Hyperlipoproteinemia

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]

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		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		Type I	Type IIA	Type IIB	Type III	Type IV	Type V
	Diabetes Mellitus	X					✔
	Alcohol Abuse	X					✔
	Estrogen Therapy	X					✔
	Glucocorticoid therapy	X					✔
	Renal Disease	X					X
	Obesity	X					✔
	High-fat diet	X					✔
	Poor physical activity	X					✔
	Paraproteinemic disorders	X					X
	Hypothyroidism	X					✔

Diagnostic Algorithm

Shown below is a diagnostic algorithm to diagnose hyperlipidemia.

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