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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 5  |  Page : 863-866
Hyperhemocysteinemia and cardiovascular risks in hemodialysis patients

Shiraz University of Medical Sciences, Shiraz, Iran

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Date of Web Publication31-Aug-2010


The risk of premature and progressive occlusive vascular disease is high in chronic uremic patients, and it accounts for more than 40% of the mortality in dialysis patients. End stage renal failure (ESRF) patients exhibit elevated plasma homocystein levels, about four fold as much as those in the controls, and it is now considered as a causative factor for increased risk of cardiovascular death among these patients. The aim of this study was to evaluate the relationship of total plasma homocysteine level and echocardiographic abnormalities as a surrogate of cardiac disease outcome in hemodialysis patients. 123 adult patients on maintenance hemodialysis and having echocardiography done during January till November 2006 were enrolled in this cross­sectional study. Plasma homocysteine level was directly related to the presence of aortic regur­gitation r= 0.27 P= 0.009. There were negative correlations between ejection fraction (EF), left ventricular systolic dimension (LV.S) (r= - 0.71, P= 0.0001), left ventricular diastolic dimension (LV.D) (r= -0.23 p= 0.01) and age (r= - 0.021 P= 0.02). In conclusion we did not find the para­doxical reverse epidemiology in our patients and plasma total homocysteine level was in direct correlation with cardiac risk factors such as left ventricular mass index and aortic regurgitation.

How to cite this article:
Sagheb MM, Ostovan MA, Sohrabi Z, Atabati E, Raisjalai GA, Roozbeh J. Hyperhemocysteinemia and cardiovascular risks in hemodialysis patients. Saudi J Kidney Dis Transpl 2010;21:863-6

How to cite this URL:
Sagheb MM, Ostovan MA, Sohrabi Z, Atabati E, Raisjalai GA, Roozbeh J. Hyperhemocysteinemia and cardiovascular risks in hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2021 Dec 4];21:863-6. Available from: https://www.sjkdt.org/text.asp?2010/21/5/863/68881

   Introduction Top

The risk of premature and progressive occlu­sive vascular disease is high in chronic uremic patients and accounts for more than 40% of the deaths in dialysis patients. [1],[2],[3] Prevention and treat­ment strategies demand precise knowledge of risk factors and of the possibility of modifying them with appropriate treatments. [4] Hyperhomo­cysteinemia has been implicated as potential trigger of atherosclerotic complications in pa­tients with chronic renal disease. [5] Hyperhomo­cysteinemia is an independent risk factor for coronary heart disease, cerebrovascular acci­dents, peripheral vascular disease and deep ve­nous thrombosis. [6],[7] End stage renal Disease (ESRD) patients exhibit elevated plasma homo­cysteine levels, about fourfold greater than con­trols, and it is now considered as a causative factor for increased risk of cardiovascular death among these patients. [8],[9] Experimental studies suggest that homocysteine may enhance lipo­protein oxidation, increases smooth muscle pro­liferation, induces endothelial dysfunction, in­duces endothelial activation of factor V, and re­duces protein C activation in endothelial cells. [10] Plasma homocysteine is independently related to aortic [11] and left ventricular hypertrophy. [12] Left ventricular hypertrophy measured by elec­trocardiography is associated with a higher risk of cardiovascular events. [13] Left ventricular hyper­trophy is the main manifestation of uremic car­diomyopathy and predicts both cardiovascular events and death independent of conventional risk factors.

The aim of this study was to evaluate the re­lation of total plasma homocysteine level and echocardiographic abnormalities as a surrogate of cardiac disease and outcome in hemodialysis patients.

   Method Top

One hundred twenty three adult patients with chronic renal failure undergoing dialysis and echocardiographic study during January till No­vember 2006 were enrolled in this cross-sec­tional study from hemodialysis centers of Shi­raz University of Medical Science. These patients were renal transplant candidates. Those who were dialyzed at least 2-3 times per week with 17-80 years old were selected. Patients with technically difficult to perform echocardiogra­phy were also excluded from the study. Informed consent was taken from all the subjects parti­cipating in the study. All the patients underwent two dimensional, M mode, Doppler and color Doppler echocardiography by ATL 3500 HDI Echo machine in the left lateral decubitus po­sition, using 3.5 MHz transducer by a consul­tant physician experienced in echocardiography.

The left ventricular ejection fraction (EF) and fractional shortening (FS) were measured as in­dices of left ventricular (LV) systolic function. EF was determined using area length method. LV mass was measured by echo machine in M­mode, short axis view of the left ventricle, Body surface area (BSA) was calculated by the formula BSA=(0.0001) Χ (71.84) Χ (weight) 0.425 Χ (height) 0.725 , where weight is measured in kilograms and height in centimeters. Left ven­tricular mass was divided by BSA to calculate LV mass index (LVMI). They filled a demogra­phic questionnaire containing information about age, sex, weight and height. Demographic data, cardiac risk factors, type, frequency and onset of dialysis were also recorded. 76 of the total 123 patients agreed to give plasma samples for determinations of homocysteine and folate, B12, parathyroid hormone, calcium and phosphorus.

Plasma total homocysteine were determined with ELISA kits. Parathyroid hormone, B12 and folate were determined by RIA kits. Cal­cium and phosphorus were determined by calo­rimetric methods.

   Statistical Analysis Top

All the data were analyzed by SPSS software, version 15. Data were statistically analyzed using univariate analysis. A P-value of less than 0.05 was considered significant.

   Results Top

The mean age of the patients was 38.8 ± 13 years and 61.5% of the patients were female. The prevalence of various cardiac risk factors was 8.1% diabetes mellitus, 49.6% hyperten­sion and 14.6% current smoking. The mean of plasma total homocysteine level was 26.82 ± 13.33 μmol/L. Patients characteristic are shown in [Table 1]. Plasma total homocysteine was in­versely related to plasma folate (r= - 0.323, P= 0.003) and plasma B12 (r= - 0.30, P= 0.005) and directly related to left ventricular mass index (r = 0.278, P= 0.01). Plasma homocys­teine level was directly related to presence of aortic regurgitation r = 0.27 P= 0.009.

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There were a negative correlations between ejection fraction (EF), left ventricular systolic dimension (LV.S) (r= -0.71, P= 0.0001), left ventricular diastolic dimension (LV.D) (r= - 0.23, P= 0.01) and age (r= - 0.021, P= 0.02) but there was a positive correlation between EF and fractional shortening (r = 0.89, P= 0.0001). We found that left ventricular mass index (LV Mass /BSA) was inversely related to sex (r - 0.19 P= 0.03), hemoglobin (r = o.325 P= 0.039 ) and was directly related to plasma total homocysteine level (r = 0.27 P= 0.01), left ventricular systolic dimension (r = 0.38 P= 0.0001) and left ventri­cular diastolic dimension (r = 0.55 P= 0.0001). We found a positive correlation between pre­sence of hypertension and left ventricular mass index (r =0.28 P= 0.002).

We did not find any significant correlation between homocysteine, cardiac ejection fraction, left ventricular masss index and other variables such as serum calcium and phosphorous and plasma parathyroid hormone level.

   Discussion Top

In the general population, increased homocys­teine concentration is a risk factor for cardio­vascular disease and mortality. [14] In this study, we found a direct correlation of plasma total homocysteine level and left ventricular mass index (P= 0.01). In other words patients with higher total plasma homocysteine level have a higher left ventricular mass index. Previous cli­nical data indicate that hyperhomocysteinemia is associated with an increased left ventricular mass and increased incidence of heart failure. [15] Existing data suggest direct effects of homocys­teine on the myocardium as well as nitrous oxide independent vascular effects. [16],[17] In some studies, homocysteine emerged as an inverse, rather than as a direct, predictor of adverse cli­nical outcomes. [19],[20],[21] We did not find this parado­xical reverse epidemiology in our patients and plasma total homocystein level was in direct correlation with cardiac risk factors such as left ventricular mass index and aortic regurgitation.

The paradoxical association between homo­cysteine and risk of death and cardiovascular events is fully justified by the confounding effect of inflammation and malnutrition. [22] Our study population consisted of renal transplant candidates who were younger and healthier he­modialysis patients with less inflammation and malnutrition and may explain the lack of majo­rity of the cardiovascular risk factors.

In conclusion, hyperhomocysteinemia was di­rectly correlated with echocardiographic findings such as Left ventricular mass index and aortic regurgitation in young ESRD patients. Further well-powered intervention studies are needed to indicate whether lowering plasma homocysteine produces beneficial effects in hemodialysis pa­tient.

   References Top

1.Walter R, Mischak H, Haller H. Haemodialysis, atherosclerosis and inflammation-identifying mo­lecular mechanisms of chronic vascular disease in ESRD patients. Nephrol Dial Transplant 2002;17 (Suppl.3):24-9.  Back to cited text no. 1      
2.Parfrey PS. Cardiac disease in dialysis patients: Diagnosis, burden of disease, prognosis, risk fac­tors and management. Nephrol Dial Transplant 2000;15(Suppl.5):58-68.  Back to cited text no. 2      
3.Parfrey PS: Cardiac and cerebrovascular disease in chronic uremia. Am J Kidney Dis 1993;21:77-80.  Back to cited text no. 3      
4.Zoccal C, Mallamacif F, Tripepi G. Novel cardio­vascular risk factors in end-stage renal disease. J Am Soc Nephrol 2004;15:S77-80.  Back to cited text no. 4      
5.Moustapha A, Naso A, Nahlawi M, et al. Prospec­tive study of hyperhomocysteinemia as an adverse cardiovascular risk factor in end-stage renal di­sease. Circulation 1998;97:138-41.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]  
6.Ueland PM, Refsum H. Plasma homocysteine, a risk factor for vascular disease: plasma levels in health, disease and drug therapy. J Lab Clin Med 1989;114:473-501.  Back to cited text no. 6  [PUBMED]    
7.Welch GN, Loscalzo J. Plasma homocysteine and atherothrombosis. N Engl J Med 1998;338:1042­-50.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Wilcken DE, Gupta VJ. Sulphur containing amino acids in chronic renal failure with particular reference to plasma homocysteine and cystine­plasma homocysteine mixed disulphide. Eur J Clin Invest 1979;9:301-7.  Back to cited text no. 8  [PUBMED]    
9.Manns BJ, Burgess ED, Hyndman ME, Parsons HG, Schaefer JP, Scott-Douglas NW. Hyperhomo­cyst(e)inemia and the prevalence of atherosclerotic vascular disease in patients with end-stage renal disease. Am J Kidney Dis 1999;34(4):669-77.  Back to cited text no. 9      
10.Lentz SR. Homocysteine and vascular dysfunc­tion. Life Sci 1997;61:1205-15.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Blacher J, Demuth K, Guerin AP, et al. Influence of biochemical alterations on arterial stiffness in patients with end stage renal disease. Arterioscler Thromb Vasc Biol 1998;18:534-41.  Back to cited text no. 11      
12.Anan F,Takahashi N, Shimomura T, et al. Hyper­plasma homocysteinemia is a significant risk fac­tor for silent cerebral infarction in patients with chronic renal failure undergoing hemodialysis. Metabolism 2006;55(5):656-61.  Back to cited text no. 12      
13.Levy D, Salomon M, D'agostino RB, et al. Prog­nostic implications of baseline electrocardiogra­phic features and their serial changes in subjects with left ventricular hypertrophy. Circulation 1994;90:1786-93.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]  
14.Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002;325:1202.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]  
15.Sundstrom J, Vasan RS. Homocysteine and heart failure: a review of investigations from the Framingham Heart Study. Clin Chem Lab Med 2005;43(10):987-92.  Back to cited text no. 15      
16.Enrico V, Ivano B, Gregoriana Z, et al. Homo­cysteine and heart failure: an overview. Recent Pat Cardiovasc Drug Discov 2009;4(1):15-21.  Back to cited text no. 16      
17.Herrmann W, Herrmann M, Joseph J, Tyagi SC. Homocysteine, brain natriuretic peptide and chro­nic heart failure: a critical review. Clin Chem Lab Med 2007;45(12):1633-44.  Back to cited text no. 17      
18.Giusti B, Marcucci R, Lapini I, Sestini I, Lenti M, Yacoub M, Pepe G. Role of hyperhomocystei­nemia in aortic disease. Cell Mol Biol (Noisy-le­grand) 2004;50(8):945-52.  Back to cited text no. 18      
19.Suliman ME, Qureshi AR, Barany P, et al. Hyper­homocysteinemia, nutritional status, and cardio­vascular disease in hemodialysis patients. Kidney Int 2000;57:1727-35.  Back to cited text no. 19      
20.Wrone EM, Hornberger JM, Zehnder JL, McCann LM, Coplon NS, Fortmann SP. Randomized trial of folic acid for prevention of cardiovascular events in end-stage renal disease. J Am Soc Nephrol 2004;15:420-6.  Back to cited text no. 20  [PUBMED]  [FULLTEXT]  
21.Kalantar-Zadeh K, Block G, Humphreys MH, McAllister CJ, Kopple JD. A low, rather than a high, total plasma homocysteine is an indicator of poor outcome in hemodialysis patients. J Am Soc Nephrol 2004;15:442-53.  Back to cited text no. 21  [PUBMED]  [FULLTEXT]  
22.Suliman M, Stenvinkel P, Qureshi AR, et al. The reverse epidemiology of plasma total homo­cysteine as a mortality risk factor is related to the impact of wasting and inflammation. Nephrol Dial Transplant 2007;22:209-17.  Back to cited text no. 22  [PUBMED]  [FULLTEXT]  

Correspondence Address:
Zahra Sohrabi
Shiraz University of Medical Sciences, Shiraz
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PMID: 20814121

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