Lipid disorders encompass a broad 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 (hyperlipoproteinemias), which are often associated with an increased risk of (or current) cardiovascular disease. Hyperlipoproteinemias are most commonly caused by lifestyle factors (diet, lack of activity, alcohol consumption). However, they may also be congenital, as is the case with familial hypertriglyceridemia, which is associated with extremely high levels of triglycerides that significantly increase the risk of pancreatitis, and familial hypercholesterolemia, which results in early atherosclerotic complications. Lipid disorders are usually detected during routine laboratory testing, such as cardiovascular risk factor screening. The blood lipid profile includes total cholesterol, LDL, HDL, and triglycerides. Treatment of hyperlipidemia is indicated to reduce the risk of cardiovascular disease in patients with LDL > 190 mg/dL, diabetes mellitus, and clinical ASCVD, and should be considered for other patients with a 10-year ASCVD risk score ≥ 7.5% after discussion of the risks and benefits. Lifestyle modifications and lipid-lowering agents (primarily statins) are the main treatment modalities. Abetalipoproteinemia is a congenital lipid disorder characterized by a deficiency of apolipoproteins (hypolipoproteinemia), which leads to impaired intestinal absorption of fats and fat-soluble vitamins. Symptoms, which usually appear early, mainly consist of failure to thrive, steatorrhea, and signs of vitamin E deficiency. The treatment includes supplementation of vitamin E.
- Dyslipidemia: an abnormal concentration of lipids in the blood (e.g., high LDL, low HDL)
- Hyperlipidemia: elevated blood lipid levels (total cholesterol, LDL, triglycerides)
- Hypercholesterolemia: total cholesterol > 200 mg/dL
- Hypertriglyceridemia: triglyceride levels > 150 mg/dL
- Hyperlipoproteinemia: elevated levels of certain lipoproteins
- In the US, the prevalence of lipid disorders is estimated as follows:
Epidemiological data refers to the US, unless otherwise specified.
|Frederickson classification of inherited hyperlipoproteinemias |
|Condition|| || || || || || |
|Frequency || || || || || |
|Pathogenesis|| || || |
|Total cholesterol|| || || || || |
|Elevated serum lipoproteins|
|Total triglycerides|| || || || || || |
|Overnight plasma|| || || || || || |
- Elevated LDL and reduced HDL → promote atherosclerosis → increased risk of cardiovascular events
- See “ .”
There are typically no specific signs or symptoms.
- Description: nodular lipid deposits in the skin and tendons
- Pathophysiology: Extremely high levels of triglycerides and/or LDL result in extravasation of plasma lipoproteins and their deposition in tissue.
|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 levels
- Lipemia retinalis
- Associated with hyperlipoproteinemia type II
- Not pathological in advanced age
- hepatic steatosis): associated conditions include (abetalipoproteinemia, metabolic syndrome, heavy consumption of alcohol
- Pancreatitis in severe hypertriglyceridemia (typically > 1,000 mg/dL): associated conditions include hyperlipoproteinemia type I and IV, hypertriglyceridemia
- Associated conditions: hyperlipoproteinemia type II, III, and IV
Manifests with secondary diseases such as:
Screening for lipid disorders
- Further testing
- Assess ASCVD risk to guide treatment decisions, e.g., via the 2013 ACC/AHA pooled cohort equation
Lipid profile 
- Includes total cholesterol, HDL, LDL, and triglycerides
- LDL can be measured directly or estimated using the Friedewald formula (LDL = total cholesterol – HDL – (triglycerides/5) 
|Parameters of fat metabolism |
|Laboratory parameter||Optimal level||Abnormal levels|
|Total cholesterol|| || |
|Triglycerides|| || |
|LDL|| || |
|HDL|| || |
|LDL/HDL ratio |
|Total cholesterol/HDL ratio |
Assessment for secondary causes of hyperlipidemia 
- Encourage all patients to make lifestyle modifications (see “”).
- Initiate pharmacologic therapy based on the patient's age, LDL level, and .
- Statins: first-line
- Nonstatin lipid-lowering agents: may be added to statins if treatment goals are not met.
- Patients with familial lipid disorders 
- Consider specialist referral.
- Treatment should involve lifestyle modifications and pharmacologic therapy with individualized treatment goals.
- Xanthomas and xanthelasmas can be treated for cosmetic reasons, but recurrence is common. 
The goal of treatment is to reduce the risk of cardiovascular diseases. Therefore, the decision to treat hypercholesterolemia should be based on a patient's .
Treatment of hypercholesterolemia in adults 
Indications for treatment 
- Patients ≥ 20 years of age with clinical ASCVD: statin therapy (see “ASCVD” for further details)
- Patients 20–75 years of age and LDL ≥ 190 mg/dL:
- Patients 40–75 years of age and LDL 70–189 mg/dL: Treatment is based on the .
- Patients 40–75 years of age with diabetes mellitus: statin therapy (see “ASCVD” for further details) 
- Patients 20–39 years of age if LDL ≥ 160 mg/dL and family history positive for premature ASCVD: Consider statin therapy.
Statins used for lipid-lowering therapy in adults 
|Statin intensity||Expected reduction in LDL level||Agents|
|Moderate intensity|| |
|Low intensity|| |
- Bile-acid sequestrants, e.g., colesevelam
- PCSK9 inhibitors, e.g., evolocumab or alirocumab
In patients with intermediate to high ASCVD risk, the risk-benefit assessment should take hypertriglyceridemia into account. Moderate to severe hypertriglyceridemia is generally a factor that favors statin therapy. 
|Treatment of hypertriglyceridemia in adults |
|Moderate hypertriglyceridemia|| |
|Severe hypertriglyceridemia|| |
Treatment of dyslipidemia in children 
- Children with LDL ≥ 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:
- 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.