Elevated Homocysteine Levels and Risk of Cardiovascular and All-cause Mortality: a Meta-analysis of Prospective Studies

Overview

Journal J Zhejiang Univ Sci B

Specialties Biology
General Medicine

Date 2015 Jan 7

PMID 25559959

Citations 35

Authors

Hui-yong Peng

Chang-Feng Man

Juan Xu

Yu Fan

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate whether elevated homocysteine levels were a predictor of subsequent coronary heart disease (CHD) mortality, cardiovascular mortality or all-cause mortality in the general population by a meta-analysis.

Methods: In a systematic search conducted in the databases of PubMed and Embase prior to October 2013, we identified relevant prospective observational studies evaluating the association between baseline homocysteine levels and CHD mortality, cardiovascular or all-cause mortality in the general population. Pooled adjust risk ratio (RR) and corresponding 95% confidence interval (CI) were calculated separately for categorical risk estimates and continuous risk estimates.

Results: Twelve studies with 23623 subjects were included in the meta-analysis. Comparing the highest to lowest homocysteine level categories, CHD mortality increased by 66% (RR 1.66; 95% CI 1.12-2.47; P=0.012), cardiovascular mortality increased by 68% (RR 1.68; 95% CI 1.04-2.70; P=0.033), and all-cause mortality increased by 93% (RR 1.93; 95% CI 1.54-2.43; P<0.001). Moreover, for each 5 μmol/L homocysteine increment, the pooled RR was 1.52 (95% CI 1.26-1.84; P<0.001) for CHD mortality, 1.32 (95% CI 1.08-1.61; P=0.006) for cardiovascular mortality, and 1.27 (95% CI 1.03-1.55; P=0.023) for all-cause mortality.

Conclusions: Elevated homocysteine levels are an independent predictor for subsequent cardiovascular mortality or all-cause mortality, and the risks were more pronounced among elderly persons.

Citing Articles

Homocysteine levels and cardiovascular disease risk factors in chronic kidney disease (CKD), hypertensive and healthy Nigerian adults: a comparative retrospective study.

Adeoye M, Hamdallah H, Adeoye A BMJ Open. 2025; 15(3):e089644.

PMID: 40074258 PMC: 11904321. DOI: 10.1136/bmjopen-2024-089644.

Correlation of Serum Homocysteine Levels With Various Types of Coronary Syndromes (CS) and In-Hospital Mortality - A Multicenter Study.

Ullah H, Huma S, Naeem L, Yasin G, Ashraf M, Tahir N Int J Gen Med. 2025; 18:725-732.

PMID: 39963520 PMC: 11830938. DOI: 10.2147/IJGM.S500973.

Association between homocysteine levels and mortality in CVD: a cohort study based on NHANES database.

Liu D, Fang C, Wang J, Tian Y, Zou T BMC Cardiovasc Disord. 2024; 24(1):652.

PMID: 39548360 PMC: 11568605. DOI: 10.1186/s12872-024-04317-9.

Homocysteine Blood Levels and Mandatory Folic Acid Fortification in Serbia.

Vasiljevic Z, Zlatic N, Rajic D, Mitrovic P, Viduljevic M, Matic D Curr Pharm Des. 2024; 31(6):484-492.

PMID: 39364862 DOI: 10.2174/0113816128326875240916050251.

The Association of Plasma Homocysteine Concentrations with a 10-Year Risk of All-Cause and Cardiovascular Mortality in a Community-Based Chinese Population.

Liang Z, Li K, Chen H, Jia J, Li J, Huo Y Nutrients. 2024; 16(12).

PMID: 38931298 PMC: 11206274. DOI: 10.3390/nu16121945.

References

Hoogeveen E, Kostense P, Jakobs C, Dekker J, Nijpels G, Heine R . Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes : 5-year follow-up of the Hoorn Study. Circulation. 2000; 101(13):1506-11. DOI: 10.1161/01.cir.101.13.1506. View

Naess H, Nyland H, Idicula T, Waje-Andreassen U . C-reactive protein and homocysteine predict long-term mortality in young ischemic stroke patients. J Stroke Cerebrovasc Dis. 2013; 22(8):e435-40. DOI: 10.1016/j.jstrokecerebrovasdis.2013.04.031. View

Vollset S, Refsum H, Tverdal A, Nygard O, Nordrehaug J, Tell G . Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study. Am J Clin Nutr. 2001; 74(1):130-6. DOI: 10.1093/ajcn/74.1.130. View

Blacher J, Benetos A, Kirzin J, Malmejac A, Guize L, Safar M . Relation of plasma total homocysteine to cardiovascular mortality in a French population. Am J Cardiol. 2002; 90(6):591-5. DOI: 10.1016/s0002-9149(02)02561-4. View

Bautista L, Arenas I, Penuela A, Martinez L . Total plasma homocysteine level and risk of cardiovascular disease: a meta-analysis of prospective cohort studies. J Clin Epidemiol. 2002; 55(9):882-7. DOI: 10.1016/s0895-4356(02)00434-1. View

de Bree A, Verschuren W, Blom H, Nadeau M, Trijbels F, Kromhout D . Coronary heart disease mortality, plasma homocysteine, and B-vitamins: a prospective study. Atherosclerosis. 2003; 166(2):369-77. DOI: 10.1016/s0021-9150(02)00373-8. View

Higgins J, Thompson S, Deeks J, Altman D . Measuring inconsistency in meta-analyses. BMJ. 2003; 327(7414):557-60. PMC: 192859. DOI: 10.1136/bmj.327.7414.557. View

Zylberstein D, Bengtsson C, Bjorkelund C, Landaas S, Sundh V, Thelle D . 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. 2004; 109(5):601-6. DOI: 10.1161/01.CIR.0000112581.96154.EA. View

Celermajer D, Sorensen K, Ryalls M, Robinson J, Thomas O, Leonard J . Impaired endothelial function occurs in the systemic arteries of children with homozygous homocystinuria but not in their heterozygous parents. J Am Coll Cardiol. 1993; 22(3):854-8. DOI: 10.1016/0735-1097(93)90203-d. View

10.

Selhub J, Jacques P, Wilson P, Rush D, Rosenberg I . Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA. 1993; 270(22):2693-8. DOI: 10.1001/jama.1993.03510220049033. View

11.

Begg C, Mazumdar M . Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994; 50(4):1088-101. View

12.

Nygard O, Vollset S, Refsum H, Stensvold I, Tverdal A, Nordrehaug J . Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. JAMA. 1995; 274(19):1526-33. DOI: 10.1001/jama.1995.03530190040032. View

13.

Nygard O, Nordrehaug J, Refsum H, Ueland P, Farstad M, Vollset S . Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med. 1997; 337(4):230-6. DOI: 10.1056/NEJM199707243370403. View

14.

Egger M, Davey Smith G, Schneider M, Minder C . Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315(7109):629-34. PMC: 2127453. DOI: 10.1136/bmj.315.7109.629. View

15.

Stehouwer C, Weijenberg M, van den Berg M, Jakobs C, Feskens E, Kromhout D . Serum homocysteine and risk of coronary heart disease and cerebrovascular disease in elderly men: a 10-year follow-up. Arterioscler Thromb Vasc Biol. 1998; 18(12):1895-901. DOI: 10.1161/01.atv.18.12.1895. View

16.

Bostom A, Silbershatz H, Rosenberg I, Selhub J, DAgostino R, Wolf P . Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med. 1999; 159(10):1077-80. DOI: 10.1001/archinte.159.10.1077. View

17.

Kark J, Selhub J, Adler B, Gofin J, Abramson J, Friedman G . Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem. Ann Intern Med. 1999; 131(5):321-30. DOI: 10.7326/0003-4819-131-5-199909070-00002. View

18.

Rossi G, Maiolino G, Seccia T, Burlina A, Zavattiero S, Cesari M . Hyperhomocysteinemia predicts total and cardiovascular mortality in high-risk women. J Hypertens. 2006; 24(5):851-9. DOI: 10.1097/01.hjh.0000222754.75196.5c. View

19.

Selhub J . The many facets of hyperhomocysteinemia: studies from the Framingham cohorts. J Nutr. 2006; 136(6 Suppl):1726S-1730S. DOI: 10.1093/jn/136.6.1726S. View

20.

Gonzalez S, Huerta J, Fernandez S, Patterson A, Lasheras C . Homocysteine increases the risk of mortality in elderly individuals. Br J Nutr. 2007; 97(6):1138-43. DOI: 10.1017/S0007114507691958. View