12/31/2020 Lipid disorders - AMBOSS

triglycerides. To con rm the diagnosis, a fasting lipid pro le must show pathological values on two different occasions. Dyslipidemia is diagnosed
REGISTER / LOG IN
if LDL levels > 130 mg/dL and/or HDL levels < 40 mg/dL. The management of lipid disorders involves lifestyle modi cations and lipid-lowering
agents (primarily statins).

De nition

The following terms are often used interchangeably, as they share common causes and are all associated with an increased risk of atherosclerosis
and cardiovascular disease. However, the terms have differing meanings.

Dyslipidemia: abnormal lipoprotein levels (LDL and HDL) in association with an increased risk of cardiovascular disease or current cardiovascular
disease

Hyperlipidemia: elevated blood lipid levels (total cholesterol, LDL, triglycerides)

Hypercholesterolemia: elevated total cholesterol> 200 mg/dL
Hypertriglyceridemia: elevated triglyceride levels
Hyperlipoproteinemia: elevated levels of a certain lipoprotein

Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease!

References:[1][2]

Epidemiology
In the US, an estimated 50% of the population has elevated cholesterol levels.

https://www.amboss.com/us/knowledge/Lipid_disorders 2/13
12/31/2020 Lipid disorders - AMBOSS

References:[2] REGISTER / LOG IN

Epidemiological data refers to the US, unless otherwise speci ed.

Etiology
Congenital (less common)
Type I – Hyperchylomicronemia: Autosomal recessive condition that is not associated with an increased risk of atherosclerosis. Patients
develop eruptive xanthomas, pancreatitis, and hepatosplenomegaly.

Type IIa – Familial hypercholesterolemia: Autosomal dominant condition associated with mutations in the LDL receptor that lead to elevated
LDL levels with early atherosclerotic complications (cardiovascular disease)
Type III – Familial dysbetalipoproteinemia: Autosomal recessive condition associated with defective ApoE that leads to elevated LDL levels
with early atherosclerotic complications (cardiovascular disease)

Type IV – Familial hypertriglyceridemia: Autosomal dominant condition associated with an increased risk of acute pancreatitis
Acquired (more common)

Obesity
Diabetes mellitus

Physical inactivity

Alcoholism
Hypothyroidism

Nephrotic syndrome
Cholestatic liver disease

Cushing disease
Drugs: oral contraceptive pill, high-dose diuretic use, metoprolol

References:[1][3][3][4][5]

https://www.amboss.com/us/knowledge/Lipid_disorders 3/13
12/31/2020 Lipid disorders - AMBOSS

REGISTER / LOG IN

Classi cation

Dyslipidemia classi cation according to Frederickson

Fredrickson I IIa IIb III IV

phenotype

Condition Familial hyperchylomicronemia [6] Familial Familial Familial Familial

hypercholesterolemia combined dysbetalipoproteinemia hypertriglyceridemia
[7] hyperlipidemia [8] [9] [10]

Frequency Rare ∼ 10% 1–15% ∼ 5% ∼ 70%

Inheritance Autosomal recessive Autosomal dominant Autosomal recessive Autosomal dominant

Pathogenesis De ciency of lipoprotein lipase Defective LDL receptors Defective ApoE Hepatic
OR OR overproduction of
VLDL
De ciency of apolipoprotein C-II Defective ApoB-100

Clinical Eruptive xanthomas [6] Premature atherosclerosis Premature Premature

atherosclerosis atherosclerosis
manifestations Hepatosplenomegaly Arcus lipoides
Tuberous/tendon xanthomas in type IIa Palmar and Tuberoeruptive
Recurrent episodes of
tuberoeruptive xanthomas
acute pancreatitis and/or Xanthelasma in type IIb xanthomas Acute
abdominal pain
pancreatitis
Lipemia retinalis
Features of
Bile duct stenosis
hyperglycemia
No increased risk for
artherosclerosis

https://www.amboss.com/us/knowledge/Lipid_disorders 4/13
12/31/2020 Lipid disorders - AMBOSS

Fredrickson IChylomicrons IIa

LDL IIb
LDL and VLDL III
Remnants of VLDL and IV
VLDL REGISTER / LOG IN
Lipoprotein
phenotype chylomicrons
defect

Total Normal to mild ↑ [11] ↑↑ ↑↑ ↑ Normal to mild ↑

cholesterol

Total ↑↑ [11] Normal ↑ ↑ ↑↑

triglycerides

Overnight Creamy top layer [11] Clear Clear Turbid Turbid

plasma

References:[11][12]

Pathophysiology
Elevated LDL and reduced HDL → promote atherosclerosis → increased risk of cardiovascular events
See pathogenesis of atherosclerosis for details.

References:[13]

Clinical features
Typically no speci c signs or symptoms

Skin manifestations
Xanthoma: nodular lipid deposits in the skin and tendons

https://www.amboss.com/us/knowledge/Lipid_disorders 5/13
12/31/2020 Lipid disorders - AMBOSS

Pathophysiology: Extremely high levels of triglycerides and/or LDL result in extravasation of plasma lipoproteins and their deposition in
REGISTER / LOG IN
tissue.
Eruptive xanthomas: yellow papules with an erythematous border; located on the buttocks, back, and the extensor surfaces of the
extremities

Occurrence: hypertriglyceridemia (chylomicron or VLDL); also lipoprotein lipase de ciency

Tendinous xanthomas: rm nodules, located in tendons (typically extensor tendons of hands and the Achilles tendon)
Occurrence: severe hypercholesterinemia, ↑ LDL levels
Palmar xanthomas: yellow plaques on the palms of the hands

Occurrence: type III hyperlipoproteinemia, ↑ VLDL

Xanthelasmas: nodular lipid deposits around the eyelids
Typically bilateral, yellow, at plaques on the upper eyelids (nasal side)

Etiology: idiopathic; often occurs in association with hypercholesterolemia (e.g., primary biliary cholangitis), hyperapobetalipoproteinemia, ↑
LDL levels
Increased incidence in

Patients suffering from diabetes mellitus

Patients with increased lipoproteins in plasma
Usually affects postmenopausal women
Eye manifestations

Lipemia retinalis: opaque, white appearance of the retinal vessels, visible on fundoscopic exam
Arcus lipoides corneae
Fatty liver (hepatic steatosis)

Severe hypertriglyceridemia (typically > 1000 mg/dL) → pancreatitis

Atherosclerosis with secondary diseases
Coronary heart disease
Myocardial infarction

Stroke
Peripheral arterial disease
https://www.amboss.com/us/knowledge/Lipid_disorders 6/13
12/31/2020 Lipid disorders - AMBOSS

Carotid artery stenosis

REGISTER / LOG IN
Cholesterol embolization syndrome

References:[1][4][14][15]

Diagnostics
Laboratory analysis
Fasting lipid pro le : total cholesterol, HDL, and triglycerides are measured
LDL level can be measured directly using assays or estimated using the Friedewald formula

Pathological values from two different occasions are required to con rm the diagnosis.
Dyslipidemia is diagnosed if LDL > 130 mg/dL. and/or if HDL levels < 40 mg/dL
Identify underlying cause

Fasting blood glucose level or Hb1Ac

TSH level
Liver function tests
Urine analysis

Parameters of fat metabolism

Laboratory parameter Optimal level (mg/dL) Pathological (mg/dL)

Total cholesterol < 200 Borderline: 200–239

High: > 240

https://www.amboss.com/us/knowledge/Lipid_disorders 7/13
12/31/2020 Lipid disorders - AMBOSS

Parameters of fat metabolism

REGISTER / LOG IN

Laboratory parameter Optimal level (mg/dL) Pathological (mg/dL)

Triglycerides

< 150 Borderline: 150–199

High: > 200
Very high: ≥ 500

LDL < 100 Near optimal: 100–129

Borderline high: > 130
High: > 160
Very high: ≥ 190

HDL ≥ 60 Low: < 40

LDL/HDL ratio: the ratio of LDL and HDL levels serves as a control measure of cholesterol metabolism

Further workup required in patients with con rmed dyslipidemia

Assess for cardiovascular disease (CVD)

Myocardial infarction

Stroke
Symptomatic carotid artery stenosis

Peripheral artery disease

Abdominal aortic aneurysm

Or CVD risk equivalents: diabetes mellitus, chronic kidney disease

Assess for other major risk factors of CVD

Smoking

https://www.amboss.com/us/knowledge/Lipid_disorders 8/13
12/31/2020 Lipid disorders - AMBOSS

Hypertension
REGISTER / LOG IN
Elevated total cholesterol, LDL, and/or low HDL

Family history of CHD ( rst degree relative ♂ < 55 years; ♀ < 65 years)
Age: ♂ ≥ 45 years; ♀ ≥ 55 years

References:[1][4][16][17][18]

Treatment
Goal: Improve serum lipid levels to reduce the risk of cardiovascular disease.

General measures: lifestyle modi cations

Dietary changes: Reduce saturated fat and cholesterol intake. A low cholesterol intake (< 300 mg per day is recommended in the US dietary
guidelines

Weight management
Physical activity

Medical therapy
Statins

Second-line lipid-lowering agents

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 congenital disorders: : lifestyle modi cations and lipid-lowering agents (high-dose statin therapy and ezetimibe for
hypercholesterolemia, brates for hypertriglyceridemia); LDL apheresis may be required in severe cases.

https://www.amboss.com/us/knowledge/Lipid_disorders 9/13
12/31/2020 Lipid disorders - AMBOSS

ACC/AHA guidelines REGISTER / LOG IN

Initiate moderate-intensity or high-intensity statin therapy.

Clinical atherosclerotic cardiovascular disease (ASCVD); : high-intensity statin therapy (age > 75 years: moderate-intensity statin therapy)

LDL ≥ 190: high-intensity statin therapy

Age 40–75 years + Diabetes (if LDL 70–189) → moderate dose statin therapy (consider high-dose statin therapy if > 7.5% 10 year ASCVD risk)
Age 40–75 years + 10 year ASCVD risk > 7.5% (if LDL 70–189)

See statins for details.

ATP III guidelines (2013)

Guidelines for lipid-lowering therapy (ATP III guidelines)

LDL goal (mg/dL) Lifestyle modi cations indicated (mg/dL) Medical therapy indicated (mg/dL)
Risk strati cation

ASCVD or risk equivalents (high risk > 20%) < 100 (or < 70 ) > 100 > 130

≥ 2 Risk factors (moderate risk) < 130 > 130 > 160

0–1 Risk factors (low risk) < 160 > 160 > 190

References:[1][4][14][19][20][21][22]

Prevention
The decision to screen for hyperlipidemia primarily depends on the patient's overall risk for cardiovascular disease.

Screening high-risk individuals (i.e., with other risk factors for cardiovascular disease): ♂ > 20–25 years; ♀ > 30–35 years

https://www.amboss.com/us/knowledge/Lipid_disorders 10/13
12/31/2020 Lipid disorders - AMBOSS

Screening low-risk individuals: ♂ > 35 years; ♀ > 45 years

REGISTER / LOG IN

References:[2]

Abetalipoproteinemia
Etiology de ciency of apolipoproteins (ApoB-48, ApoB-100)
Due to mutation in the microsomal triglyceride transfer protein (MTTP) gene

Pathophysiology: autosomal recessive disease; de ciency of chylomicrons, VLDL, and LDL.

Clinical features
Early: steatorrhea, failure to thrive, fat malabsorption, fat-soluble vitamin de ciency, acanthocytosis.

Late: developmental delay, retinitis pigmentosa, myopathy, progressive ataxia, spinocerebellar degeneration.

Diagnosis
Extremely low levels of plasma cholesterol (< 50 mg/dL)

Acanthocytes in the blood

Absent LDL in the blood

Other tests performed include: complete blood count with differential, stool studies, fasting lipid pro le

Con rmatory test: genetic testing to detect mutations in the MTTP gene.
Intestinal biopsy: microscopic evaluation may reveal lipid-laden enterocytes

Treatment

Restriction of long-chain fatty acids

Large doses of oral vitamin E

References
https://www.amboss.com/us/knowledge/Lipid_disorders 11/13
12/31/2020 Lipid disorders - AMBOSS

1. Le T, Bhushan V, Bagga HS. First Aid for the USMLE Step 2 CK. McGraw-Hill Medical ; 2009 REGISTER / LOG IN

2. Vijan S. Screening for Lipid Disorders in Adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate.
https://www.uptodate.com/contents/screening-for-lipid-disorders-in-adults .Last updated: December 14, 2016. Accessed: May 10, 2017.
3. Le T, Bhushan V. First Aid for the USMLE Step 1 2015. McGraw-Hill Education ; 2014
4. Jenkins B, McInnis M, Lewis C. Step-Up to USMLE Step 2 CK. Lippincott Williams & Wilkins ; 2015

5. Rosenson RS. Secondary Causes of Dyslipidemia. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate.
https://www.uptodate.com/contents/secondary-causes-of-dyslipidemia .Last updated: February 10, 2016. Accessed: May 10, 2017.
6. HYPERLIPOPROTEINEMIA, TYPE I. https://www.omim.org/entry/238600 . Updated: September 7, 2016. Accessed: April 3, 2019.
7. HYPERLIPOPROTEINEMIA, TYPE II, AND DEAFNESS. https://www.omim.org/entry/144300 . Updated: January 21, 2009. Accessed: April 3,
2019.
8. 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.
9. HYPERLIPOPROTEINEMIA, TYPE III. https://www.omim.org/entry/617347 . Updated: March 22, 2018. Accessed: April 3, 2019.

10. HYPERLIPOPROTEINEMIA, TYPE IV. https://www.omim.org/entry/144600 . Updated: November 22, 2010. Accessed: April 3, 2019.

11. HYPERLIPOPROTEINEMIA, TYPE V. https://www.omim.org/entry/144650 . Updated: June 3, 2018. Accessed: April 3, 2019.
12. Rosenson RS, JP Kastelein JJP. Hypertriglyceridemia. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate.
https://www.uptodate.com/contents/hypertriglyceridemia .Last updated: February 28, 2017. Accessed: January 14, 2018.
13. Le T, Bhushan V, Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. McGraw-Hill Medical ; 2017

14. Torres KMT. Xanthomas. In: Elston DM, Xanthomas. New York, NY: WebMD. https://emedicine.medscape.com/article/1103971 . Updated:
December 15, 2017. Accessed: January 14, 2018.

15. Zak A, Zeman M, Slaby A, Vecka M. Xanthomas: clinical and pathophysiological relations. Biomed Pap. 2014 . doi: 10.5507/bp.2014.016 .|
Open in Read by QxMD

16. 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) nal report. https://www.nhlbi.nih.gov/ les/docs/resources/heart/atp-3-cholesterol-full-
report.pdf . Updated: September 1, 2002. Accessed: May 10, 2017.
17. Hennekens CH, Lopez-Sendon J. Prevention of Cardiovascular Disease Events in Those with Established Disease or at High Risk. In: Post TW, ed.
UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/prevention-of-cardiovascular-disease-events-in-those-with-

https://www.amboss.com/us/knowledge/Lipid_disorders 12/13
12/31/2020 Lipid disorders - AMBOSS

established-disease-or-at-high-risk .Last updated: February 1, 2017. Accessed: May 10, 2017.

REGISTER / LOG IN
18. Rosenson RS. Measurement of Blood Lipids and Lipoproteins. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate.
https://www.uptodate.com/contents/measurement-of-blood-lipids-and-lipoproteins .Last updated: September 7, 2017. Accessed: September
22, 2017.
19. De Ferranti SD, Newburger JW. Dyslipidemia in Children: Management. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate.
https://www.uptodate.com/contents/dyslipidemia-in-children-management .Last updated: April 4, 2016. Accessed: May 10, 2017.
20. Lambert M. ACC/AHA release updated guideline on the treatment of blood cholesterol to reduce ASCVD risk. Am Fam Physician. 2014; 90 (4):
p.260-265.
21. Stone NJ, Robinson JG, Lichtenstein AH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic
cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.. J Am
Coll Cardiol. 2014; 63 (25 Pt B): p.2889-2934. doi: 10.1016/j.jacc.2013.11.002 . | Open in Read by QxMD
22. Yang EH. Lipid Management Guidelines . In: Yang EH, Lipid Management Guidelines . New York, NY: WebMD.
http://emedicine.medscape.com/article/2500032 . Updated: December 30, 2015. Accessed: May 10, 2017.
23. Rosenson RS. Lipoprotein Classi cation, Metabolism, and Role in Atherosclerosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate.
https://www.uptodate.com/contents/lipoprotein-classi cation-metabolism-and-role-in-atherosclerosis .Last updated: May 5, 2017. Accessed:
May 10, 2017.
24. Bays HE, Jones PH, Orringer CE, Brown WV, Jacobson TA. National Lipid Association Annual Summary of Clinical Lipidology 2016. Journal of
Clinical Lipidology. 2016; 10 (1): p.S1-S43. doi: 10.1016/j.jacl.2015.08.002 . | Open in Read by QxMD
25. National Heart, Lung, and Blood Institute. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and
Adolescents: Summary Report. Pediatrics. 2011; 128 (Supplement): p.S213-S256. doi: 10.1542/peds.2009-2107c . | Open in Read by QxMD

© 2020 AMBOSS Medical Knowledge Terms and Conditions Privacy Legal Notice Get Support & Contact Us

https://www.amboss.com/us/knowledge/Lipid_disorders 13/13