 |
 |
|
Home |
Current Issue |
Past Issues |
In the Clinic |
ACP Journal Club |
CME |
Collections |
Audio/Video |
Mobile |
Subscribe |
Tools |
Help |
ACP Online
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
7 September 1999 | Volume 131 Issue 5 | Pages 321-330
Background: Elevated plasma total homocysteine level has been associated with cardiovascular disease in many studies, mostly in Europe and North America. Data on persons from other areas and on associations with overall mortality are sparse.
Objective: To determine the relation of plasma homocysteine level to all-cause and cause-specific mortality.
Design: Prospective observational study with 9- to 11-year follow-up.
Setting: A free-living, multiethnic Jewish population in western Jerusalem, Israel.
Participants: 1788 residents of Jerusalem (808 men and 980 women) who were at least 50 years of age and were examined between 1985 and 1987 as part of the Kiryat Yovel Community Health Study.
Measurements: Nonfasting plasma homocysteine level was determined in frozen stored samples. Deaths during follow-up were identified by linkage with the national population registry.
Results: Plasma homocysteine levels exceeded 14 µmol/L in 28% of men and 20% of women. During the study period, 405 deaths occurred. In multivariate Cox models that controlled for possible confounders, a nonmonotonic increase in mortality hazard ratios was associated with ascending quintile of homocysteine level: 1.0, 1.4, 1.3, 1.5, and 2.0 (P < 0.001 for trend). The relation was similar for cardiovascular and noncardiovascular causes of death (excluding cancer). The association was weaker when deaths that occurred during the first 5 years of follow-up were excluded; corresponding hazard ratios for ascending quintile of homocysteine level were 1.0, 1.0, 1.2, 1.1, and 1.6 (P = 0.063 for trend). Age- and sex-adjusted percentages of deaths "attributable" to elevated plasma homocysteine level (
Conclusions: A mildly to moderately elevated nonfasting plasma homocysteine level is a substantial risk marker for death from all causes. The association seems to be stronger during the first 5 years of follow-up.
Author and Article Information
From Hadassah University Hospital and Hebrew University-Hadassah School of Public Health and Community Medicine, Ein Kerem, Jerusalem; and Tufts University, Boston, Massachusetts.
Grant Support: In part by the U.S. Department of Agriculture, Agricultural Research Service (contract 53-3K06-5-10); by the Ridgefield Foundation (Ridgefield, Connecticut); and by the German Federal Ministry of Education and Research (BMBF) and the Israeli Ministry of Science under the aegis of the GSF- Forschungszentrum fuer Umwelt und Gesundheit GmbH, Neuherberg, Germany.
Requests for Reprints: Jeremy D. Kark, MD, PhD, Department of Social Medicine, Hadassah University Hospital, POB 12000, Ein Kerem 91120, Jerusalem; e-mail, jeremy1{at}vms.huji.ac.il.
Current Author Addresses: Drs. Kark, Abramson, and Gofin and Ms. Adler: Department of Social Medicine, Hadassah University Hospital, POB 12000, Ein Kerem 91120, Jerusalem.
Drs. Selhub and Rosenberg: The Jean Mayer USDA Human Nutrition Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111.
Dr. Friedman: Geriatric Unit, Hadassah University Hospital, POB 12000, Ein Kerem 91120, Jerusalem. ARTICLE
Nonfasting Plasma Total Homocysteine Level and Mortality in Middle-Aged and Elderly Men and Women in Jerusalem
14 µmol/L) were 12.5% (95% CI, 6.7% to 18.8%) for all deaths, 16.0% (CI, 7.2% to 25.6%) for deaths during the first 5 years of follow-up, and 8.3% (CI, 1.5% to 16.1%) for later deaths.
Related articles in Annals:
This article has been cited by other articles:
|
|
 |
|
  V. Menon, M. J. Sarnak, A. A. Pereira, A. S. Levey, T. Greene, X. Wang, G. J. Beck, J. W. Kusek, J. Selhub, A. J. Collins, et al. Response to Letter Regarding Article, "Relationship Between Homocysteine and Mortality in Chronic Kidney Disease" Circulation, October 17, 2006; 114(16): e548 - e548. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Refsum, E. Nurk, A. D. Smith, P. M. Ueland, C. G. Gjesdal, I. Bjelland, A. Tverdal, G. S. Tell, O. Nygard, and S. E. Vollset The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease J. Nutr., June 1, 2006; 136(6): 1731S - 1740S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Calderon-Margalit, B. Adler, J. H. Abramson, J. Gofin, and J. D. Kark Butyrylcholinesterase Activity, Cardiovascular Risk Factors, and Mortality in Middle-Aged and Elderly Men and Women in Jerusalem Clin. Chem., May 1, 2006; 52(5): 845 - 852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Cho, S. H Zeisel, P. Jacques, J. Selhub, L. Dougherty, G. A Colditz, and W. C Willett Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. Am. J. Clinical Nutrition, April 1, 2006; 83(4): 905 - 911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Menon, M. J. Sarnak, T. Greene, X. Wang, A. A. Pereira, G. J. Beck, J. W. Kusek, J. Selhub, A. J. Collins, A. S. Levey, et al. Relationship Between Homocysteine and Mortality in Chronic Kidney Disease Circulation, March 28, 2006; 113(12): 1572 - 1577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-K. Kuo, F. A. Sorond, J.-H. Chen, A. Hashmi, W. P. Milberg, and L. A. Lipsitz The Role of Homocysteine in Multisystem Age-Related Problems: A Systematic Review J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2005; 60(9): 1190 - 1201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. McKay, J. M. Berkowitz, J. B. Blumberg, and J. P. Goldberg Communicating Cardiovascular Disease Risk Due to Elevated Homocysteine Levels: Using the EPPM to Develop Print Materials Health Educ Behav, June 1, 2004; 31(3): 355 - 371. [Abstract] [PDF]
|
|
|
|
|
|
D. E. Zylberstein, C. Bengtsson, C. Bjorkelund, S. Landaas, V. Sundh, D. Thelle, and L. Lissner Serum Homocysteine in Relation to Mortality and Morbidity From Coronary Heart Disease: A 24-Year Follow-Up of the Population Study of Women in Gothenburg Circulation, February 10, 2004; 109(5): 601 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Fonseca, C. Desouza, S. Asnani, and I. Jialal Nontraditional Risk Factors for Cardiovascular Disease in Diabetes Endocr. Rev., February 1, 2004; 25(1): 153 - 175. [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]
|
|
|
|
 |
|
 S. Matetzky, D. Freimark, S. Ben-Ami, I. Goldenberg, J. Leor, R. Doolman, I. Novikov, M. Eldar, and H. Hod Association of Elevated Homocysteine Levels With a Higher Risk of Recurrent Coronary Events and Mortality in Patients With Acute Myocardial Infarction Arch Intern Med, September 8, 2003; 163(16): 1933 - 1937. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. El-Khairy, S. E. Vollset, H. Refsum, and P. M. Ueland Plasma Total Cysteine, Mortality, and Cardiovascular Disease Hospitalizations: The Hordaland Homocysteine Study Clin. Chem., June 1, 2003; 49(6): 895 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D Kark, N. A Kaufmann, F. Binka, N. Goldberger, and E. M Berry Adipose tissue n-6 fatty acids and acute myocardial infarction in a population consuming a diet high in polyunsaturated fatty acids Am. J. Clinical Nutrition, April 1, 2003; 77(4): 796 - 802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Meleady, P. M Ueland, H. Blom, A. S Whitehead, H. Refsum, L. E Daly, S. E. Vollset, C. Donohue, B. Giesendorf, I. M Graham, et al. Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European Concerted Action Project Am. J. Clinical Nutrition, January 1, 2003; 77(1): 63 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. De Bree, W. M. M. Verschuren, D. Kromhout, L. A. J. Kluijtmans, and H. J. Blom Homocysteine Determinants and the Evidence to What Extent Homocysteine Determines the Risk of Coronary Heart Disease Pharmacol. Rev., December 1, 2002; 54(4): 599 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. De Bree, W. M. Verschuren, D. Kromhout, L. I Mennen, H. J Blom, E. S Ford, S J. Smith, D. F Stroup, K. K Steinberg, P. W Mueller, et al. Homocysteine and coronary heart disease: the importance of a distinction between low and high risk subjects Int. J. Epidemiol., December 1, 2002; 31(6): 1268 - 1272. [Full Text] [PDF]
|
|
|
|
 |
|
 Homocysteine Studies Collaboration Homocysteine and Risk of Ischemic Heart Disease and Stroke: A Meta-analysis JAMA, October 23, 2002; 288(16): 2015 - 2022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Weiss, C. Keller, U. Hoffmann, and J. Loscalzo Endothelial dysfunction and atherothrombosis in mild hyperhomocysteinemia Vascular Medicine, August 1, 2002; 7(3): 227 - 239. [Abstract] [PDF]
|
|
|
|
 |
|
 A. K. Majors, S. Sengupta, B. Willard, M. T. Kinter, R. E. Pyeritz, and D. W. Jacobsen Homocysteine Binds to Human Plasma Fibronectin and Inhibits Its Interaction With Fibrin Arterioscler. Thromb. Vasc. Biol., August 1, 2002; 22(8): 1354 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Nurk, G. S. Tell, S. E. Vollset, O. Nygard, H. Refsum, and P. M. Ueland Plasma Total Homocysteine and Hospitalizations for Cardiovascular Disease: The Hordaland Homocysteine Study Arch Intern Med, June 24, 2002; 162(12): 1374 - 1381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.D. Kark, R. Sinnreich, I.H. Rosenberg, P.F. Jacques, and J. Selhub Plasma Homocysteine and Parental Myocardial Infarction in Young Adults in Jerusalem Circulation, June 11, 2002; 105(23): 2725 - 2729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Sesmilo, W. P. Fairfield, L. Katznelson, K. Pulaski, P. U. Freda, V. Bonert, E. Dimaraki, S. Stavrou, M. L. Vance, D. Hayden, et al. Cardiovascular Risk Factors in Acromegaly before and after Normalization of Serum IGF-I Levels with the GH Antagonist Pegvisomant J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1692 - 1699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Knekt, A. Reunanen, G. Alfthan, M. Heliovaara, H. Rissanen, J. Marniemi, and A. Aromaa Hyperhomocystinemia: A Risk Factor or a Consequence of Coronary Heart Disease? Arch Intern Med, July 9, 2001; 161(13): 1589 - 1594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M R. Malinow Plasma concentrations of total homocysteine predict mortality risk Am. J. Clinical Nutrition, July 1, 2001; 74(1): 3 - 3. [Full Text] [PDF]
|
|
|
|
|
|
S. E. Vollset, H. Refsum, A. Tverdal, O. Nygard, J. E. Nordrehaug, G. S Tell, and P. M. Ueland Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study Am. J. Clinical Nutrition, July 1, 2001; 74(1): 130 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Sesmilo, B. M. K. Biller, J. Llevadot, D. Hayden, G. Hanson, N. Rifai, and A. Klibanski Effects of Growth Hormone (GH) Administration on Homocyst(e)ine Levels in Men with GH Deficiency: A Randomized Controlled Trial J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1518 - 1524. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. Descombes, O. Boulat, L.-F. Bersier, and G. Fellay Difference in the homocysteine-lowering effect of folic acid in haemodialysis patients with and without occlusive vascular disease Nephrol. Dial. Transplant., March 1, 2001; 16(3): 585 - 589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-M. Saw, J.-M. Yuan, C.-N. Ong, K. Arakawa, H.-P. Lee, G. A Coetzee, and M. C Yu Genetic, dietary, and other lifestyle determinants of plasma homocysteine concentrations in middle-aged and older Chinese men and women in Singapore Am. J. Clinical Nutrition, February 1, 2001; 73(2): 232 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. McKay, G. Perrone, H. Rasmussen, G. Dallal, and J. B. Blumberg Multivitamin/Mineral Supplementation Improves Plasma B-Vitamin Status and Homocysteine Concentration in Healthy Older Adults Consuming a Folate-Fortified Diet J. Nutr., December 1, 2000; 130(12): 3090 - 3096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Shpichinetsky, I. Raz, Y. Friedlander, N. Goldschmidt, I. D. Wexler, A. Ben-Yehuda, and G. Friedman The Association between Two Common Mutations C677T and A1298C in Human Methylenetetrahydrofolate Reductase Gene and the Risk for Diabetic Nephropathy in Type II Diabetic Patients J. Nutr., October 1, 2000; 130(10): 2493 - 2497. [Abstract] [Full Text]
|
|
|
|
|
|
P. M Ueland, H. Refsum, S. A. Beresford, and S. E. Vollset The controversy over homocysteine and cardiovascular risk Am. J. Clinical Nutrition, August 1, 2000; 72(2): 324 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Eisner Nonfasting Plasma Total Homocysteine Level and Mortality Ann Intern Med, May 2, 2000; 132(9): 759 - 760. [Full Text] [PDF]
|
|
|
|
 |
|
 Homocysteine Associated with Stroke and Death Journal Watch Neurology, November 1, 1999; 1999(1101): 15 - 15. [Full Text]
|
|
|
|
 |
|
 Homocysteine and Mortality Journal Watch Cardiology, October 14, 1999; 1999(1014): 10 - 10. [Full Text]
|
|
|
|
 |
|
 Homocysteine Associated with Stroke and Death Journal Watch (General), September 17, 1999; 1999(917): 3 - 3. [Full Text]
|
|
|
|
|
|
I. Graham Homocysteine in Health and Disease Ann Intern Med, September 7, 1999; 131(5): 387 - 388. [Full Text] [PDF]
|
|
Article
