hypo3

Overview: lipoprotein disorders
- Evaluation: Serum lipid measurement following 10-hour fast
- CHD risk:
  - directly proportional to atherogenic lipoproteins concentration
  - indirectly proportional to HDL levels
  - triglyceride levels, preferably less than 150 mg/dL
Primary Hypertriglyceridemia:
- Definition: triglyceride plasma concentration > 90th or 95th percentile for age and gender (as determined following an overnight fast)
- Isolated plasma triglycerides elevation may be due to increased VLDL or combinations of elevated VLDL and chylomicrons (rarely a result of elevated chylomicrons only)
  - Eruptive xanthomas may occur in isolated hypertriglyceridemia
    - small, orange-red papules {trunk/extremities; triglyceride levels > 1000 mg/dL chylomicronemia}
  - at 1000 mg/dL:
    - orange-yellow retinal vessels (lipemia retinalis)
    - Major risk at this plasma triglyceride concentration: pancreatitis
- Typical plasma triglycerides elevation: caused by increased hepatic VLDL triglyceride synthesis and secretion
  - Regulation of hepatic triglyceride synthesis:
    - free fatty acid availability
    - hepatic glycogen levels
    - balance between insulin and glucagon
  - Conditions associated with hypertriglyceridemia:
    - obesity, insulin resistance, alcohol consumption, inactivity, excessive intake of simple sugars and saturated fats.
    - at VLDL triglyceride levels > 1000 mg/dL, lipoprotein lipases may become saturated
- Familial Hypertriglyceridemia: (severe)
  - Autosomal dominant (For mixed lipemia-- various modes of inheritance)
  - Possible mechanisms: VLDL over production & reduced triglyceride-rich lipoprotein catabolism
  - Fasting triglyceride range: 200-750 mg/dL, with increased VLDL triglycerides only
  - Factors that increase VLDL production worsens lipemia (VLDL & chylomicrons -- competing lipoprotein lipase substrates)
  - Most patients: obese
  - Clinical complaints (depending on lipemia severity): eruptive xanthomas, epigastric pain, lipemia retinalis, pancreatitis
  - Treatment: dietary -- alcohol avoidance, reduced fat intake, avoid exogenous estrogen, weight reduction; some patients may require gemfibrozil (Lopid) or niacin (vitamin B3)
- Familial Hypertriglyceridemia: (moderate, endogenous lipemia)
  - Multiple genetic factors
  - Made worse by factors that increased hepatic VLDL secretion (hypertrophic obesity, alcohol, exogenous estrogen intake, diabetes)
  - Treatment: -- indication presence of atherosclerosis (in the patient or in the patient's family)
    - weight reduction
    - dietary fat restriction
    - alcohol avoidance
    - if necessary, gemfibrozil (Lopid) or niacin (vitamin B3)
- Familial Combined Hyperlipoproteinemia:
  - Elevated VLDL and/or LDL
  - Mechanism: 200% increase in hepatic VLDL secretion
  - Increased CHD risk: Drug therapy (niacin or a resin in combination with niacin)
- Familial Lipoprotein Lipase Deficiency:
  - Autosomal recessive (absence/impairment of lipoprotein lipase/lipoprotein lipase cofactor)
  - Dramatic chylomicron accumulation in plasma:
  - Lipemia worsened by estrogens & pregnancy
  - Clinical presentations (beginning in infancy) include:
    - pancreatitis
    - eruptive xanthomas
    - hepatomegaly
    - splenomegaly
    - bone marrow foam cell infiltration
    - at triglyceride levels > 1000 mg/dL --lipemia retinalis
- Familial Apoprotein CII Deficiency:
  - rare autosomal recessive
  - Presentations similar to familial lipoprotein lipase deficiency
- Familial Dysbetalipoproteinemia:
  - Accumulation of chylomicrons and VLDL reminants
  - Low LDL; high serum cholesterol & triglycerides
  - Clinical Presentations:Familial Dysbetalipoproteinemia:
    - tuberous/tuberoeruptive xanthomas
    - planar xanthomas:palmar creases
    - common: obesity & impaired glucose tolerance-- worsening lipemia
    - Peripheral/coronary atherosclerosis
  - Treatment:Familial Dysbetalipoproteinemia:
    - weight reduction
    - reduced fat, cholesterol, alcohol intake
    - niacin (vitamin B3) or gemfibrozil (Lopid) may be needed (typically at low doses)

Primary Reference: Malloy, M. J, and Kane, J. P., Agents Used in Hyperlipidemia, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 563-577.

Primary Reference: Ginsberg, H. N and Goldberg, I. J. Disorders of Intermediary Metabolism: Disorders of Lipoprotein Metabolism, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2138-2149.