Differential Diagnosis
Best Tests
Best Therapy
Best References
Definition/Key Clinical Features
- A range of disorders that include both abnormally high and low lipoprotein levels, as well as disorders in the composition of these particles
- Clinically important because of their contribution to atherogenesis
- Isolated elevation of LDL cholesterol levels
- Isolated elevation of triglyceride levels
- Elevated cholesterol and triglyceride levels (with small-dense LDL)
- Low HDL cholesterol levels
- Atherosclerosis and normal lipid levels
Differential Diagnosis (Causes of Dyslipidemia)
- Genetic causes
- The metabolic syndrome
- Type 2 diabetes mellitus
- Familial combined hyperlipidemia (FCHL)
- Familial hypertriglyceridemia (FHTG)
- Familial hypercholesterolemia (FH)
- Familial defective apolipoprotein B-100
- Remnant removal disease
- Secondary causes
- Untreated hyperglycemia
- Hypothyroidism
- Dyslipidemia secondary to estrogen and progestin therapy
- Nephrotic syndrome
- Chronic renal failure
- Primary biliary cirrhosis
- Alcohol-induced hypertriglyceridemia
- Adverse effects of drugs
- Tests
- Fasting triglyceride
- Total cholesterol
- HDL cholesterol
- Calculated LDL cholesterol
- Family history
- Triglyceride levels: elevated when triglycerides > 250 mg/dl
- Low HDL cholesterol levels
- In men, < 40 mg/dl
- In women, < 50 mg/dl
- LDL cholesterol goals based on CVD risk
- High to very high risk: goal, < 100 mg/dl
- Drug therapy when > 100 mg/dl
- Moderately high risk: goal, < 130 mg/dl
- Drug therapy when > 130 mg/dl
- Moderate risk: goal, < 130 mg/dl
- Drug therapy when > 160 mg/dl
- Lower risk: goal, < 160 mg/dl
- Drug therapy when > 190 mg/dl
- High to very high risk: goal, < 100 mg/dl
Hypercholesterolemia/Elevated LDL Cholesterol Levels
- Reduced consumption of dietary saturated fat and cholesterol
- Lifestyle changes, particularly diet (also smoking cessation)
- Will reduce LDL cholesterol levels sufficiently in some patients
- Patients with familial forms of high LDL will require addition of cholesterol-lowering drugs [see Drug Treatment of Lipid Disorders, below]
- Statins [see Drug Treatment of Lipid Disorders, below]
- Statins plus bile acid–binding resins and drugs that block cholesterol absorption for patients who do not respond to statins alone
- Consider adding nicotinic acid as third drug when needed. [see Drug Treatment of Lipid Disorders, below]
- Fibrates: drugs of choice for patients with marked hypertriglyceridemia
- Will raise HDL cholesterol levels modestly
- Can be used in combination with statins [see Drug Treatment of Lipid Disorders, below]
- Niacin: worsens insulin sensitivity (use care in patients with type 2 diabetes mellitus)
- Can be used in combination with statins [see Drug Treatment of Lipid Disorders, below]
- Omega-3 fatty acids: found in marine oils
- Might be used when other modalities have failed to reduce markedly elevated triglyceride levels
- Usually accompanies hypertriglyceridemia
- Isolated low HDL cholesterol levels (20–30 mg/dl) are rare but are a risk factor for cardiovascular disease; treatment is controversial
- Manage the underlying hypertriglyceridemia
- Niacin: can increase HDL cholesterol levels
- Dose: start with 250 mg q.d. with meals; increase to 0.5 g three times a day after meals; slow-release forms available (Niaspan)
- Cost/mo: $7; slow-release forms more expensive
- For use when both LDL cholesterol and triglyceride levels are elevated and when monotherapy fails to achieve target lipid and lipoprotein levels
- Statins + fibrates
- Statins + niacin
- Statins + bile-acid sequestrants
- Ezetimibe + statins
- Statins + niacin + an intestinally active agent
- Start with one packet (2 g for colestipol tabs) b.i.d., increase over 1–2 wk to desired dose
- Take other drugs 1 hr before or 4 hr after
- May be used with nicotinic acid, statins, or fibrates
- Cholestyramine
- Dose: maximum 24 g/day b.i.d. or t.i.d.
- Cost/mo: $69
- Colestipol: t.i.d. more effective
- Dose: maximum 30 g/day b.i.d. or t.i.d.
- Cost/mo: $305
- Colestipol tablets
- Dose: maximum 16 g/day
- Cost/mo: $268
- Colesevelam: better tolerated than other resins
- Dose: Three 625 mg tablets b.i.d. with meals or 6 tablets/day with a meal; maximum 7 tablets/day
- Cost/mo: $190
- Dose: 10 mg/day
- Cost/mo: $72
- May be used with bile acid–binding resins or nicotinic acid
- Decrease dose with severe renal disease
- Fenofibrate
- Dose: 200 mg/day
- Cost/mo: $73
- Gemfibrozil
- Dose: 600 mg b.i.d.
- Cost/mo: $17
- May be used with bile acid–binding resins or fibrates
- Dose: start with 250 mg q.d. with meals; increase to 0.5 g three times a day after meals; slow-release forms available as Niaspan
- Cost/mo: $7; slow release form more expensive
- Possibly useful for patients in whom both LDL and triglycerides are elevated
- May be used with bile acid–binding resins or ezetimibe
- Atorvastatin
- Dose: start with 10–20 mg/day; maximum 80 mg/day
- Cost/mo: $95
- Fluvastatin
- Dose: start with 20 mg/day; maximum 80 mg/day
- Cost/mo: $68
- Lovastatin
- Dose: start with 20 mg/day; maximum 80 mg/day
- Cost/mo: $126
- Pravastatin: may be used with drugs that are cleared by hepatic enzymes CYP450, CYP3A4
- Dose: start with 40 mg/day; maximum 80 mg/day
- Cost/mo: $120
- Resuvastatin
- Dose: start with 10 mg/day; maximum 40 mg/day
- Cost/mo: NA
- Simvastatin
- Dose: start with 20–40 mg/day; maximum 80 mg/day
- Cost/mo: $124
Carr MC, et al: J Clin Endocrinol Metab 89:2601, 2004 [PMID 15181030]
Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 285:2486, 2001 [PMID 11368702]
Grundy SM: Am J Cardiol 90:11i, 2002 [PMID 12419477]
Grundy SM, et al: Circulation 110:227, 2004 [PMID 15249516]
Yusuf S, et al: Lancet 364:937, 2004 [PMID 15364185]
April 2006