Abstract
Purpose
The relationship between plasma homocysteine and stroke is controversial in many studies. There are only a few serial-sample studies which have looked at changes in stroke homocysteine during acute stroke. None of these studies investigated the changes in homocysteine in the first 3 days after stroke onset. Therefore, we designed this serial-sample prospective study to elucidate patterns of homocysteine concentration fluctuation at 0, 24 and 48 hours post stroke.
Material and Methods
Thirty one (22 ischemic and 9 hemorrhagic) patients with stroke and thirty three controls were selected. Three homocysteine levels were obtained from all stroke patients, while only one sample was taken from controls.
Results
Plasma homocysteine concentration was higher in males and in hemorrhagic stroke patients at all time points. Paired sample testing revealed significant differences in the mean values of homocysteine taken at 48 hours (p=0.047, 95% CI: −1.467 to −0.011) for all cases. For patients with hemorrhagic stroke, significant values were again obtained at 48 hours only (p=0.024, 95% CI:−8.266 to −0.763). After gender stratification, we found significantly higher mean homocysteine concentrations at all time points in male patients (at 0 hour: p=0.043, 95%CI: −5.197 to −0.908; after 24 hours: p=0.002, 95%CI: −7.899 to −2.279; after 48 hours: p=0.032, 95%CI: −4.644 to −0.246).
Conclusions
In this pilot study, we found that, on average, homocysteine levels initially decrease and then gradually rise in stroke patients, especially patients with hemorrhagic stroke. Also, there are significant genderbased differences in plasma homocysteine levels in our study population. In addition to increased levels of homocysteine after 48 hours in stroke patients, we found moderate hyperhomocysteinemia in our healthy controls, consistent with previous data from Pakistan.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Hankey G. J., Stroke: how large a public health problem, and how can the neurologist help? Arch. Neurol., 1999, 56, 748–754
Kim A. S., Johnston S.C., Global variation in the relative burden of stroke and ischemic heart disease, Circulation, 2011, 124, 314–323
Mattson M. P., Shea T. B., Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders, Trends Neurosci., 2003, 26, 137–146
Zou C. G., Banerjee R., Homocysteine and redox signaling, Antioxid. Redox Signal., 2005, 7, 547–559
Schroecksnadel K., Frick B., Winkler C., Leblhuber F., Wirleitner B., Fuchs D., Hyperhomocysteinemia and immune activation, Clin. Chem. Lab. Med., 2003, 41, 1438–1443
Alfthan G., Pekkanen J., Jauhiainen M., Pitkäniemi J., Karvonen M., Tuomilehto J. et al., Relation of serum homocysteine and lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish population based study, Atherosclerosis, 1994, 106, 9–19
Howard V. J., Sides E. G., Newman G. C., Cohen S. N., Howard G., Malinow M. R. et al., Changes in plasma homocyst(e)ine in the acute phase after stroke, Stroke, 2002, 33, 473–478
Karttunen V., Alfthan G., Hiltunen L., Rasi V., Kervinen K., Kesäniemi Y. A. et al., Risk factors for cryptogenic ischaemic stroke, Eur. J. Neurol., 2002, 9, 625–632
Kristensen B., Malm J., Nilsson T.K., Hultdin J., Carlberg B., Dahlén G. et al., Hyperhomocysteinemia and hypofibrinolysis in young adults with ischemic stroke, Stroke, 1999, 30, 974–980
Lindgren A., Brattström L., Norrving B., Hultberg B., Andersson A., Johansson B.B., Plasma homocysteine in the acute and convalescent phases after stroke, Stroke, 1995, 26, 795–800
Meiklejohn D. J., Vickers M. A., Dijkhuisen R., Greaves M., Plasma homocysteine concentrations in the acute and convalescent periods of atherothrombotic stroke, Stroke, 2001, 32, 57–62
Lonn E., Yusuf S., Arnold M.J., 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, 1567–1577
Bønaa K. H., Njølstad I., Ueland P. M., Schirmer H., Tverdal A., Steigen T. et al., Homocysteine lowering and cardiovascular events after acute myocardial infarction, N. Engl. J. Med., 2006, 354, 1578–1588
Toole J. F., Malinow M. R., Chambless L. E., Spence J. D., Pettigrew L. C., Howard V. J. 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, JAMA, 2004, 291, 565–575
National Institute for Health and Clinical Excellence, Clinical guideline on Stroke: Diagnosis and initial management of acute stroke and transient ischemic attack (TIA), NICE clinical guideline 68, London: National Institute for Health and Clinical Excellence, 2008
Voortman A., Melse-Boonstra A., Schulz J. M., Burema J., Katan M. B., Verhoef P., Optimal time interval between repeated blood sampling for measurements of total homocysteine in healthy individuals, Clin. Chem., 2001, 47, 1839–1841
Haapaniemi E., Helenius J., Soinne L., Syrjala M., Kaste M., Tatlisumak T., Serial measurements of plasma homocysteine levels in early and late phases of ischemic stroke, Eur. J. Neurol., 2007, 14, 12–17
Egerton W., Silberberg J., Crooks R., Ray C., Xie L., Dudman N., Serial measures of plasma homocyst(e)ine after acute myocardial infarction, Am. J. Cardiol., 1996, 77, 759–761
Sastry B. K., Indira N., Anand B., Kedarnath, Prabha B. S., Raju B. S., A case-control study of plasma homocysteine levels in South Indians with and without coronary artery disease, Indian Heart J., 2001, 53, 749–753
Iqbal M. P., Ishaq M., Kazmi K. A., Yousuf F. A., Mehboobali N., Ali S. A. et al., Role of vitamins B6, B12 and folic acid on hyperhomocysteinemia in a Pakistani population of patients with acute myocardial infarction, Nutr. Metab. Cardiovasc. Dis., 2005, 15, 100–108
Iqbal M. P., Fatima T., Parveen S., Yousuf F. A., Shafiq M., Mehboobali N. et al., Lack of association of methylenetetrahyclrofolate reductase 677C>T mutation with coronary artery disease in Pakistani population, J. Mol. Genet. Med., 2005, 1, 26–32
Holmes M. V., Newcombe P., Hubacek J. A., Sofat R., Ricketts S. L., Cooper J. et al., Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials, Lancet, 2011, 378, 584–594
Hultdin J., Van Guelpen B., Winkvist A., Hallmans G., Weinehall L., Stegmayr B. et al., Prospective study of first stroke in relation to plasma homocysteine and MTHFR 677C>T and 1298A>C genotypes and haplotypes — evidence for an association with hemorrhagic stroke, Clin. Chem. Lab. Med., 2011, 49, 1555–1562
Somarajan B. I., Kalita J., Mittal B., Misra U. K., Evaluation of MTHFR C677T polymorphism in ischemic and hemorrhagic stroke patients. A case-control study in a Northern Indian population, J. Neurol. Sci., 2011, 304, 67–70
Iso H., Moriyama Y., Sato S., Kitamura A., Tanigawa T., Yamagishi K. et al., Serum total homocysteine concentrations and risk of stroke and its subtypes in Japanese, Circulation, 2004, 109, 2766–2772
Li Z., Sun L., Zhang H., Liao Y., Wang D., Zhao B. et al., Elevated plasma homocysteine was associated with hemorrhagic and ischemic stroke, but methylenetetrahydrofolate reductase gene C677T polymorphism was a risk factor for thrombotic stroke: a Multicenter Case-Control Study in China, Stroke, 2003, 34, 2085–2090
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Bokhari, F.A., Butt, A., Hassan, S.A.A. et al. Serial changes in plasma homocysteine in acute clinical stroke. Translat.Neurosci. 3, 41–45 (2012). https://doi.org/10.2478/s13380-012-0005-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.2478/s13380-012-0005-1