Dyslipidemia Flashcards
Triglycerides serve what function in the body?
Essential energy source
Cholesterol is needed for what in the body?
Cell membrane structure, bile acid formation, steroid hormone synthesis
Hyperlipidemia can be..
Hypercholesterolemia
Hypertriglyceridemia
Elevated LDL
Physical exam findings in hyperlipidemia
Xanthelasma
Circumferential arcus
PVD
Thickened achilles
HTN
If not fasting for lab testing, which values should you pay attention to?
Only Total and HDL. If TC are over 200mg/dl or HDL<40, retest
Total cholesterol numbers
Good- 240 mg/dl
HDL numbers
Low- 60 (very good)
LDL numbers
Optimal- 190
Are numbers supposed to be important anymore?
No, should be focusing on RISK
What are the typical total cholesterol and TC in someone with primary hyperlipidemia?
Total >200, TC often >500
Causes of secondary hyperlipidemia
DM Hypothyroid Obstructive liver disease Chronic renal failure Drugs such as progestins, corticosteroids, anabolic steroids
When should lipid screening start? When to re-screen?
All adults 20 and older. Every 4-6 years if numbers/risk normal.
A lipid screen should include which tests?
Total, LDL, HDL, TC, ALT, CK, HbA1c. Complete 10 year estimated ASCVD risk assessment.
What intervention should everyone receive, regardless of risk or numbers?
Therapeutic lifestyle changes. Reduce saturated fats/cholesterol, increase activity, control weight.
Diet effects on HDL
ETOH, saturated fats, and weight loss RAISE HDL
Low fat diet, sugar intake, excess calories, and excess polyunsaturated fats LOWER HDL
Diet effects on LDL
Saturated fat, trans fatty acids, and cholesterol RAISE LDL
MUFAs, complex carbs, and soy LOWER LDL
Diet effects on total cholesterol
Saturated fats and trans fatty acids RAISE total cholesterol
Substituting MUFAs and complex carbs for saturated fats, soy LOWER total cholesterol
Diet effects on TC
ETOH, sugar, high carb diet, excess calories RAISE TC
Weight loss, omega 3 fatty acids LOWER TC
Total fat recs
25-35%
Total carb recs
50-60%
Daily fiber recs
20-30 grams
Total protein recs
15%
Total daily cholesterol intake should be
less then 200mg
ASCVD risk factors
Gender, age, race, total cholesterol, HDL, systolic BP, treatment for BP, diabetes, smoker
What drug class is the focus of ASCVD prevention?
Statins
Name the four main categories established for statin therapy for secondary prevention of ASCVD
Clinical ASCVD
LDL >/= 190
Diabetes
> /= 7.5% estimated 10-yr ASCVD risk
You would expect to see an LDL reduction of _____ in moderate intensity statin therapy
30-50%
You would expect to see an LDL reduction of _____ in high intensity statin therapy
50% or greater
What is the LDL level at which there is generally a reduction in ASCVD risk with statin therapy
LDL >70
Primary agents and doses for low intensity statin therapy
Pravastatin 10-20mg
Lovastatin 20mg
What reduction in LDL can be expected with low intensity statin therapy?
<30%
What are the primary agents and doses for moderate intensity statin therapy?
Atorvastatin 40mg
Rosuvastatin 10mg
SImvastatin 20-40mg
Pravastatin 40mg
Lovastatin 40mg
Fluvastatin 40mg BID
Which agents and doses are used in high intensity statin therapy?
Atorvastatin 80mg
Rosuvastatin 20mg
How do statins work?
Inhibition of HMG-CoA reductase, which is the rate limiting enzyme is the formation of cholesterol
What effect do statins have in general on lipid profile
Decrease LDL
Decrease TG
Increase HDL
Statin therapy recs for clinical ASCVD
75 and under- high intensity statin therapy
Over 75 or unable to tolerate high intensity therapy- moderate intensity therapy
In primary hyperlipidemia, a reduction in LDL of 39mg/dl results in ASCVD risk reduction by
~20%
Statin therapy for primary hyperlipidemia is for patients with an LDL of
190 or more
What is a secondary concern for patients with primary hyperlipidemia?
High TG level, which may require therapy in addition to statins
When considering statin therapy for ASCVD risk reduction in diabetes, does the type (I or II) matter?
No, Type I or II treated the same for ASCVD risk
Which level of therapy is acceptable for diabetics with an LDL greater than 190?
Moderate intensity therapy
When is high intensity therapy needed in diabetes?
LDL greater than 190 and 10yr ASCVD risk > 7.5%
When should a 10yr ASCVD risk assessment be completed?
In patients without ASCVD or DM with an LDL<190
Why are statins so great?
They demonstrate substantial ASCVD risk reduction across all LDL levels, especially for those with high ASCVD risk
What are some areas that need additional investigation in the new ASCVD risk reduction guidelines?
- Other biomarkers to guide treatment
- Best non-invasive imaging for risk assessment
- Lifetime vs 10yr risk and optimal age to begin statins
- Other subgroups such as HF, ESRD on HD, HIV, solid organ transplant, etc.
What are the secondary treatment goals of the guidelines?
Treat TG >200 if LDL goal has been achieved
Treat low HDL (<40)
Cholestyramin (Questran), Colestipol, and Colesevelam are all _____ and work by
Bile acid sequestrants
Bind bile acids in the intestines –> liver uses more hepatic cholesterol to produce bile –> decreased LDL and increase in HDL
What effect does nicotinic acid have on blood lipoproteins?
Causes a reduction in the synthesis of VLDLs which results in decreased LDLs and TGs and an increase in HDLs
Gemfibrozil (Lopid), Fenofibrate, and Clofibrate are all ________. How do these agents work?
Fibric acid derivatives
They reduce synthesis and increase the breakdown of VLDLs which results in decreased LDLs and TGs and an increase in HDLs
How does Ezetimibe (Zetia) work?
Inhibits absorption of cholesterol and phytosterol at the brush border.
Has little effect on vitamin A,D,E, and K (fat soluble vitamins) or the CYP450 system.
Used in conjunction with a statin
Statin plus Ezetimibe results in an LDL reduction of ______
Statin plus bile acid sequestrant results in an LDL reduction of ______
~25%
~8-16%
Nasty risk associated with statin use
Myopathies
Statin plus fibric acid derivative is used for _______, increases the risk of ________ and is contraindicated in _________.
decreasing TGs
myopathies
severe hepatic disease
Statin+Niacin=
:-(
Also, increased risk of hepatic dysfunction
Significant drug interactions with Lovastatin and Simvastatin
Itraconazole (Sporanox) Ketoconazole (Nizoral) Erythromycin Clarithromycin (Biaxin) Gemfibrozil Grapefruit juice
Individuals at increased risk for statin induced myopathies
>80 Small body frame Frailty Impaired renal/hepatic function ETOH
Drug combos with statins that increase myopathy risk
Niacin Gemfibrozil Cyclosporin HIV protease inhibitors Verapamil Amiodarone
Currently the only lipoprotein lowering agent safe for use during pregnancy
Bile acid sequestrants
In the future we’ll be using
Cholesteryl ester transfer protein inhibitors (CETP)
Exchanges lipoprotein particles in a reverse cholesterol transport process (Sounds pretty serious…)
Significant DROP in LDL along with a bump in HDL
Anacetrapib and Dalcetrapib are possible candidates
(Fun fact- Anacetrapib can stick around in the body for 4 years after cessation of therapy, kind of freaks some researchers out, but YOLO, right?)
Another potential future therapy for altering lipoprotein profile is Eprotirome. Whats it do?
Thyroid hormone acts to mediate lipid lowering activity. Eprotirome is an analog of thyroid hormone.
Up to an additional 30% reduction in lipoproteins when added to statin therapy
(Apparently the company developing this drug pulled the plug a year ago due to really bad “unwanted effects after long term exposure”…why are we learning this crap?)
Microsomal triglyceride transfer protein inhibitors, another possible future treatment, does what
Reduces the secretion of VLDL in the liver
Provides up to 50% reduction in plasma LDL levels
Mipomersen, future therapy candidate, does what
May reduce plasma levels of lipoprotein A
Being tested in severe hypercholesterolemia and statin intolerant pts
Take home message-
The focus should be on assessing a patient’s risk for Atherosclerotic Cardiovascular Disease and whether they fall into one of the four statin therapy groups, which are…..
Clinical ASCVD
LDL > 189
Individuals 40-75 with Diabetes and LDL 70-189 without ASCVD
Individuals 40-75 with Diabetes and LDL 70-189 and a 10-year ASCVD risk of 7.5% or higher
What determines the intensity of statin therapy?
Presence of Clinical ASCVD
Risk of Developing ASCVD
Presence of Diabetes with/without hyperlipidemia
Presence of isolated hyperlipidemia (genetic component)
