneal arcus?
White or grey ring around cornea (can be common in pts over 40 WITHOUT elevated lipids)
What is the DASH diet?
- Dietary Approaches to Stop Hypertension*
- Rich in fruits and veggies
- Moderate in low-fat dairy products
- Low in animal protein
- Contains many plant sources of protein (legumes and nuts)
- Low sodium
What is a form of treatment that can actually increase HDL levels?
Exercise!
What is the recommendation for exercise in a pt with hyperlipidemia?
3-4 session/week (40 min, mod-vigorous exercise)
What is another name for statins?
HMG Co-A Reductase Inhibitors
What is the MOA for statins? (describe the process)
- Inhibit HMG Co-A Reductase (part of RLS in cholesterol synthesis in liver)
- Less cholesterol produced and blood cholesterol levels decrease
- Liver enzymes detect low cholesterol = increased LDL and VLDL receptors at liver = cholesterol digestion
What are the adverse effects of using statins? (4)
- Liver toxicity
- Mild GI complaints
- Myalgias, myositis, myopathy
- Rhabdomyolysis
When should statins be taken (time of day)?
Bedtime (that is when most cholesterol is synthesized)
What are the contraindications for statins? (List absolute and cautionary situations)
Absolute: Active liver disease, Pregnancy
Use with caution: Concomitant use of CYP3A4 inhibitors and various drugs (drug interactions!), chronic kidney/liver disease
How do you monitor statin therapy?
- Baseline lipid panel, liver function test, and creatine kinase labs
- While pt takes meds and makes life style changes, repeat lipid panel every 4-12 weeks after initiation or dose adjustment
- Repeat every 3-12 months as needed
What are the 3 things you should do if pt has a poor response or intolerance to statin therapy?
- Reinforce adherence to medication and lifestyle changes
- Exclude secondary causes of hyperlipidemia
- Investigate statin intolerance
How should you treat an individual who is at high risk for atherosclerotic cardiovascular disease and who is already taking max tolerated statin but has an insufficient response?
Consideration for addition of a non-statin LDL lowering agent to their therapy
Which medications should NOT be given during pregnancy?
- Statins
- Nicotinic Acid (Niacin)
- Fibric acid derivatives
- Ezetimibe
Which medications are safe to use during pregnancy?
-Bile acid sequestrants (resins)
What is the primary purpose of statin use?
Lowers LDL
What 3 primary things should you be cautious of when prescribing statins?
- Liver toxicity
- Myopathy
- Drug interactions
What should you do if myositis (rhabdomyolysis) is suspected with statin therapy?
Discontinue statin and check CK level
What is the primary purpose of fibrate use?
Decrease triglycerides (most useful with hypertriglyceridemia)
What are the absolute and relative contraindications with fibrates?
Absolute: Severe hepatic or renal disease, pre existing gall stones, taking simvastatin
Relative: Other statin use (myopathy risk), concurrent warfarin use
***INCREASED RISK OF TOXICITIES WHEN USED WITH STATINS
What is the primary purpose of niacin use?
Raise HDL, Lower LDL
What are the absolute and relative contraindications with nicotinic acid (niacin) use?
Absolute: Active liver disease (check LFTs)
Relative: Hyperuricemia, hyperglycemia, unstable angina
What is the primary side effect of fibrate use and how do you help prevent this?
Flushing; titrate slowly
What is the primary purpose of bile acid sequestrants (resins)?
Lower LDL
Which drug acts synergistically with statins?
Bile acid sequestrants (resins)
What are the absolute and relative contraindications for resins?
CAN INCREASE TRIGLYCERIDES
Absolute: TGs > 400 mg/dL
Relative: TGs > 200 mg/dL
What is the primary side effect associated with resins?
GI side effects
What is the primary purpose of Ezetimibe?
Decreases LDL, Statin add-on
What is are the contraindications associated with Ezetimibe use?
Use with a statin in active liver disease, pregnancy
What is the primary purpose of PCSK9 inhibitors?
Decreases LDL
How should PCSK9 inhibitors be used?
Adjunctive w/ statins or if statins not tolerated
Which medication is expensive and requires injections?
PCSK9 inhibitors
Which medications can be used in adjunct with statins?
- Resins
- Ezetimibe
- PCSK9 inhibitors
Which medications should NOT be used in adjunct with statins?
- Nicotinic acid (Niacin)
- Fibrates
According to 2018 guidelines, what are the primary goals for tx of hyperlipidemia?
- Reduce ASCVD events in secondary and primary prevention
- Focus on ASCVD risk reduction rather than target lipid levels
- Risk reduction = decrease in LDL level
Which 4 groups would benefit from statin therapy? Specify which is secondary and primary prevention)
- Individuals with clinical ASCVD (secondary prevention)
- Individuals with LDL >/= 190 mg/dL
- Individuals with diabetes aged 40-75 yo with LDL >/= 70 mg/dL
- Individuals without ASCVD or DM but with LDL levels at 70-189 mg/dL and estimated 10-year ASCVD risk >/= 7.5% (estimated via pooled cohort equations)
