J Korean Med Sci.  2012 May;27(5):500-505. 10.3346/jkms.2012.27.5.500.

Use of Serum Homocysteine to Predict Cardiovascular Disease in Korean Men with or without Metabolic Syndrome

Affiliations
  • 1Radiation Health Research Institute, Korea Hydro & Nuclear Power Co., Ltd, Seoul, Korea. choimd@khnp.co.kr
  • 2Department of Medical Nutrition, Kyung Hee University, Yongin, Korea.
  • 3Research Institute of Clinical Nutrition, Kyung Hee University, Seoul, Korea.

Abstract

The aim of this study was to examine whether serum homocysteine (Hcy) levels correlated with cardiovascular disease (CVD) depending on the presence or absence of metabolic syndrome (MetS) in Korean men. We conducted a case-control study, including 138 CVD and 290 non-CVD age-matched control subjects. The subjects were divided into four subgroups: 34 CVD/MetS, 104 CVD, 77 MetS, and 213 normal subgroups. The mean Hcy was significantly higher, whereas HDL and intake of vitamin B1 and B2 were lower in the CVD group (P < 0.05) than non-CVD group. When compared to the control group, subjects with CVD/MetS, CVD and MetS exhibited high Hcy levels, with the highest observed in the CVD/MetS subgroup (P < 0.001). Multivariate stepwise linear regression between CVD and markers of CVD showed Hcy significantly correlated with CVD (P < 0.05). To predict CVD based on Hcy, Hcy threshold of 11.72 microM in non-MetS subjects had an area under the curve (AUC) of 0.664 (95% CI 0.598-0.731). In MetS subjects, the AUC was 0.618 and Hcy threshold was 13.32 microM (95% CI 0.509-0.726). The results of our study show that the presence of MetS needs to be considered when using Hcy levels for predicting CVD.

Keyword

Homocysteine; Cardiovascular Diseases; Metabolic Syndrome; Cut-off Points

MeSH Terms

Adult
Area Under Curve
Cardiovascular Diseases/*blood/complications/epidemiology
Case-Control Studies
Cholesterol, HDL/blood
Dietary Supplements
Homocysteine/blood
Humans
Linear Models
Male
Metabolic Syndrome X/*complications
Middle Aged
Predictive Value of Tests
Republic of Korea/epidemiology

Figure

  • Fig. 1 Receiver-operating-characteristic curves of Hcy for CVD according to the (A) non-MetS subjects, (B) MetS subjects.


Reference

1. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998. 97:1837–1847.
2. Hamer M, Stamatakis E. Physical activity and risk of cardiovascular disease events: inflammatory and metabolic mechanisms. Med Sci Sports Exerc. 2009. 41:1206–1211.
3. Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C, Jacques PF, Rifai N, Selhub J, Robins SJ, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006. 355:2631–2639.
4. Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, Montori VM. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol. 2007. 49:403–414.
5. Ozkan Y, Ozkan E, Simşek B. Plasma total homocysteine and cysteine levels as cardiovascular risk factors in coronary heart disease. Int J Cardiol. 2002. 82:269–277.
6. Sun Y, Chien KL, Hsu HC, Su TC, Chen MF, Lee YT. Use of serum homocysteine to predict stroke, coronary heart disease and death in ethnic Chinese: 12-year prospective cohort study. Circ J. 2009. 73:1423–1430.
7. Kang SS, Wong PW, Malinow MR. Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease. Annu Rev Nutr. 1992. 12:279–298.
8. Rossi GP, Maiolino G, Seccia TM, Burlina A, Zavattiero S, Cesari M, Sticchi D, Pedon L, Zanchetta M, Pessina AC. Hyperhomocysteinemia predicts total and cardiovascular mortality in high-risk women. J Hypertens. 2006. 24:851–859.
9. Shin KP, Lee SY, Kim YJ, Lee JG, Kim DH, Jung DW, Yi YH, Park SK, Cho YH. The association of homocysteine and metabolic syndrome. Korean J Obes. 2011. 20:16–22.
10. Fallon UB, Elwood P, Ben-Shlomo Y, Ubbink JB, Greenwood R, Smith GD. Homocysteine and ischaemic stroke in men: the Caerphilly study. J Epidemiol Community Health. 2001. 55:91–96.
11. DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care. 1991. 14:173–194.
12. Björck J, Hellgren M, Råstam L, Lindblad U. Associations between serum insulin and homocysteine in a Swedish population: a potential link between the metabolic syndrome and hyperhomocysteinemia: the Skaraborg project. Metabolism. 2006. 55:1007–1013.
13. Choi JW, Kim SH, Yeon CH, Jung KC. The association between homocysteine and features of the metabolic syndrome. Kwandong Med J. 2006. 10:31–37.
14. Nabipour I, Ebrahimi A, Jafari SM, Vahdat K, Assadi M, Movahed A, Moradhaseli F, Obeidi N, Sanjdideh Z. The metabolic syndrome is not associated with homocysteinemia: the Persian Healthy Heart Study. J Endocrinol Invest. 2009. 32:406–410.
15. Lim DM, Park KY, Koh GP. The biochemical markers of coronary heart disease correlates better to metabolic syndrome defined by WHO than by NCEP-ATP III or IDF in Korean type 2 diabetic patients. Korean Diabetes J. 2008. 32:157–164.
16. Lim DM, Park KY, Kim BJ, Lee KW, Lee MJ, Yom YS, Koh GP. Cardiovascular risk according to the components of metabolic syndrome in type 2 diabetes. Korean Clin Diabetes. 2009. 10:196–203.
17. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005. 112:2735–2752.
18. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004. 363:157–163.
19. Hilden J, Glasziou P. Regret graphs, diagnostic uncertainty and Youden's Index. Stat Med. 1996. 15:969–986.
20. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitave assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA. 1995. 274:1049–1057.
21. Das M, Ghose M, Borah NC, Choudhury N. A community based study of the relationship between homocysteine and some of the life style factors. Indian J Clin Biochem. 2010. 25:295–301.
22. Kim SJ, Lim KS, Song MS, Kang YJ, Lee SY. Prevalence of hyperhomocysteinemia and related factors in a community-based health examination survey: a cross-sectional study. J Prev Med Public Health. 2009. 42:337–342.
23. Chew SC, Khor GL, Loh SP. Association between dietary folate intake and blood status of folate and homocysteine in Malaysian adults. J Nutr Sci Vitaminol (Tokyo). 2011. 57:150–155.
24. Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Selhub J. Determinants of plasma total homocysteine concentration in the Famingham Offspring cohort. Am J Clin Nutr. 2001. 73:613–621.
25. Ntaios G, Savopoulos C, Chatzopoulos S, Mikhailidis D, Hatzitolios A. Iatrogenic hyperhomocysteinemia in patients with metabolic syndrome: a systematic review and metaanalysis. Atherosclerosis. 2011. 214:11–19.
26. Karatela RA, Sainani GS. Plasma homocysteine in obese, overweight and normal weight hypertensives and normotensives. Indian Heart J. 2009. 61:156–159.
27. Real JT, Martinez-Hervas S, Garcia-Garcia AB, Chaves FJ, Civera M, Ascaso JF, Carmena R. Association of C677T polymorphism in MTHFR gene, high homocysteine and low HDL cholesterol plasma values in heterozygous familial hypercholesterolemia. J Atheroscler Thromb. 2009. 16:815–820.
28. Veerkamp MJ, de Graaf J, den Heijer M, Blom HJ, Stalenhoef AF. Plasma homocysteine in subjects with familial combined hyperlipidemia. Atherosclerosis. 2003. 166:111–117.
29. Jacobs RL, House JD, Brosnan ME, Brosnan JT. Effects of streptozotocin-induced diabetes and of insulin treatment on homocysteine metabolism in the rat. Diabetes. 1998. 47:1967–1970.
30. Pitla S, Nagalla B. Gender-related difference in the relationship between plasma homocysteine, anthropometric and conventional biochemical coronary heart disease risk factors in middle-aged Indians. Ann Nutr Metab. 2009. 54:1–6.
31. Koehler KM, Romero LJ, Stauber PM, Pareo-Tubbeh SL, Liang HC, Baumgartner RN, Garry PJ, Allen RH. Vitamin supplementation and other variables affecting serum homocysteine and methylmalonic acid concentrations in elderly men and women. J Am Coll Nutr. 1996. 15:364–376.
32. Nygård O, Vollset SE, Refsum H, Stensvold I, Tverdal A, Nordrehaug JE, Ueland M, Kvåle G. Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteint Study. JAMA. 1995. 274:1526–1533.
33. Obeid R, Herrmann W. Homocysteine and lipids: S-adenosyl methionine as a key intermediate. FEBS Lett. 2009. 583:1215–1225.
34. Namekata K, Enokodi Y, Ishii I, Nagai Y, Harada T, Kimura H. Abnormal lipid metabolism in cystathionine beta-synthase-deficient mice, an animal model for hyperhomocysteinemia. J Biol Chem. 2004. 279:52961–52969.
35. Finkelstein JD. The metabolism of homocysteine: pathways and regulation. Eur J Pediatr. 1998. 157:S40–S44.
36. Brouwer IA, van Dusseldorp M, Thomas CM, Duran M, Hautvast JG, Eskes TK, Steegers-Theunissen RP. Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomised trial. Indian Heart J. 2000. 52:S53–S58.
37. Chang NS, Kim JM, Kim HS, Cho YW. Plasma total homocysteine and macrovascular complications are associated with food and nutrient intake in patients with type II diabetes mellitus. Nutr Res Pract. 2007. 1:79–83.
38. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA. 1993. 270:2693–2698.
39. Chambers JC, Obeid OA, Refsum H, Ueland P, Hackett D, Hooper J, Turner RM, Thompson SG, Kooner JS. Plasma homocysteine concentrations and risk of coronary heart disease in UK Indian, Asian and European men. Lancet. 2000. 355:523–527.
40. Shahram F, Faridar A, Hamedani MG, Nadji A, Naderi N, Mojarad Shafiee N, Rasker JJ, Davatchi F. Plasma homocysteine level in patients with Behcet's disease with or without thrombosis. Arch Iran Med. 2010. 13:476–481.
Full Text Links
  • JKMS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr