Hypocholesterolemia

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Hypocholesterolemia

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Cholesterolpoison?As low as possible?

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Definition

• Conversely, hypolipidemia can be defined as
  plasma cholesterol concentrations less than 3.4
  nmol/L(130mg/dl)
• Plasma lipid levels vary among individuals of
  different population owing to genetic and dietary
  factors.
• For example, the mean plasma cholesterol
  concentration for Western men is 210 mg/dl,
  whereas for Japanese men it is 165 mg/dl
• -Williams Textbook of
  Endocrinology tenth edition 1167

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Primary hypocholesterolemia

• Genetic disorder of HDL metabolismTangier
  disease
• Familial hypobetalipoprotienemia
• Abetalipoproteinemia

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Primary hypocholesterolemia

• Tangier disease is a rare autosomal recessively
  inherited disorder characterized by the absence
  or severe deficiency of HDL in plasma.
• Clinical featurehepatosplenomeagaly and orange
  yellow tonsils
• Biological featureshypocholesterolemia with
  absence of plasmatic HDL cholesterol.

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Primary hypocholesterolemia

• Familial hypobetalipoprotienemia, an autosomal
  dominant disorder of apo-B metabolism, is
  associated with less than one-half normal in
  heterozygotes and marked hypocholesterolemia (
  lt50 mg/dl in homozygotes
• Low LDL, cholesterol, TG but normal HDL
• Heterozygotes usually asymptomatic
• Homozygotes may present with fat malsborption
  (Vit E deficiency, retinitis pigmentosa
  acanthocytosis. The latter is caused by
  alteration in RBC membrane lipids.

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Primary hypocholesterolemia

• Abetalipoproteinemia is a rare autosomal
  recessive disorder caused by a deficiency of MTP
  (micosomal triglyceride transfer protein) which
  resulted in a absence of the apo-B-containing
  lipoproteins in the plasma
• Clinical features like homozygotic
  hypobetalipoprotienemia
• The disorder is frequently detected in infancy
  because of fat malabsorption associated with mark
  decreases in the levels of plasma chol and TG

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Secondary hypocholesterolemia

• Well known causes
• Liver diseases
• Hyperthyroidism
• Digestive malnutrition

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Secondary hypocholesterolemia

• Less obvious
• Malignancy
• Fever
• Traumatism
• Inflammatory disease(RA, SLE)
• Depression illness
• Violent death(?)-Revue de Medecine
  Interne.19(3)180-4,1998 Mar

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Liver disease and hypocholesterolemia

• Hypocholesterolemia is frequently found in severe
  chronic hepatic insufficiency because the liver
  is the most active organ of cholesterol
  metabolism.
• Baseline serum cholesterol levels lower than 100
  mg/dl identify a subgroup of Child-C cirrhotic
  patients with high mortality risk within a 2-year
  follow-up.-Scandinavian Journal of
  Gastroenterology 33(11)1213-8,1998

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Digestive Malabsorption and Hypocholesterolemia

• Hypocholesterolemia was characteristic of
  congenital and acquired disordered intestinal
  absorption.
• Hypoalbuminemia only demonstrated a significant
  relationship with nutrition-associated
  complications, whereas hypocholesterolemia was
  associated with death-Journal of the American
  college of nutrion. 19(5)570-7,2000

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Digestive malnutrition

• The metabolic consequences of AIDS patientss with
  malabsorption included osteomalcia, gall stone,
  renal stones and hypocholesterolemia.

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Secondary hypocholesterolemia

• Less obvious
• Malingancy
• Fever
• Traumatism-Critical Care Medicine
  25(8)1437-9,1997
• Inflammatory disease(RA, SLE)
• Depression illness

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Malignance and Hypocholesterolemia

• Hypocholesterolemia is a frequent finding in
  patients with acute myelogenous leukemia and in
  other types of malignancies(included brain
  tumor).
• Epidemiological studies indicate that low serum
  cholesterol level may increased the risk of death
  due to cancer
• The hypocholesterolemia is related to lowered LDL
  and HDL cholesterol level

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Malignance and Hypocholesterolemia

• Cytokine effects on different enzymes of lipid
  metabolism.
• High expression of LDL receptors on tumor
  cell-Molecular Pharmacology52(3)445-55,1997
• Marked hypochoelsterolemia in cases with adrenal
  adenoma-enhance catabolism of LDL and LDL
  receptors
• Hypocholesterolemia may be associated with low
  serum antioxidant reserve,possibly increasing
  susceptiblity to oxidatative stress-Free Radical
  Research 25(3)329-45,1996
• May result from the conversion of cholesterol to
  bile acids suppression(suppressed levels of a
  circulating marker for bile acid synthesis-Cancer
  letters 170(2)165-75,2001 Sep 20

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Blood V.S. Hypocholesterolemia

• Acute myelogenous leukemia
• Malaria
• Some authors suggested that the pretreatment
  serum cholesterol level may reflect hemotopoietic
  activity within the bone marrow and can help to
  predict the therapeutic response of each case of
  aplastic anemia.-Padiatrics International.
  42(6)613-9,2000 Dec

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Blood V.S. Hypocholesterolemia

• Children and adolescents with beta-thalassemia
  intermedia have significant lower cholesterol
  level than patients with beta-thalassemia
  major-Journal of pediactircs 141(4)543-7,2002

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Hypocholesterolemia and Intracerebral hemorrhage
in previous healthy adult

• Hypocholesterolemia below 4.14 mmol/l can be
  found in young, healthy adults have all been
  described in the literature as contributors to
  the risk of ICH-brain Injury. 16(5)397-105, 2002
  May
• ICH in young people are mainly result from
  vascular malformation.

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Fever V.S. Hypocholesterolemia

• Hypocholesterolemia often accompanies infection
  has been suggested to serve as a prognostic maker
  in hospitalized patients.
• Immune system differences in men with hypo- or
  hypocholesterolemia-Hypocholesterolemic men had
  significantly fewer circulationg lymphocyte,
  fewer total T cell and fewer CD8 cell-Clinical
  Immunology Immunopathology 84(2)145-9,1997

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Fever V.S. Hypocholesterolemia- malaria

• Contribution to the diagnosis of malaria in
  febrile travelers returning for endemic
  areas.(129 malaria ,92 control )-Journal of
  Travel Medicine 9(3)117-21, 2002 May-JUN
• Alternations of cholesterol and phospholipid
  contentgt Changes in the lipid matrix fluidity of
  plasma membrane gtaffect the membrame functions
  of cellsgtthe pathogenesis of immune invasion and
  clinical manifestation of Falciparum Malaria
  Medical hypotheses 51(2)105-10,1998

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Critical illness

• Prior studies established a negative correlation
  of total cholesterol to infection parameter at
  the early stage of infection
• Cholesterolemia improves the prognostic power of
  the APACHE II score-Intensive Care medicine
  22(8)790-4,1996

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HIV Infection

• Hypocholesterolemia is observed in asymptomatic
  HIV subjects, then hypertriglyceridemia appears
  in patients with AIDS.
• Psychological distress in HIV disease in
  relationship to hypocholesterolemia had been
  noted.-International Journal of Psychiatry in
  Medicine.27(2)159-97,1997

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Malnutrition(?) V.S. Hypocholesterolemia

• Hypocholesterolemia is a significant independent
  predictor of death in a cohort of chronic
  hemodialysis patients-(N1167 patient form 1991
  to 2001)Kidney International.61(5)1887-93,2002
  May
• Survival in ARF is significantly altered by the
  levels of albumin and cholesterol. Their presence
  in ARF should be considered ominous Kidney
  Inernational 56(3)1058-63,1999

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Malnutrition(?) V.S. Hypocholesterolemia

• Increased mortality in eleder persons with
  hypocholesterolemia
• It has been postulated that hypomagnesemia,
  hypocholesterolemi, corticosteroids and
  neurotoxic subtances can induce cyclosporin-A
  neurotoxicity.

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Depression V.S. Hypocholesterolemia

• An association of relative cholesterol with both
  depression and suicide had been reported
• Fasting serum cholesterol levels are low in manic
  patients, especially during mixed bipolar
  episodes.-European Arch of Psychiatry clinical
  neuroscience 252(3)110-4,2002
• Psychological distress in HIV disease in
  relationship to hypocholesterolemia had been
  noted.-International Journal of Psychiatry in
  Medicine.27(2)159-97,1997
• There is no evidence that low cholesterol could
  cause or worsen affective disorder.

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CARDIA study(Coronary Artery Risk Development in
Young Adults)

• 720 black men, 922 white men, 899 black women,944
  white women
• Age18-30 ,7 year follow up
• Plasma cholesterol below the 10th percentile
  remained below the same percentile 7 years later
• gtYoung adults with low plasma total cholesterol
  level have characteristics generally associated
  with good cardiovascular health.

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Prospective 10-year evaluation of
hypocholesterolemia in a cohort study

• 10-year prospective study of 772 Cincinnati
  firemen(age 26-46 years)
• 44 entry low LDL(lt75) and cholesterol(lt130mg/dl)
  level, 12 with persistent low LDL level
• One died of melanoma by 9 years and one died of
  alcoholism by 2 years-Metabolismclinical
  Experimental.46(6)625-33,1997

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As Hypoglycemia?As Sick Euthyroid Syndrome?As
Hypoalbuminemia?

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Mechanism

• Cytokine effects on different enzymes of lipid
  metabolism.
• -TNF(inflammatory states,
  Malignancy)
• -IL-2-journal of clinical
  Endocrinoloagy Metabolism82(5)1527-81,1997
• -IL-6
• High expression of LDL receptors on tumor cellh
• Hypocholesterolemia may be associated with low
  serum antioxidant reserve,possibly increasing
  susceptiblity to oxidatative stress
• Intracellular accumulation of lipid
• Impaired the conversion of cholesterol to bile
  acid

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Conclusion

• About illness(Infection, Malignancy, blood
  disorder,ESRD)
• About mood disorder
• About mortality