Lipid disorders encompass a spectrum of metabolic conditions that affect blood lipid levels. They are generally characterized by elevated levels of cholesterol, triglycerides, and/or lipoproteins in the blood, which are often associated with atherosclerotic cardiovascular disease (ASCVD). Hyperlipidemia is most commonly a result of genetic predisposition in combination with lifestyle factors (e.g., diet, lack of activity, alcohol consumption). Hyperlipidemia resulting from single-gene disorders, e.g., familial hypercholesterolemia, can cause severe elevations in lipoprotein levels and early atherosclerotic complications. Lipid disorders are usually detected during laboratory testing as part of an ASCVD risk assessment. A serum lipid panel includes total cholesterol, LDL, HDL, and triglyceride levels. Lipid-lowering therapy is indicated to reduce the risk of cardiovascular disease in patients with LDL > 190 mg/dL, diabetes mellitus, and established ASCVD, and should be considered for other patients based on individual ASCVD risk. The main treatment modalities are lifestyle modifications and lipid-lowering agents such as statins.
Abetalipoproteinemia is a congenital lipid disorder in which a deficiency of apolipoproteins (hypolipoproteinemia) leads to impaired intestinal absorption of fats and fat-soluble vitamins. Symptoms usually appear during childhood and mainly consist of failure to thrive, steatorrhea, and signs of vitamin E deficiency. Treatment includes vitamin E supplementation.
- Dyslipidemia: an abnormal concentration of lipids in the blood (e.g., high or low LDL cholesterol)
- Hyperlipidemia: elevated blood lipid levels (e.g., total cholesterol, LDL cholesterol, and/or triglycerides)
- Usually multifactorial 
- Secondary causes of dyslipidemia
- Genetic causes
- (less common)
- See also “Frederickson classification of inherited hyperlipidemias.”
|Secondary causes of dyslipidemia |
|Elevated LDL cholesterol||Elevated triglycerides|
|Lifestyle factors|| |
- Dyslipidemia is usually asymptomatic.
- Severe and/or persistent elevation can cause:
- In genetic lipid disorders, symptoms generally occur at an earlier age and are more severe than in acquired lipid disorders.
- Description: nodular lipid deposits in the skin and tendons
- Pathophysiology: : Extremely high levels of triglycerides and/or LDL cholesterol result in extravasation of plasma lipoproteins and their deposition in tissue.
- Histology: large perivascular infiltrates with foam cells (lipid-laden macrophages) and multinucleated histiocytes called Touton giant cells
|Types of xanthomas|
|Eruptive xanthoma|| || |
|Tuberous xanthoma|| |
| || |
| || |
- Description: typically bilateral, yellow, flat plaques on the upper eyelids (nasal side)
- Associated conditions: hypercholesterolemia (e.g., primary biliary cholangitis), hyperapobetalipoproteinemia, ↑ LDL cholesterol levels
- Lipemia retinalis
- Associated with hyperlipoproteinemia type II
- Not pathological in advanced age
Overview of inherited hyperlipoproteinemias
|Frederickson classification of inherited hyperlipoproteinemias |
|I||Type II hyperlipoproteinemia||III||Type IV hyperlipoproteinemia||V|
|Condition|| || || || || || |
|Frequency || || || || || |
|Pathogenesis|| || || |
|Total cholesterol|| || || || || |
|Elevated serum lipoproteins|
|Total triglycerides|| || || || || || |
|Overnight plasma|| || || || || || |
- Clinical features
- Extremely low levels of plasma cholesterol (< 50 mg/dL)
- Acanthocytes in the blood
- Other tests performed include complete blood count with differential, stool studies, and fasting lipid profile.
- Confirmatory test: genetic testing to detect mutations in the MTTP gene
- Intestinal biopsy: Histology may reveal lipid-laden enterocytes.
General principles 
- Order a lipid panel when evaluating patients with a known secondary cause of dyslipidemia, e.g., diabetes mellitus or nephrotic syndrome.
- Screen for lipid disorders based on age and family history.
- If lipid levels are abnormal:
Screening for lipid disorders 
A nonfasting or fasting lipid panel is acceptable. 
Adults age 20–75 years
- Screen at least every 4–6 years. 
- See “ASCVD risk assessment" for details.
- Children and adolescents age < 20 years
Diagnostic confirmation 
- Lipid panel: includes total cholesterol, HDL, LDL, and triglycerides
- Other tests
Optimal lipid levels
- Total cholesterol: < 200 mg/dL
- HDL cholesterol: ≥ 40 mg/dL for men; ≥ 50 mg/dL for women 
LDL cholesterol: depends on ASCVD risk 
- < 100 mg/dL in adults at average risk
- < 70 mg/dL in patients with ASCVD or at high risk
- Triglycerides: < 150 mg/dL
- Lipoprotein(a): < 50 mg/dL
- Apolipoprotein B: < 130 mg/dL
Additional evaluation 
Secondary causes 
- Obtain the following studies based on clinical suspicion.
- Consider other secondary causes based on patient history, e.g., antipsychotic use or lifestyle factors
Monogenic causes 
- Clinical scoring systems (e.g., Dutch Lipid Clinic Network criteria) may be used to diagnose familial hypercholesterolemia.
- Refer for targeted gene sequencing if results will influence management decisions. 
- Factors that increase suspicion for a monogenic disorder include: 
Encourage for all patients, including:
- Physical activity
- Dietary modifications
- Mitigate .
- Initiate pharmacotherapy based on the type and severity of dyslipidemia.
- Consult a lipid specialist for patients with:
Very high LDL cholesterol 
- Indication: LDL cholesterol ≥ 190 mg/dL in adults 20–75 years of age 
- Goals: LDL cholesterol < 100 mg/dL or ≥ 50% reduction in levels
- First-line agents: : , e.g., atorvastatin or rosuvastatin 
- Subsequent treatment
Severe hypertriglyceridemia 
- Indication: fasting triglycerides > 500 mg/dL
- First-line agents
Subsequent treatment: if triglycerides remain > 500 mg/dL 
- Fibrate PLUS omega-3-acids (recommended)
- Consider adding niacin . 
Xanthoma and xanthelasma 
- Treatment may be considered for cosmetic reasons, but recurrence is common.
- Methods include surgical, laser, and/or topical therapy.
- Hepatic steatosis: associated with abetalipoproteinemia
- May occur in severe hypertriglyceridemia (typically > 1,000 mg/dL)
- Associated conditions include hyperlipoproteinemia types I and IV.
We list the most important complications. The selection is not exhaustive.
Special patient groups
Treatment of dyslipidemia in children 
- Children with LDL cholesterol ≥ 130 mg/dL or elevated triglycerides : lifestyle modifications
- Children ≥ 10 years
- Children < 10 years: medical therapy not generally recommended, except in the following situations:
- Consult a lipid specialist for treatment of: