Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter November 8, 2012

Trends in clinical laboratory homocysteine testing from 1997 to 2010: the impact of evidence on clinical practice at a single institution

  • Corinne M. Klykov and Steven R. Lentz EMAIL logo


Background: During the past decade, several clinical trials investigating the potential benefits of homocysteine-lowering therapy for the secondary prevention of vascular events were completed and published. The objective of the study was to determine trends in clinical laboratory testing for homocysteine at a single institution over the time period from 1997 to 2010.

Methods: A single-center, retrospective analysis was performed at a large, academic, tertiary care medical center in the USA. The database was searched for clinical laboratory measurements of plasma or serum homocysteine between January 1, 1997 and December 31, 2010. Individual medical records were reviewed for a subset of 221 unique patients in the 10-year period from 2001 to 2010 who had homocysteine values ≥20 μmol/L.

Results: From 1997 to 2003, there was a 16-fold increase in the annual number of homocysteine assays performed. Testing for homocysteine declined in 2004 and 2006, coinciding with the publication of intervention trials that failed to support a clinical benefit of homocysteine-lowering therapy for the secondary prevention of vascular events. Subgroup analysis suggested that homocysteine testing for the indication of suspected nutritional deficiency or hypercoagulability remained steady despite a decline in testing for the indication of cardiac risk assessment.

Conclusions: The frequency of clinical laboratory testing for plasma or serum homocysteine changed bimodally over the time period from 1997 to 2010. These observations suggest that clinical practice was impacted by emerging evidence from association studies and intervention trials investigating homocysteine as a potentially treatable cardiac risk factor.

Corresponding author: Steven R. Lentz, MD, PhD, Department of Internal Medicine, The University of Iowa Carver College of Medicine, 200 Hawkins Drive, C32 GH, Iowa City, IA 52242, USA, Phone: +1 319 356 4048, Fax: +1 319 353 8383


The authors would like to acknowledge John Hellman for developing the algorithm used to retrieve patient data from the clinical information database.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.


1. Mudd SH, Finkelstein JD, Refsum H, Ueland PM, Malinow MR, Lentz SR, et al. Homocysteine and its disulfide derivatives: a suggested consensus terminology. Arterioscler Thromb Vasc Biol 2000;20:1704–6.10.1161/01.ATV.20.7.1704Search in Google Scholar

2. Carmel R, Jacobsen D. Homocysteine in health and disease. Cambridge: Cambridge University Press, 2009.Search in Google Scholar

3. Clarke R, Daly L, Robinson K, Naughton E, Cahalane S, Fowler B, et al. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 1991;324:1149–55.10.1056/NEJM199104253241701Search in Google Scholar PubMed

4. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. J Am Med Assoc 1995;274:1049–57.10.1001/jama.1995.03530130055028Search in Google Scholar PubMed

5. den Heijer M, Koster T, Blom HJ, Bos GM, Briet E, Reitsma PH, et al. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med 1996;334:759–62.10.1056/NEJM199603213341203Search in Google Scholar PubMed

6. Cattaneo M, Martinelli I, Mannucci PM. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med 1996;335:974–5.10.1056/NEJM199609263351313Search in Google Scholar PubMed

7. Homocysteine Studies C. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. J Am Med Assoc 2002;288:2015–22.10.1001/jama.288.16.2015Search in Google Scholar PubMed

8. den Heijer M, Rosendaal FR, Blom HJ, Gerrits WB, Bos GM. Hyperhomocysteinemia and venous thrombosis: a meta-analysis. Thromb Haemost 1998;80:874–7.10.1055/s-0037-1615380Search in Google Scholar

9. den Heijer M, Willems HP, Blom HJ, Gerrits WB, Cattaneo M, Eichinger S, et al. Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial. Blood 2007;109:139–44.10.1182/blood-2006-04-014654Search in Google Scholar PubMed

10. Clarke R, Halsey J, Lewington S, Lonn E, Armitage J, Manson JE, et al. Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: meta-analysis of 8 randomized trials involving 37 485 individuals. Arch Inter Med 2010;170:1622–31.10.1001/archinternmed.2010.348Search in Google Scholar PubMed

11. Clarke R, Halsey J, Bennett D, Lewington S. Homocysteine and vascular disease: review of published results of the homocysteine-lowering trials. J Inherit Metab Dis 2011;34: 83–91.10.1007/s10545-010-9235-ySearch in Google Scholar PubMed

12. Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. J Am Med Assoc 2004;291:565–75.10.1001/jama.291.5.565Search in Google Scholar PubMed

13. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567–77.10.1056/NEJMoa060900Search in Google Scholar PubMed

14. Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006; 354:1578–88.10.1056/NEJMoa055227Search in Google Scholar PubMed

15. Carmel R. Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II. Am J Clin Nutr 2011;94:348S-58S.10.3945/ajcn.111.013441Search in Google Scholar PubMed PubMed Central

16. Chatthanawaree W. Biomarkers of cobalamin (vitamin B12) deficiency and its application. J Nutr Health Aging 2011;15: 227–31.10.1007/s12603-010-0280-xSearch in Google Scholar PubMed

Received: 2012-9-20
Accepted: 2012-10-4
Published Online: 2012-11-08
Published in Print: 2013-03-01

©2013 by Walter de Gruyter Berlin Boston

Downloaded on 26.2.2024 from
Scroll to top button