Best Dx/Best Rx: Diagnosis and Treatment of Dyslipidemia

Diagnosis and Treatment of Dyslipidemia

John D. Brunzell, MD, FACP
R. Alan Failor, MD
University of Washington School of Medicine, Seattle, WA

Definition/Key Clinical Features
Differential Diagnosis (Causes of Dyslipidemia)
Best Tests and Goals
Best Therapy
Best Evidence

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 low-density lipoprotein (LDL) cholesterol levels
Isolated elevation of triglyceride levels
Elevated cholesterol and triglyceride levels (with small-dense LDL)
Low high-density lipoprotein (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

Best Tests and Goals

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 cardiovascular disease 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

Best Therapy*

Hypercholesterolemia/Elevated LDL Cholesterol Levels

Reduced consumption of dietary saturated fat and cholesterol
Lifestyle changes, particularly diet (also smoking cessation) and increased exercise

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]

Hypercholesterolemia/Elevated Triglycerides

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

Low HDL Cholesterol 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)

Combination Therapy

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

Drug Treatment of Lipid Disorders

Bile Acid-Binding Resins: for elevated LDL, normal triglycerides (will increase triglyceride levels)

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.

Colestipol: t.i.d. more effective

Dose: maximum 30 g/day b.i.d. or t.i.d.

Colestipol tablets

Dose: maximum 16 g/day

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

Ezetimibe: can reduce LDL cholesterol by ~ 20% without increasing plasma triglyceride levels

Dose: 10 mg/day

Fibrates: for elevated triglycerides and patients in whom both LDL and triglycerides are elevated

May be used with bile acid–binding resins or nicotinic acid
Decrease dose with severe renal disease
Fenofibrate

Dose: 200 mg/day

Gemfibrozil

Dose: 600 mg b.i.d.

Niacin: for elevated LDL, triglycerides, or both with low HDL cholesterol

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

Statins: for elevated LDL

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

Fluvastatin

Dose: start with 20 mg/day; maximum 80 mg/day

Lovastatin

Dose: start with 20 mg/day; maximum 80 mg/day

Pravastatin: may be used with drugs that are cleared by hepatic enzymes CYP450, CYP3A4

Dose: start with 40 mg/day; maximum 80 mg/day

Resuvastatin

Dose: start with 10 mg/day; maximum 40 mg/day

Simvastatin

Dose: start with 20–40 mg/day; maximum 80 mg/day

Best Evidence

Carr MC, et al. J Clin Endocrinol Metab 2004;89:2601–7. [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 2001;285:2486–97. [PMID 11368702]

Grundy SM. Am J Cardiol 2002;90(8A):11i–21i. [PMID 12419477]

Grundy SM, et al. Circulation 2004;110:227–39. [PMID 15249516]

Yusuf S, et al. Lancet 2004;364:937–52. [PMID 15364185]

* To obtain additional drug information, click on the DrugInfo tab in the left column, or click on the following link: http://search.medscape.com/drug-reference-search?queryText=

October 2010