Published Online
on May 6, 2002

A more recent version of this article appeared on June 11, 2002

This Article Full Text (PDF) All Versions of this Article: 105/23/2725    most recent 01.CIR.0000017360.99531.26v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kark, J. D. Articles by Selhub, J. Search for Related Content PubMed Articles by Kark, J. D. Articles by Selhub, J. Related Collections Nutrition Risk Factors Acute myocardial infarction Epidemiology

Submitted on December 18, 2001
Revised on March 22, 2002
Accepted on March 22, 2002

Plasma Homocysteine and Parental Myocardial Infarction in Young Adults in Jerusalem

J. D. Kark MD, PhD^*, R. Sinnreich PhD, I. H. Rosenberg MD, P. F. Jacques ScD, and J. Selhub PhD

From the Epidemiology Unit, Hadassah University Hospital, Jerusalem, Israel (J.D.K., R.S.); and US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Mass (I.H.R., P.F.J., J.S.).

^* To whom correspondence should be addressed. E-mail: jeremykark{at}hujc.ac.il.

Background—A causal role for mildly elevated plasma homocysteine (tHcy) in cardiovascular disease remains undetermined. To address the unresolved issue of the antecedent-consequent directionality of the relationship, we assessed the familial association of tHcy with parental myocardial infarction (MI) in young Israeli men and women. We also compared tHcy concentrations in Jerusalem, where rates of coronary heart disease (CHD) are high, with the United States Third National Health and Examination Survey (NHANES III).

Methods and Results—A total of 8646 17-year-olds and 6952 parents were examined from 1976 to 1979 in Jerusalem. At ages 28 to 32 years, offspring of parents who experienced a documented MI during a 10-year follow-up (n=133 men, 62 women; 72% response) and offspring of CHD-free parents (n=389 men, 208 women; 71% response) were reexamined. tHcy levels were determined by the same laboratory for the NHANES non-Hispanic white population aged 25 to 34 years (n=379) and the Jerusalem population sample (n=858). Men from Jerusalem, but not women, had clearly higher tHcy levels than the sample from the United States (90th percentile, 23 versus 14 µmol/L). This difference was largely attributable to lower plasma vitamin B₁₂ levels in the Israeli population. Male case offspring had higher adjusted tHcy than did controls (1.9 µmol/L, P=0.002). Logistic modeling revealed a graded increase in risk of parental MI across quintiles of offspring tHcy, with an adjusted odds ratio of 2.7 in the 5th quintile (P=0.0026 for trend).

Conclusions—The higher tHcy in young male offspring of parents with CHD suggests that elevated tHcy precedes manifestation of CHD. The elevated population tHcy in men may contribute to the high incidence of CHD in Israel.

Key words: myocardial infarction • coronary disease • epidemiology • homocysteine

This article has been cited by other articles:

				M. Tomaszewski, F. J. Charchar, T. Barnes, M. Gawron-Kiszka, A. Sedkowska, E. Podolecka, J. Kowalczyk, W. Rathbone, Z. Kalarus, W. Grzeszczak, et al. A Common Variant in Low-Density Lipoprotein Receptor-Related Protein 6 Gene (LRP6) Is Associated With LDL-Cholesterol Arterioscler Thromb Vasc Biol, September 1, 2009; 29(9): 1316 - 1321. [Abstract] [Full Text] [PDF]

				E. Zittan, M. Preis, I. Asmir, A. Cassel, N. Lindenfeld, S. Alroy, D. A. Halon, B. S. Lewis, A. Shiran, J. E. Schliamser, et al. High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H860 - H865. [Abstract] [Full Text] [PDF]

				J. R. Ruiz, R. Sola, M. Gonzalez-Gross, F. B. Ortega, G. Vicente-Rodriguez, M. Garcia-Fuentes, A. Gutierrez, M. Sjostrom, K. Pietrzik, and M. J. Castillo Cardiovascular Fitness Is Negatively Associated With Homocysteine Levels in Female Adolescents Arch Pediatr Adolesc Med, February 1, 2007; 161(2): 166 - 171. [Abstract] [Full Text] [PDF]

				R.-E. W. Kavey, V. Allada, S. R. Daniels, L. L. Hayman, B. W. McCrindle, J. W. Newburger, R. S. Parekh, and J. Steinberger Cardiovascular Risk Reduction in High-Risk Pediatric Patients: A Scientific Statement From the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: Endorsed by the American Academy of Pediatrics Circulation, December 12, 2006; 114(24): 2710 - 2738. [Abstract] [Full Text] [PDF]

				T. Suhara, K. Fukuo, O. Yasuda, M. Tsubakimoto, Y. Takemura, H. Kawamoto, T. Yokoi, M. Mogi, T. Kaimoto, and T. Ogihara Homocysteine Enhances Endothelial Apoptosis via Upregulation of Fas-Mediated Pathways Hypertension, June 1, 2004; 43(6): 1208 - 1213. [Abstract] [Full Text] [PDF]

				H. Refsum, A. D. Smith, P. M. Ueland, E. Nexo, R. Clarke, J. McPartlin, C. Johnston, F. Engbaek, J. Schneede, C. McPartlin, et al. Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion Clin. Chem., January 1, 2004; 50(1): 3 - 32. [Abstract] [Full Text] [PDF]

				A. Must, P. F. Jacques, G. Rogers, I. H. Rosenberg, and J. Selhub Serum Total Homocysteine Concentrations in Children and Adolescents: Results from the Third National Health and Nutrition Examination Survey (NHANES III) J. Nutr., August 1, 2003; 133(8): 2643 - 2649. [Abstract] [Full Text] [PDF]

				A. L. Bjorke Monsen and P. M. Ueland Homocysteine and methylmalonic acid in diagnosis and risk assessment from infancy to adolescence Am. J. Clinical Nutrition, July 1, 2003; 78(1): 7 - 21. [Abstract] [Full Text] [PDF]