TEST 3 Flashcards
Epidemiology of Hyperlipidemia
In the US by far, the leading cause of death is coronary artery disease. It accounts for over 500,000 deaths per year.
Why do we have Cholesterol?
Physiological cholesterol is:
- A component of our cell membranes.
- Important in the synthesis of hormones.
- It also makes up the majority of our Bile Acids which are squirted out by the gall bladder to help digest food.
- It is also part of the biophospholipid layer of the skin. This helps to protect the body from stuff that is trying to get in, but also keeps stuff in that could otherwise get out.
This is why we cannot lower cholesterol to zero. It has important roles within the body.
** Production of Cholesterol
we do get some of our cholesterol from nutritional intake, however the vast majority of cholesterol is endogenously produced by the liver.
Is TLC as effective in Hyperlipidemia as it is in Hypertention?
No
Unlike HTN, where we have TLC that is just as effective as Pharmacotherapy, this is not the case with Hyperlipidemia. Especially as it pertains to bad cholesterol.
TLC is not nearly as effective for patients who have had an MI and think that they can eat their way to an exceptable cholesterol level. It cannot be done because it is part of your genertic make-up.
There are 6 major classes of plasma lipoproteins. Out of the 6, which 3 have the most CLINICAL relevance?
- VLDL
- LDL
- HDL
What does VLDL stand for?
Very Low Density Lipoproteins (VLDL)
What does LDL stand for?
Low Density Lipoprotiens (LDL)
What does HDL stand for?
High Density Lipoproteins (HDL)
What are Very Low Density Lipoproteins (VLDL)?
**The majority of Very Low Density Lipoproteins (VLDL) is Triglycerides.
Back in the day, they thought that Triglycerides were way to big to have a DIRECT effect on your risk for coronary artery disease ect…But, we have found out more recently that they do have a direct effect on your risk.
Therefore, we are starting to pay more attention to Triglycerides.
**Triglycerides ARE considered a INDEPENDENT risk factor for Coronary Artery Disease,
What are Low Density Lipoprotiens (LDL)?
**Low Density Lipoprotiens (LDL) are the most important BY FAR.
The role of LDL is to DELIVER cholesterol away from the liver to NON-Hepatic Tissues.
So essentially it is a deliverer of Cholesterol.
This is notoriously called the “BAD” cholesterol.
The Higher your LDL, there is a DIRECT correlation with risks of diseases caused by cholesterol.
For every 1% REDUCTION in LDL, there is a 1% reduction of risk for cardiovascular disease. (Direct Correlation)
What are High Density Lipoproteins (HDL)?
High Density Lipoproteins (HDL) are kind-of like a vacuum cleaner. It runs around and picks up cholesterol remnants, and takes them back to the liver to be metabolized.
HDL instead of delivering cholesterol, it grabs it and RETURNS it to the liver.
This is the good stuff. We call this the “GOOD” cholesterol.
The HIGHER your HDL, the better off you are going to be. For instance, probably the best reason that women typically live longer than men because they naturally have a higher HDL level.
** The HIGHER your HDL level, the LOWER your risk is of having Cardiovascular Disease.
What is the role of LDL in Atherosclerosis?
LDL can pass freely from the arterial lumen into the sub-endothelial space,
In the sub-endothelial space, LDL can become Oxidized.
Oxidation attracts macrophages, which go into the sub-endothelial space and engulf the oxidized LDL and eventually become to fat to come back into the lumen. They then are white foam cells.
An accumulation of these foam cells causes a fatty streak within the artery which eventually herniates inward (stenoses). This makes a rough fibrous cap.
Which causes a supply and demand mismatch because not enough blood can flow through. (Angina).
If sheer forces occur, such as from sexual activity, elevated Blood Pressure, constipation,sudden stress, the fibrous cap can tear off (like a scab) and lipid contents can spill out causing a thrombus formation that can lead to a complete bloackage.
This causes an infarct of the area that the artery supplied.
What does NCEP stand for?
National Cholesterol Education Program (NCEP)
What does the National Cholesterol Education Program (NCEP) do?
They make the guidelines (bible) that Doctors follow in order to properly manage a patients cholesterol.
What is the first step that the NCEP recommends that patients follow?
Screening:
The first step is educating patients to get their initial screening at 20 years of age or older.
This should be a FASTING lipid panel .
Once they have their initial screening, they need to repeat it every 5 years or so.
Who is at greatest risk for hyperlipidemia?
Patients who already have established CHD (coronary heart disease)
Always ask the patient if they have any kind of heart disease or previous MI. (including people the had by-pass, stents ect)
What is secondary prevention?
This refers to a person who already has Established CHD (coronary heart disease)
What is primary prevention?
People that have RISK EQUIVALENTS for CHD but to NOT have CHD yet.
What are the 5 risk equivalent categories?
Patients with:
- Peripheral Vascular Disease
- Carotid Artery Disease
- Type 2 Diabetes
- AAA
- Framingham of <20% risk
These patients, along with pre-existing CHD are at greatest risk for an MI
According to NCEP, first we identify patients according to PMHx, then risk equivalents such as AAA, PVD, T2DM, and CAD. At this stage, if we have not found anything, what do we look for next?
screen for Major Risk factors.
The order of screening is:
- Past history of CHD
- Risk Equivalents
- Risk Factors
The higher on the list you are, the more likely you are to have problems.
What are the Major Risk Factors that NCEP has you screen for?
- Cigarette Smoking- 1 cig within the last month would count.
- HTN- 140/90 - even if on BP meds and well controlled.
- LOW HDL- if less than 40
- Positive Family History for CHD
- Age- male 55, female 65
This is the one negative risk factor. (meaning it is a good thing)
- If HDL >= 60
If your patient already has existing CHD, do you need to screen them for risk equivalents or risk factors?
No, if they have existing CHD, they go straight to the top of the list.
(Secondary Prevention)
If your patient does not have existing CHD but they do have a risk equivalent, do you need to screen them for risk factors?
No, even though they do not have existing CHD, if they have a risk equivalent it takes them to the top of the list
(Primary Prevention)
If you have evaluated your patent and they do not have existing CHD, they do not have any risk equivalents, but they do have 2 or more major risk factors, what would you complete next?
If 2 or more risk factors are present, calculate Framingham 10 year risk assessment and place the patient in the correct category of risk.
What is FRAMINGHAM?
it is an estimation of 10 Year risk for CHD for men and women.
What are the major factors in FRAMINGHAM? (5 of them)
- Age
- Smoking
- Systolic BP
- Total Cholesterol
- HDL
These are the things that you need to know in order to evaluate the patients risk. There is a different sheet to use for men and women. What you do is plug these variables in and it comes out with some sort of risk. This is used to categorize the patient. This is important in determining how aggressive you will treat the patient as well as what medication and dose they should be on.
What are the categories of risk in Framingham?
Patient Populations are:
- High Risk
- Moderate Risk
- Low Risk
Who falls into the High Risk Population in a Framingham assessment and what is their treatment goal?
High Risk Patient Population includes:
Patients with CHD and CHD risk equivalents.
(10 year risk of MI of >20%)
Their LDL goal is <100
Who falls into the Moderate Risk Population in a Framingham assessment and what is their treatment goal?
Moderate Risk Patient Population includes:
Multiple 2+ risk factors
(10 year risk of MI of 10-20%)
Their LDL goal is < 130
Who falls into the Low Risk Population in a Framingham assessment and what is their treatment goal?
Low Risk Patient Population includes:
0-1 Risk Factor
(10 Year risk of <160
Patients with:
- Peripheral Vascular Disease
- Carotid Artery Disease
- Type 2 Diabetes
- AAA
- Framingham of
Once we establish the risk establishment goals from the framingham assessment, What is the next thing that we do?
We look for secondary causes of dyslipidemia BEFORE initiation of various therapies.
Just like in HTN, we learned that diseases such as Pheocromocytoma can be a secondary cause of HTN and if you fix it, it can resolve the patients HTN.
Patients can also have secondary causes to their dyslipidemia that if fixed could resolve it.
What are the secondary causes of Dyslipidemia?
- Uncontrolled Diabetes
- Hypothyroid Disease
- Protein Wasting Syndromes
- Certain Medications such as anabolic steroids and certain progesterone types of medications.
If you identify a secondary cause, you MUST try and control it first.
In most cases it is not caused by secondary issues.
TRUE OR FALSE
TLC in patients with Dyslipidemia is just as effective as Pharmacotherapy, like TLC in HTN was
False
TLC may only lower the Patients LDL about 10% even if they ate like a bird.
It is generally not enough to keep the patient from having to utilize pharmacotherapy.
Any reduction is better than nothing so we do teach the patient about TLC.
Therapeutic Lifestyle Changes (TLC) are non-drug measures used to positively impact the lipid panel.
What do they consist of?
- Diet- reduce saturated fat and cholesterol in the diet by drinking low fat milk, trimming the fat off of meat ect.. and also increasing your fiber.
- Weight Reduction
- Increasing Physical Activity.
Metabolic syndrome is a secondary target of therapy. What is it defined by?
Metabolic Syndrome is defined when 3 or more of the following are present within the same patient:
- Abdominal Obesity - < 35 in for women. Central Adiposity is the worst fat to have because it surrounds the vital organs.
- Triglycerides- >= 150
- HDL < 40 in men and 130/85 (just know elevated)
- FBG >100
(normal FBS is 70-99. takes FBS of 126 to diagnose diabetes.)
Patients that have Metabolic Syndrome need to be educated about what?
They need to be educated about their extreme risk for a major event.
Their treatment is aggressive and you have to treat the underlying causes such as pre-diabetes.
TLC is PARAMOUNT
Is a diabetics LDL the same as a normal Persons LDL?
No, Normal peoples LDL is big and Fluffy.
Diabetics have an LDL that is more small and dense.
The reason for this is because high triglycerides can have a impact on LDL which makes it small and dense. This means that even though a diabetics LDL is the same number as a normal person, it is a worse form of LDL because it is smaller and more likely to get oxidized.
TRUE OR FALSE
Triglycerides a risk factor for CHD
TRUE
BUT, they are an INDEPENDENT risk factor for CHD and important as a SECONDARY cause
The theory is that when triglycerides are gobbled up and metabolized, they leave remnants behind that are small enough to get oxidized and to form plaques just like LDL.
THUS- VLDL can be a secondary target of therapy.
What are the factors for Hypertriglyceridemia?
obesity physical inactivity smoking excess ETOH high carb diets diabetes chronic renal failure nephrotic syndrome genetics drugs- corticosteroids, estrogens, retinoids, high dose beta blockers
What are the normal triglyceride levels
< 150
What are borderline triglyceride levels
150 - 199
What are high triglyceride levels?
200 - 499
What are Very high triglyceride levels?
<= 500
When triglycerides are over 500 what are you at risk for?
Pancreatitis.
When over 500, VLDL becomes your primary target because if pancreatitis is not treated it can cause a septic like syndrome and the patient can die.
Once the triglycerides are back below 500, the primary target goes back to LDL.
When a patients LDL has been treated and is at goal, what do you perform next?
You re-evaluate the patients triglycerides.
If they are greater than 200, you need to calculate a NON-HDL calculation.
This is done by taking the patients Total Cholesterol and subtracting the HDL.
That number should be less than 30 points higher than the patients LDL goal.
If the patient has an LDL goal of < 100, what is their NON-HDL goal?
130
What are the secondary targets of therapy for CHD?
Metabolic Syndrome
Hypertriglyceridemia if <200
Low HDL
TRUE OR FALSE
Triglycerides respond great to TLC
TRUE
If you eat right, your triglycerides go down
if you exercise, your triglycerides go down
If you control your diabetes, your triglycerides typically improve.
If you drink excessive alcohol, your triglycerides will improve.
What is Low HDL defined as
< 40.
Patients that have high triglycerides have low HDL.
TRUE OR FALSE
Through randomized controlled trials, we actually found that using pharmacotherapy to manipulate a persons HDL makes a huge impact in CHD
FALSE
It actually showed no evidence that it even makes a difference.
HDL also responds to TLC so better to use that instead of Pharmacotherapy
What is Pressor?
The most powerful statin
True or False
The lower you get someones LDL, the better off they will be
True
Studies proved that significantly lowering a patients LDL especially after the patient has already had By-pass or stents placed, the better off they are
we have yet to figure out how low is too low.
patients are now being kept below 70 even though they are at their LDL of less than 100.
Some people have decreased all the way to 30 and are fine.
This only pertains to secondary prevention patients.
65 year old male
PMH- PCI, type 2 diabetes
Drinks excessively
Smokes 2 packs PD
TOT CH- 324
HDL- 37
VLDL- 675
LDL- 193
What do you ask yourself first?
Is it primary or secondary prevention.
This is secondary prevention because of PCI
This already puts him at the very top risk of getting a MI
65 year old male
PMH- PCI, type 2 diabetes
Drinks excessively
Smokes 2 packs PD
TOT CH- 324
HDL- 37
VLDL- 675
LDL- 193
What is his LDL goal?
since it is secondary prevention his LDL goal is < 100 or less than 70
65 year old male
PMH- PCI, type 2 diabetes
Drinks excessively
Smokes 2 packs PD
TOT CH- 324
HDL- 37
VLDL- 675
LDL- 193
What is his VLDL goal?
< 150
65 year old male
PMH- PCI, type 2 diabetes
Drinks excessively
Smokes 2 packs PD
TOT CH- 324
HDL- 37
VLDL- 675
LDL- 193
What is his Non- HDL goal
< 130 or <100
65 year old male
PMH- PCI, type 2 diabetes
Drinks excessively
Smokes 2 packs PD
TOT CH- 324
HDL- 37
VLDL- 675
LDL- 193
Which of these would you address first?
VLDL- because over 500 puts him at risk for pancreatitis
Need to address drinking and triglycerides
What is The most effective and widely used cholesterol medication that we have?
Statins:
The most potent LDL reducers that we have that is what makes them the most effective.
They can reduce events by up to 30-35%
It is prolonging how long we live.
What is the MOA of Statins?
hydroxymethylglutaryl coenzyme A (HMG-CoA) Reductase Inhibitor.
This is an enzyme that is critical in the synthesis of cholesterol. So if we wipe this enzyme out, out body cannot make an adequate amount of cholesterol.
If you wipe out (HMG-CoA) Reductase and the body needs more cholesterol, what does the liver do?
it sucks it out of the blood stream because it cannot make it,
This is how it lowers LDL
Are statins linear or non linear drugs?
Non- Linear
This means that you get a big bang for your buck at the lowest doses.
This means that if you double your dose, it will not lower your LDL any more than like 6%.
What are the net results of Statin therapy?
It can lower your LDL up to 60%
can lower VLDL by like 3%
What are the Kinetics of Statin therapy
SAL
Simvastatin
Atorvastain
Lovastatin
are metabolized by CYP3A4
These have significant drug interactions
What is the category for pregnancy for statins?
x
Not safe during pregancy
What are the side effects of Statin therapy?
- Myalgia (1-5%)- myalgia simply means that something is going on with the muscles.
- Myositis- (Moderate elevation in CPK) Inflammation of the muscles.
- Large muscles like thighs and butt, back.
- Is terrible, like being beaten with a bat.
- It is BILATERAL, usually associated with a fever.
- Older people show signs of weakness and less pain
- Rhabdomyolysis- this is where muscles start to break down. It can lead to kidney failure. (Very rare)
- Transaminase Elevation- Approx 0.5-2%.- which is AST/ALT. When these are elevated it means that the liver is inflamed or irritated. Not indicative of function. Very Rare.
- For Liver function we test- Albumin is low, Billirubin is high, PT/INR is high. Those are indicative of liver function.
What is the MOA of Niacin?
Decreases production of VLDL.
**Increases HDL
Decreases LDL
This is the one drug that does everything correctly.
***It is THE BEST HDL increaser.
It is the 2nd Best LDL reducer (2nd to statins)
It is the 2nd best VLDL reducer
If a patient cannot take a Statin due to true Myosytis, than which drug are you going to put them on to lower their LDL?
Niacin
Reduces LDL by about 35%
To what percent does Niacin lower VLDL?
up to 40%
To what percent does Niacin increase HDL?
up to 35%
What are the adverse effects of Niacin?
Flushing (More common with IR)
GI Toxicity
Hepatoxicity (more common with SR)
Hyperglycemia - only 1/3 of diabetics will require any adjustment in dose
Hyperuricemia- (can cause gout)
What is your counseling for Niacin?
**1. Start low and go slow
**2. Take it with food.
**3. Take an NSAID or Aspirn 30 min before Niacin
**4. Avoid taking with alcohol and hot or spicy foods or beverages.
**5.After a week or 2, you will become tolerant to that dose. Teach them to take IR at night.
**6. Avoid Interruption of therapy. If you run out of it, you have to start over with your tolerance level. (flushing, burning, itching)
- 2 grams per day cap on SR niacin. Not a cap on IR Niacin
What are the fibrates?
Gemfibrozil and Fenofibrate (Tricor)
What is the MOA of fibrates?
Gemfibrozil and Fenofibrate (Tricor)
interacts with peroxisome proliferator-activated receptor alpha (PPAR Alpha) witch increases synthesis of Lipoprotein Liapase. This accelerates the clearance of VLDL.
This is the most effective VLDL reducer.
Typically in a case where you have to address Triglycerides first, this is what you would give them.
They are the 2nd most effective HDL increaser (2nd to Niacin)
They do not do diddly for LDL
What are the effects of Fibrates? Gemfibrozil and Fenofibrate (Tricor)
can reduce VLDL up to 90% so these are the best triglyceride reducers.
Can increase HDL by about 20% (2nd best)
No effect on LDL
What are the side effects of Fibrates? Gemfibrozil and Fenofibrate (Tricor)
**It can cause irritation of the liver. So need to check baseline transaminase levels.
-If the patient complains of flu like symptoms or abdominal pain, you would want to repeat the transaminase levels and compare to the baseline.
**It can also produce myopathies similar to statins. You can use fibrates in combination with statins so that can double the risk of myalgias.
-need to council the patient on the symptoms.
What are the drug interactions of Fibrates? Gemfibrozil and Fenofibrate (Tricor)
Can increase Warfarin concentrations. Will Elevate the INR. Will need to reduce Warfarin,
When Combined with statins can increase the chances of Myopathies.
What drugs are Bile Acid Sequestrants (BAS)?
**Cholestyramine
Colestipol
Colesevelam
What is the MOA of Bile Acid Sequestrants (BAS)? **Cholestyramine
form insouluable complex in the small intestine with bile acids that are RICH in cholesterol, reducing the reabsorption of the bile acids (Enterohepatic recirculation). Through the loss of Bile Acids, causes a demand for increased bile acid synthesis which requires cholesterol. Thus LDL receptors are increased on the liver to allow additional uptake. The Net Result is reduction in plasma LDL concentration.
What are the effects of Bile Acid Sequestrants (BAS)? **Cholestyramine
Can reduce LDL by about 20%. So not as effective as Statins or Niacin.
Has no effect on HDL
**Can Increase Triglycerides.
This is typically an add on therapy to Niacin, or Statins.
What are the Kinetics of Bile Acid Sequestrants (BAS)? **Cholestyramine
It is not absorbed, it just passes on through
comes in a powder form that you have to mix with water and drink it. It is like drinking Sand, its nasty.
It also comes in tablets but they are HUGE. 8-12 of them at a time.
What are the side effects of Bile Acid Sequestrants (BAS)? **Cholestyramine
GI side effects-
devoid of systemic side effects.
This stuff looks like sand going in and a brick coming out.
Constipation
Bloating
Indigestion
Reduces absorption of fat-soluable vitamins (A,D,E,K)
Welchol- has less of these side effects but is more expensive.
What are the drug interactions of Bile Acid Sequestrants (BAS)? **Cholestyramine
Just like it can grab bile acids and make you poop them out, it can also grab medications and make you poop them out as well.
Warfarin
Thyroid Replacement
Recommendation is to take your other drugs 1 hour before the BAS so that they get a 1 hour head start or take the BAS first and the medications 4 hours later.
What is the MOA of Etetimibe (Zetia)
Inhibits the passage of dietary and biliary cholesterol absorption across the brush border of the small intestine.
Actually blocks the absorption of cholesterol in the small intestine.
What are the effects of Etetimibe (Zetia)?
Very similar to BAS
lowers LDL by about 20%
Will be an add on therapy to either Niacin or Statins for additional LDL reduction.
Neutral for VLDL
HDL Neutral
When you take up to 6-8 grams a day, it is a pretty significant _______ reducer.
Triglyceride
What is the problem with taking that much fish oil?
You get fish burps
Acid Reflux Disease
GI Things
smelling it through your skin
What is Omacor, now called Lovaza.
Very concentrated fish oil tablets.
2 caps BID is equivalent to taking about 16 over the counter fish oil tablets.
Through very high concentrations of EPA and DHA, it can reduce Triglycerides by 20-50%
we have zero data that tells us that it changes the outcome of CHD,
