Lipid disorders encompass a broad spectrum of metabolic conditions that affect blood lipid levels. They can be 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) but can also be congenital, e.g., 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. Abetalipoproteinemia is a congenital lipid disorder that is characterized by a deficiency of apolipoproteins (hypolipoproteinemia), which leads to impaired intestinal absorption of fats and fat-soluble vitamins. Symptoms mainly consist of failure to thrive, steatorrhea, and signs of vitamin E deficiency. 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. To confirm the diagnosis, a fasting lipid profile must show pathological values on two different occasions. Dyslipidemia is diagnosed if LDL levels are > 130 mg/dL and/or HDL levels are < 40 mg/dL. The management of hyperlipoproteinemia involves lifestyle modifications and lipid-lowering agents (primarily statins). The treatment of abetalipoproteinemia includes supplementation of vitamin E.
- Dyslipidemia: 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 “ .”
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|| |
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- 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:
Laboratory analysis 
Fasting lipid profile : Total cholesterol, HDL, and triglycerides are measured.
- The LDL level can be measured directly using assays or estimated using the Friedewald formula (LDL = total cholesterol – HDL – (triglycerides/5) ).
- Pathological values on two different occasions are required to confirm the diagnosis.
- Dyslipidemia is diagnosed if LDL > 130 mg/dL. and/or if HDL levels < 40 mg/dL.
- Identify the underlying cause.
- Fasting lipid profile : Total cholesterol, HDL, and triglycerides are measured.
|Parameters of fat metabolism |
|Laboratory parameter||Optimal level||Pathological (mg/dL)|
|Total cholesterol|| || |
|Triglycerides|| || |
|LDL|| || |
|HDL|| || |
|LDL/HDL ratio |
Further workup: required in patients with confirmed dyslipidemia
- Assess for cardiovascular disease (CVD).
- Assess for other major risk factors of CVD.
- Goal: improve serum lipid levels to reduce the risk of cardiovascular disease
Nonpharmacological measures: lifestyle modifications
- Dietary changes
- Reduce saturated fat and cholesterol intake.
- Reduce or eliminate consumption of alcohol. 
- Maintaining a healthy weight
- Physical activity
- Dietary changes
- if there is a poor response to statins
Treatment of xanthomas and xanthelasmas
- Not required in most cases
- Surgical removal for cosmetic reasons is possible but is associated with a high rate of recurrence
- Management of familial disorders
ACC/AHA guidelines on the management of blood cholesterol (2018) 
- Initiate moderate-intensity or high-intensity statin therapy.
|Guidelines for lipid-lowering therapy in adults|
|Risk factors||Moderate intensity||High intensity|
|Clinical atherosclerotic cardiovascular disease (ASCVD)|| || |
|Diabetes|| || |
|Guidelines for lipid-lowering therapy in children|
|LDL goal (mg/dL)||Lifestyle modifications indicated (mg/dL)||Medical therapy indicated (mg/dL)|
|Children < 10 years old|| || || |
|Children > 10 years old|| |
|**Moderate-risk CVD conditions: E.g., hypertension, obesity, HDL < 40, Kawasaki disease with regressed coronary aneurysms, chronic inflammatory disease, HIV infection, nephrotic syndrome, adolescent depressive and bipolar disorders.|
- The decision to screen for hyperlipidemia primarily depends on the patient's overall risk of cardiovascular disease.
- Screening of high-risk individuals (i.e., with other risk factors for cardiovascular disease): ♂ > 20–25 years; ♀ > 30–35 years
- Screening of low-risk individuals: ♂ > 35 years; ♀ > 45 years
- 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.