Homocysteine And Cardiovascular Disease


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This is a presentation that I gave to my graduate level Vitamins and Minerals class depicting how the amino acid homocysteine effects cardiovascular disease.

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Homocysteine And Cardiovascular Disease

  1. 1. Homocysteine and Cardiovascular Disease Aharon Roberts FCSFN 648
  2. 2. Homocysteine  :Sulfur containing nonessential amino acid that is not found in the diet. Dietary methionine is converted to homocysteine. Methionine Homocysteine NH3+ H l | CH3-S-Ch2-CH2-CH-CO2- → +H3N-C-COO- | CH2-CH2-SH
  3. 3. Homocysteine  Varying forms  1% free  70-80% bound to albumin via a disulfide link  20-30% either as a homocysteine dimer or a cysteine-homocysteine-mixed disulfide. * The type(s) of species responsible for the CVD pathology have yet to be determined.
  4. 4. Etiology of Hyperhomocysteinemia  Causes  Genetic mutations  Nutritional deficiencies  Disease states  Drugs
  5. 5. Etiology of Hyperhomocysteinemia  Genetic Mutations  5-methyleneterahydrofolate reductase (MTHFR) polymorphism due to a point mutation on chromosome 1.
  6. 6. Etiology of Hyperhomocysteinemia  Nutritional deficiencies  Folate deficiency  Cobalamine deficiency  Pyridoxine deficiency
  7. 7. Mechanism for Homocysteine Metabolism
  8. 8. Etiology of Hyperhomocysteinemia  Disease states  Cystathione β-synthase deficiency  Homocysteinuria  Methionine synthase deficiency * Both are rare autosomal recessive disorders that are correlated with hyperhomocysteinemia and vascular thrombosis.  Chronic renal failure regardless of etiology, duration, or type of dialysis  Severe psoriasis  Possibly through increased cell turnover  Pernicious anemia  Cobalamine deficiency
  9. 9. Etiology of Hyperhomocysteinemia  Drugs  Cholestryamine (reduces cholesterol in blood)  Impairs folate absorption  Methotrexate (treatment of psoriasis)  Depletes folate metabolites  Anti-epileptics (carbemazapine, phenytoin)  Lower folate concentrations *Tobacco and caffeinated coffee are also associated with increased homocysteine concentrations
  10. 10. How Homocysteine effects CVD  Homocysteine is one of many damaging agents to endothelial cells  LDL and platelets invade  Platelets secrete chemoattractants for monocytes  PDGF - Platelet derived growth factor stimulates smooth muscle proliferation and thickening of the tunica media. Smooth muscle cells from the tunica media invade the tunica intima.  Monocytes invade and are activated to macrophages/scavenger cells.
  11. 11. How Homocysteine effects CVD  Smooth muscle cells and macrophages ingest LDL  Foam cells/Fatty streaks  The high amounts of cholesterol ester consumed will precipitate into crystalline deposits.  Deposits calcify and become rough stimulating clot formation creating a fibrous plaque.  Narrows the lumen of the vessels, restricting blood flow.
  12. 12. Research  1969 – Dr. Kilmer McCully, M.D.  Compared an 8 y/o patient with homocysteinuria who died of a stroke and an infant with an inherited defect of cobalamine metabolism who died of cardiac arrest.  Concluded that elevated homocysteine levels result in premature atherosclerosis.  Later expanded to include general populations with mild hyperhomocysteinemia, typically associated with dietary deficiencies.
  13. 13. Research  VITATOPS  Vitamins to Prevent Stroke  Stated that an adjustment for renal function eliminated the relationship between total homocysteine levels and intima media thickness as well as flow-mediated dilation of the brachial artery.
  14. 14. Research  VISP  Vitamin Intervention for Stroke Prevention  Reduction in total plasma homocysteine concentration was reported at 21% in participants after exclusion of those with impaired renal status, those with malabsorption of B vitamins, or those taking other B vitamins not associated with the study.
  15. 15. Research  HOPE  Heart Outcomes Prevention Evaluation  For patients with vascular disease, B vitamin therapy significantly reduced stroke by 25% but not myocardial infarction or death.
  16. 16. Research  Severe homocysteinuria  Treatment with high-dose B vitamins in combination with dietary methionine restriction resulted in markedly reduced results. * Results for mild homocysteinuria have not shown such significant results. Contradictory results may be due to trial design, adverse effects from vitamin supplementation, and using homocysteine as a risk factor or not as a risk factor.
  17. 17. Reduction in Homocysteine Levels  Supplementation of B vitamins  Folate, B6, and B12  Restriction of methionine containing substances  Sesame seeds, brazil nuts, fish, meats  Exercise
  18. 18. Bibliography  Gauthier, G.M., Keevil, J.G., McBride, P.E., The Association of Homocysteine and Coronary Artery Disease. Clin. Cardiol. 2003; 26:563-8.  Gropper, S.S., Groff, J.L., and Smith, J.L., Advanced Nutrition and Human Metabolism. 5th Edition, Wadsworth Publishing, 2009.  Lavie, C.J., Milani, R.V., Homocysteine The Rubik’s Cube of Cardiovascular Risk Factors. Mayo Clinic Proceedings. 2008; 83(11):1200-02.  Scott, J., Weir, D. Homocysteine and cardiovascular disease. Q J Med. 1996; 89:561-3.