Hyperlipoproteinemia

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Lipoprotein Disorders Main Page

Hyperlipoproteinemia Microchapters

Hypercholesterolemia Patient Information

Hypertriglyceridemia Patient Information

Overview

Classification

Familial hyperchylomicronemia
Familial hypercholesterolemia
Familial combined hyperlipidemia
Dysbetalipoproteinemia
Primary hypertriglyceridemia
Mixed hyperlipoproteinemia

Differential Diagnosis

Screening

ACC/AHA Guideline Recommendations

Summary

Treatment

Major recommendations for statin therapy

Therapeutic response to statin therapy

Blood cholesterol LDL and non-HDL treatment goals

Treatment in heart failure and hemodialysis

Primary prevention

Secondary prevention

Intensity of statin therapy in primary and secondary prevention

Safety Recommendations

Guideline on Lifestyle Management

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tarek Nafee, M.D. [2]

Overview

Classification

 
 
 
 
 
 
 
 
 
 
 
 
 
Hyperlipoproteinemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Type I:
Familial hyperchylomicronemia
 
 
Type II
 
Type III:
Dysbetalipoproteinemia
 
Type IV:
Primary hypertriglyceridemia
 
Type V:
Mixed hyperlipoproteinemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Type A:
Familial hypercholesterolemia
 
Type B:
Familial combined hyperlipidemia
 

Synopsis

Hyperlipoproteinemia Synonyms Problems Labs description Treatment
Type I Buerger-Gruetz syndrome, primary hyperlipoproteinaemia, or familial hyperchylomicronemia Decreased lipoprotein lipase (LPL) or altered ApoC2 Elevated chylomicrons Diet control
Type IIa Polygenic hypercholesterolaemia or familial hypercholesterolemia LDL receptor deficiency Elevated LDL only Bile acid sequestrants, statins, niacin
Type IIb Combined hyperlipidemia Decreased LDL receptor and increased ApoB Elevated LDL, VLDL and triglycerides Statins, niacin, gemfibrozil
Type III Familial Dysbetalipoproteinemia Defect in ApoE synthesis Increased IDL Drug of choice: Gemfibrozil
Type IV Endogenous Hyperlipemia Increased VLDL production and decreased elimination Increased VLDL Drug of choice: Niacin
Type V Familial Hypertriglyceridemia Increased VLDL production and decreased LPL Increased VLDL and chylomicrons Niacin, gemfibrozil

Differential Diagnosis

↑- Elevated

↑ ↑- Moderately Elevated

↑ ↑ ↑- Markedly Elevated

Diseases Mode of Inheritance Laboratory Findings Other Findings Management Complications Prognosis
Lipid Profile Other Laboratory Findings
Total Cholesterol LDL HDL Triglycerides Plasma Appearance Chylomicrons VLDL Genetic mutations
Primary Hyperlipoprotenemia Type I Autosomal Recessive

&

Autosomal Dominant(Rare)

Normal or   ↓↓↓ ↑↑↑ Milky ↑↑↑   -LPL gene mutation -Fat tolerance markedly abnormal

-Carbohydrate inducibility may be abnormal

Treatment for hyperlipoproteinemia type 1 is intended to control blood triglyceride levels with a very low-fat diet -Recurrent Pancreatitis

-Rarely life threatening

Good
Type IIA Autosomal Dominant & Autosomal Recessive(Rare) ↑↑ ↑↑↑ Normal/ Normal Clear - LDL recptor mutation

- Apolipoportein B gene mutation

-Proprotein convertase subtilisin/kexin type 9 mutation.

Lipid management with lifestyle modifications and pharmacotherapy -Symptomatic coronary artery disease by 50-60 years and half of the men and 15%-30% of the women will have died Good
Type IIB Mostly Dominant mode ↑↑ ↑↑ ↑↑ Clear or turbid -Locus 1q21-q23

-APOAI/CIII/AIV cluster

-Gene encoding upstream transcription factor 1 (USF1)

Lipid management with lifestyle modifications and pharmacotherapy -Coronary heart disease

-Coronary artery disease

-Peripheral artery disease

-Gangrene of the extremities

Type III Autosomal Recessive ↑↑ Normal ↑↑↑ Clear, cloudy,or turbid -Apo E mutations -IDL is elevated Lipid management with lifestyle modifications and pharmacotherapy -Atherosclerotic complications (e.g., coronary artery disease)

-Pancreatitis

-Stroke

-Peripheral vascular disease

-Intermittent claudication

Type IV Autosomal Recessive

&

Autosomal Dominant

Normal or Prebeta-HDL

&

HDL-C

↑↑ Clear or Cloudy Normal -LPL genes (Gly188Glu,Asp9Asn, Asn291Ser,Ser447Ter)

-APOA5

-LMF1

-GPIHBP1

Hyperglycemia, Pancytopneia and pseudo-Niemann

pick cells

-Weight reduction

-Niacin or Fibrates

-Gene therapy

-Ischemic Heart Disease

-Recurrent Pancreatitis

-NIDDM

-NAFLD

Type V Variable
to ↑↑
↓↓↓
↑↑↑
Creamy supernatant and turbid infranatant
↑↑↑
❑ Apo E, Apo A5 mutations
❑ LPL gene mutation in 10% of western population patients
❑ Restriction of dietary fat eliminates Chylomicrons and reverts to type IV HLP
❑ When triglyceride levels are >1000mg/dl given the rarity of type I it is almost always type V HLP
- Weight reduction
- Niacin or Fibrates or Strong statins
- Low fat diet
❑ Recurrent Pancreatitis
Good
Secondary Causes of
Hyperlipoprotenemia
LDL HDL Triglycerides Total Cholesterol
Diabetes Mellitus[1][2]
Alcohol Abuse[3][4][5]
Estrogen Therapy[6]
Glucocorticoid therapy[7][8][9] or N
Renal Disease [10][11] [11] [5] or N
Obesity[12] -
Pregnancy[13]
Paraproteinemic disorders[14][15] - -
Hypothyroidism[16][17] ↑↑↑ or N

Diagnostic Algorithm

Shown below is a diagnostic algorithm to diagnose hyperlipidemia.[18]

 
 
 
 
 
 
 
 
Hyperlipidemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Triglycerides > 75th Percentile
 
 
NO
 
 
Type IIa
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YES
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Types I, IIb, IV, V
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total Cholesterol/Apo B ratio ≥ 6.2
 
 
NO
 
 
Types IIb, IV
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YES
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Types I, III, V
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Triglycerides/Apo B ratio < 10.0
 
 
NO
 
 
Types I, V
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YES
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Type III
 
 
 
 
 

Screening

Screening in children and adolescents

Lipid screening recommendations vary by age and risk factors as shown below:[19][20] [21]

Pediatric dyslipidemia screening guidelines from the 2011 Expert Panel Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents

Age Screening recommendation Reommendation level
birth- <2years No lipid screening C
2-8years ( No routine lipid screening,

however screen if one of the following is present using FLP two times)

Parent, grandparent, aunt/uncle, or sibling with myocardial infarction (MI), angina, stroke, coronary artery bypass graft Strongly recommend (CABG)/stent/angioplasty at <55 years in males, <65 years in females B
Parent with TC ≥ 240 mg/dL or known dyslipidemia B
Child has diabetes, hypertension, BMI ≥ 95th percentile or smokes cigarettes B
Child has a moderate- or high-risk medical condition (eg. Diabetes mellitus type 1 and type 2, chronic renal disease/end-stage renal disease/ postrenal transplant, Postorthotopic heart transplant, Kawasaki disease with current aneurysms) B
9-11years (Universal Screening) Universal screening with a non-FLP screening using non-HDL-C levels ( Non-HDL–C = TC – HDL–C) when Non-HDL ≥ 145 mg/dL, HDL < 40 mg/dL check FLP × 2 B
Do further FLP if LDL–C ≥ 130 mg/dL, non-HDL–C ≥ 145 mg/dL HDL–C < 40 mg/dL, TG ≥ 100 mg/dL if < 10 years; ≥ 130 mg/dL if ≥ 10 years. Repeat FLP after 2 weeks but within 3 months B
12-16years (Selective screening using FLP x 2) Lipid screening is not recommended for those ages 12–16 years because of significantly decreased sensitivity and specificity for predicting adult LDL–C levels and significantly increased false-negative results in this age group. Selective screening ( Interval between FLP measurements: after 2 weeks but within 3 months) is recommended for those with the clinical indications outlined below: B
Parent, grandparent, aunt/uncle or sibling with MI, angina, stroke, CABG/stent/ Strongly recommend angioplasty, sudden death at < 55 years in males, < 65 years in females B
• Parent with TC ≥ 240 mg/dL or known dyslipidemia B
Patient has diabetes, hypertension, BMI ≥ 85th pr\ercentile or smokes cigarettes B
Patient has a moderate- or high-risk medical condition (eg. Diabetes mellitus type 1 and type 2, chronic renal disease/end-stage renal disease/ postrenal transplant, Postorthotopic heart transplant, Kawasaki disease with current aneurysms) B
17-19years Universal screening once during this time period with a nonfasting lipid screening using non-HDL-C levels. If Non-HDL-C ≥ 145 mg/dL, HDL-C < 40 mg/dL do FLP × 2, Further screening with FLP if LDL-C ≥ 130 mg/dL, non-HDL-C ≥ 145 mg/dL HDL-C < 40 mg/dL, TG ≥ 130 mg/dL repeat FLP after 2 weeks but within 3 months B
17-21years Universal screening once during this time period with a nonfasting lipid screening using non-HDL-C levels. If Non-HDL-C ≥ 190 mg/dL, HDL-C < 40 mg/dL do FLP × 2, Further screening with FLP when LDL-C ≥ 160 mg/dL, non-HDL-C ≥ 190 mg/dL, HDL-C < 40 mg/dL, TG ≥ 150 mg/dL repeat FLP after 2 weeks but within 3 months B

References

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