American Journal of Ophthalmology
Volume 148, Issue 6 , Pages 902-909 , December 2009

The Associations Between Blood Levels of Homocysteine, Folate, Vitamin B12, and Retinal Vascular Caliber

  • Bamini Gopinath

      Affiliations

    • Centre for Vision Research, Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia
    • Menzies Centre for Health Policy, University of Sydney, Sydney, New South Wales, Australia
  • ,
  • Jie Jin Wang

      Affiliations

    • Centre for Vision Research, Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia
    • Centre for Eye Research Australia, Department of Ophthalmology, University of Melbourne, Melbourne, Australia
  • ,
  • Victoria M. Flood

      Affiliations

    • Centre for Vision Research, Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia
    • Public Health Nutrition Group, Institute of Obesity, Nutrition and Exercise, University of Sydney, New South Wales, Australia
  • ,
  • George Burlutsky

      Affiliations

    • Centre for Vision Research, Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia
  • ,
  • Tien Y. Wong

      Affiliations

    • Centre for Eye Research Australia, Department of Ophthalmology, University of Melbourne, Melbourne, Australia
    • Singapore Eye Research Institute, National University of Singapore, Singapore
  • ,
  • Paul Mitchell

      Affiliations

    • Centre for Vision Research, Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia
    • Corresponding Author InformationInquiries to Paul Mitchell, Centre for Vision Research, University of Sydney, Westmead Hospital, Hawkesbury Road, Westmead, NSW, 2145, Australia

,Accepted 16 July 2009.

References 

  1. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002;88:2015–2022
  2. Mennen LI, de Courcy GP, Guilland JC, et al. Homocysteine, cardiovascular disease risk factors, and habitual diet in the French Supplementation with Antioxidant Vitamins and Minerals Study. Am J Clin Nutr. 2002;76:1279–1289
  3. Van Guldener C, Stehouwer CD. Hyperhomocysteinemia, vascular pathology, and endothelial dysfunction. Semin Thromb Hemost. 2000;26:281–289
  4. Nygard O, Refsum H, Ueland PM, Vollset SE. Major lifestyle determinants of plasma total homocysteine distribution: the Hordaland Homocysteine Study [see comments]. Am J Clin Nutr. 1998;67:263–270
  5. Nygard O, Vollset SE, Refsum H, et al. Total plasma homocysteine and cardiovascular risk profile (The Hordaland Homocysteine Study). JAMA. 1995;274:1526–1533
  6. Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Selhub J. Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr. 2001;73:613–621
  7. Lussier-Cacan S, Xhignesse M, Piolot A, Selhub J, Davignon J, Genest J. Plasma total homocysteine in healthy subjects: sex-specific relation with biological traits. Am J Clin Nutr. 1996;64:587–593
  8. Patton N, Aslam T, MacGillivray T, Pattie A, Deary IJ, Dhillon B. Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures. J Anat. 2005;206:319–348
  9. Hubbard LD, Brothers RJ, King WN, et al. Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study. Ophthalmology. 1999;106:2269–2280
  10. Kwa VI. Our eyes: windows to our souls or crystal balls?. Lancet Neurol. 2006;5:108–110
  11. Tedeschi-Reiner E, Strozzi M, Skoric B, Reiner Z. Relation of atherosclerotic changes in retinal arteries to the extent of coronary artery disease. Am J Cardiol. 2005;96:1107–1109
  12. Chua B, Kifley A, Wong TY, Mitchell P. Homocysteine and retinal vein occlusion: a population-based study. Am J Ophthalmol. 2005;139:181–182
  13. Cahill MT, Stinnett SS, Fekrat S. Meta-analysis of plasma homocysteine, serum folate, serum vitamin B(12), and thermolabile MTHFR genotype as risk factors for retinal vascular occlusive disease. Am J Ophthalmol. 2003;136:1136–1150
  14. Goldstein M, Leibovitch I, Yeffimov I, Gavendo S, Sela BA, Loewenstein A. Hyperhomocysteinemia in patients with diabetes mellitus with and without diabetic retinopathy. Eye. 2004;18:460–465
  15. Huang EJ, Kuo WW, Chen YJ, et al. Homocysteine and other biochemical parameters in type 2 diabetes mellitus with different diabetic duration or diabetic retinopathy. Clin Chim Acta. 2006;366:293–298
  16. Van Hecke MV, Dekker JM, Nijpels G, et al. Homocysteine, S-adenosylmethionine and S-adenosylhomocysteine are associated with retinal microvascular abnormalities: the Hoorn Study. Clin Sci (Lond). 2008;114:479–487
  17. Mitchell P, Smith W, Attebo K, Wang JJ. Prevalence of age-related maculopathy in Australia (The Blue Mountains Eye Study). Ophthalmology. 1995;102:1450–1460
  18. Wang JJ, Mitchell P, Leung H, Rochtchina E, Wong TY, Klein R. Hypertensive retinal vessel wall signs in a general older population: the Blue Mountains Eye Study. Hypertension. 2003;42:534–541
  19. Sherry LM, Wang JJ, Rochtchina E, et al. Reliability of computer-assisted retinal vessel measurement in a population. Clin Experiment Ophthalmol. 2002;30:179–182
  20. Clarke R, Grimley EJ, Schneede J, et al. Vitamin B12 and folate deficiency in later life. Age Ageing. 2004;33:34–41
  21. Refsum H, Smith AD, Ueland PM, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem. 2004;50:3–32
  22. 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003;21:1983–1992
  23. Wright S. The method of path coefficients. Annals of Mathematical Statistics. 1934;5:161–215
  24. Willett W. Reproducibility and validity of food-frequency questionnaires. In:  Willett W editors. Nutritional Epidemiology. Oxford: Oxford University Press; 1990;p. 92–126
  25. Wong TY, Islam FM, Klein R, et al. Retinal vascular caliber, cardiovascular risk factors, and inflammation: the multi-ethnic study of atherosclerosis (MESA). Invest Ophthalmol Vis Sci. 2006;47:2341–2350
  26. Wong TY, Klein R, Klein BE, Tielsch JM, Hubbard L, Nieto FJ. Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality. Surv Ophthalmol. 2001;46:59–80
  27. Wang JJ, Liew G, Klein R, et al. Retinal vessel diameter and cardiovascular mortality: pooled data analysis from two older populations. Eur Heart J. 2007;28:1984–1992
  28. Leung H, Wang JJ, Rochtchina E, et al. Relationships between age, blood pressure and retinal vessel diameters in an older population. Invest Ophthalmol Vis Sci. 2003;44:2900–2904
  29. Sharrett AR, Hubbard LD, Cooper LS, et al. Retinal arteriolar diameters and elevated blood pressure: the Atherosclerosis Risk in Communities Study. Am J Epidemiol. 1999;150:263–270
  30. Huang A, Sun D, Koller A, Kaley G. 17beta-estradiol restores endothelial nitric oxide release to shear stress in arterioles of male hypertensive rats. Circulation. 2000;101:94–100
  31. Leung H, Wang JJ, Rochtchina E, Wong TY, Klein R, Mitchell P. Does hormone replacement therapy influence retinal microvascular caliber?. Microvasc Res. 2004;67:48–54
  32. Kaushik S, Wang JJ, Mitchell P. Retinal vessel diameter. Ophthalmology. 2006;113:886–887
  33. Ikram MK, de Jong FJ, Vingerling JR, et al. Are retinal arteriolar or venular diameters associated with markers for cardiovascular disorders? (The Rotterdam Study). Invest Ophthalmol Vis Sci. 2004;45:2129–2134
  34. MacMahon S, Peto R, Cutler J, et al. Blood pressure, stroke, and coronary heart disease (Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias [see comments]). Lancet. 1990;335:765–774
  35. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med. 1998;338:1042–1050
  36. De Vriese AS, Blom HJ, Heil SG, et al. Endothelium-derived hyperpolarizing factor–mediated renal vasodilatory response is impaired during acute and chronic hyperhomocysteinemia. Circulation. 2004;109:2331–2336
  37. Jager A, Kostense PJ, Nijpels G, et al. Serum homocysteine levels are associated with the development of (micro)albuminuria: the Hoorn Study. Arterioscler Thromb Vasc Biol. 2001;21:74–81
  38. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med. 1998;338:1042–1050
  39. Knudtson MD, Klein BE, Klein R, et al. Variation associated with measurement of retinal vessel diameters at different points in the pulse cycle. Br J Ophthalmol. 2004;88:57–61
  40. Lanigan LP, Clark CV, Hill DW. Retinal circulation responses to systemic autonomic nerve stimulation. Eye. 1988;2:412–417

PII: S0002-9394(09)00516-9

doi: 10.1016/j.ajo.2009.07.018

American Journal of Ophthalmology
Volume 148, Issue 6 , Pages 902-909 , December 2009