Hyperlipidemia Flashcards
What is the function of lipoproteins?
Because lipids are insoluble in plasma, circulating lipids are carried in these
Used for energy, storage, hormone production and bile acid formation
What happens after abnormal lipoprotein metabolism?
Atherosclerosis (usually genetic because of defective receptors so there is overproduction/impaired removal of lipoproteins)
What are the 5 types of lipoproteins?
Chylomicrons, VLDL, IDL, LDL and HDL
Function of chylomicrons
Carry dietary lipids from intestine to liver, skeletal muscle and adipose tissue
Function of VLDLs
Carry newly synthesized triglycerides from liver to adipose tissue
Function of IDLs
Intermediate between VLDL and LDL (usually not detectable in blood)
Function of LDLs
Carry cholesterol from liver to body’s cells
Function of HDLs
Collect excess cholesterol from body’s tissues (including vascular endothelium) and return it to the liver
Basically reverse cholesterol transport to provide protection against heart disease
What do you want to suspect in anyone with a family history of premature atherosclerotic cardiovascular disease?
An inherited increased lipid disorder (familial hypercholesterolemia, polygenic hypercholesterolemia or familial combined hyperlipidemia)
What is familial hypercholesterolemia?
Monogenic and very rare
Homozygotes have much more LDL than heterozygotes
Treat with a statin (and maybe add on)
What is polygenic hypercholesterolemia?
Very similar to familial but multiple genes!
Increased LDL with premature onset of CHD
Treat with a statin (and maybe add on)
What is familial combined hyperlipidemia?
Polygenic with a wide variety of lipid abnormalities
Present in almost half of people with familial CHD
Treat with a statin (and maybe add on)
What is secondary hyperlipidemia?
Etiology that does not relate to lipid metabolism (diabetes and excessive alcohol most common, also obesity, smoking, renal/liver disease, drugs etc)
Process of atherosclerosis
LDLs diffuse through endothelium at a rate that is dependent on the concentration in the blood!
Macrophages follow, absorb them, become foam cells and then die to release cholesterol and form deposits
Body reacts with increased collagen to form a cap
Cap ruptures and thrombus forms leading to a potential infarct
When is it recommended to screen?
Between 9-11 and again at 17-21 yrs
Non-modifiable risk factors of CHD
Family history of premature ASCVD Age (male over 45 and female over 55) Male Symptomatic cardiovascular disease (angina etc) Chronic kidney disease
Modifiable risk factors of CHD
HTN (BP over 140/90 or on antihypertensive) DM Smoking Obesity Hyperlipidemia or HDL<40
What is a negative risk factor of CHD?
HDL > 60
What is on a fasting lipid panel?
Total cholesterol, triglycerides, LDL and HDL
Total cholesterol= HDL + LDL + (TAGs/5)
Why do you need to 12 hour fast before a fasting lipid panel?
Cholesterol isn’t really affected by eating but TAGs are and they are done at the same time
Cholesterol levels and acute MI
Levels can drop 24-48 hrs after acute MI and can persist up to 60 days
Lipid profile cutoffs
Cholesterol: <200 mg/dL good, 240 high risk
TAGs: <150 good, 200-499 high risk
HDL: 60 good, <35 high risk
LDL: 60-130 good, 160-189 high risk
What are plane xanthomas?
Cholesterol-filled, soft, yellow plaques that appear in various places (can indicate familial or secondary causes)
What are tuberous xanthomas?
Yellow-orange nodules often over knees and elbows (can also be in tendons)
Associate with familial hypercholesterolemia
What are eruptive xanthomas?
Crops of small red-yellow papules with ABRUPT ONSET
Seen on extensor surfaces and butt
Caused by elevated TAGs >1500 (indicate familial HLD
What is corneal arcus?
White or grey ring around the cornea
Abnormal in pts under 40!
What is the approach to lipid management?
Diet, exercise and meds
DASH diet
For HTN/hyperlipidemia
Rich in fruits and veggies, moderate low fat dairy, low animal protein, plant sources of protein, low sodium
Goal is to decrease BP, LDL and hopefully decrease risk of CHD and stroke
What can increase HDL cholesterol?
Exercise
Types of medications used
HMG Co-A reductase inhibitors (statins) Fibrates Nicotinic acid Bile acid sequestrants Cholesterol absorption inhibitors PCSK9 inhibitors
Why are statins used?
To decrease incidence of major vascular events and coronary mortality
Think they stabilize vulnerable plaques and reduce inflammation
How do statins work?
Inhibit HMG-CoA reductase (rate limiting step in cholesterol synthesis in liver)
Less cholesterol is produced to decrease blood levels
Liver enzymes sense this and increase LDL receptors
Relocate to membrane and bind LDL and VLDL to take more cholesterol out of blood
LDL and VLDL goes to liver and gets digested
Lipid panel changes with a statin
Lower LDL by 20-60%
Lower TAGs by 15-30%
Adverse effects of statins
Mild GI, liver toxicity, myalgia, myositis, myopathy, rhabdo
Contraindications of statins
Absolute: Active liver disease and pregnancy
Caution: use of other CYP3A4 inhibitors and various drugs, chronic kidney/liver disease
What baseline should you obtain before statin therapy?
Lipid panel, LFTs and creatine kinase levels
What should you consider when there is a poor response or intolerance to statin therapy?
Reinforce adherence to meds and lifestyle changes
Exclude secondary causes
Investigate statin intolerance
When should the addition of a nonstatin LDL lowering agent be considered?
In ppl at high ASCVD risk that are getting the maximum tolerated statin and there is an insufficient response
What are bile acid sequestrants (resins)?
Ex: cholestyramine, colesevelam, colestipol
Bind bile acids in the intestine to inhibit their absorption
Decrease LDL by up to 24%
Act synergistically with statins
Safe in pregnancy!
Adverse effects of resins
Constipation, gas, may interfere with fat soluble vitamin absorption, affect warfarin management, increase TAGs
Contraindications of resins
Absolute: TAGs >400
Relative: TAGs >200
What does nicotinic acid do?
Reduce production of LDL, increase HDL and may reduce TAGs
Adverse effects of nicotinic acid
Flushing and pruritus, liver damage, safety concerns when combo with statin
Contraindications of nicotinic acid
Absolute: active liver disease
Relative: hyperuricemia, hyperglycemia, unstable angina
Don’t use in pregnancy
What do fibric acid derivatives do?
(Gemfibrozil, fenofibrate, bezafibrate)
Mostly lower TAGs, raise HDL
Don’t usually use in pregnancy
Adverse effects of fibric acid derivatives
May induce gall stones, hepatitis and myositis
Contraindications of fibric acid derivatives
Absolute: severe hepatic or renal disease, preexisting gallstones, taking simvastatin
Relative: other statin use (risk of myopathy), concurrent warfarin use
What does Ezetimibe do?
Blocks intestinal absorption of dietary and biliary cholesterol via transporter
Lower LDL up to 17%
Can use with statin
Contra: do not use with statin in active liver disease and pregnancy
PCSK9 inhibitors
(Evolocumab, alirocumab)
Limited experience and data but should reduce LDL levels
What are the 4 statin benefit groups?
Individuals with clinical ASCVD (acute coronary syndromes, history of MI, stable or unstable angina)
Individuals with LDL>190
Individuals with diabetes aged 40-75 yrs with LDL 70-189 and without clinical ASCVD
Individuals without ASCVD or diabetes with LDL 70-189 and estimated 10 yr ASCVD risk is >7.5%
What statin level is used for people with clinical ASCVD?
Less than 75: high intensity
Over 75: moderate intensity
What statin level is used for group 2?
High intensity
What statin level is used for group 3?
Moderate intensity (high when 10 yr wisk is over 7.5%)
What statin level is used for group 4?
Moderate to high
What is the biggest contributor to ASCVD risk calculator?
Age
What factors can also be used to initiate stain therapy if not in the 4 groups?
LDL >160, family history of premature ASCVD, Hs-CRP>2 mg/L, ABI
