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Lipid disorders

Last updated: December 23, 2020

Summary

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.

Definition

Epidemiology

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Classification

Frederickson classification of inherited hyperlipoproteinemias [3]
I IIa IIb III IV V
Condition
  • Familial hyperchylomicronemia [4]
  • Familial hypercholesterolemia [5]
  • Familial combined hyperlipidemia [6]
  • Familial hypertriglyceridemia [8]
  • Mixed hyperlipidemia [9]
Frequency [10]
  • Rare
  • 1:50–1:200
  • 1:1000–1:5000
  • 1:50–1:100
  • Very rare
Inheritance
Pathogenesis
  • Hepatic overproduction of VLDL or defective ApoA-V
  • Defective ApoA5
Clinical manifestations
Lipoprotein defect
Total cholesterol
  • Normal to mildly ↑
  • Massively ↑
  • Normal to mildly ↑
Elevated serum lipoproteins
Total triglycerides
  • Massively ↑
  • Can be > 2,000 mg/dL
  • Normal
  • Massively ↑
  • Massively ↑
Overnight plasma
  • Creamy top layer
  • Clear
  • Clear
  • Turbid
  • Turbid
  • Creamy top and turbid bottom layer

Pathophysiology

Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease.

Clinical features

Typically no specific signs or symptoms

Skin manifestations

Xanthomas

  • 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
Types of xanthomas
Description Location Associated condition
Eruptive xanthoma
  • Yellow papules with an erythematous border
  • May be tender and itchy
  • Buttocks, back, and extensor surfaces of the extremities
Tuberous xanthoma
  • Firm, painless, reddish-yellow nodules located in pressure areas
  • Severe hypercholesterinemia (LDL and/or VLDL levels)

Tendinous xanthoma

  • Firm nodules, located in tendons
  • Severe hypercholesterinemia (LDL and/or VLDL levels)

Palmar xanthoma

  • Palms of the hands

Plane xanthoma

  • Larger body areas, e.g., trunk, neck, shoulders

:

Xanthelasmas

Eye manifestations

Gastrointestinal manifestations

Premature atherosclerosis

Diagnostics

Parameters of fat metabolism [11]
Laboratory parameter Optimal level Pathological (mg/dL)
Total cholesterol
  • < 200 mg/dL
  • Borderline: 200–239 mg/dL
  • High: > 240 mg/dL
Triglycerides
  • < 150 mg/dL
  • Borderline: 150–199 mg/dL
  • High: > 200 mg/dL
  • Very high: ≥ 500 mg/dL
LDL
  • < 100 mg/dL
  • Near optimal: 100–129 mg/dL
  • Borderline high: > 130 mg/dL
  • High: > 160 mg/dL
  • Very high: ≥ 190 mg/dL
HDL
  • ≥ 60 mg/dL
  • Low: < 40 mg/dL
LDL/HDL ratio [12]

Treatment

General

  • 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. [14]
    • Maintaining a healthy weight
    • Physical activity
  • Medical therapy
  • 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) [15][16][17]

  • 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)
  • At age > 75 years
  • Regardless of age
Diabetes
  • At age 40–75 years
High LDL
  • Age 40–75 years and LDL 70–189 mg/dL with no diabetes and estimated 10-year risk of ASCVD 5–20%
  • Age 40–75 years and LDL 70–189 mg/dL with no diabetes and estimated 10-year risk of ASCVD ≥ 20%
  • LDL ≥ 190 mg/dL and age 20–75 years

National Heart, Lung, and Blood Institute pediatric guidelines (2011) [18]

Guidelines for lipid-lowering therapy in children

Age stratification

LDL goal (mg/dL) Lifestyle modifications indicated (mg/dL) Medical therapy indicated (mg/dL)
Children < 10 years old
  • < 130
  • > 130
  • One or more of the following
    • High-risk CVD condition*
    • LDL > 400
    • TG > 500
Children > 10 years old
  • Children who fail to achieve target LDL levels after 6 months of lifestyle modifications and

* High-risk CVD conditions: E.g., diabetes (type 1 or type 2), chronic kidney disease, heart transplant, Kawasaki disease with current aneurysms

**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.

Prevention

Abetalipoproteinemia

References

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  2. HYPERLIPOPROTEINEMIA, TYPE I. https://www.omim.org/entry/238600. Updated: September 7, 2016. Accessed: April 3, 2019.
  3. HYPERLIPOPROTEINEMIA, TYPE II, AND DEAFNESS. https://www.omim.org/entry/144300. Updated: January 21, 2009. Accessed: April 3, 2019.
  4. Rosenson RS, Durrington P. Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/inherited-disorders-of-ldl-cholesterol-metabolism-other-than-familial-hypercholesterolemia.Last updated: March 27, 2018. Accessed: April 3, 2019.
  5. HYPERLIPOPROTEINEMIA, TYPE III. https://www.omim.org/entry/617347. Updated: March 22, 2018. Accessed: April 3, 2019.
  6. HYPERLIPOPROTEINEMIA, TYPE IV. https://www.omim.org/entry/144600. Updated: November 22, 2010. Accessed: April 3, 2019.
  7. HYPERLIPOPROTEINEMIA, TYPE V. https://www.omim.org/entry/144650. Updated: June 3, 2018. Accessed: April 3, 2019.
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  9. 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) final report. https://www.nhlbi.nih.gov/files/docs/resources/heart/atp-3-cholesterol-full-report.pdf. Updated: September 1, 2002. Accessed: May 10, 2017.
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