Cholesterol is necessary for production of:
Cell membranes, bile acids, and steroid hormones
Physical s/s of hyperlipidemia:
Xanthelasma Circumferential arcus PVD Thickened Achilles HTN
What is xanthelasma?
Nodules in the skin
What is circumferential arcus?
Lipid deposits around the iris
Lab tests for cholesterol that are reliable even if non-fasting:
Total cholesterol
HDL-cholesterol
Desirable/high total cholesterol levels:
Desirable < 200
High > 240
Low/high HDL levels:
Low < 40
High > 60
Range of LDL levels:
Optimal < 100
Very high > 190
Near optimal, borderline high, high in the middle - 30 pt ranges for each
Describe primary hyperlipidemia:
Genetic/inherited and heterozygous
TC > 200, trigs > 500
Aka familial hypercholesteremia
Causes of secondary hyperlipidemia:
Diabetes Hypothyroid Obstructive liver disease Chronic renal failure Drugs (progestins, steroids)
Effects of ETOH use on lipids:
↑ TG, HDL
This is where the “a glass of wine with dinner is good for you” thought comes from!
Effects of HIV/AIDS wasting on lipids:
↑ TG
↓ TC, HDL, LDL
Effects of HIV/AIDS on HAART on lipids:
↑ TG, LDL, TG
Long-term effects of HAART can be deleterious
Effects of inactivity on lipids:
↓ HDL
Effects of obesity on lipids:
↑ TG, LDL
Who/when to screen lipids:
All adults 20yrs+
4-6 year intervals
What to include in lipid screening:
TC, LDL, HDL, Trigs ALT CK HbA1C 10 year ASCVD risk
Therapeutic lifestyle changes include:
↓ saturated fats, cholesterol
↑ physical activity
Weight control
Dietary influences on HDL:
HDL ↑ by alcohol, saturated fats, weight loss
HDL ↓ by low fat diets, sugar, excess calories/polyunsaturated fats
Dietary influences on LDL:
LDL ↑ by saturated fat, trans fatty acids, dietary cholesterol
LDL ↓ by monounsaturated fats, complex carbs, soy
Dietary influences on total cholesterol:
TC ↑ by saturated fats, trans fatty acids
TC ↓ by MUFAs, complex carbs, soy
Dietary influences on triglycerides:
TGs ↑ by ETOH, sugar, high carb diet, excess calories
TGs ↓ by weight loss, fish oil
History risk factors for ASCVD:
Hx of coronary heart disease (angina, MI, coronary interventions) PAD CAD AAA Stroke/TIA
Demographic/comorbidity risk factors for ASCVD:
Gender, age, race
Cholesterol
Blood pressure
Diabetes/smoker
Four categories for preventative statin therapy:
Clinical ASCVD
LDL > 190
Diabetes
> 7.5% 10yr risk
% LDL reduction from moderate intensity statin therapy:
30-50%
% LDL reduction from high intensity statin therapy:
> 50% reduction
Two drugs considered high-intensity statin therapy:
Atorvastatin 80mg
Rosuvastatin 20mg
Statin class of drug:
HMG-CoA Reductase Inhibitors
Statins MoA:
Inhibit the rate-limiting enzyme in formation of cholesterol to ↓ LDL, TGs and ↑ HDLs
Statin guidelines for clinical ASCVD:
If < 75yo: high intensity statin
If > 75 or contraindications: moderate intensity
Statins should be used for primary HLD if LDL ≥:
190
Reduction of LDL by _____ decreases ASCVD by 20%.
39 mg/dl
Statin guidelines for DM:
Moderate-intensity acceptable
High-intensity if 10yr risk > 7.5%
10 year (vs. lifetime) ASCVD risk should be assessed for:
Patients without ASCVD/DM and LDL < 190 to determine if preventative statin tx will be useful
Additional tx for triglycerides indicated when:
TG > 200 and LDL goal achieved
Additional tx for HDL indicated when:
HDL < 40
Bile sequestrant MoA:
Binds bile acid in the intestines so liver uses cholesterol to make more; ↓ LDL, ↑ HDL
Examples of bile sequestrants:
Questran, Colestipol, Colesevelam
S/E of bile sequestrants:
Oily stools
Low compliance d/t needing to mix powder in drink
Nicotinic acid MoA:
Reduced production of VLDLs; effect is ↓ LDL, TG and ↑ HDL
Examples of nicotinic acid:
Niaspan and generics
S/E of nicotinic acid:
Flushing
MoA of fibric acid derivatives:
Reduces the synthesis and increases breakdown of VLDLs
Examples of fibric acid derivatives:
Gemfibrozil (Lopid)
Fenofibrate
Clifibrate
All have -fib-
S/E of fibric acid derivatives:
Hard on the liver
MoA of ezetimibe (Zetia):
Inhibits cholesterol/phytosterol aborption from brush border
Ezetimibe effect on vitamin absorption and CYP450 enzomes:
None!
Ezetimibe should be paired with:
A statin
Statin + ezetimibe = LDL reduction of:
25%
Statin + bile acid sequestrant = LDL reduction of:
8-16%
Statin + fibric acid derivative primarily for:
Decreasing trigs
Statin + fibric acid derivative risks and contraindication:
↑ risk of myopathies
C/I in severe hepatic disease
Statin + niacin risk:
↑ risk of hepatic dysfunction
Drug interactions with statins:
Itraconazole/ketoconazole Erythromycin Clarithromycin Gemfibrozil Grapefruit juice
Biggest s/e of statins:
Myopathies
Relation of statin dose to myopathy incidence:
None - any statin, any dose
Individuals at risk for statin myopathy:
Age > 80
Small body frame/frailty
Impaired renal/hepatic
ETOH abuse
Drugs that ↑ risk of statin myopathy:
Niacin Gemfibrozil Cyclosporin HIV protease inhibitors Verapamil Amiodarone
Lipid-lowering medications safe to use during pregnancy:
Only bile acid sequestrants!
Four statin tx groups:
LDL > 189
Clinical ASCVD
40-75yo with DM, LDL > 70 without ASCVD
40-75yo with DM, LDL > 70, and 10-yr risk 7.5%+