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Etiology
Primary hyperlipidemia
Familial hypercholesterolemia
Secondary hyperlipidemia
Disease states: hypothyroidism, nephrotic syndrome, obesity, DM, alcoholism Drugs: thiazides, B-blockers, isotretinoin, prednisone, progestins, estrogens, protease inhibitors, anabolic steroids, cyclosporine
Diagnosis
Check fasting lipoprotein profile (9-12 hours of fasting) Screening:
Every 5 yrs. in patients > 20yo
Other method
Non-fasting total cholesterol and HDL
Assessment
If total cholesterol <200mg/dL and HDL >40mg/dL. No follow-up for patients without CHD and <2 risk factors.
HDL cholesterol 60 mg/dL counts as a negative risk factor; its presence removes one risk factor from the total count.
High risk:
CHD or CHD Risk Equivalents (10-year risk >20%)
< 100mg/dL
(optional < 70mg/dL)
Moderate risk:
2+ Risk Factors (10-year risk <10%)
Lower risk:
01 Risk Factor
Drug Therapy
Drug therapy should decrease LDL levels by 30-40% in high-risk and moderately high-risk pts. For patients hospitalized for coronary events or procedures
Measure LDL within 24 hours Discharge on LDL-lowering drug if LDL-C 70 Start lifestyle therapies simultaneously with drug
Therapeutic Options
Statins Bile acid sequestrants Cholesterol absorption inhibitors Nicotinic acid Fibric acids
LDL
- 18-55%
HDL
+ 5-15%
TG
- 7-30%
- 15-30%
- 17%
+ 3-5%
+ 1.3%
+ 3-10%
- 6%
Nicotinic acid
Fibric acids
- 5-25%
- 5-20% (nl TG) +10% (high TG)
+ 15-35%
+ 10-20%
- 20-50%
- 20-50%
Reduce major coronary events Reduce CHD mortality Reduce coronary procedures (PTCA/CABG) Reduce stroke Reduce total mortality
Comparison of Statins
Lovastatin (MevacorR) Doseresponse LDL Reduction 20mg: 29% Pravastatin Simvastatin Fluvastatin (LescolR) Atorvastatin Rosuvastatin (LipitorR) 10mg: 38% (CrestorR) 5mg: 41% (PravacholR) (ZocorR) 10mg: 19%
40mg: 31%
80mg: 48%
20mg: 24%
40mg: 34%
20mg: 46%
40mg: 51% 80mg: 54%
10mg: 48%
20mg: 55% 40mg: 62% Not signif.
Metabolism
CYP3A4
Sulfation
CYP3A4
CYP2C9
CYP3A4
Contraindications
Moderate to severe hepatic impairment
Nicotinic Acid
Drug Form Range Immediate release (crystalline) Extended release Sustained release Dose 1.53 g 12 g 12 g
Contraindications/cautions
liver disease, severe gout, peptic ulcer
Monitoring
LFTs (baseline and q 6-12 wks x 1 yr, then periodically and/or prn symptoms) uric acid, glucose, GI adverse effects, flushing, CPK prn symptoms
Fibric Acids
Drug
Gemfibrozil Fenofibrate
Dose
600 mg BID 200 mg QD
Clinical Identification
Diagnosis requires 3 or more of the following risk factors:
Abdominal obesity: M waist >40 in., F waist >35 in. Triglycerides >150mg/dL Low HDL: M <40mg/dL, F <50mg/dL Blood pressure: >130/>85 mmHg Fasting glucose: >110mg/dL
Treatment
Primary target is LDL Intensify weight management Increase physical activity If a high risk pt has high TG or low HDL-C, may consider adding a fibrate or nicotinic acid to LDL-lowering drug If TG are >200mg/dL after LDL goal is reached, determine non-HDL goal
Non-HDL Cholesterol
Non-HDL cholesterol = VLDL + LDL cholesterol = (Total Cholesterol HDL cholesterol)
VLDL cholesterol: denotes atherogenic remnant lipoproteins Non-HDL cholesterol: secondary target of therapy when serum triglycerides are 200 mg/dL (esp. 200499 mg/dL) Non-HDL cholesterol goal:
High risk:
CHD or CHD Risk Equivalents (10-year risk >20%)
< 100mg/dL
(optional < 70mg/dL)
< 130mg/dL
(optional < 100mg/dL)
< 130mg/dL
(optional < 100mg/dL)
< 160mg/dL
(optional < 130mg/dL)
Moderate risk:
2+ Risk Factors (10-year risk <10%)
< 130mg/dL
< 160mg/dL
< 160mg/dL
< 190mg/dL
Lower risk:
01 Risk Factor
Treatment (continued)
Management of High Triglycerides (200-499 mg/dL)
If TG remain elevated after LDL goal is reached: Intensify therapy with lipid-lowering drug Add nicotinic acid or fibrate to lower VLDL
Treatment (continued)
Management of Very High Triglycerides (500 mg/dL)
Reduce triglycerides before LDL lowering Goal of therapy: prevent acute pancreatitis Very low fat diets (15% of caloric intake) Triglyceride-lowering drug usually required (fibrate or nicotinic acid)
Place in Therapy
Statins: high LDL Bile acid sequestrants: young, not high TG Ezetimibe: high LDL, combined with statin Nicotinic acid: high TG and/or high LDL Fibric acids: high TG Combination therapy: statin and ezetimibe, statin and bile acid sequestrant, statin and nicotinic acid, statin and fibric acid