J Korean Ophthalmol Soc.  2016 Mar;57(3):461-467. 10.3341/jkos.2016.57.3.461.

Analysis of Serum Homocysteine and Risk of Coronary Heart Disease in Patients with Pseudoexfoliation Syndrome

  • 1Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Korea. sccha@yumail.ac.kr
  • 2Department of Ophthalmology, Daegu Veterans Hospital, Daegu, Korea.


To investigate levels of serum homocysteine in patients with pseudoexfoliation syndrome and the association between serum homocysteine levels and risk of coronary heart disease.
From March 2013 to September 2013, 37 patients with pseudoexfoliation syndrome and 59 age-matched patients (control group) were enrolled in this prospective study. Serum homocysteine levels were compared between the 2 groups. We compared the estimated 10-year risk of coronary heart disease based on Framingham risk score between the 2 groups. Additionally, we analyzed correlations between risk of coronary heart disease and serum homocysteine levels.
The mean homocysteine level of patients with pseudoexfoliation syndrome was significantly higher than the control group (13.3 ± 6.8 µmol/L vs. 10.0 ± 5.2 µmol/L, p = 0.009). The rate of high risk defined as a 10-year coronary heart disease risk >20% in the patients with pseudoexfoliation syndrome was significantly higher than in the control group (21.4% vs. 4.4%, p = 0.048). Correlation between serum homocysteine levels and estimated 10-year risk of coronary heart disease was statistically significant (r = 0.578, p < 0.001).
Hyperhomocysteinemia and high risk of coronary heart disease were observed in patients with pseudoexfoliation syndrome. Therefore, we suggest efforts to prevent coronary heart disease in pseudoexfoliation syndrome patients with hyperhomocysteinemia are necessary.


Coronary heart disease; Exfoliation syndrome; Framingham risk score; Homocysteine; Pseudoexfoliation syndrome

MeSH Terms

Coronary Disease*
Exfoliation Syndrome*
Prospective Studies


  • Figure 1. Correlations between risk of coronary heart disease and serum homocysteine levels. Serum homocysteine levels were positively correlated to Framingham 10-year coronary heart disease risk in all subjects without diabetics (N = 73, r = 0.578, p < 0.001, Pearson's correlation coefficient). CHD = coronary heart disease; XFS = pseudoexfoliation syndrome.



1. Ritch R, Schlötzer-Schrehardt U. Exfoliation (pseudoexfoliation) syndrome: toward a new understanding. Proceedings of the First International Think Tank. Acta Ophthalmol Scand. 2001; 79:213–7.
2. Ritch R, Schlotzer-Schrehardt U. Exfoliation syndrome. Surv Ophthalmol. 2001; 45:265–315.
3. Schlötzer-Schrehardt UM, Koca MR, Naumann GO, Volkholz H. Pseudoexfoliation syndrome. Ocular manifestation of a systemic disorder? Arch Ophthalmol. 1992; 110:1752–6.
4. Streeten BW, Li ZY, Wallace RN, et al. Pseudoexfoliative fibrillopathy in visceral organs of a patient with pseudoexfoliation syndrome. Arch Ophthalmol. 1992; 110:1757–62.
5. Tarkkanen A. Is exfoliation syndrome a sign of systemic vascular disease? Acta Ophthalmol. 2008; 86:832–6.
6. Mujumdar VS, Aru GM, Tyagi SC. Induction of oxidative stress by homocyst(e)ine impairs endothelial function. J Cell Biochem. 2001; 82:491–500.
7. Hankey GJ, Eikelboom JW, Ho WK, van Bockxmeer FM. Clinical usefulness of plasma homocysteine in vascular disease. Med J Aust. 2004; 181:314–8.
8. Pianka P, Almog Y, Man O, et al. Hyperhomocystinemia in patients with nonarteritic anterior ischemic optic neuropathy, central retinal artery occlusion, and central retinal vein occlusion. Ophthalmology. 2000; 107:1588–92.
9. Clarke R, Daly L, Robinson K, et al. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med. 1991; 324:1149–55.
10. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002; 288:2015–22.
11. Brown BA, Marx JL, Ward TP, et al. Homocysteine: a risk factor for retinal venous occlusive disease. Ophthalmology. 2002; 109:287–90.
12. Wang W, He M, Zhou M, Zhang X. Ocular pseudoexfoliation syndrome and vascular disease: a systematic review and meta-analysis. PLoS One. 2014; 9:e92767.
13. Mitchell P, Wang JJ, Smith W. Association of pseudoexfoliation syndrome with increased vascular risk. Am J Ophthalmol. 1997; 124:685–7.
14. Schlötzer-Schrehardt U, Naumann GO. Ocular and systemic pseudoexfoliation syndrome. Am J Ophthalmol. 2006; 141:921–37.
15. Citirik M, Acaroglu G, Batman C, et al. A possible link between the pseudoexfoliation syndrome and coronary artery disease. Eye (Lond). 2007; 21:11–5.
16. Bleich S, Roedl J, Von Ahsen N, et al. Elevated homocysteine levels in aqueous humor of patients with pseudoexfoliation glaucoma. Am J Ophthalmol. 2004; 138:162–4.
17. Roedl JB, Bleich S, Reulbach U, et al. Homocysteine in tear fluid of patients with pseudoexfoliation glaucoma. J Glaucoma. 2007; 16:234–9.
18. Choo BJ, Hwang YH, Lee JH, Kim TJ. Comparison of serum homocysteine, vitamin B12, vitamin B6 and folate levels in different glaucoma types. J Korean Ophthalmol Soc. 2013; 54:104–11.
19. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation. 2002; 106:3143–421.
20. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001; 285:2486–97.
21. Wilson PW, D'Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation. 1998; 97:1837–47.
22. Kannel WB, McGee D, Gordon T. A general cardiovascular risk profile: the Framingham Study. Am J Cardiol. 1976; 38:46–51.
23. Kim Y, Hwang I, Kang HC. The relation of coronary artery calcium scores with Framingham risk scores. J Korean Acad Fam Med. 2008; 29:762–7.
24. Kim HJ, Min HG, Kim YL, Lee SK. Correlation between serum homocysteine level and Framingham risk score. Korean J Fam Pract. 2014; 4:227–31.
25. Vessani RM, Ritch R, Liebmann JM, Jofe M. Plasma homocysteine is elevated in patients with exfoliation syndrome. Am J Ophthalmol. 2003; 136:41–6.
26. Altintaş O, Maral H, Yüksel N, et al. Homocysteine and nitric oxide levels in plasma of patients with pseudoexfoliation syndrome, pseudoexfoliation glaucoma, and primary open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol. 2005; 243:677–83.
27. Leibovitch I, Kurtz S, Shemesh G, et al. Hyperhomocystinemia in pseudoexfoliation glaucoma. J Glaucoma. 2003; 12:36–9.
28. Saricaoglu MS, Karakurt A, Sengun A, Hasiripi H. Plasma homocysteine levels and vitamin B status in patients with Pseudoexfoliation syndrome. Saudi Med J. 2006; 27:833–7.
29. Tranchina L, Centofanti M, Oddone F, et al. Levels of plasma homocysteine in pseudoexfoliation glaucoma. Graefes Arch Clin Exp Ophthalmol. 2011; 249:443–8.
30. Stampfer MJ, Malinow MR, Willett WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA. 1992; 268:877–81.
31. Perry IJ, Refsum H, Morris RW, et al. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet. 1995; 346:1395–8.
32. Vine AK. Hyperhomocysteinemia: a risk factor for central retinal vein occlusion. Am J Ophthalmol. 2000; 129:640–4.
33. Andrikopoulos GK, Mela EK, Georgakopoulos CD, et al. Pseudoexfoliation syndrome prevalence in Greek patients with cataract and its association to glaucoma and coronary artery disease. Eye (Lond). 2009; 23:442–7.
34. Katsi V, Pavlidis AN, Kallistratos MS, et al. Cardiovascular repercussions of the pseudoexfoliation syndrome. N Am J Med Sci. 2013; 5:454–9.
35. Zakrzewski PA, Mackenzie PJ, Tsai G, et al. Does an association exist between pseudoexfoliation syndrome and chronic kidney disease? J Glaucoma. 2012; 21:562–6.
36. Browne JG, Ho SL, Kane R, et al. Connective tissue growth factor is increased in pseudoexfoliation glaucoma. Invest Ophthalmol Vis Sci. 2011; 52:3660–6.
37. Djordjević-Jocić J, Zlatanović G, Veselinovic D, et al. Transforming growth factor beta1, matrix-metal loproteinase-2 and its tissue inhibitor in patients with pseudoexfoliation glaucoma/syndrome. Vojnosanit Pregl. 2012; 69:231–6.
38. Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular disease risk profiles. Am Heart J. 1991; 121(1 Pt 2):293–8.
39. Humphrey LL, Fu R, Rogers K, et al. Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis. Mayo Clin Proc. 2008; 83:1203–12.
40. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists’ Collaboration. BMJ. 1998; 316:894–8.
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