Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter November 7, 2006

Increased homocysteine in heart failure: a result of renal impairment?

Nur Aksoy, Mehmet Aksoy, Mahmut Cakmak, Hasan Serdar Gergerlioglu, Vedat Davutoglu, Serdar Soydinc and Iclal Meram

Abstract

Background: Hyperhomocysteinemia may constitute a risk factor for patients with severe heart failure. This study examines the relationship between plasma homocysteine concentration and left ventricular ejection fraction with renal function in heart failure patients free of coronary artery disease.

Methods: Left ventricular ejection fraction was documented in 62 patients with advanced heart failure who had no proven significant coronary artery stenosis. Glomerular filtration rate was measured using the Cockroft-Gault equation.

Results: Elevated homocysteine levels (≥15μmol/L) were detected in 22 patients. Low glomerular filtration rate was observed in patients who had normal serum creatinine concentration. Homocysteine was strongly correlated with age, duration of disease, left ventricular ejection fraction, serum creatinine, and glomerular filtration rate. Statistically significant trends were observed across respective homocysteine quartiles. However, by multivariate regression, the strongest predictor of homocysteine was the glomerular filtration rate.

Conclusions: Impaired renal function leads to a diminished clearance rate, which can be a prominent pathophysiological mechanism in the elevation of homocysteine concentration in heart failure.

Clin Chem Lab Med 2006;44:1324–9.


Corresponding author: Nur Aksoy, MD, University of Gaziantep, Vocational School of Higher Education for Health Services, Gaziantep 27310, Turkey Phone: +90-342-3601200, Fax: +90-342-3603928

References

1. Bostom AG, Selhub J. Homocysteine and arteriosclerosis. Circulation 1999; 99:2361–3.10.1161/01.CIR.99.18.2361Search in Google Scholar

2. Eikelboom JW, Lonn E, Genest J Jr, Hankey G, Yusuf S. Homocyst(e)ine and cardiovascular disease. Ann Intern Med 1999; 131:363–75.10.7326/0003-4819-131-5-199909070-00008Search in Google Scholar

3. Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med 1998; 49:31–62.10.1146/annurev.med.49.1.31Search in Google Scholar

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

5. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, et al. Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. 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

6. Nahlawi M, Seshadri N, Boparai N, Naso A, Jacobsen DW, McCarthy P, et al. Usefulness of plasma vitamin B6, B12, folate, homocysteine, and creatinine in predicting outcomes in heart transplant recipients. Am J Cardiol 2002; 89:834–37.10.1016/S0002-9149(02)02194-XSearch in Google Scholar

7. Schofield RS, Wessel TR, Walker TC, Cleeton TS, Hill JA, Aranda JM Jr, et al. Hyperhomocysteinemia in patients with heart failure referred for cardiac transplantation: preliminary observations. Clin Cardiol 2003; 26:407–10.10.1002/clc.4960260904Search in Google Scholar PubMed PubMed Central

8. Bokhari SW, Bokhari ZW, Zell JA, Lee DW, Faxon DP. Plasma homocysteine levels and left ventricular systolic function in coronary artery disease patients. Coron Artery Dis 2005; 16:153–61.10.1097/00019501-200505000-00004Search in Google Scholar PubMed

9. Gibelin P, Serre S, Candito M, Houcher B, Berthier F, Baudouy M. Prognostic value of homocysteinemia in patients with congestive heart failure. Clin Chem Lab Med 2006; 44:813–6.10.1515/CCLM.2006.138Search in Google Scholar PubMed

10. Vasan RS, Beiser A, D'Agostino R, Levy D, Selhub J, Jacques PF, et al. Plasma homocysteine and risk for congestive heart failure in adults without prior myocardial infarction. J Am Med Assoc 2003; 289:251–57.10.1001/jama.289.10.1251Search in Google Scholar PubMed

11. Araki A, Sako Y. Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr 1987; 422:43–52.10.1016/0378-4347(87)80438-3Search in Google Scholar

12. Ajayi AA. Estimation of creatinine clearance from serum creatinine: utility of the Cockroft and Gault equation in Nigerian patients. Eur J Clin Pharmacol 1991; 40:429–31.10.1007/BF00265859Search in Google Scholar

13. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16:31–41.10.1159/000180580Search in Google Scholar

14. Luke DR, Halstenson CE, Opsahl JA, Matzke GR. Validity of creatinine clearance estimates in the assessment of renal function. Clin Pharmacol Ther 1990; 48:503–8.10.1038/clpt.1990.186Search in Google Scholar

15. Robert S, Zarowitz BJ, Peterson EL, Dumler F. Predictability of creatinine clearance estimates in critically ill patients. Crit Care Med 1993; 21:1487–95.10.1097/00003246-199310000-00016Search in Google Scholar

16. Robertshaw M, Lai KN, Swaminathan R. Prediction of creatinine clearance from plasma creatinine: comparison of five formulae. Br J Clin Pharmacol 1989; 28:275–80.10.1111/j.1365-2125.1989.tb05427.xSearch in Google Scholar

17. Waller DG, Fleming JS, Ramsey B, Gray J. The accuracy of creatinine clearance with and without urine collection as a measure of glomerular filtration rate. Postgrad Med J 1991; 67:42–6.10.1136/pgmj.67.783.42Search in Google Scholar

18. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography: American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989; 2:358–67.10.1016/S0894-7317(89)80014-8Search in Google Scholar

19. Ljungman S, Kjekshus J, Swedberg K. Renal function in severe congestive heart failure during treatment with enalapril (the Cooperative North Scandinavian Enalapril Survival Study [CONSENSUS] trial). Am J Cardiol 1992; 70:479–87.10.1016/0002-9149(92)91194-9Search in Google Scholar

20. Van den Broek SA, Van Veldhuisen DJ, De Graeff PA, Landsman ML, Hillege H, Lie KI. Comparison between New York Heart Association classification and peak oxygen consumption in the assessment of functional status and prognosis in patients with mild to moderate chronic congestive heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1992; 70:359–63.10.1016/0002-9149(92)90619-ASearch in Google Scholar

21. Lieverse AG, Van Veldhuisen DJ, Smit AJ, Zijlstra JG, Meijer S, Reitsma WD, et al. Renal and systemic hemodynamic effects of ibopamine in patients with mild to moderate congestive heart failure. J Cardiovasc Pharmacol 1995; 25:361–67.10.1097/00005344-199503000-00003Search in Google Scholar PubMed

22. Ljungman S, Laragh JH, Cody RJ. Role of the kidney in congestive heart failure: relationship of cardiac index to kidney function. Drugs 1990; 39(Suppl 4):10–21.10.2165/00003495-199000394-00004Search in Google Scholar PubMed

23. Wollesen F, Brattstrom L, Refsum H, Ueland PM, Berglund L, Berne C. Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. Kidney Int 1999; 55:1028–35.10.1046/j.1523-1755.1999.0550031028.xSearch in Google Scholar PubMed

24. Bostom AG, Gohh RY, Bausserman L, Hakas D, Jacques PF, Selhub J, et al. Serum cystatin C as a determinant of fasting total homocysteine levels in renal transplant recipients with a normal serum creatinine. J Am Soc Nephrol 1999; 10:164–6.10.1681/ASN.V101164Search in Google Scholar PubMed

25. Norlund L, Grubb A, Fex G, Leksell H, Nilsson JE, Schenck H, et al. The increase of plasma homocysteine concentrations with age is partly due to the deterioration of renal function as determined by plasma cystatin C. Clin Chem Lab Med 1998; 36:175–8.10.1515/CCLM.1998.032Search in Google Scholar PubMed

26. Bostom AG, Bausserman L, Jacques PF, Liaugaudas G, Selhub J, Rosenberg IH. Cystatin C as a determinant of fasting plasma total homocysteine levels in coronary artery disease patients with normal serum creatinine. Arterioscler Thromb Vasc Biol 1999; 19:2241–4.10.1161/01.ATV.19.9.2241Search in Google Scholar PubMed

27. Siroka R, Trefil L, Rajdl D, Racek J, Rusnakova H, Cibulka R, et al. Asymmetric dimethylarginine, homocysteine and renal function – is there a relation? Clin Chem Lab Med 2005; 43:1147–50.10.1515/CCLM.2005.199Search in Google Scholar PubMed

28. Arnadottir M, Hultberg B, Nilsson-Ehle P, Thysell H. The effect of reduced glomerular filtration rate on plasma total homocysteine concentration. Scand J Clin Lab Invest 1996; 56:41–6.10.3109/00365519609088586Search in Google Scholar PubMed

29. Fliser D, Franek E, Joest M, Block S, Mutschler E, Ritz E. Renal function in the elderly: impact of hypertension and cardiac function. Kidney Int 1997; 51:1196–204.10.1038/ki.1997.163Search in Google Scholar PubMed

30. Ventura P, Panini R, Veriato C, Scarpetta G, Salvioli G. Hyperhomocysteinemia and related factors in 600 hospitalized elderly subjects. Metabolism 2001; 50:1466–71.10.1053/meta.2001.28079Search in Google Scholar PubMed

31. Guttormsen AB, Ueland PM, Svarstad E, Refsum H. Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure. Kidney Int 1997; 52:495–502.10.1038/ki.1997.359Search in Google Scholar PubMed

32. Herzlich BC, Lichstein E, Schulhoff N, Weinstock M, Pagala M, Ravindran K, et al. Relationship among homocysteine, vitamin B-12 and cardiac disease in the elderly: association between vitamin B-12 deficiency and decreased left ventricular ejection fraction. J Nutr 1996; 126:1249S–53S.10.1093/jn/126.suppl_4.1249SSearch in Google Scholar PubMed

33. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary heart disease. N Engl J Med 1997; 337:230–6.10.1056/NEJM199707243370403Search in Google Scholar PubMed

34. Homocysteine Studies Collaboration. 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

Received: 2006-6-11
Accepted: 2006-8-25
Published Online: 2006-11-7
Published in Print: 2006-11-1

©2006 by Walter de Gruyter Berlin New York